|
1
|
Song J, Zeng J, Chen X, Wang J, Zhang Y, Gao Y, Wang R, Jiang N, Lin Y, Li R. Anti-neuroinflammatory agent rhein lysinate-based self-assembled injectable hydrogel loaded with ZL006 for promoting post-stroke functional recovery. Biomaterials 2025; 318:123124. [PMID: 39884131 DOI: 10.1016/j.biomaterials.2025.123124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 12/27/2024] [Accepted: 01/23/2025] [Indexed: 02/01/2025]
Abstract
The therapeutic agent-based self-assembled hydrogel is gaining interest for biomedical applications, because it overcomes the poor biodegradability and low therapeutic agent loading of conventional polymer gelator-based hydrogel. Here, we present rhein lysinate (RHL), a therapeutic agent that self-assembles to form a stable hydrogel through the π-π stacking and hydrogen bonding interactions, while also exerting anti-neuroinflammatory effect. As a small molecular hydrogelator, RHL has significantly improved water solubility and enhanced self-assembly and gelation capabilities compared to the natural anthraquinone rhein. The relaxed gel-forming conditions enhance the practical application potential of self-assembled hydrogel of RHL (RHL gel). The RHL gel can be loaded with the bioactive agents such as 5-Fluorouracil, temozolomide, edaravone, and ZL006, mainly based on efficient stacking between aromatic rings in the bioactive agents and anthraquinone rings in the hydrogel network structure. The pre-gelled RHL gel and ZL006-loaded RHL gel (ZL006-RHL gel) exhibit shear-thinning behavior, flowing like a liquid under high shear stress during injection. Once this shear stress is removal within the body, they rapidly recover to the initial solid-like state. When a single dose of ZL006-RHL gel is administrated to stroke cavity in the subacute phase of stroke, RHL gel matrix effectively reduces post-stroke neuroinflammation, creates a favorable environment for ZL006 to enhance neuroplasticity, and confers a sustained and stable action to ZL006, leading to a long-lasting improvement of motor performance. This study may provide a valuable strategy for therapeutic intervention to promote post-stroke functional recovery, for which there are no clinically available drugs.
Collapse
Affiliation(s)
- Jiamei Song
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Jiaqi Zeng
- The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China
| | - Xi Chen
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Jiayu Wang
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Ying Zhang
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Yuhao Gao
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Ruiqi Wang
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China
| | - Nan Jiang
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China; National Vaccine Innovation Platform, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
| | - Yuhui Lin
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
| | - Rui Li
- School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
| |
Collapse
|
|
2
|
Luo JX, Zhan Y, Liu YL, Wu ZP, Liu YQ, Cheng XY, Sun DL, Liang XL, Li YM, Xiong YX, Li Q, Liu WJ. Integrating network pharmacology and multi-omics to explore the potentiating effect and mechanism of Shenlingcao oral liquid on cisplatin chemotherapy in Lewis lung cancer mice. JOURNAL OF ETHNOPHARMACOLOGY 2025; 348:119843. [PMID: 40258526 DOI: 10.1016/j.jep.2025.119843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/21/2025] [Accepted: 04/18/2025] [Indexed: 04/23/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Shenlingcao oral liquid (SLC), derived from traditional clinical formulations, can enhance physical strength and vitality during chemotherapy for malignant tumors. Previous studies have indicated that SLC can enhance the quality of life and daily functioning of patients with non-small cell lung cancer (NSCLC) within 6 months after adjuvant chemotherapy following radical surgery. Nevertheless, its precise mechanism of action is unclear. AIM OF THE STUDY To elucidate the function and underlying mechanism of SLC in enhancing the effect of cisplatin in treating NSCLC. MATERIALS AND METHODS UPLC-Q-Exactive Plus-MS/MS was used to characterize the chemical constituents of SLC. The main gene targets and the pathways of SLC that impact NSCLC were predicted using network pharmacology. A mouse model of Lewis lung cancer and the combination of transcriptomics, metabolomics, and 16S rRNA analysis were used to investigate the underlying mechanisms of the SLC-cisplatin combination in influencing the pathology of NSCLC. RESULTS The SLC-cisplatin combination significantly reduced tumor volume and weight (P < 0.01), boosted T lymphocytes (P < 0.05), increased cleaved-caspase-3/caspase-3 expression (P < 0.05), and decreased p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax protein levels (P < 0.05) compared with cisplatin monotherapy. It also improved the gut flora by enriching the abundance of Bacteroidaceae, S24-7, and Porphyromonadaceae, while modulating metabolic pathways, including caffeine metabolism and fatty acid degradation. CONCLUSIONS SLC enhanced the effect of cisplatin in inhibiting NSCLC by inducing cell apoptosis, augmenting immune responses, balancing the gut microbiota, and regulating key metabolic pathways. Our findings highlight the potential of SLC as an effective adjuvant therapy for NSCLC.
Collapse
MESH Headings
- Animals
- Cisplatin/pharmacology
- Cisplatin/administration & dosage
- Cisplatin/therapeutic use
- Carcinoma, Lewis Lung/drug therapy
- Carcinoma, Lewis Lung/pathology
- Carcinoma, Lewis Lung/genetics
- Mice, Inbred C57BL
- Drugs, Chinese Herbal/pharmacology
- Drugs, Chinese Herbal/administration & dosage
- Network Pharmacology
- Mice
- Lung Neoplasms/drug therapy
- Lung Neoplasms/pathology
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/pathology
- Male
- Metabolomics
- Antineoplastic Agents/pharmacology
- Drug Synergism
- Administration, Oral
- Cell Line, Tumor
- Multiomics
Collapse
Affiliation(s)
- Jia-Xin Luo
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, PR China.
| | - Yang Zhan
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi, 330103, PR China; Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, PR China.
| | - Yong-Lin Liu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi, 330103, PR China.
| | - Zhen-Peng Wu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, PR China.
| | - Yu-Qing Liu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, PR China.
| | - Xiao-Ying Cheng
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi, 330103, PR China.
| | - Deng-Long Sun
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi, 330103, PR China.
| | - Xin-Li Liang
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, PR China.
| | - Ying-Meng Li
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi, 330103, PR China.
| | - Yan-Xia Xiong
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi, 330103, PR China.
| | - Qiong Li
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, PR China.
| | - Wen-Jun Liu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, Jiangxi, 330096, PR China; School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, PR China.
| |
Collapse
|
|
3
|
Lin Z, Wang J, Luo H, Huang L, Pan Z, Yang S, Zhong C, Shan NC, Ye Z, Tan H, Yang X, Zhang B, Huang C, Zhang H. Changdiqing decoction (CDQD) ameliorates colitis via suppressing inflammatory macrophage activation and modulating gut microbiota. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 143:156856. [PMID: 40412060 DOI: 10.1016/j.phymed.2025.156856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 05/11/2025] [Accepted: 05/13/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND Ulcerative colitis (UC) is a non-specific inflammatory bowel disease. Unlike any single form of cell death reported previously, macrophage PANoptosis, a unique programmed cell death characterized by inflammation and necrosis, plays a crucial role in the pathogenesis of colitis. Changdiqing Decoction (CDQD), an empirical hospital prescription enema, has been used to treat UC for decades. This study aimed to investigate the multi-target anti-colitic effects of CDQD by examining its impact on intestinal homeostasis and its anti-inflammatory properties. METHODS A dextran sulfate sodium (DSS)-induced mouse model of acute colitis was employed. Interferon-gamma (IFN-γ) and KPT-330 were used to induce macrophage PANoptosis. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLCHRMS) was utilized to identify the chemical constituents of CDQD. Multi-omics analysis and fecal microbiota transplantation (FMT) were used to explore the therapeutic targets and gut microbiota alterations induced by CDQD. RESULTS CDQD treatment significantly alleviated colitis symptoms in mice, with a dose-dependent therapeutic effect. The decoction mitigated PANoptosis in colon tissues and bone marrow-derived macrophages (BMDMs). 16S rRNA sequencing analysis and metabonomics revealed that CDQD administration significantly altered the gut microbiota composition and metabolite profiles. Notably, CDQD-modulated gut microbiota exhibited anti-colitic effects through FMT. Integrated transcriptomics and network pharmacology analysis revealed that CDQD significantly downregulated the PI3K/Akt signaling pathway in colitis. This finding was further validated using the inhibitors LY294002 and MK2206. CONCLUSIONS CDQD alleviates colitis by suppressing inflammatory macrophage activation and modulating the gut microbiota. Our research provides a novel traditional Chinese medicine strategy for the treatment of UC via enema administration.
Collapse
Affiliation(s)
- Zelong Lin
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
| | - Jun Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment for Refractory Chronic Diseases, China
| | - Huishan Luo
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China
| | - Linwen Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China
| | - Zhaoyu Pan
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China
| | - Shilong Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China
| | - Cailing Zhong
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China
| | - Ng Chong Shan
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China
| | - Ziwen Ye
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Huishi Tan
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
| | - Xiaobo Yang
- Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510120, China.
| | - Beiping Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, China.
| | - Chongyang Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China.
| | - Haiyan Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510120, China.
| |
Collapse
|
|
4
|
Du X, Liu M, Li J, Liu Y, Ge S, Gao H, Zhang M. Bifidobacterium animalis Supplementation Improves Intestinal Barrier Function and Alleviates Antibiotic-Associated Diarrhea in Mice. Foods 2025; 14:1704. [PMID: 40428484 PMCID: PMC12110814 DOI: 10.3390/foods14101704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 05/09/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Probiotics have gained increasing recognition for their potential to mitigate antibiotic-associated diarrhea (AAD). However, the precise mechanisms underlying their effects remain unclear. This study developed a mouse model of AAD using ceftriaxone to investigate the alleviating effects and mechanisms of Bifidobacterium animalis A6 (A6). The findings indicated that A6 supplementation effectively attenuated ceftriaxone-associated diarrhea in mice. The morphological damage to the villi and crypts was partially restored and more neatly reorganized following the A6 intervention. Additionally, intestinal morphology observations revealed a significant increase in the thickness of the mucus layer in the A6-treated group. Further examination of key regulatory genes associated with mucus secretion demonstrated that the A6 intervention effectively upregulated the expression of mucin1, thereby reinforcing the mucus layer. Concurrently, the A6 intervention upregulated the expression of the AQP4 and SLC26A3 genes in the intestine, which is responsible for restoring water absorption capacity in AAD mice. Additionally, the A6 treatment reduced ceftriaxone-induced harm to the intestinal microbiota of the mice, boosting beneficial bacteria like Bacteroidales, Akkermansia, Bifidobacterium, and Lactobacillus. Overall, this study offers valuable insights into the potential therapeutic role of A6 in restoring intestinal homeostasis and alleviating symptoms associated with AAD.
Collapse
Affiliation(s)
- Xiaoyu Du
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Mingkun Liu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230000, China
| | - Jingyu Li
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Yue Liu
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Shaoyang Ge
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Haina Gao
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Ming Zhang
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| |
Collapse
|
|
5
|
Li L, Dai L, Lin M, He S, Du H, Lin D, Wang Y, Zhang F, Tao S, Sun X, Huang X, Liu H, Wang Q, He L, Wu K, You J, Zhang M, Fu C, Tu H, Ye N, Liu J, Gao F. Colonic Submucosa Targeted Delivery of Probiotic and Rhein for Ulcerative Colitis Treatment. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e2409711. [PMID: 40344311 DOI: 10.1002/advs.202409711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 04/01/2025] [Indexed: 05/11/2025]
Abstract
Ulcerative colitis (UC) is a chronic disease. A significant challenge for the management of UC is to achieve delivery of drugs to the multi-layer colonic barriers, as existing drugs are difficult to penetrate these depths. In this study, a novel drug delivery system using yeast cell wall microparticles (YPs) are developed to co-encapsulate Bacillus subtilis (BS) and Rhein (Rh) termed Rh-YBS. This system specifically targets colonic microfold cells, enabling direct delivery of BS to the colonic submucosa. Additionally, Rh enhances BS colonization in the submucosa through floral regulation. Studies indicate that Rh-YBS can effectively reach and proliferate within the submucosa in vivo. In a DSS-induced UC mouse model, Rh-YBS stimulates the CGRP-related neural pathway; BS activation in the submucosa leads to increased CGRP secretion, prompting goblet cells to secrete mucus and thereby repairing the mucosa. Furthermore, the Rh-YBS also provide a preventive benefit against UC. In summary, Rh-YBS represents an innovative drug delivery system for mucosal repair in UC treatment, activating a unique mechanism involving the CGRP-related neural pathway.
Collapse
Affiliation(s)
- Lingqiang Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Linxin Dai
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Meisi Lin
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Shuang He
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Hongye Du
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Dasheng Lin
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
- Chengdu Huashen Technology Group Co., Ltd., Chengdu, 611137, China
| | - Yanbin Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Fenglian Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Sian Tao
- College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Xiaoluo Sun
- College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Xinggui Huang
- College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Haihui Liu
- College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Qian Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Lingling He
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Kunhe Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Jieshu You
- College of Pharmacy, Shenzhen Technology University, Shenzhen, Guangdong, 518118, China
| | - Minyue Zhang
- Division of Hematology of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Chaomei Fu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - He Tu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Naijing Ye
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Jibin Liu
- College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| | - Fei Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China
| |
Collapse
|
|
6
|
Jia Y, Liu X, Gao X, Yin S, Wu K, Meng X, Ren H, Liu J, Liu Z, Li H, Jiang Y. Plantamajoside alleviates DSS-induced ulcerative colitis by modulating gut microbiota, upregulating CBS, and inhibiting NF-κB. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 143:156827. [PMID: 40381501 DOI: 10.1016/j.phymed.2025.156827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 04/18/2025] [Accepted: 05/02/2025] [Indexed: 05/20/2025]
Abstract
BACKGROUND Plantamajoside (PMS) is a natural bioactive compound derived from medicinal, food homologous plants of the genus Plantago. PURPOSE AND METHODS This study aimed to investigate the protective effects of PMS on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and explore the associated mechanisms. RESULTS We found that PMS treatment significantly alleviated UC symptoms in mice by preventing body weight loss, increasing colon length, and reducing disease activity index scores. Moreover, PMS alleviated colonic lesions, increased the number of goblet cells, upregulated the expression of intestinal barrier proteins (ZO-1, occludin, and claudin-3), and decreased the levels of pro-inflammatory factors. PMS treatment modulated the gut microbiota by increasing the relative abundance of Bacteroidota and Verrucomicrobiota and decreasing that of Firmicutes and Proteobacteria at the phylum level. At the genus level, PMS suppressed the abundance of pathogenic bacteria, such as Turicibacter and upregulated the abundance of [Eubacterium]_xylanophilum_group. Fecal microbiota transplantation experiments further confirmed that PMS treatment alleviated UC by modulating the gut microbiota. Transcriptomic analysis of colon tissues, coupled with reverse transcription-quantitative polymerase chain reaction and western blotting, showed that PMS treatment upregulated cystathionine beta-synthase (CBS) expression and inhibited NF-κB pathway activation. In a lipopolysaccharide-induced inflammation model in RAW264.7 cells, PMS treatment inhibited the secretion of pro-inflammatory cytokines, upregulated CBS expression, and prevented NF-κB pathway activation. CONCLUSION PMS protects against UC in mice via multiple mechanisms, including modulating the gut microbiota, increasing the expression levels of CBS, and inhibiting the NF-κB pathway.
Collapse
Affiliation(s)
- Yongheng Jia
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Xianjun Liu
- College of Biological and Food Engineering, Jilin Engineering Normal University, No. 3050 Kaixuan Street, Changchun 130000, China; Postdoctoral Research Workstation, Changchun Gangheng Electronics Company Limited, Changchun 130000, China
| | - Xinyi Gao
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Siyuan Yin
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Kun Wu
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Xianglong Meng
- Department of Gastroenterology, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Hui Ren
- Department of General surgery, the China-Japan Union Hospital of Jilin University, Changchun 130000, China
| | - Jiawei Liu
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Zijing Liu
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China
| | - Hao Li
- College of Biological and Food Engineering, Jilin Engineering Normal University, No. 3050 Kaixuan Street, Changchun 130000, China
| | - Yang Jiang
- Department of Gastrointestinal Colorectal and Anal Surgery, the China-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun 130000, China.
| |
Collapse
|
|
7
|
Liu T, He Z, Lv W, Deng L, Sun X, Chen Y. Characterization of the Active Ingredients and Prediction of the Potential Anticolitis Mechanism of the Feng-Liao-Chang-Wei-Kang Capsule via Mass Spectrometry and Network Pharmacology. JOURNAL OF ANALYTICAL METHODS IN CHEMISTRY 2025; 2025:2948965. [PMID: 40365509 PMCID: PMC12069849 DOI: 10.1155/jamc/2948965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 04/04/2025] [Indexed: 05/15/2025]
Abstract
The Feng-Liao-Chang-Wei-Kang (FLCWK) capsule is a nationally protected Chinese patent medicine for the treatment of colitis. However, the potential active components and the pharmacological mechanism underlying the anticolitis effect of the FLCWK capsule remain unclear. This study aimed to reveal the active ingredients and possible anticolitis mechanism of the FLCWK capsule using an integrated approach combining mass spectrometry and network pharmacology analysis. Ultra-performance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap MS) was applied to identify the components of the FLCWK capsule. A network pharmacology study, including target gene prediction and functional enrichment, was applied to screen the active ingredients of the FLCWK capsule and explore its potential mechanism for the treatment of colitis. A total of 115 components were identified in the FLCWK capsule. Network pharmacology results showed that 46 of these compounds with good bioavailability and drug-likeness, such as 4',5-dihydroxyflavone, pinostrobin, naringenin chalcone, apigenin, and morin, were selected as active ingredients. The active ingredients may act on 352 core protein targets, including EGFR, AKT1, PIK3R1, PIK3CB, and MAPK1, thereby modulating relevant pathways, such as MAPK and PI3K-Akt signaling pathways, and thus alleviating inflammation and intestinal damage in colitis. This study provided a useful approach to identify active components and the anticolitis mechanism of the FLCWK capsule and built up a reliable foundation for its clinical treatment.
Collapse
Affiliation(s)
- Tingting Liu
- School of Hainan Provincial Drug Safety Evaluation Research Center, Hainan Medical University, Haikou, China
| | - Zhijiang He
- Department of Orthopedics, Hainan Provincial Corps Hospital of Chinese People's Armed Police Force, Haikou, China
| | - Witiao Lv
- School of Pharmacy, Hainan Medical University, Haikou, China
| | - Liyun Deng
- School of Pharmacy, Hainan Medical University, Haikou, China
| | - Xizhe Sun
- School of Hainan Provincial Drug Safety Evaluation Research Center, Hainan Medical University, Haikou, China
| | - Yanfei Chen
- School of Hainan Provincial Drug Safety Evaluation Research Center, Hainan Medical University, Haikou, China
| |
Collapse
|
|
8
|
Duo R, Wang Y, Ma Q, Wang X, Zhang Y, Shen H. MTX-induced gastrointestinal reactions in RA: Prevotella enrichment, gut dysbiosis, and PI3K/Akt/Ras/AMPK pathways. Clin Rheumatol 2025:10.1007/s10067-025-07406-y. [PMID: 40198451 DOI: 10.1007/s10067-025-07406-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 03/12/2025] [Accepted: 03/17/2025] [Indexed: 04/10/2025]
Abstract
OBJECTIVES To investigate the role of gut microbiota in methotrexate (MTX)-induced gastrointestinal reactions (MRGR) in patients with rheumatoid arthritis (RA). METHODS As a prospective, single-center, convenience sampling study, stool samples were obtained from 28 RA patients (male: female = 10:18) at Lanzhou University Second Hospital who were undergoing MTX treatment for analysis of their gut microbiota using 16S rRNA gene sequencing. Clinical disease activity (CDAI) and MRGR were assessed after two months of MTX therapy. All data collection periods exceeded one year. Intestinal germ-free mice, generated through antibiotic treatment, received fecal microbiota transplantation (FMT) from the patients, followed by varying doses of MTX to observe MRGR. Intestinal transcriptomics and markers related to intestinal barrier function were subsequently examined. RESULTS Females (84.6%) and high disease activity (CDAI scores, 39.6 ± 11.2 vs 26.3 ± 9.2) were prone to have MRGR in RA patients. Patients with MRGR (PT-GR) showed lower gut microbial diversity versus non-MRGR (PT-noGR). Prevotella abundance, positively correlated with CDAI and MRGR (p < 0.05), was elevated in PT-GR. Administering 10 mg/kg MTX to mice caused intestinal damage. FMT-GR-MTX mice exhibited weight loss (95.2%), morphological deterioration (86.4%), and reduced tight junction proteins (Claudin-1:72.4%; ZO-1:81.2%). Transcriptomics linked upregulated Gβγ/CREB/Atp4b to PI3K/Akt/Ras pathways and downregulated PFK2/PP2 to AMPK signaling in MRGR. CONCLUSION Our study identified notable gut microbiota alterations in RA patients prone to MRGR, with changes in intestinal gene expression and reduced intestinal barrier function potentially contributing to MRGR. These findings suggest potential strategies to mitigate MRGR in RA patients undergoing MTX treatment. Key Points • The RA-related MRGR is correlated with the intestinal microbiota. • Females, low gut diversity, and Prevotella enrichment are MRGR risks in RA. • Upregulated DEGs in MRGR linked to PI3K/Akt, Ras pathways. • Downregulated DEGs in MRGR focus on the AMPK pathway.
Collapse
Affiliation(s)
- Ruixue Duo
- Department of Rheumatology and Immunology, Lanzhou University Second Hospital, 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu Province, China
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Yining Wang
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Quanzhi Ma
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Xiaoyuan Wang
- Department of Rheumatology and Immunology, Lanzhou University Second Hospital, 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu Province, China
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Yan Zhang
- Department of Rheumatology and Immunology, Lanzhou University Second Hospital, 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu Province, China
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Haili Shen
- Department of Rheumatology and Immunology, Lanzhou University Second Hospital, 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu Province, China.
- The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
| |
Collapse
|
|
9
|
Xu CC, Zhao WX, Sheng Y, Yun YJ, Ma T, Fan N, Song JQ, Wang J, Zhang Q. Serum homocysteine showed potential association with cognition and abnormal gut microbiome in major depressive disorder. World J Psychiatry 2025; 15:102567. [PMID: 40109991 PMCID: PMC11886347 DOI: 10.5498/wjp.v15.i3.102567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/18/2024] [Accepted: 01/06/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression. AIM To investigate the relationship between Hcy, microbiome, and cognition in depressive patients. METHODS We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function. RESULTS Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05). CONCLUSION Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.
Collapse
Affiliation(s)
- Chen-Chen Xu
- Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
| | - Wen-Xuan Zhao
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Yu Sheng
- Department of Psychiatry, Chinese People’s Liberation Army Unit 94710, Wuxi 214141, Jiangsu Province, China
| | - Ya-Jun Yun
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Ting Ma
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Ning Fan
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Jia-Qi Song
- Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Jun Wang
- Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
- Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
| | - Qi Zhang
- Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
- Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
| |
Collapse
|
|
10
|
Li Z, Chu T, Sun X, Zhuang S, Hou D, Zhang Z, Sun J, Liu Y, Li J, Bian Y. Polyphenols-rich Portulaca oleracea L. (purslane) alleviates ulcerative colitis through restiring the intestinal barrier, gut microbiota and metabolites. Food Chem 2025; 468:142391. [PMID: 39675274 DOI: 10.1016/j.foodchem.2024.142391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/03/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024]
Abstract
Ulcerative colitis (UC) is a recurrent intestinal disease caused by a complex of factors, and there are serious adverse effects and tolerance problems associated with the current long-term use of therapeutic drugs. The development of natural food sources and multi-targeted drugs for the treatment of UC is imminent. Portulaca oleracea L. (PO), as a vegetable, has been shown in studies to have an anti-UC effects. However, the relationship between the abundant active ingredients contained in Portulaca oleracea L. and the improvement of intestinal barrier, gut microbiota and metabolites is unclear. In the present study, Portulaca oleracea L. which was found to be rich in phenolic acid-based active ingredients, were effective in alleviating dextran sulfate sodium (DSS)-induced body weight loss, disease activity index (DAI) score and colon length in mice. It also decreased C-reactive protein (CRP) and myeloperoxidase (MPO) responses, reduced the permeation of fluorescein isothiocyanate (FITC)-dextran, lipopolysaccharide (LPS) and evans blue (EB), and improved histopathological scores. Meanwhile, in vitro and in vivo validation revealed the protective effects of purslane on the intestinal barrier indicators ZO-1, Occludin and Claudin-1, and inhibited the expression of inflammation-associated iNOS and NLRP3 proteins through the NF-κB signaling pathway. In addition, purslane increased the diversity of the intestinal flora, enhancing the proportion of the genera Butyricoccus, Dorea and Bifidobacterium and decreasing the percentage of Bacteroides, Turicibacter and Parabacteroides. Serum metabolomics analysis showed that the imbalance of 39 metabolites was significantly reversed after PO deployment. Enrichment analysis showed that Pentose phosphate pathway and Pyruvate metabolism pathway were the key pathways of PO against UC. Overall, purslane effectively improved the intestinal barrier disruption and intestinal inflammation by inhibiting the NF-κB signaling pathway, and adjusted the disorder of gut microbiota and metabolites to exert anti-UC effects.
Collapse
Affiliation(s)
- Zheng Li
- School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Tianjiao Chu
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Xin Sun
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Shen Zhuang
- College of Veterinary Medicine & Institute of Traditional Chinese Veterinary Medicine, Northwest A&F University, Yangling 712100, China
| | - Dianbo Hou
- School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Zhaohan Zhang
- College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Jialu Sun
- School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Yuhong Liu
- School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
| | - Jing Li
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
| | - Yifei Bian
- School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
| |
Collapse
|
|
11
|
Lin L, Han L, Gu C, Wang L, Zhang Z. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea. Open Life Sci 2025; 20:20220931. [PMID: 40092732 PMCID: PMC11909579 DOI: 10.1515/biol-2022-0931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/22/2024] [Accepted: 06/27/2024] [Indexed: 03/19/2025] Open
Abstract
To investigate fecal short-chain fatty acid (SCFA) levels in hematological malignancies (HMs) patient with antibiotic-associated diarrhea (AAD), and explore the impacts of SCFAs on intestinal inflammation and gut microbiota in rats with AAD. Fecal SCFA concentrations were determined by high-performance liquid chromatography. Histologic examination was conducted by hematoxylin-eosin and alcian blue-Periodic acid-Schiff. Interleukin (IL)-10 and IL-18 mRNAs were assessed by quantitative real-time polymerase chain reaction. Claudin3 (CLDN3), Zona Occludens 1 (ZO-1), and plasmalemma vesicle-associated protein (PLVAP) proteins were evaluated by immunofluorescence and western blot. Gut microbiota was assessed by 16S rRNA sequencing. SCFAs are decreased in fecal samples of HM patients with AAD. AAD incidence is correlated with serum albumin level and type/duration of antibiotics administered. SCFAs attenuate colon shortening and intestinal pathology, and reinstate functionality of intestinal barrier by upregulating CLDN3/ZO-1 and downregulating PLVAP. Control (ctrl) group harbors an increased abundance of Lactobacillus, AAD group exhibits an enrichment of Enterorhabdus, AAD + low (L)-SCFAs group displays a predominance of Turicibacter, and AAD + high (H)-SCFAs group exerts an enrichment of Clostridium IV. Altogether, SCFAs alleviate colonic inflammation by regulating gut microbial composition, and provide insight into enhancing intestinal SCFAs content to alleviate AAD-induced symptoms in HM patients by modifying dietary structure.
Collapse
Affiliation(s)
- Li Lin
- Department of Hematology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, China
| | - Lihong Han
- Department of Geratology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, China
| | - Cuihong Gu
- Department of Hematology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, China
| | - Lihong Wang
- Department of Hematology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, China
| | - Zhihua Zhang
- Department of Hematology, The Affiliated Hospital of Chengde Medical College, No. 36, Nanyingzi Street, Chengde, Hebei 067000, China
| |
Collapse
|
|
12
|
Xu H, Zhu J, Lin X, Chen C, Tao J. A Comprehensive Review of Traditional Chinese Medicine in the Management of Ulcerative Colitis. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2025; 53:435-473. [PMID: 40066486 DOI: 10.1142/s0192415x2550017x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2025]
Abstract
Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disorder characterized by symptoms such as abdominal pain, diarrhea, hematochezia, and urgency during defecation. While the primary site of involvement is the colon, UC can extend to encompass the entire rectum and colon. The causes and development mechanisms of UC are still not well understood; nonetheless, it is currently held that factors including environmental influences, genetic predispositions, intestinal mucosal integrity, gut microbiota composition, and immune dysregulation contribute to its development. Dysregulated immune responses are pivotal in the pathophysiology of UC, and these aberrant responses are considered key contributors to the disease onset. In patients with UC, immune cells become hyperactive and erroneously target normal intestinal tissue, resulting in inflammatory cascades and damage to the intestinal mucosa. The therapeutic strategies currently employed for UC include immunosuppressive agents such as aminosalicylates and corticosteroids. However, these treatments often prove costly and carry significant adverse effects - imposing a considerable burden on patients. Traditional Chinese Medicine (TCM) has attracted worldwide attention because of its multi-target approach, minimal side effects, cost-effectiveness, and favorable efficacy profiles. In this review, the ways in which TCM modulates inflammatory responses in the treatment of ulcerative colitis have been outlined. Research into TCM modalities for modulating inflammatory pathways in the treatment of UC, which has yielded promising advancements, including individual herbs, herbal formulations, and their derivatives, has been summarized. TCM has been utilized to treat UC and the immune system plays a key role in regulating intestinal homeostasis. It is imperative to facilitate large-scale evidence-based medical research and promote the clinical application of TCM in the management of UC.
Collapse
Affiliation(s)
- Huate Xu
- School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
- School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
| | - Jinhui Zhu
- School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
| | - Xiangyun Lin
- School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
- Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
| | - Chao Chen
- School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
- Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
| | - Jinhua Tao
- School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
- School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
- Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, P. R. China
| |
Collapse
|
|
13
|
Filipiuc SI, Simionescu N, Stanciu GD, Coroaba A, Marangoci NL, Filipiuc LE, Pinteala M, Uritu CM, Tamba BI. Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study. Pharmaceutics 2025; 17:307. [PMID: 40142971 PMCID: PMC11944368 DOI: 10.3390/pharmaceutics17030307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 02/22/2025] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Objectives: This work aimed to develop and investigate liposomes incorporating Rhein (Lip-Rh) into the liposomal membrane to enhance the compound's water solubility and oral bioavailability. Methods: Liposomes were produced by the thin lipid film technique, with a phosphatidylcholine-to-cholesterol molar ratio of 5:1, dissolved in chloroform and methanol, and thereafter hydrated with ultrapure water and subjected to sonication. The resultant liposomes were studied from a physicochemical perspective using DLS, zeta potential, STEM, UV-Vis, and fluorescence spectroscopies, while oral bioavailability was assessed by fluorescence imaging. Additionally, cell viability assays were performed on tumour cells (MCF-7) in comparison to normal cells (HGFs). Results: The resultant nanoparticles exhibited relatively uniform sizes and narrow size distribution. In vivo fluorescence imaging studies performed on Wistar rats demonstrated significantly enhanced oral bioavailability for Lip-Rh, with rapid absorption into the bloodstream observed one hour after administration, in contrast to the free compound dissolved in vegetable oil. Cell viability assays demonstrated higher cytotoxicity of Lip-Rh towards MCF-7 cells compared to HGF cells, highlighting the selective therapeutic potential of the product. Moreover, we determined that the optimal dose of Rhein per kilogram of body weight, when encapsulated in liposomes, is approximately 2.5 times less than when Rhein is delivered in its unencapsulated form. Conclusions: Lip-Rh is a promising candidate for oncological treatments, presenting three key advantages: increased cytotoxicity towards tumour cells, protection of normal tissues, and the practicality of oral delivery. Additional investigation is required to explore its application in anticancer therapy, whether as monotherapy or as a complementary treatment.
Collapse
Affiliation(s)
- Silviu Iulian Filipiuc
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania; (S.I.F.); (N.S.); (A.C.); (N.L.M.); (M.P.)
- Advanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.D.S.); (L.E.F.); (B.I.T.)
| | - Natalia Simionescu
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania; (S.I.F.); (N.S.); (A.C.); (N.L.M.); (M.P.)
| | - Gabriela Dumitrița Stanciu
- Advanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.D.S.); (L.E.F.); (B.I.T.)
| | - Adina Coroaba
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania; (S.I.F.); (N.S.); (A.C.); (N.L.M.); (M.P.)
| | - Narcisa Laura Marangoci
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania; (S.I.F.); (N.S.); (A.C.); (N.L.M.); (M.P.)
| | - Leontina Elena Filipiuc
- Advanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.D.S.); (L.E.F.); (B.I.T.)
| | - Mariana Pinteala
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania; (S.I.F.); (N.S.); (A.C.); (N.L.M.); (M.P.)
| | - Cristina Mariana Uritu
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania; (S.I.F.); (N.S.); (A.C.); (N.L.M.); (M.P.)
- Advanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.D.S.); (L.E.F.); (B.I.T.)
| | - Bogdan Ionel Tamba
- Advanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.D.S.); (L.E.F.); (B.I.T.)
| |
Collapse
|
|
14
|
Yang CC, Zhang S, Zhang R, Zhao YN, Yang DW, Yang MY, Huang LJ. Application of Saccharomyces boulardii in combination with sulfasalazine in ulcerative colitis patients demonstrates significant effectiveness. World J Gastrointest Surg 2025; 17:102342. [DOI: 10.4240/wjgs.v17.i2.102342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/07/2024] [Accepted: 12/26/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a complex inflammatory bowel disease, and its etiology and pathogenesis remain incompletely elucidated.
AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.
METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted. All patients met complete inclusion and exclusion criteria. Based on the treatment interventions received, they were divided into a control group (n = 63) and an observation group (n = 64). Both groups of patients received routine treatment upon admission. The control group received sulfasalazine in addition to routine interventions, while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment. The clinical efficacy, improvement in symptoms, modified Baron endoscopic scores, quality of life “inflammatory bowel disease questionnaire (IBDQ)”, levels of intestinal microbial indicators (such as Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli), intestinal mucosal barrier function indicators [diamine oxidase (DAO), lipopolysaccharide (LPS), D-lactic acid (D-LA)], and adverse reaction occurrences were compared between the two groups.
RESULTS (1) Clinical efficacy: The total effective rate in the control group was 79.37%, while in the observation group, it was 93.75%, significantly higher than that of the control group (P < 0.05); (2) Improvement in symptoms: The observation group showed significantly lower relief time for abdominal pain, diarrhea, rectal bleeding, fever symptoms, and mucosal healing time compared to the control group (P < 0.05); (3) Baron endoscopic scores and IBDQ scores: Before treatment, there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups (P > 0.05). However, after treatment, the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group (P < 0.05); (4) Levels of intestinal microbial indicators: Before treatment, there was no significant difference in the levels of Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli between the two groups (P > 0.05). After treatment, the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group, while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group (P < 0.05); (5) Levels of intestinal mucosal barrier function indicators: Before treatment, there was no significant difference in the levels of DAO, LPS, and D-LA between the two groups (P > 0.05). However, after treatment, the levels of DAO, LPS, and D-LA in the observation group were significantly lower than those in the control group (P < 0.05); and (6) Occurrence of adverse reactions: The incidence of adverse reactions in the control group was 9.52%, while in the observation group, it was 10.94%. There was no significant difference in the occurrence of adverse reactions between the two groups (P > 0.05).
CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness. Compared to sole sulfasalazine intervention, the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients, alleviates intestinal mucosal inflammation, and improves the quality of life. Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function. Moreover, the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients, indicating a higher level of medication safety and advocating for its clinical promotion and application.
Collapse
Affiliation(s)
- Chun-Chun Yang
- Department of Gastroenterology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Sui Zhang
- Department of Hepatic, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Rui Zhang
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ya-Nan Zhao
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Da-Wei Yang
- Department of Hepatic, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ming-Yue Yang
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Li-Jing Huang
- Department of Rheumatology and Immunology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| |
Collapse
|
|
15
|
Kang N, Fan Z, Yang L, Shen J, Shen Y, Fang Z, Li B, Yang B, Wang J. Camel Milk Protein Ameliorates Ulcerative Colitis by Modulating Gut Microbiota and Amino Acid Metabolism. Nutrients 2025; 17:780. [PMID: 40077650 PMCID: PMC11902107 DOI: 10.3390/nu17050780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 02/09/2025] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
The protective effects of the milk fat globule membrane (MFGM) in alleviating inflammation have been reported. However, limited attention has been paid to the key fraction of milk fat globule membrane protein (MFGMP). This study investigated the protective effects of camel MFGMP against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results revealed that administering 50 mg/kg MFGMP significantly alleviated colonic inflammation, as evidenced by a marked decrease in IL-6, IL-1β, and TNF-α levels, along with pathological damage in DSS-induced mice with UC. MFGMP supplementation partially regulated gut microbiota dysbiosis in mice with UC by increasing α-diversity and the relative abundance of beneficial gut bacteria, such as Lactobacillus, while decreasing the abundance of Akkermansia. Additionally, MFGMP treatment exhibited significant regulatory effects on metabolites, particularly amino acid metabolism, in the feces. Specifically, this treatment restored L-valine to normal physiological levels and increased the concentrations of L-leucine, L-lysine, and L-tyrosine to nearly twice their baseline levels, whereas the concentration of L-tryptophan increased threefold. These upregulated amino acids were negatively correlated with pro-inflammatory cytokines and positively correlated with the anti-inflammatory cytokine IL-10, as indicated by Spearman's correlation analysis. Furthermore, the significant reduction in the mRNA expression levels of WNT-1, β-catenin, and Cyclin D1 suggests that MFGMP exerts a positive effect on UC via the Wnt/β-catenin pathway. These findings indicate that MFGMP exerts a protective effect against UC by modulating intestinal microbiota and amino acid metabolism in mice, with potential implications for treating intestinal inflammatory diseases.
Collapse
Affiliation(s)
- Ning Kang
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
| | - Zhexin Fan
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
- Functional Food Center, Key Laboratory of Xinjiang Medicinal Plant Resources Utilization, Ministry of Education, Shihezi University, Shihezi 832000, China
| | - Li Yang
- Alashankou Customs Technology Center, Alashankou 833418, China;
| | - Jie Shen
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
| | - Yuechenfei Shen
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
| | - Zhifeng Fang
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
- Functional Food Center, Key Laboratory of Xinjiang Medicinal Plant Resources Utilization, Ministry of Education, Shihezi University, Shihezi 832000, China
| | - Baokun Li
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
- Functional Food Center, Key Laboratory of Xinjiang Medicinal Plant Resources Utilization, Ministry of Education, Shihezi University, Shihezi 832000, China
| | - Bo Yang
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China;
- International Joint Research Laboratory for Maternal-Infant Microbiota and Health, Jiangnan University, Wuxi 214122, China
| | - Jiancheng Wang
- Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (Co-Construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi 832000, China; (N.K.); (Z.F.); (J.S.); (Y.S.); (Z.F.); (B.L.)
- Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi 832000, China
- Engineering Research Center of Storage and Processing of Xinjiang Characteristic Fruits and Vegetables, Ministry of Education, School of Food Science and Technology, Shihezi University, Shihezi 832000, China
- Functional Food Center, Key Laboratory of Xinjiang Medicinal Plant Resources Utilization, Ministry of Education, Shihezi University, Shihezi 832000, China
| |
Collapse
|
|
16
|
Zhou T, Ye Y, Chen W, Wang Y, Ding L, Liu Y, Luo L, Wei L, Chen J, Bian Z. Glaucocalyxin A alleviates ulcerative colitis by inhibiting PI3K/AKT/mTOR signaling. Sci Rep 2025; 15:6556. [PMID: 39994449 PMCID: PMC11850606 DOI: 10.1038/s41598-025-91358-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/19/2025] [Indexed: 02/26/2025] Open
Abstract
Isodon japonicus (Burm.f.) Hara var. glaucocalyx (Maxim.) Hara is a herbaceous perennial plant. Historically, it has often been used to treat dysentery and other diseases, indicating its potential efficacy in the treatment of inflammatory conditions affecting the intestines. Glaucocalyxin A (GLA) is a diterpenoid isolated from I. japonicus; recent studies have revealed that it exhibits a range of biological activities, including neuroprotective, anticancer, anti-inflammatory, hepatoprotective, and anti-fibrotic effects. However, previous studies have not specifically explored the mechanism whereby GLA alleviates ulcerative colitis (UC). Therefore, in the present study, we generated a DSS-induced UC mouse model and lipopolysaccharide-induced RAW264.7 inflammation model and performed network pharmacology analysis and peripheral blood analysis of patients with acute UC to investigate the mechanisms underlying the positive effects of GLA on UC. This study demonstrated the anti-inflammatory effects of GLA in a mouse model of DSS-induced UC. Network pharmacology analysis revealed that AKT is a common target of GLA and inflammatory bowel disease (IBD). The changes in LPS-induced RAW264.7 cell inflammation further verified that GLA reduced the expression of inflammatory cytokines by inhibiting PI3K/AKT/mTOR signaling. Finally, in vitro magnetic bead sorting experiments showed that GLA could be used in the treatment of UC patients.
Collapse
Affiliation(s)
- Tongtong Zhou
- Medical School, Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Yujing Ye
- Medical School, Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Weijie Chen
- Medical School, Nantong University, Nantong, 226001, Jiangsu Province, China
- Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Yanyan Wang
- Medical School, Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Lulu Ding
- Medical School, Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Yicun Liu
- Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, No. 60 Middle Qingnian Road, Nantong, 226006, Jiangsu Province, China
| | - Leilei Luo
- Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, No. 60 Middle Qingnian Road, Nantong, 226006, Jiangsu Province, China
| | - Lixian Wei
- Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, No. 60 Middle Qingnian Road, Nantong, 226006, Jiangsu Province, China
| | - Jian Chen
- Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, No. 60 Middle Qingnian Road, Nantong, 226006, Jiangsu Province, China
| | - Zhaolian Bian
- Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, No. 60 Middle Qingnian Road, Nantong, 226006, Jiangsu Province, China.
| |
Collapse
|
|
17
|
Kong W, Ding X, Wang Z, Lu L, Fan S. NVP-AUY922 relieves radiation-induced intestinal injury via regulating EPHX1. Life Sci 2025; 363:123382. [PMID: 39798648 DOI: 10.1016/j.lfs.2025.123382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 01/15/2025]
Abstract
As a common side effect of radiotherapy, radiation-induced intestinal injury (RIII) greatly affects the prognosis of patients and the efficacy of radiotherapy. Current therapeutic strategies for RIII are still very limited. Thus, the identification of effective radioprotective agents is of great importance. NVP-AUY922 is an HSP90 inhibitor with favorable anti-inflammatory and antioxidant activities. It has been proven to mitigate radiation-induced lung injury. However, its effects on the alleviation of RIII remain unclear. In this study, our data indicated that NVP-AUY922 remarkably increased the survival rate after radiation exposure. NVP-AUY922 treatment could enhance the viability of intestinal stem cells (ISCs) and promote the recovery of the small intestine. In addition, it also inhibited intestinal inflammation and reshaped the gut microbiota structure. We found that the radioprotective effect of NVP-AUY922 is partially dependent on EPHX1. In addition, NVP-AUY922 could attenuate dextran sulfate sodium (DSS)-induced colitis and promote intestinal barrier recovery. Thus, our results suggest that NVP-AUY922 contributes to the amelioration of intestinal injury after radiation exposure, which offers a new approach for the prevention of RIII.
Collapse
Affiliation(s)
- Wenzhe Kong
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China
| | - Xudong Ding
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China
| | - Zhaoyu Wang
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China
| | - Lu Lu
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China.
| | - Saijun Fan
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China.
| |
Collapse
|
|
18
|
Kitnithiprapha T, Panthong S, Sakpakdeejaroen I, Kondo S. Anti-Inflammatory and Antimicrobial Effects of Herbal Formulation Called Apo-Taat Using Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolates. ScientificWorldJournal 2025; 2025:6151640. [PMID: 39949663 PMCID: PMC11824490 DOI: 10.1155/tswj/6151640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 01/14/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
Pathogens contaminate drinking water in tropical countries causing diarrheal diseases. The conventional treatment for diarrhea is antibiotics. However, overuse and misuse of antibiotics has enabled pathogens to adapt, causing global antibiotic resistance and proliferation of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli), which causes diarrhea and high levels of inflammatory cytokines. Apo-taat, consisting of equal proportions of Phyllanthus emblica and Caesalpinia sappan, has been used to treat diarrhea and bloody diarrhea. Its antibacterial activity against E. coli ATCC 25922 has been reported, but its inhibitory effect against ESBL-E. coli has yet to be documented. This study investigated the antibacterial effect of Apo-taat extract against ESBL-E. coli and its anti-inflammatory activity. Antibacterial activity was determined by the microtiter plate-based method. HPLC was used to determine the brazilin and gallic acid contents in Apo-taat extract. Effects of herbal extracts on nitric oxide, IL-6, and TNF-α were investigated in RAW 264.7 cells. Results were that Apo-taat extract showed MIC values against ESBL-E. coli in the range of 0.625 to 2.5 mg/mL. Its 50% inhibitory concentration against nitric oxide and IL-6 production was 83.96 ± 10.60 and 83.06 ± 2.07 μg/mL, respectively, and it had slight inhibition against TNF-α. These findings suggest that Apo-taat may have an antibacterial impact on ESBL-E. coli and anti-inflammatory activity. Furthermore, safety and clinical trials should be conducted in the future.
Collapse
Affiliation(s)
- Thanakan Kitnithiprapha
- Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Sumalee Panthong
- Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Intouch Sakpakdeejaroen
- Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Sumalee Kondo
- Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| |
Collapse
|
|
19
|
Nie W, Zhong W, Qian L, Zhong H, Hou Y, Xu H, Qi S, Dai L, Han X, Yang X, Xu R, He Y, Lin D, Gao F. Oral chitosan-cyclodextrin "shell-core" nanoparticles co-loaded Rhein and chlorogenic acid for ulcerative colitis treatment. Int J Biol Macromol 2025; 288:138493. [PMID: 39647762 DOI: 10.1016/j.ijbiomac.2024.138493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 12/02/2024] [Accepted: 12/05/2024] [Indexed: 12/10/2024]
Abstract
The food-derived ingredients Rhein (RH) and chlorogenic acid (CGA) have DEMONSTRATED a potential synergistic effect in the treatment of ulcerative colitis (UC) through their anti-inflammatory and antioxidant properties. However, the oral co-delivery of RH and CGA faces challenges such as differences in hydrophilicity and hydrophobicity, gastrointestinal instability, and inadequate colonic targeting. To address these issues, shell-core nanoparticles were developed for the co-encapsulation of RH and CGA (CP@CGA-FA/TA@RH NPs). These nanoparticles utilize cyclodextrin-based polymers and folate-amantadine polymers to form a supramolecular core that targets macrophages for anti-inflammatory action with RH, while chitosan cross-link to CGA in the outer shell provides microenvironment-sensitive antioxidant release. The results indicate that CP@CGA-FA/TA@RH NPs could effectively inhibit the classical TLR4/MyD88/NF-κB-mediated anti-inflammatory pathway and activate the Nrf2/HO-1-mediated antioxidant pathway, offering a novel approach to UC treatment. Q-value analysis confirms the substantial co-medication effect between RH and CGA. This study is the first to develop a nano-system combining two food-derived ingredients for the integrated treatment of UC.
Collapse
Affiliation(s)
- Wenbiao Nie
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Wenzhen Zhong
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Lin Qian
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Huiyun Zhong
- Sichuan Vocational College of Health and Rehabilitation, Zigong 643000, China
| | - Yusen Hou
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.
| | - Haiting Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Shanshan Qi
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Linxin Dai
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Xiaoqin Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Xinyue Yang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Runchun Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
| | - Yao He
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.
| | - Dasheng Lin
- Chengdu Huashen Technology Group Co., Ltd., Chengdu 611137, China.
| | - Fei Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.
| |
Collapse
|
|
20
|
Huang Y, Xu L, He H, Peng L, Liao Q, Wan K, Qin S, Cao L, Zhang J. Effects of rosemary extract and its residue on production, immune performance, and gut microbiota in geese. Front Microbiol 2025; 15:1483626. [PMID: 39845044 PMCID: PMC11751043 DOI: 10.3389/fmicb.2024.1483626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/16/2024] [Indexed: 01/24/2025] Open
Abstract
Introduction To explore the effects of rosemary extract (RE) and its residue (RR) on the production, immune performance, and gut microbiota of geese. Methods We treat 28-day-old Sichuan white geese (n = 180) with three diets: (1) basal diet (control), (2) basal diet supplemented with 0.02% RE, and (3) basal diet supplemented with 15% RR for 42 days. Results and discussion On day 70, compared with control treatment, the final body weight, average daily gain and lysozyme levels in the RE treatment increased significantly (p < 0.05). In the RE and RR treatments, there was a significant decrease in alkaline phosphatase, globulin, and high-density lipoprotein levels compared to the control treatment, and there was also a significant increase in aspartate aminotransferase/alanine aminotransferase (p < 0.05). Moreover, for both RE and RR treatments, semi-eviscerated, eviscerated weights, and calcium apparent digestibility increased significantly, along with a decrease in the duodenal index (p < 0.05). Compared with RE treatment, those in the RR treatment had significantly higher duodenal and jejunum relative lengths, aspartate aminotransferase, uric acid, total cholesterol, and low-density lipoprotein levels, and decreased chest depth, chest angle, neck length, semi-eviscerated and eviscerated weights, crude protein digestibility, and levels of globulin, triglyceride, and lysozyme (p < 0.05). There were no differences in gut microbiota α or β diversities among treatments (p > 0.05). Compared to the control treatment, the relative abundance of Turicibacter significantly increased in the RR and RE treatments, and the relative abundance of Sporobacter, Alistipes, and Barnesiella significantly increased in the RR treatment (p < 0.05). Rikenellaceae, Succinivibrionaceae, and Aeromonadales were enriched in the RR treatment, and Lachnospiraceae, Turicibacteraceae, Fusobacteriaceae, and Enterobacteriaceae were enriched in the RE treatment. While we demonstrate the RR diet to be less effective than the RE diet, it did improve production and the gut microbiota of geese to a certain extent.
Collapse
Affiliation(s)
- Yuzhi Huang
- College of Animal Science and Technology, Southwest University, Chongqing, China
| | - Lanmeng Xu
- College of Animal Science and Technology, Southwest University, Chongqing, China
| | - Hang He
- College of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing, China
| | - Lijuan Peng
- College of Animal Science and Technology, Southwest University, Chongqing, China
| | - Qinfeng Liao
- College of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing, China
| | - Kun Wan
- College of Animal Science and Technology, Southwest University, Chongqing, China
| | - Simeng Qin
- College of Animal Science and Technology, Southwest University, Chongqing, China
| | - Lijing Cao
- Chongqing Rongchang District Vocational Education Center, Chongqing, China
| | - Jie Zhang
- College of Animal Science and Technology, Southwest University, Chongqing, China
| |
Collapse
|
|
21
|
Yang S, Duan H, Yan Z, Xue C, Niu T, Cheng W, Zhang Y, Zhao X, Hu J, Zhang L. Luteolin Alleviates Ulcerative Colitis in Mice by Modulating Gut Microbiota and Plasma Metabolism. Nutrients 2025; 17:203. [PMID: 39861331 PMCID: PMC11768085 DOI: 10.3390/nu17020203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/02/2025] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Ulcerative colitis (UC) is a chronic and easily recurrent inflammatory bowel disease. The gut microbiota and plasma metabolites play pivotal roles in the development and progression of UC. Therefore, therapeutic strategies targeting the intestinal flora or plasma metabolites offer promising avenues for the treatment of UC. Luteolin (Lut), originating from a variety of vegetables and fruits, has attracted attention for its potent anti-inflammatory properties and potential to modulate intestinal flora. METHODS The therapeutic efficacy of Lut was evaluated in an established dextran sodium sulfate (DSS)-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination and the evaluation of the epithelial barrier function, microbiome, and metabolomics. RESULTS The findings revealed that Lut administration at a dose of 25 mg/kg significantly ameliorated systemic UC symptoms in mice, effectively reduced the systemic inflammatory response, and significantly repaired colonic barrier function. Furthermore, Lut supplementation mitigated gut microbiota dysbiosis in a UC murine model, increasing the abundance of Muribaculaceae, Rikenella, and Prevotellaceae while decreasing Escherichia_Shigella and Bacteroides levels. These alterations in gut microbiota also influenced plasma metabolism, significantly increasing phosphatidylcholine (PC), 6'-Deamino- 6'-hydroxyneomycin C, and gamma-L-glutamyl-butyrosine B levels and decreasing Motapizone and Arachidoyl-Ethanolamide (AEA) levels. CONCLUSIONS This study reveals that Lut supplementation modulates intestinal inflammation by restoring the gut microbiota community structure, thereby altering the synthesis of inflammation-related metabolites. Lut is a potential nutritional supplement with anti-inflammatory properties and offers a novel alternative for UC intervention and mitigation. In addition, further studies are needed to ascertain whether specific microbial communities or metabolites can mediate the recovery from UC.
Collapse
Affiliation(s)
- Shuai Yang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Hongwei Duan
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Zhenxing Yan
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Chen Xue
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Tian Niu
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Wenjing Cheng
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Yong Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Xingxu Zhao
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Junjie Hu
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Lihong Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; (S.Y.); (H.D.)
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| |
Collapse
|
|
22
|
Zhang Y, Zhu M, Dai Y, Gao L, Cheng L. Research Progress in Ulcerative Colitis: The Role of Traditional Chinese Medicine on Gut Microbiota and Signaling Pathways. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2024; 52:2277-2336. [PMID: 39756829 DOI: 10.1142/s0192415x24500885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
Ulcerative colitis (UC), one among other refractory diseases worldwide, has shown an increasing trend of progression to colorectal cancer in recent years. In the treatment of UC, traditional Chinese medicine has demonstrated good efficacy, with a high cure rate, fewer adverse effects, great improvement in the quality of patient survival, and reduction in the tendency of cancerous transformation. It shows promise as a complementary and alternative therapy. This review aims to evaluate and discuss the current research on UC, signaling pathways, and gut microbiota. We also summarized the mechanisms of action of various Chinese medicines (active ingredients or extracts) and herbal formulas, through signaling pathways and gut microbiota, with the expectation that they can provide references and evidence for treating UC and preventing inflammation-associated colorectal cancer by traditional Chinese medicine. We illustrate that multiple signaling pathways, such as TLR4, STAT3, PI3K/Akt, NF-[Formula: see text]B, and Keap1/Nrf2, can be inhibited by Chinese herbal treatments through the combined regulation of signaling pathways and gut microbiota, which can act individually or synergistically to inhibit intestinal inflammatory cell infiltration, attenuate gut oxidative responses, and repair the intestinal barrier.
Collapse
Affiliation(s)
- Yuyi Zhang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
| | - Mingfang Zhu
- Graduate School, Zunyi Medical University Zunyi, P. R. China
| | - Yueying Dai
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
| | - Longying Gao
- Department of Anorectal, The First Affiliated Hospital of Heilongjiang, University of Chinese Medicine Harbin, P. R. China
| | - Limin Cheng
- Department of Anorectal, The First Affiliated Hospital of Heilongjiang, University of Chinese Medicine Harbin, P. R. China
| |
Collapse
|
|
23
|
Chantanaskul T, Patumcharoenpol P, Roytrakul S, Kingkaw A, Vongsangnak W. Exploring Protein Functions of Gut Bacteriome and Mycobiome in Thai Infants Associated with Atopic Dermatitis Through Metaproteomic and Host Interaction Analysis. Int J Mol Sci 2024; 25:13533. [PMID: 39769296 PMCID: PMC11676981 DOI: 10.3390/ijms252413533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/14/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Atopic dermatitis (AD), a prevalent allergic skin condition in children, has been closely associated with imbalances in the gut microbiome. To investigate these microbial alterations and their functional implications, we investigated protein expression, functions and interactions of the gut bacteriome and mycobiome as well as the human proteome in Thai infants with AD using integrative metaproteomic and host interaction analysis. As we observed, probiotic species, such as Lactobacillus acidophilus and Bacteroides salyersiae, were reduced in abundance in the AD group while key pathogenic bacteria and fungi, such as Streptococcus constellatus and Penicillium chrysogenum, increased in abundance. Additionally, the functional analysis of expressed proteins was enriched in response to stress and DNA repair in the bacteriome and ribosome biogenesis-related processes in the mycobiome of the AD group, potentially associated to increased reactive oxygen species (ROS), intestinal inflammation, fungal growth and microbial dysbiosis. Further, a protein-protein interactions (PPIs) network analysis incorporating the human proteome revealed 10 signature proteins related to stress and immune system processes associated with AD. Our findings propose the interactions of the key species and signature protein functions between the gut microbes and the human host in response to AD in Thai infants. To our knowledge, this study serves as the first framework for monitoring bacteriome-mycobiome-human gut studies associated with AD and other allergic diseases in infants.
Collapse
Affiliation(s)
- Thanawit Chantanaskul
- Genetic Engineering and Bioinformatics Program, Graduate School, Kasetsart University, Bangkok 10900, Thailand;
| | | | - Sittirak Roytrakul
- Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park, Phaholyothin Road, Pathum Thani 12120, Thailand;
| | - Amornthep Kingkaw
- Interdisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand;
| | - Wanwipa Vongsangnak
- Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand;
- Omics Center for Agriculture, Bioresources, Food and Health, Kasetsart University (OmiKU), Bangkok 10900, Thailand
| |
Collapse
|
|
24
|
Fu Y, Yang L, Liu L, Kong L, Sun H, Sun Y, Yin F, Yan G, Wang X. Rhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications. Pharmaceuticals (Basel) 2024; 17:1665. [PMID: 39770507 PMCID: PMC11679290 DOI: 10.3390/ph17121665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/08/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Rhein is a natural active ingredient in traditional Chinese medicine that has attracted much attention due to its wide range of pharmacological activities. However, its clinical application is limited by low water solubility, poor oral absorption, and potential toxicity to the liver and kidneys. Recently, advanced extraction and synthesis techniques have made it possible to develop derivatives of rhein, which have better pharmacological properties and lower toxicity. This article comprehensively summarizes the biological activity and action mechanism of rhein. Notably, we found that TGF-β1 is the target of rhein improving tissue fibrosis, while NF-κB is the main target of its anti-inflammatory effect. Additionally, we reviewed the current research status of the pharmacokinetics, toxicology, structural optimization, and potential drug applications of rhein and found that the coupling and combination therapy of rhein and other active ingredients exhibit a synergistic effect, significantly enhancing therapeutic efficacy. Finally, we emphasize the necessity of further studying rhein's pharmacological mechanisms, toxicology, and development of analogs, aiming to lay the foundation for its widespread clinical application as a natural product and elucidate its prospects in modern medicine.
Collapse
Affiliation(s)
- Yuqi Fu
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
| | - Le Yang
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou 510006, China; (L.Y.); (Y.S.)
| | - Lei Liu
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
| | - Ling Kong
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
| | - Hui Sun
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
| | - Ye Sun
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou 510006, China; (L.Y.); (Y.S.)
| | - Fengting Yin
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
| | - Guangli Yan
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
| | - Xijun Wang
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; (Y.F.); (L.L.); (L.K.); (F.Y.); (G.Y.)
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou 510006, China; (L.Y.); (Y.S.)
| |
Collapse
|
|
25
|
Yao T, Wu Y, Fu L, Lv J, Lv L, Li L. Christensenellaceae minuta modulates epithelial healing via PI3K-AKT pathway and macrophage differentiation in the colitis. Microbiol Res 2024; 289:127927. [PMID: 39393129 DOI: 10.1016/j.micres.2024.127927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 08/26/2024] [Accepted: 10/05/2024] [Indexed: 10/13/2024]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disorder with an unsatisfactory cure rate and mucosal healing is a key treatment objective. Christensenellaceae minuta (C. minuta) has emerged as a next-generation of probiotic for maintaining intestinal health. We investigated the therapeutic efficacy of C. minuta in dextran sulfate sodium (DSS)-induced colitis, focusing on mucosal healing and the underlying mechanisms. C. minuta effectively alleviated colitis and promoted the regeneration of intestinal epithelial cells (IECs). Using 16S rRNA sequencing and metabolomics, we found that C. minuta administration increased beneficial bacteria, decreased pathogenic bacteria, and significantly elevated propionic acid levels. Additionally, C. minuta activated the PI3K-AKT pathway by upregulating systemic and local IGF-1 expression. Inhibiting the PI3K-AKT pathway reduced the therapeutic effects of C. minuta and impaired IEC regeneration. Furthermore, C. minuta promoted macrophage differentiation into the M2 phenotype and decreased proinflammatory factors. We propose that C. minuta alleviates colitis by regulating the gut microbiota, modulating macrophage differentiation, and enhancing mucosal healing by activating the PI3K-AKT pathway via IGF-1 secretion induced by short-chain fatty acids. Our findings provide evidence from animal experiments to support future clinical trials and the therapeutic translation of C. minuta.
Collapse
Affiliation(s)
- Ting Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China
| | - Youhe Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China
| | - Liyun Fu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China
| | - Jiawen Lv
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China
| | - Longxian Lv
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China.
| |
Collapse
|
|
26
|
Wang N, Cui J, Sun Z, Chen F, He X. Exploring the protective effect and molecular mechanism of betulin in Alzheimer's disease based on network pharmacology, molecular docking and experimental validation. Mol Med Rep 2024; 30:232. [PMID: 39392030 PMCID: PMC11529172 DOI: 10.3892/mmr.2024.13356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 09/11/2024] [Indexed: 10/12/2024] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder that impairs learning and memory, with high rates of mortality. Birch bark has been traditionally used in the treatment of various skin ailments. Betulin (BT) is a key compound of birch bark that exhibits diverse pharmacological benefits and therapeutic potential in AD. However, the therapeutic effects and molecular mechanisms of BT in AD remain unclear. The present study aimed to predict the potential therapeutic targets of BT in the treatment of AD, and to determine the specific underlying molecular mechanisms through network pharmacology analysis and experimental validation. PharmMapper was used to predict the target genes of BT, and four disease databases were searched to screen for AD targets. The intersection targets were identified using the jveen website. Drug‑disease target protein‑protein interaction networks and hub genes were obtained and visualized using the Search Tool for the Retrieval of Interacting Genes/Proteins database and Cytoscape. The Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and AutoDock was used for molecular docking analysis of BT and hub genes. Subsequently, the network‑predicted mechanisms of BT in AD were verified in vitro. A total of 495 BT and 1,386 AD targets were identified, and 120 were identified as potential targets of BT in the treatment of AD. The results of the molecular docking analysis revealed a strong binding affinity between BT and the hub genes. In addition, enrichment analyses of GO and KEGG pathways indicated that the neuroprotective effects of BT mainly involved the 'PI3K‑Akt signaling pathway'. The results of in vitro experiments demonstrated that pretreatment with BT for 2 h may ameliorate formaldehyde (FA)‑induced cytotoxicity and morphological changes in HT22 cells, and decrease FA‑induced Tau hyperphosphorylation and reactive oxygen species levels. Furthermore, the PI3K/AKT signaling pathway was activated and the expression levels of downstream proteins, namely GSK3β, Bcl‑2 and Bax, were modified following pre‑treatment with BT. Overall, the results of network pharmacology and in vitro analyses revealed that BT may reduce FA‑induced AD‑like pathology by modulating the PI3K/AKT signaling pathway, highlighting it as a potential multi‑target drug for the treatment of AD.
Collapse
Affiliation(s)
- Na Wang
- Laboratory of Brain and Cognitive Science, School of Basic Medical Sciences, Dali University, Dali, Yunnan 671003, P.R. China
| | - Jiali Cui
- Yunnan Institute of Materia Medica, Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation, Kunming, Yunnan 650111, P.R. China
| | - Ziteng Sun
- Laboratory of Brain and Cognitive Science, School of Basic Medical Sciences, Dali University, Dali, Yunnan 671003, P.R. China
| | - Fan Chen
- Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi, Jiangsu 214151, P.R. China
- Laboratory of Heart Disease Mechanism and Translational Research, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China
| | - Xiaping He
- Laboratory of Brain and Cognitive Science, School of Basic Medical Sciences, Dali University, Dali, Yunnan 671003, P.R. China
| |
Collapse
|
|
27
|
Shoji H, Maeda Y, Miyakawa T. Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice. Mol Brain 2024; 17:79. [PMID: 39511657 PMCID: PMC11545877 DOI: 10.1186/s13041-024-01146-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 09/26/2024] [Indexed: 11/15/2024] Open
Abstract
Chronic exposure to glucocorticoids in response to long-term stress is thought to be a risk factor for major depression. Depression is associated with disturbances in the gut microbiota composition and peripheral and central energy metabolism. However, the relationship between chronic glucocorticoid exposure, the gut microbiota, and brain metabolism remains largely unknown. In this study, we first investigated the effects of chronic corticosterone exposure on various domains of behavior in adult male C57BL/6J mice treated with the glucocorticoid corticosterone to evaluate them as an animal model of depression. We then examined the gut microbial composition and brain and plasma metabolome in corticosterone-treated mice. Chronic corticosterone treatment resulted in reduced locomotor activity, increased anxiety-like and depression-related behaviors, decreased rotarod latency, reduced acoustic startle response, decreased social behavior, working memory deficits, impaired contextual fear memory, and enhanced cued fear memory. Chronic corticosterone treatment also altered the composition of gut microbiota, which has been reported to be associated with depression, such as increased abundance of Bifidobacterium, Turicibacter, and Corynebacterium and decreased abundance of Barnesiella. Metabolomic data revealed that long-term exposure to corticosterone led to a decrease in brain neurotransmitter metabolites, such as serotonin, 5-hydroxyindoleacetic acid, acetylcholine, and gamma-aminobutyric acid, as well as changes in betaine and methionine metabolism, as indicated by decreased levels of adenosine, dimethylglycine, choline, and methionine in the brain. These results indicate that mice treated with corticosterone have good face and construct validity as an animal model for studying anxiety and depression with altered gut microbial composition and brain metabolism, offering new insights into the neurobiological basis of depression arising from gut-brain axis dysfunction caused by prolonged exposure to excessive glucocorticoids.
Collapse
Affiliation(s)
- Hirotaka Shoji
- Division of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan
| | - Yasuhiro Maeda
- Open Facility Center, Fujita Health University, Toyoake, Aichi, 470-1192, Japan
| | - Tsuyoshi Miyakawa
- Division of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
| |
Collapse
|
|
28
|
Zhao W, Li Q, He P, Li C, Aryal M, Fabiilli ML, Xiao H. Charge balanced aggregation: A universal approach to aqueous organic nanocrystals. J Control Release 2024; 375:552-573. [PMID: 39276800 DOI: 10.1016/j.jconrel.2024.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 09/08/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024]
Abstract
Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications.
Collapse
Affiliation(s)
- Wenwen Zhao
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China
| | - Qiu Li
- College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266000, Shandong, China
| | - Peng He
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China
| | - Changqing Li
- Department of Electrical Engineering, University of California Merced, Merced 95343, CA, USA
| | - Muna Aryal
- Chemical, Biological, and Bioengineering Department, College of Engineering, North Carolina Agricultural and Technical State University, Greensboro 27411, NC, USA
| | - Mario L Fabiilli
- Department of Biomedical Engineering, University of Michigan, Ann Arbor 48109, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, 48109, MI, USA; Department of Radiology, University of Michigan, Ann Arbor, 48109, MI, USA
| | - Haijun Xiao
- Department of Radiology, University of Michigan, Ann Arbor, 48109, MI, USA.
| |
Collapse
|
|
29
|
Chen Y, Tu Y, Cao J, Wang Y, Ren Y. Rhein Alleviates Doxorubicin-Induced Myocardial Injury by Inhibiting the p38 MAPK/HSP90/c-Jun/c-Fos Pathway-Mediated Apoptosis. Cardiovasc Toxicol 2024; 24:1139-1150. [PMID: 39240427 DOI: 10.1007/s12012-024-09917-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 08/30/2024] [Indexed: 09/07/2024]
Abstract
Doxorubicin (Dox) has been limited in clinical application due to its cardiac toxicity that varies with the dose. This study aimed to explore how Rhein modulates Dox-induced myocardial toxicity. The general condition and echocardiographic changes of mice were observed to evaluate cardiac function and structure, with myocardial cell injury and apoptosis checked by TUNEL and HE staining. The ELISA assessed markers of myocardial damage and inflammation. The TCMSP and SwissTargetPrediction databases were used to retrieve Rhein's targets while GeneCards was used to find genes related to Dox-induced myocardial injury. Intersection genes were analyzed by Protein-Protein Interaction Networks. The core network genes underwent GO and KEGG enrichment analysis using R software. Western blot was used to detect protein expression. Compared to the Dox group, there was no remarkable difference in heart mass /body mass ratio in the Rhein+Dox group. However, heart mass/tibia length increased. Mice in the Rhein+Dox group had significantly increased LVEF, LVPWs, and LVFS compared to those in the Dox group. Myocardial cell damage, inflammation, and apoptosis significantly reduced in the Rhein+Dox group compared to the model group. Eleven core network genes were selected. Further, Rhein+Dox group showed significantly downregulated expression of p38/p-p38, HSP90AA1, c-Jun/p-c-Jun, c-Fos/p-c-Fos, Bax, and cleaved-caspase-3/caspase-3 while Bcl-2 expression significantly upregulated compared to the Dox group. The study suggests that Rhein mediates cardioprotection against Dox-induced myocardial injury, at least partly, by influencing multiple core genes in the MAPK signaling pathway to inhibit myocardial cell apoptosis.
Collapse
Affiliation(s)
- Yong Chen
- Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, China
| | - Yadan Tu
- Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, China
| | - Jin Cao
- Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, China
| | - Yigang Wang
- Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, China
| | - Yi Ren
- Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, China.
| |
Collapse
|
|
30
|
Lu ZH, Ding Y, Wang YJ, Chen C, Yao XR, Yuan XM, Bu F, Bao H, Dong YW, Zhou Q, Li L, Chen T, Li Y, Zhou JY, Wang Q, Shi GP, Jiang F, Chen YG. Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent colitis-associated colorectal cancer. JOURNAL OF ETHNOPHARMACOLOGY 2024; 333:118260. [PMID: 38685367 DOI: 10.1016/j.jep.2024.118260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/11/2024] [Accepted: 04/23/2024] [Indexed: 05/02/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC. RESULTS WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1β, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.
Collapse
Affiliation(s)
- Zhi-Hua Lu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yang Ding
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Yu-Ji Wang
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Chen Chen
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xing-Ran Yao
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xiao-Min Yuan
- Department of Nursing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Fan Bu
- Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Han Bao
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yu-Wei Dong
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Qiao Zhou
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Lu Li
- Department of Colorectal Surgery, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, Jiangxi, China
| | - Tuo Chen
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
| | - Yang Li
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Jin-Yong Zhou
- Central Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, China
| | - Qiong Wang
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Guo-Ping Shi
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
| | - Feng Jiang
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
| | - Yu-Gen Chen
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China; Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
| |
Collapse
|
|
31
|
Xing C, Sheng Y, Wu Y, Huang Y, Lv L, Chen F, Yan B. Carrier-Free Small Molecule-Assembled Nanoparticles for Treatment of Sepsis. ACS APPLIED NANO MATERIALS 2024; 7:24049-24060. [DOI: 10.1021/acsanm.4c04630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Chengyuan Xing
- Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
| | - Yiyu Sheng
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
| | - Yu Wu
- Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China
| | - Yao Huang
- Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China
| | - Lei Lv
- Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China
| | - Feilong Chen
- Institute of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China
| | - Binyuan Yan
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
| |
Collapse
|
|
32
|
Liu T, Fan S, Meng P, Ma M, Wang Y, Han J, Wu Y, Li X, Su X, Lu C. Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:23211-23223. [PMID: 39393822 DOI: 10.1021/acs.jafc.4c03278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/13/2024]
Abstract
Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.
Collapse
Affiliation(s)
- Tong Liu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Siqing Fan
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Pengfei Meng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Mingxia Ma
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Yanxin Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Jiaojiao Han
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Yufei Wu
- The Affiliated People's Hospital of Ningbo University, Ningbo 315040, China
| | - Xiao Li
- Xiangshan First People's Hospital Medical and Health Group, Ningbo 315700, China
| | - Xiurong Su
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
| | - Chenyang Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China
| |
Collapse
|
|
33
|
Zhang P, Yang D, Xiao J, Hong W, Sun H, Xie Q, Zeng C. Artemisia argyi polysaccharide alleviates osmotic diarrhea by enhancing intestinal barrier protection and anti-inflammation. Int J Biol Macromol 2024; 282:136779. [PMID: 39442837 DOI: 10.1016/j.ijbiomac.2024.136779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 09/08/2024] [Accepted: 10/19/2024] [Indexed: 10/25/2024]
Abstract
Artemisia argyi polysaccharide (AAP) is a homogeneous polysaccharide with a molecular weight of 16 kDa, displaying anti-inflammatory, antioxidant, and anti-tumorigenic properties, and potential protective effects on intestinal barrier function. It is anticipated to serve as an efficient component in diarrhea treatment. This study aims to examine the impact of AAP on diarrhea severity, intestinal barrier function, and inflammation in diarrhea-induced rats. The results demonstrated that AAP treatment notably decreased the incidence of diarrhea, reduced its severity, and lowered the disease activity score in rats, while also increasing body weight. Oral administration of AAP augmented goblet cell counts and elevated mucin-2 expression, aiding in the restoration of the mucus barrier. Additionally, AAP treatment enhanced colonic microbial diversity by increasing the abundance of S24-7 and Lactobacillus, while decreasing the levels of Bacteroides, Clostridium, and Sutterella. Moreover, the AAP administration elevated the levels of steroid hormones, prostaglandins, and their derivatives. By inhibiting the TLR4/MyD88/NF-κB pathway, AAP mitigated the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased the secretion of anti-inflammatory factor (IL-10). Overall, oral AAP administration effectively combats osmotic diarrhea by fortifying mucus barrier integrity and exerting anti-inflammatory effects, suggesting its potential use as an adjunctive agent in oral rehydration therapy.
Collapse
Affiliation(s)
- Pengfei Zhang
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Dexin Yang
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Jiahai Xiao
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China
| | - Weitao Hong
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China
| | - Huimin Sun
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Qingqing Xie
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Changchun Zeng
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China; Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China..
| |
Collapse
|
|
34
|
Xie Y, Li X, Xu D, He D, Wang J, Bi J, Liu J, Fu S. Hordenine Alleviates Lipopolysaccharide-Induced Mastitis by Suppressing Inflammation and Oxidative Stress, Modulating Intestinal Microbiota, and Preserving the Blood-Milk Barrier. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:21503-21519. [PMID: 39289834 DOI: 10.1021/acs.jafc.4c02867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Mastitis is a common mammalian disease occurring in the mammary tissue and poses a major threat to agriculture and the dairy industry. Hordenine (HOR), a phenylethylamine alkaloid naturally extracted from malt, has various pharmacological effects, but its role in mastitis is unknown. The aim of this study was to investigate the role of HOR and its underlying mechanism in a lipopolysaccharide (LPS)-induced inflammatory response model of mouse mammary epithelial cells (EpH4-Ev) and mouse mastitis model. The experimental results showed that HOR attenuated LPS-induced mammary tissue damage (from 3.75 ± 0.25 to 1.75 ± 0.25) and restored the integrity of the blood-milk barrier. Further mechanistic studies revealed that HOR inhibited LPS-induced overactivation of the TLR4-MAPK/NF-κB signaling pathway and activated the AMPK/Nrf2/HO-1 signaling pathway. Additionally, HOR altered the composition of the intestinal microbiota in mice, ultimately reducing the extent of inflammatory injury (from 3.33 ± 0.33 to 0.67 ± 0.33) and upregulating the expression of tight junction proteins (ZO-1, occludin, and claudin-3). The findings of this study provide a theoretical basis in the rational use of HOR for the prevention and treatment of mastitis and the maintenance of mammalian mammary gland health.
Collapse
Affiliation(s)
- Yachun Xie
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Xinyi Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Dianwen Xu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Dewei He
- College of Animal Science, Jilin University, Changchun 130062, China
| | - Jiaxin Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Junlong Bi
- College of Animal Veterinary Medicine, Yunnan Agricultural University, Kunming, Yunnan 650201, China
| | - Juxiong Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Shoupeng Fu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China
| |
Collapse
|
|
35
|
Long J, Ren Z, Duan Y, Tao W, Li X, Li S, Li K, Huang Q, Chen J, Yang M, Li Y, Luo X, Liu D. Empagliflozin rescues lifespan and liver senescence in naturally aged mice. GeroScience 2024; 46:4969-4986. [PMID: 38922380 PMCID: PMC11336130 DOI: 10.1007/s11357-024-01250-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 06/06/2024] [Indexed: 06/27/2024] Open
Abstract
Empagliflozin is currently known to decrease blood glucose levels, delay renal failure, and reduce the risk of cardiovascular death and all-cause mortality in patients with type 2 diabetes with cardiovascular disease. However, the effects of empagliflozin on the lifespan and health of naturally aged organisms are unclear. This study was designed to investigate the impacts and potential mechanisms of empagliflozin on lifespan and liver senescence in naturally aged mice. Our study revealed that empagliflozin improved survival and health in naturally aged mice. Empagliflozin extended the median survival of male mice by 5.9%. Meanwhile, empagliflozin improved learning memory and motor balance, decreased body weight, and downregulated the hepatic protein expression of P21, P16, α-SMA, and COL1A1. Empagliflozin modulates the structure of the intestinal flora, increasing the relative abundance of Lachnospiraceae, Ruminococcaceae, Lactobacillus, Blautia, and Muribaculaceae and decreasing the relative abundance of Erysipelotrichaceae, Turicibacter, and Dubosiella in naturally aged mice. Further exploration discovered that empagliflozin increased the concentration of SCFAs, decreased the levels of the inflammatory factors TNF-α, IL-6, and CXCL9, and regulated the PI3K/AKT/P21 and AMPK/SIRT1/NF-κB pathways, which may represent the underlying mechanisms involved in these beneficial hepatic effects. Taken together, the above results indicated that empagliflozin intervention could be considered a potential strategy for extending lifespan and slowing liver senescence in naturally aged mice.
Collapse
Affiliation(s)
- Jiangchuan Long
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Ziyu Ren
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Yaqian Duan
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Wei Tao
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400010, China
| | - Xi Li
- Institute of Life Sciences, School of Basic Medicine, Chongqing Medical University, Chongqing, 400010, China
| | - Shengbing Li
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Ke Li
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Qixuan Huang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Jie Chen
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Mengliu Yang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Yang Li
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Xie Luo
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Dongfang Liu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
- Chongqing Clinical Research Center for Geriatrics and Gerontology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
| |
Collapse
|
|
36
|
Li Z, Li C, Chen B, Li B, Huang G, Huang Y, Hou Y, Zhong P, Jin J, Li D, Tsim KWK, Gan L, Chen WH, Wu R. Parabacteroides goldsteinii enriched by Pericarpium Citri Reticulatae 'Chachiensis' polysaccharides improves colitis via the inhibition of lipopolysaccharide-involved PI3K-Akt signaling pathway. Int J Biol Macromol 2024; 277:133726. [PMID: 39084973 DOI: 10.1016/j.ijbiomac.2024.133726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 08/02/2024]
Abstract
Epidemiological and preclinical studies have indicated a factual association between gut microbiota dysbiosis and high incidence of colitis. Dietary polysaccharides can specifically shift the composition of gut microbiome response to colitis. Here we validated the preventive role of polysaccharides from Pericarpium Citri Reticulatae 'Chachiensis' (PCRCP), a well-known traditional Chinese medicine, in colitis induced by dextrose sodium sulfate (DSS) in both rats and mice. We found that treatment with PCRCP not only significantly reduced DSS-induced colitis via down-regulating colonic inflammatory signaling pathways including PI3K-Akt, NLRs and NF-κB, but also enhanced colonic barrier integrity in rats. These protective activities of PCRCP against DSS-induced injuries in rats were in part due to the modulation of the gut microbiota revealed by both broad-spectrum antibiotic (ABX)-deleted bacterial and non-oral treatments. Furthermore, the improvement of PCRCP on colitis was impaired by intestinal neomycin-sensitive bacteria in DSS-exposed mice. Specifically, in vivo and in vitro treatment with PCRCP led to a highly sensible enrichment in the gut commensal Parabacteroides goldsteinii. Administration of Parabacteroides goldsteinii significantly alleviated typical symptoms of colitis and suppressed the activation of PI3K-Akt-involved inflammatory response in DSS-exposed mice. The anti-colitic effects of Parabacteroides goldsteinii were abolished after the activation of PI3K-Akt signaling pathway by lipopolysaccharide treatment in mice exposed to DSS. This study provides new insights into an anti-colitic mechanism driven by PCRCP and highlights the potential prebiotic of Parabacteroides goldsteinii for the prevention of ulcerative colitis.
Collapse
Affiliation(s)
- Zi Li
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China
| | - Chengguo Li
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China
| | - Baizhong Chen
- Guangdong Xinbaotang Biotechnology Co. Ltd., Jiangmen 529100, PR China; Guangdong Xinbaotang Pharmaceutical Co. Ltd., Jiangmen 529100, PR China
| | - Bing Li
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China
| | - Gang Huang
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China
| | - Yuhao Huang
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China
| | - Yajun Hou
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China
| | - Pengjun Zhong
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China
| | - Jingwei Jin
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China
| | - Dongli Li
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China
| | - Karl Wah Keung Tsim
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, 999077, Hong Kong, China
| | - Lishe Gan
- School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China.
| | - Wen-Hua Chen
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China.
| | - Rihui Wu
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, PR China.
| |
Collapse
|
|
37
|
Qin X, Li B, Hu B, Huang J, Tian X, Zhang X, Wang Y, Huang W. Rhein inhibits M1 polarization of BV2 microglia through MAPK/IκB signalling pathway and reduces neurotoxicity caused by neuroinflammation. Int J Dev Neurosci 2024; 84:533-545. [PMID: 38858813 DOI: 10.1002/jdn.10352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 01/29/2024] [Accepted: 05/23/2024] [Indexed: 06/12/2024] Open
Abstract
BACKGROUND Rhein is an anthraquinone compound with anti-inflammatory pharmacological activity. It has been found to play a neuroprotective role in neurological diseases, but the neuroprotective mechanism of rhein remains unclear. METHODS SH-SY5Y cells serving as neuron-like cells and BV2 microglia were used. The toxicity of rhein on BV2 microglia and the viability of SH-SY5Y cells were measured by CCK-8 assay. The mRNA expression and secretion of pro-inflammatory cytokines were detected by qPCR and ELISA. Iba1, CD86 and pathway signalling protein in BV2 microglia were assessed by Western blot and immunofluorescence. Apoptosis of SH-SY5Y cells exposed to neuroinflammation was analysed through flow cytometry. RESULTS Rhein inhibited MAPK/IκB signalling pathways. Further studies revealed that rhein inhibited the production of pro-inflammatory cytokines TNF-α, IL-6, IL-1β and iNOS in BV2 cells and also inhibited the expression of M1 polarization markers Iba1 and CD86 in BV2 cells. Furthermore, rhein reduced the apoptotic rate and restored cell viability of SH-SY5Y cells exposed to neuroinflammation. CONCLUSIONS Our study demonstrated that rhein inhibited microglia M1 polarization via MAPK/IκB signalling pathway and protected nerve cells through suppressing neuroinflammation.
Collapse
Affiliation(s)
- Xin Qin
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Yichang Central People's Hospital, Yichang, China
| | - Bowen Li
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Binbin Hu
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Juan Huang
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xingfu Tian
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xinyue Zhang
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ye Wang
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wei Huang
- The Second Affiliated Hospital of Nanchang University, Nanchang, China
| |
Collapse
|
|
38
|
Lin S, Liang Y, Geng J, Yan Y, Ding R, He M. Gestational Interrelationships among Gut-Metabolism-Transcriptome in Regulating Early Embryo Implantation and Placental Development in Mice. Microorganisms 2024; 12:1902. [PMID: 39338576 PMCID: PMC11434064 DOI: 10.3390/microorganisms12091902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/07/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Decidualization of the uterine endometrium is a critical process for embryo implantation in mammals, primarily occurring on gestational day 8 in pregnant mice. However, the interplay between the maternal gut microbiome, metabolism, and the uterus at this specific time point remains poorly understood. This study employed a multi-omics approach to investigate the metabolic, gut microbiome, and transcriptomic changes associated with early pregnancy (gestational day 8 (E8)) in mice. Serum metabolomics revealed a distinct metabolic profile at E8 compared to controls, with the differential metabolites primarily enriched in amino acid metabolism pathways. The gut microbial composition showed that E8 mice exhibited higher alpha-diversity and a significant shift in beta-diversity. Specifically, the E8 group displayed a decrease in pathogenic Proteobacteria and an increase in beneficial Bacteroidetes and S24-7 taxa. Transcriptomics identified myriads of distinct genes between the E8 and control mice. The differentially expressed genes were enriched in pathways involved in alanine, aspartate, and glutamate metabolism, PI3K-Akt signaling, and the PPAR signaling pathway. Integrative analysis of the multi-omics data uncovered potential mechanistic relationships among the differential metabolites, gut microbiota, and uterine gene expression changes. Notably, the gene Asns showed strong correlations with specific gut S24-7 and metabolite L-Aspartatic acid, suggesting its potential role in mediating the crosstalk between the maternal environment and embryo development during early pregnancy. These findings provide valuable insights into the complex interplay between the maternal metabolome, the gut microbiome, and the uterine transcriptome in the context of early pregnancy, which may contribute to our understanding of the underlying mechanisms of embryo implantation and development.
Collapse
Affiliation(s)
- Shuai Lin
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Yuqi Liang
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Jingqi Geng
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Yunfei Yan
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Ruipei Ding
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Maozhang He
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| |
Collapse
|
|
39
|
Liu X, Liu Y, Song M, Zhu K, Shen J. A Rhein-Based Derivative Targets Staphylococcus aureus. Antibiotics (Basel) 2024; 13:882. [PMID: 39335055 PMCID: PMC11428220 DOI: 10.3390/antibiotics13090882] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/08/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
The rise in antibiotic-resistant bacteria highlights the need for novel antimicrobial agents. This study presents the design and synthesis of a series of rhein (RH)-derived compounds with improved antimicrobial properties. The lead compound, RH17, exhibited a potent antibacterial activity against Staphylococcus aureus (S. aureus) isolates, with minimum inhibitory concentrations (MICs) ranging from 8 to 16 μg/mL. RH17 disrupted bacterial membrane stability, hindered metabolic processes, and led to an increase in reactive oxygen species (ROS) production. These mechanisms were confirmed through bacterial growth inhibition assays, membrane function assessments, and ROS detection. Notably, RH17 outperformed the parent compound RH and demonstrated bactericidal effects in S. aureus. The findings suggest that RH17 is a promising candidate for further development as an antimicrobial agent against Gram-positive pathogens, addressing the urgent need for new therapies.
Collapse
Affiliation(s)
- Xiaojia Liu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Yuan Liu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Meirong Song
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Kui Zhu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
| | - Jianzhong Shen
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
| |
Collapse
|
|
40
|
Zhu HZ, Li CY, Liu LJ, Tong JB, Lan ZH, Tian SG, Li Q, Tong XL, Wu JF, Zhu ZG, Li SY, Li JS. Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial. JOURNAL OF INTEGRATIVE MEDICINE 2024; 22:561-569. [PMID: 39060126 DOI: 10.1016/j.joim.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/29/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be effectively treated by traditional Chinese medicine (TCM). Qingfei Huatan, a TCM formula, has been reported to effectively alleviate the clinical symptoms of COPD patients. However, there is a lack of multi-centre, randomised, double-blind, controlled clinical trials documenting the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD (AECOPD). OBJECTIVE This study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD, thereby providing high-quality clinical evidence. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS A total of 276 patients with AECOPD were included in this multi-centre, randomised, double-blind, placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:1. Patients in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day, for 14 days, in addition to Western medicine treatment. All patients were followed up for 3 months. MAIN OUTCOME MEASURES The primary outcome was time taken to symptom stabilisation. The secondary outcomes included duration of antibiotic use, clinical symptom and sign score, TCM syndrome score, dyspnoea score, and quality of life (QOL) score. Meanwhile, the safety of the formula was assessed through routine urine and stool tests, electrocardiograms, liver and kidney function tests, and the observation of adverse events throughout the trial. RESULTS The time taken for effective stabilisation (P < 0.05) and obvious stabilisation (P < 0.01), and the duration of antibiotic use (P < 0.05) were significantly shorter in the treatment group than in the control group. On days 6, 9, 12 and 14 of treatment, clinical symptom and sign score decreased in both groups, particularly in the treatment group (P < 0.01). On days 9, 12 and 14 of treatment, the TCM syndrome scores of both groups were reduced (P < 0.01), with more significant reductions in the treatment group. At 3 months after the end of treatment, the treatment group continued to have lower clinical symptom and sign score and TCM syndrome score than the control group (P < 0.01). On days 6, 9, 12 and 14 of treatment, dyspnoea and QOL scores were markedly reduced in the two groups (P < 0.05 and P < 0.01, respectively), especially in the treatment group. At 3 months after the end of treatment, dyspnoea and QOL scores were lower in the treatment group than those in the control group (P < 0.01). No serious adverse events were observed in either group. CONCLUSION The Qingfei Huatan formula can effectively shorten the duration of AECOPD and antibiotic use, significantly relieve clinical symptoms, and increase QOL for AECOPD patients, with a favourable safety profile. These results suggest that this formula can be used as a complementary treatment for AECOPD patients. TRIAL REGISTRATION The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1900026576). Please cite this article as: Zhu HZ, Li CY, Liu LJ, Tong JB, Lan ZH, Tian SG, Li Q, Tong XL, Wu JF, Zhu ZG, Li SY, Li JS. Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial. J Integr Med. 2024; 22(5): 561-569.
Collapse
Affiliation(s)
- Hui-Zhi Zhu
- Department of Respiratory Medicine, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, Anhui Province, China
| | - Cheng-Yi Li
- Graduate School, Anhui University of Traditional Chinese Medicine, Hefei 230012, Anhui Province, China
| | - Liang-Ji Liu
- Department of Respiratory Medicine, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi Province, China
| | - Jia-Bing Tong
- Department of Respiratory Medicine, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, Anhui Province, China
| | - Zhi-Hui Lan
- Department of Respiratory Medicine, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi Province, China
| | - Shu-Guang Tian
- Department of Respiratory Diseases, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Qiao Li
- Department of Pulmonary Diseases, Taihe Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Traditional Chinese Medicine, Fuyang 236600, Anhui Province, China
| | - Xiang-Li Tong
- Department of Respiratory Medicine, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, Anhui Province, China
| | - Ji-Feng Wu
- Department of Respiratory and Critical Care Medicine, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang 330002, Jiangxi Province, China
| | - Zhen-Gang Zhu
- Department of Respiratory Medicine, the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Su-Yun Li
- Department of Respiratory Diseases, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China.
| | - Jian-Sheng Li
- Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou 450046, Henan Province, China.
| |
Collapse
|
|
41
|
Guo X, Luo W, Wu L, Zhang L, Chen Y, Li T, Li H, Zhang W, Liu Y, Zheng J, Wang Y. Natural Products from Herbal Medicine Self-Assemble into Advanced Bioactive Materials. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2403388. [PMID: 39033533 PMCID: PMC11425287 DOI: 10.1002/advs.202403388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/09/2024] [Indexed: 07/23/2024]
Abstract
Novel biomaterials are becoming more crucial in treating human diseases. However, many materials require complex artificial modifications and synthesis, leading to potential difficulties in preparation, side effects, and clinical translation. Recently, significant progress has been achieved in terms of direct self-assembly of natural products from herbal medicine (NPHM), an important source for novel medications, resulting in a wide range of bioactive supramolecular materials including gels, and nanoparticles. The NPHM-based supramolecular bioactive materials are produced from renewable resources, are simple to prepare, and have demonstrated multi-functionality including slow-release, smart-responsive release, and especially possess powerful biological effects to treat various diseases. In this review, NPHM-based supramolecular bioactive materials have been revealed as an emerging, revolutionary, and promising strategy. The development, advantages, and limitations of NPHM, as well as the advantageous position of NPHM-based materials, are first reviewed. Subsequently, a systematic and comprehensive analysis of the self-assembly strategies specific to seven major classes of NPHM is highlighted. Insights into the influence of NPHM structural features on the formation of supramolecular materials are also provided. Finally, the drivers and preparations are summarized, emphasizing the biomedical applications, future scientific challenges, and opportunities, with the hope of igniting inspiration for future research and applications.
Collapse
Affiliation(s)
- Xiaohang Guo
- School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Weikang Luo
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Lingyu Wu
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Lianglin Zhang
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Yuxuan Chen
- Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, 519087, China
| | - Teng Li
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Haigang Li
- Hunan key laboratory of the research and development of novel pharmaceutical preparations, Changsha Medical University, Changsha, 410219, China
| | - Wei Zhang
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Yawei Liu
- School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
| | - Jun Zheng
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Yang Wang
- Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| |
Collapse
|
|
42
|
Li H, Guo J, Zhang G, Zhou J, Wang Q. Protective Effect of a Isothiazolinone Derivative on Acute Lung Injury by Regulating PI3K-AKT Signaling Pathway. Chem Biodivers 2024; 21:e202400892. [PMID: 38924251 DOI: 10.1002/cbdv.202400892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 06/17/2024] [Accepted: 06/20/2024] [Indexed: 06/28/2024]
Abstract
Acute lung injury (ALI) is a prevalent organ injury in sepsis, characterized by an inflammatory reactive disorder. Both the incidence and mortality rates of ALI have been steadily increasing. Isothiazolinone derivatives have displayed anti-inflammatory activity and have shown effectiveness in treating pneumonia. The objective of the study is to assess the effects and mechanisms of the isothiazolinone derivative 4-benzoyl-2-butyl-5-(ethylsulfinyl)isothiazol-3(2H)-one (C6) on sepsis-induced ALI.The analysis of biological function and signal pathway enrichment demonstrated that C6 primarily exhibited anti-inflammatory effects. Administration of different doses of C6 through intraperitoneal injection significantly improved the survival rate, body temperature, and body mass of mice with ALI induced by cecal ligation and puncture (CLP). Additionally, it mitigated lung tissue injury, pulmonary edema, lung permeability, inflammatory cell infiltration, apoptosis, and the expression of inflammatory cytokines. Network targeting analysis and experimental validation in mouse leukemia cells of monocyte macrophage (RAW264.7) cells and CLP-induced ALI mice revealed that the anti-inflammatory effect of C6 was mediated by the inhibition of the phosphatidylinositol 3 kinase -protein kinase B (PI3K-AKT) signaling pathway. The research suggest that C6 has protective effects against ALI by inhibiting the PI3K-AKT signaling pathway. This information could be valuable in developing potential treatments for ALI.
Collapse
Affiliation(s)
- Hua Li
- College of Acu-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang, 712046, P. R. China
| | - Jie Guo
- The Second College of Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang, P. R. China
| | - Gaiyue Zhang
- College of Acu-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang, 712046, P. R. China
| | - Jing Zhou
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, P. R. China
| | - Qiang Wang
- College of Acu-Moxibustion and Tuina, Shaanxi University of Chinese Medicine, Xianyang, 712046, P. R. China
| |
Collapse
|
|
43
|
Feng Y, Pan M, Li R, He W, Chen Y, Xu S, Chen H, Xu H, Lin Y. Recent developments and new directions in the use of natural products for the treatment of inflammatory bowel disease. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155812. [PMID: 38905845 DOI: 10.1016/j.phymed.2024.155812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/13/2024] [Accepted: 06/06/2024] [Indexed: 06/23/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) represents a significant global health challenge, and there is an urgent need to explore novel therapeutic interventions. Natural products have demonstrated highly promising effectiveness in the treatment of IBD. PURPOSE This study systematically reviews the latest research advancements in leveraging natural products for IBD treatment. METHODS This manuscript strictly adheres to the PRISMA guidelines. Relevant literature on the effects of natural products on IBD was retrieved from the PubMed, Web of Science and Cochrane Library databases using the search terms "natural product," "inflammatory bowel disease," "colitis," "metagenomics", "target identification", "drug delivery systems", "polyphenols," "alkaloids," "terpenoids," and so on. The retrieved data were then systematically summarized and reviewed. RESULTS This review assessed the different effects of various natural products, such as polyphenols, alkaloids, terpenoids, quinones, and others, in the treatment of IBD. While these natural products offer promising avenues for IBD management, they also face challenges in terms of clinical translation and drug discovery. The advent of metagenomics, single-cell sequencing, target identification techniques, drug delivery systems, and other cutting-edge technologies heralds a new era in overcoming these challenges. CONCLUSION This paper provides an overview of current research progress in utilizing natural products for the treatment of IBD, exploring how contemporary technological innovations can aid in discovering and harnessing bioactive natural products for the treatment of IBD.
Collapse
Affiliation(s)
- Yaqian Feng
- Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Mengting Pan
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Ruiqiong Li
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Weishen He
- Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Yangyang Chen
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
| | - Shaohua Xu
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
| | - Hui Chen
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, China.
| | - Huilong Xu
- Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
| | - Yao Lin
- Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
| |
Collapse
|
|
44
|
Song Y, Song Q, Tan F, Wang Y, Li C, Liao S, Yu K, Mei Z, Lv L. Seliciclib alleviates ulcerative colitis by inhibiting ferroptosis and improving intestinal inflammation. Life Sci 2024; 351:122794. [PMID: 38866218 DOI: 10.1016/j.lfs.2024.122794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 05/28/2024] [Accepted: 06/04/2024] [Indexed: 06/14/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic, recurrent, non-specific inflammatory disease, and the pathogenesis of the disease remains unclear. Ferroptosis is a form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which are simultaneously closely related to reactive oxygen species (ROS). Although seliciclib is highly effective against immune inflammation, its mechanism on colitis is unclear. This study demonstrated that seliciclib administration partially inhibited ferroptosis, alleviating symptoms and inflammation in experimental colitis. METHODS The mouse UC model was induced by 3.0 % dextran sodium sulfate (DSS) for 7 days and treated with seliciclib (10 mg/kg) for 5 days. In the in vitro model, LPS (100 μg/mL) was used for induction and seliciclib (10 μM) was applied for 2 h. Meanwhile, appropriate histopathology, inflammatory response, oxidative stress, and ferroptosis regulators were measured. RESULTS This study primarily investigated the role of seliciclib in regulating ferroptosis in UC. Bioinformatics analysis indicated that Dual oxidase 2 (DUOX2) may serve a role involved in the ferroptosis of UC. The experimental findings demonstrated that seliciclib alleviates symptoms and inflammation in DSS-induced UC mice and partially mitigates the occurrence of ferroptosis both in vivo and in vitro, possibly through the modulation of DUOX2. CONCLUSIONS Ferroptosis is strongly associated with the development of colitis, and seliciclib plays an essential role in ferroptosis and inflammation in UC. The suppression of ferroptosis in the intestinal epithelium could be a therapeutic approach for UC.
Collapse
Affiliation(s)
- Ya Song
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China.
| | - Qian Song
- The Second College of Clinical Medicine, Chongqing Medical University, 1 Yixue Road, Yuzhong, 400016 Chongqing, China.
| | - Fangyan Tan
- Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China.
| | - Yanhui Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China
| | - Chuanfei Li
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China
| | - Shengtao Liao
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China.
| | - Keqi Yu
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China
| | - Zhechuan Mei
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China.
| | - Lin Lv
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong, 400010 Chongqing, China.
| |
Collapse
|
|
45
|
Li A, Liu A, Wang J, Song H, Luo P, Zhan M, Zhou X, Chen L, Zhang L. The prophylaxis functions of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 on ulcerative colitis via modulating gut microbiota of mice. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:5816-5825. [PMID: 38406876 DOI: 10.1002/jsfa.13410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 12/09/2023] [Accepted: 02/18/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis. RESULTS The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids. CONCLUSIONS This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.
Collapse
Affiliation(s)
- Ao Li
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| | | | - Jun Wang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Hainan Song
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| | | | | | | | | | - Lin Zhang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| |
Collapse
|
|
46
|
Huang Y, Wu Q, Li S, Lin X, Yang S, Zhu R, Fu C, Zhang Z. Harnessing nature's pharmacy: investigating natural compounds as novel therapeutics for ulcerative colitis. Front Pharmacol 2024; 15:1394124. [PMID: 39206263 PMCID: PMC11349575 DOI: 10.3389/fphar.2024.1394124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 07/01/2024] [Indexed: 09/04/2024] Open
Abstract
Backgrounds Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease, and UC diagnosis rates continue to rise throughout the globe. The research and development of new drugs for the treatment of UC are urgent, and natural compounds are an important source. However, there is a lack of systematic summarization of natural compounds and their mechanisms for the treatment of UC. Methods We reviewed the literature in the databases below from their inception until July 2023: Web of Science, PubMed, China National Knowledge Infrastructure, and Wanfang Data, to obtain information on the relationship between natural compounds and UC. Results The results showed that 279 natural compounds treat UC through four main mechanisms, including regulating gut microbiota and metabolites (Mechanism I), protecting the intestinal mucosal barrier (Mechanism II), regulating intestinal mucosal immune response (Mechanism III), as well as regulating other mechanisms (Mechanism Ⅳ) such as cellular autophagy modulation and ferroptosis inhibition. Of these, Mechanism III is regulated by all natural compounds. The 279 natural compounds, including 62 terpenoids, 57 alkaloids, 52 flavonoids, 26 phenols, 19 phenylpropanoids, 9 steroids, 9 saponins, 8 quinonoids, 6 vitamins, and 31 others, can effectively ameliorate UC. Of these, terpenoids, alkaloids, and flavonoids have the greatest potential for treating UC. It is noteworthy to highlight that a total of 54 natural compounds exhibit their therapeutic effects by modulating Mechanisms I, II, and III. Conclusion This review serves as a comprehensive resource for the pharmaceutical industry, researchers, and clinicians seeking novel therapeutic approaches to combat UC. Harnessing the therapeutic potential of these natural compounds may significantly contribute to the improvement of the quality of life of patients with UC and promotion of disease-modifying therapies in the future.
Collapse
Affiliation(s)
- You Huang
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiuhong Wu
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Sha Li
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xia Lin
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shasha Yang
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rui Zhu
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chaomei Fu
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhen Zhang
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
47
|
Du H, Cui L, Zhao X, Yu Z, He T, Zhang B, Fan X, Zhao M, Zhu R, Zhang Z, Li M, Li J, Oh Y, Gu N. Butylparaben induces glycolipid metabolic disorders in mice via disruption of gut microbiota and FXR signaling. JOURNAL OF HAZARDOUS MATERIALS 2024; 474:134821. [PMID: 38850927 DOI: 10.1016/j.jhazmat.2024.134821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 05/14/2024] [Accepted: 06/03/2024] [Indexed: 06/10/2024]
Abstract
Butylparaben, a common preservative, is widely used in food, pharmaceuticals and personal care products. Epidemiological studies have revealed the close relationship between butylparaben and diabetes; however the mechanisms of action remain unclear. In this study, we administered butylparaben orally to mice and observed that exposure to butylparaben induced glucose intolerance and hyperlipidemia. RNA sequencing results demonstrated that the enrichment of differentially expressed genes was associated with lipid metabolism, bile acid metabolism, and inflammatory response. Western blot results further validated that butylparaben promoted hepatic lipogenesis, inflammation, gluconeogenesis, and insulin resistance through the inhibition of the farnesoid X receptor (FXR) pathway. The FXR agonists alleviated the butylparaben-induced metabolic disorders. Moreover, 16 S rRNA sequencing showed that butylparaben reduced the abundance of Bacteroidetes, S24-7, Lactobacillus, and Streptococcus, and elevated the Firmicutes/Bacteroidetes ratio. The gut microbiota dysbiosis caused by butylparaben led to decreased bile acids (BAs) production and increased inflammatory response, which further induced hepatic glycolipid metabolic disorders. Our results also demonstrated that probiotics attenuated butylparaben-induced disturbances of the gut microbiota and hepatic metabolism. Taken collectively, the findings reveal that butylparaben induced gut microbiota dysbiosis and decreased BAs production, which further inhibited FXR signaling, ultimately contributing to glycolipid metabolic disorders in the liver.
Collapse
Affiliation(s)
- Haining Du
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China; School of Chinese Material Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
| | - Lili Cui
- Key Laboratory of External Drug Delivery System and Preparation Technology, Yunnan University of Chinese Medicine, 650500, China
| | - Xinyi Zhao
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Ziteng Yu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Tianyue He
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Boya Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Xingpei Fan
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Meimei Zhao
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Ruijiao Zhu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Ziyi Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Mengcong Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Jiaxin Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Yuri Oh
- Faculty of Education, Wakayama University, Wakayama 640-8441, Japan
| | - Ning Gu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China; School of Chinese Material Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China.
| |
Collapse
|
|
48
|
Ren J, Li Y, Ni H, Zhang Y, Zhao P, Xiao Q, Hong X, Zhang Z, Yin Y, Li X, Zhang Y, Yang Y. Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs. Anim Biosci 2024; 37:1428-1439. [PMID: 38575121 PMCID: PMC11222855 DOI: 10.5713/ab.23.0475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 01/17/2024] [Accepted: 02/08/2024] [Indexed: 04/06/2024] Open
Abstract
OBJECTIVE Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors. METHODS A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 μL of bacterial solution at concentrations of 0, 0.1, and 0.2 g/15 mL, respectively. RESULTS The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p<0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae, and Megasphaera (p<0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body. CONCLUSION FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.
Collapse
Affiliation(s)
- Jing Ren
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Yumei Li
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Hongyu Ni
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Yan Zhang
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin 132109,
China
| | - Puze Zhao
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Qingxing Xiao
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Xiaoqing Hong
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Ziyi Zhang
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Yijing Yin
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Xiaohui Li
- Center of Animal Experiment, College of Basic Medical Sciences, Jilin University, Changchun 130021,
China
| | - Yonghong Zhang
- College of Animal Science, Jilin University, Changchun 130062,
China
| | - Yuwei Yang
- College of Animal Science, Jilin University, Changchun 130062,
China
| |
Collapse
|
|
49
|
Yin L, Azi F, Xia X, Jin Y, Lu X, Cheng J, Guan Y, Cheng J, Lu G, Pang L. Microbiome-metabolomics-based insight into the protective effects of dietary fiber from sweetpotato residues on the high-fat diet-induced intestinal integrity damage. Int J Biol Macromol 2024; 275:133620. [PMID: 38960238 DOI: 10.1016/j.ijbiomac.2024.133620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 06/24/2024] [Accepted: 06/30/2024] [Indexed: 07/05/2024]
Abstract
Dietary fibers have attracted much attention due to their multiple benefits on gut health. In this work, the protective mechanism of dietary fiber from sweetpotato residues (SRDF) on the high-fat diet (HFD)-induced intestinal barrier injury was investigated using microbiome-metabolomics-based approach. The physicochemical property analysis demonstrated a thermal stability below 200 °C and porous pectin-polysaccharide structure of SRDF with high in vitro functional activities. The biochemical analysis indicated that SRDF significantly ameliorated intestinal barrier function by improving intestinal morphology and permeability and inhibiting inflammatory response. Microbiome analysis demonstrated that SRDF significantly reversed the HFD-induced dysbacteriosis, decreased the ratio of Firmicutes/Bacteroides and enhanced the relative abundance of probiotics, such as Muribaculaceae and Bifidobacteriaceae. Metabolomics analysis showed that SRDF also significantly altered the metabolic profile in the colon, wherein the differential metabolites were mainly involved in amino acid metabolism (especially tryptophan). Pearson correlation coefficient identified the beneficial relationship between intestinal microbiome and metabolome induced by SRDF. The limitation of this study was that the mouse model may not fully replicate the human intestinal responses due to the difference between the standard environmental conditions and natural world. Generally, our results implied the great potential of SRDF as a functional food ingredient.
Collapse
Affiliation(s)
- Liqing Yin
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China.
| | - Fidelis Azi
- Department of Chemical Engineering, Guangdong Technion-Israel Institute of Technology (GTIIT), Shantou, Guangdong 515063, China
| | - Xiudong Xia
- Institute of Agricultural Product Processing, Jiangsu Academy of Agricultural Sciences, No 50 Zhongling Street, Nanjing, PR China
| | - Yunyi Jin
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China
| | - Xinghua Lu
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China
| | - Jiyu Cheng
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China
| | - Yuge Guan
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China
| | - Junfeng Cheng
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China
| | - Guoquan Lu
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China
| | - Linjiang Pang
- College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China.
| |
Collapse
|
|
50
|
Du X, Li H, Zhao H, Cui S, Sun X, Tan X. Causal relationship between gut microbiota and ankylosing spondylitis and potential mediating role of inflammatory cytokines: A mendelian randomization study. PLoS One 2024; 19:e0306792. [PMID: 39083521 PMCID: PMC11290680 DOI: 10.1371/journal.pone.0306792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/24/2024] [Indexed: 08/02/2024] Open
Abstract
Associations between gut microbiota and ankylosing spondylitis have been discovered in previous studies, but whether these associations reflect a causal relationship remains inconclusive. Aiming to reveal the bidirectional causal associations between gut microbiota and ankylosing spondylitis, we utilized publicly available genome wide association study summary data for 211 gut microbiota (GM) taxa and ankylosing spondylitis (AS) to conduct two sample mendelian randomization analyses. Mediation analysis was performed to explore mediating inflammatory cytokines. We found that genetically predicted higher abundance of Lactobacillaceae family, Rikenellaceae family and Howardella genus had suggestive associations with decreased risk of ankylosing spondylitis while genetic proxied higher abundance of Actinobacteria class and Ruminococcaceae_NK4A214_group genus was associated with increased risk of ankylosing spondylitis. IL23 and IFN-γ were potential mediating cytokines for GM dysbiosis, especially for Actinobacteria class, leading to AS. Our study provided a new exploration direction for the treatment of AS. Lactobacillaceae family, Rikenellaceae family, Howardella genus, Actinobacteria class and Ruminococcaceae_NK4A214_group genus are expected to become new therapeutic targets and monitoring indicators for AS.
Collapse
Affiliation(s)
- Xinyu Du
- Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine, Tianjin Hospital, Tianjin, China
| | - Haibo Li
- Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine, Tianjin Hospital, Tianjin, China
| | - Hongzhou Zhao
- Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine, Tianjin Hospital, Tianjin, China
| | - Shuangshuang Cui
- Orthopedics Institute, Tianjin Hospital, Tianjin University, Tianjin, China
| | - Xiaozhuo Sun
- Preventive Treatment of Disease Department, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaochan Tan
- Acupuncture Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| |
Collapse
|