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Zhang L, Hu Y, Zhai M, Sun G. A novel quality evaluation strategy for natural medicines integrated with HPLC Euclidean quantitative fingerprinting, UV total fingerprint dissolution and in vitro antioxidant activity: A case study of Gegen Qinlian tablet. Talanta 2025; 292:127960. [PMID: 40132407 DOI: 10.1016/j.talanta.2025.127960] [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: 08/01/2024] [Revised: 03/10/2025] [Accepted: 03/15/2025] [Indexed: 03/27/2025]
Abstract
A reliable quality control system is essential for ensuring the clinical efficacy and safety of medicines. However, past work on quality control of natural medicines has been focused mainly on the quantification of indicator components and the characteristic chemical fingerprint which provide qualitative information only and rarely provide quantitative information. Herein, a fusion of the Comprehensive Euclidean quantitative fingerprinting method (CEQFM) and multi-component quantification, on-line UV total dissolution methods based on the Dissolution-systematically quantitative fingerprint method (DSQFM) were developed for quality control of Gegen Qinlian tablets (GQTs). Furthermore, DPPH• was used to evaluate the antioxidant activity of GQTs and construct the spectrum-effect relationship. Based on these strategies, the 22 batches of GQTs were classified into six grades by CEQFM (0.898 ≤ Sm ≤ 0.986, 74.4 % ≤ PE ≤ 149.7 %) and seven grades by DSQFM (0.978 ≤ Sm ≤ 1.000, 50.64 % ≤ Pm ≤ 142.3 %), and 8 active ingredients were quantified simultaneously, with the total contents of all the 8 components spanned from 66.47 to 120.40 mg/g. In the in vitro dissolution test, the dissolution curves of 10 batches of GQTs were very similar (Sm > 0.9, 70 %< Pm<130 %, f2>50). Furthermore, the spectrum-effect relationship was applied to screen out the potential antioxidant active components, such as puerarin, baicalein, baicalin, berberine hydrochloride, palmatine chloride, etc. This method can quickly evaluate the quality of GQTs from the aspects of quantitative fingerprinting, dissolution, multi-component, and antioxidant efficacy. The study provides a new approach to quality control and quality consistency evaluation of natural medicines.
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Affiliation(s)
- Liuwei Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Yanlei Hu
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
| | - Manhuayun Zhai
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
| | - Guoxiang Sun
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
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Liu M, Zou G, Lu M, Fu J, Chen H, Pan C, Liu HM, Fu L. Mechanism of Rabdosia rubescens extract against gastric cancer microenvironment by SIRT1/NF-κB/p53 pathway and promoting tumor-associated macrophage polarization. JOURNAL OF ETHNOPHARMACOLOGY 2025; 349:119935. [PMID: 40345273 DOI: 10.1016/j.jep.2025.119935] [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: 02/07/2025] [Revised: 04/23/2025] [Accepted: 05/06/2025] [Indexed: 05/11/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The traditional action of Rabdosia rubescens (Hemsl.) H. Hara is heat-clearing and detoxifying, relieve sore throat, dissipate binds and disperse swelling. DLC, as an extract prepared from Rabdosiae Rubescentis Herba, could regulate the polarization of tumor associated macrophages (TAMs). For TAMs play an important role in the tumor microenvironment. It is worthy to further explore the mechanism of DLC on the polarized function of macrophages. AIM OF THE STUDY The aim of this study is to investigate the activity and molecular mechanisms of DLC on dissipating binds and dispersing swelling by modulating the gastric cancer microenvironment and macrophage polarization. MATERIALS AND METHODS We conducted comprehensive qualitative and quantitative chromatographic analyses to characterize the main components of DLC. To evaluate its anti-tumor effects, immunofluorescence, MTT assay, plate cloning, transcriptomics analysis, western blotting, and siRNA knockdown experiments were performed to assess DLC's action on gastric cancer cell proliferation. Additionally, we utilized Trypan blue staining, a THP-1 and MGC-803 co-culture model, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and a mouse xenograft model with five distinct dosage groups to systematically investigate DLC's effects on macrophage polarization. RESULTS Key compounds in DLC were identified. The vivo tests demonstrated the tumor inhibition rate of the 5 g/kg DLC group reached 66.99 %, surpassing that of the 5-fluorouracil group (59.94 %). Mechanistically, DLC upregulated SIRT1 expression and suppressed NF-κB pathway, thereby preventing p65 from translocating into nuclear and modulating downstream p53/MDM2/USP7 signaling. Moreover, DLC enhanced M1 macrophage factors such as TNF-α, IL-6 while inhibiting M2 marker TGF-β, effectively repolarizing M2 TAMs toward an M1 phenotype. This effect was associated with suppressed protein expression of HIF-1α, p-p65, and p-PI3K. CONCLUSION This study provides insights into DLC's mechanisms in regulating tumor microenvironment remodeling and promoting macrophage polarization toward an anti-tumor phenotype. These results provide a solid basis for DLC's potential clinical treament in gastric cancer, highlighting its promise as a natural therapeutic agent.
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Affiliation(s)
- Mengran Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China
| | - Guona Zou
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China
| | - Mengyao Lu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China
| | - Jiayue Fu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China
| | - Han Chen
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China
| | - Chengxue Pan
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China
| | - Hong-Min Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China.
| | - Ling Fu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China.
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Zu R, Lu H, Liu W, Shao S, Zheng J, Ying X, Zhou Y, Li Z, Wang W, Li D, Peng Q, Ma H, Zhang Z, Sun Y. Research Progress in the Molecular Mechanism of NLRP3 Inflammasome in Alzheimer's Disease and Regulation by Natural Plant Products. Mol Neurobiol 2025; 62:7296-7312. [PMID: 39875780 DOI: 10.1007/s12035-025-04715-w] [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: 10/02/2024] [Accepted: 01/19/2025] [Indexed: 01/30/2025]
Abstract
Alzheimer's disease (AD) is a prominent neurodegenerative disorder affecting the central nervous system in the elderly. Current understanding of AD primarily centers on the gradual decline in cognitive and memory functions, believed to be influenced by factors including mitochondrial dysfunction, β-amyloid aggregation, and neuroinflammation. Emerging research indicates that neuroinflammation plays a significant role in the development of AD, with the inflammasome potentially mediating inflammatory responses that contribute to neurodegeneration. Recent studies in AD pathology have identified a novel form of inflammasome referred to as NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Pathological alterations closely associated with NLRP3 inflammasome activation have been observed in the brain tissues of AD patients, transgenic mice, and in vitro neurocyte models. Numerous studies have demonstrated the potent neuroprotective properties of natural plant products (NPPs) against NLRP3 inflammasome-mediated AD pathology. This review provides a comprehensive examination of the NLRP3 inflammasome, its involvement in AD pathology, and the mechanisms underlying the therapeutic effects of NPP targeting the NLRP3 inflammasome.
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Affiliation(s)
- Runru Zu
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Hao Lu
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Wanting Liu
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Simai Shao
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Jiayao Zheng
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Xiran Ying
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Yangang Zhou
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Zhonghua Li
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Wang Wang
- School of Basic Medicine, Nanchang Medical College, Nanchang, 330052, Jiangxi, PR China
| | - Dejuan Li
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Quekun Peng
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
| | - Huifen Ma
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
| | - Zhenqiang Zhang
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
| | - Yiran Sun
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
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Wu Y, Li F, Shu S, Feng Z, Qiu Y, Li S, Zhu Z. Baicalin alleviates intervertebral disc degeneration by inhibiting the p38 MAPK signaling pathway. Exp Gerontol 2025; 204:112743. [PMID: 40174870 DOI: 10.1016/j.exger.2025.112743] [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: 12/03/2024] [Revised: 03/18/2025] [Accepted: 03/30/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND Intervertebral disc degeneration (IVDD) represents a prevalent degenerative pathology of the spinal, primarily precipitated by inflammatory processes and the deterioration of extracellular matrix (ECM). Baicalin has an effective anti-inflammatory effect on degenerative diseases. In addition, the P38 mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in the pathogenesis of IVDD. OBJECTIVE To investigate the therapeutic potential of baicalin in modulating pathological changes in IVDD. METHODS To design an in vitro model of degeneration of nucleus pulposus cells (NPCs) stimulated by IL-1β and an in vivo mouse model of needling to assess the protective effect of baicalin against IVDD and its underlying mechanism. RESULTS Baicalin down-regulated inflammatory factors (INOS, COX-2, IL-6) and catabolic factors (MMP-3, MMP-13, ADAMTS-5) while up-regulating anabolic factors (collagen II, SOX-9) by inhibiting the activation of the p38 MAPK signaling pathway, in addition to slowing down the progression of IVDD in the mouse acupuncture model. CONCLUSION Our study demonstrated in vitro experiments that baicalin attenuates IL-1β-stimulated IVDD by inhibiting activation of the P38 MAPK signaling pathway. Meanwhile, the effects of baicalin were also confirmed in vivo experiments, Consequently, we propose that baicalin is a promising therapeutic agent for the treatment of disc degeneration.
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Affiliation(s)
- Yating Wu
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Fengrui Li
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shibin Shu
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhenhua Feng
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yong Qiu
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Sen Li
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zezhang Zhu
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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Sun H, Hu L, Hao P, Liu Y, Tian Y. BAICALIN INHIBITS CELL APOPTOSIS, INFLAMMATION, AND FERROPTOSIS IN ULCERATIVE COLITIS BY INFLUENCING SP1-MEDIATED TRANSCRIPTION OF SLC6A14. Shock 2025; 63:900-907. [PMID: 40138728 DOI: 10.1097/shk.0000000000002587] [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] [Indexed: 03/29/2025]
Abstract
ABSTRACT Background: Baicalin is considered to be able to alleviate the progression of ulcerative colitis (UC), but the underlying molecular mechanism needs to be further elucidated. Methods: TNF-α-induced human normal colorectal mucosa cells (FHC) were used to mimic UC models in vitro , and trinitrobenzene sulfonic acid (TNBS)-injected rats were used to construct UC models in vivo . Cell proliferation and apoptosis were determined by CCK8 assay, EdU assay and flow cytometry. Inflammation factors were examined by ELISA, and ferroptosis-related markers were detected by corresponding kit. The mRNA and protein levels of solute carrier family 6 member 14 (SLC6A14) and specific protein 1 (SP1) were analyzed by qRT-PCR and western blot. The interaction between SP1 and SLC6A14 promoter was verified by ChIP assay and dual-luciferase reporter assay. Results: Baicalin enhanced proliferation, while repressed apoptosis, inflammation, and ferroptosis in TNF-α-induced FHC cells. SLC6A14 was upregulated in UC patients, and baicalin could decrease SLC6A14 expression. SLC6A14 overexpression reversed the inhibitory effect of baicalin on TNF-α-induced FHC cell injury. SP1 could bind to SLC6A14 promoter region to upregulate its expression, and ectopic expression of SLC6A14 also abolished the suppressive effect of SP1 knockdown on TNF-α-induced FHC cell injury. Baicalin reduced SP1 expression to downregulate SLC6A14. In addition, baicalin alleviated UC process in vivo via repressing inflammation, and ferroptosis. Conclusion: Baicalin repressed SP1-mediated transcription of SLC6A14 to restrain cell apoptosis, inflammation, and ferroptosis, thus alleviating UC progression.
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Affiliation(s)
- Huifang Sun
- Department of Internal Medicine, Luquan District People's Hospital, Shijiazhuang, Hebei, China
| | - Lijuan Hu
- Department of Emergency, Hebei Yiling Hospital (Affiliated Hospital of Hebei Medical University), Shijiazhuang, Hebei, China
| | - Peipei Hao
- Department of Pediatrics, Renqiu People's Hospital, Cangzhou, Hebei, China
| | - Yawei Liu
- Department of endocrinology, Renqiu People's Hospital, Cangzhou, Hebei, China
| | - Ying Tian
- Department of Internal Medicine, Guangyang District People'S Hospital, Langfang, Hebei China
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Liu B, Peng Y, Wang C, Wei H, Xu S, Liu Y, Yin X, Bi H, Guo D. Baicalin prevents experimental autoimmune uveitis by promoting macrophage polarization balance through inhibiting the HIF-1α signaling pathway. Sci Rep 2025; 15:16424. [PMID: 40355594 PMCID: PMC12069706 DOI: 10.1038/s41598-025-01286-7] [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: 02/24/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025] Open
Abstract
Uveitis is a series of autoimmune eye diseases that can seriously damage people's eyesight. This study aimed to explore the therapeutic potential of baicalin in treating uveitis, focusing on its modulation of HIF-1α expression and macrophage polarization. Using an experimental autoimmune uveitis (EAU) rat model, we found that baicalin can significantly reduce fundus inflammation in EAU rats. Spectral-domain optical coherence tomography revealed retinal vascular thickening in the EAU group, indicating severe inflammation, which baicalin effectively mitigated. Histopathological analysis confirmed reduced inflammatory cell infiltration in the ciliary body and retina. Co-immunoprecipitation analyses showed that HIF-1αinteracted with macrophage-related factors, including iNOS and ARG1. Baicalin downregulated HIF-1α and iNOS while upregulating ARG1, balancing pro-inflammatory M1 and anti-inflammatory M2 macrophage polarization. Flow cytometry demonstrated a reversal of M1/M2 macrophage ratios in the EAU group after baicalin treatment. Additionally, baicalin improved macrophage mitochondrial membrane potential and decreased reactive oxygen species (ROS) levels, shifting macrophage polarization toward an anti-inflammatory state. These findings confirm that baicalin can effectively reduce inflammation and restore immune balance by orchestrating the HIF-1α pathway, establishing a promising therapeutic candidate for uveitis and highlighting the potential of natural bioactive compounds in treating and preventing inflammatory diseases through targeted immune modulation.
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Affiliation(s)
- Bin Liu
- Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China
| | - Yuan Peng
- Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China
| | - Congling Wang
- Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China
| | - Huixia Wei
- Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
- Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, 250002, China
| | - Shuqin Xu
- Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China
| | - Yunfeng Liu
- Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China
| | - Xuewei Yin
- Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
- Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, 250002, China
| | - Hongsheng Bi
- Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
- Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, 250002, China
| | - Dadong Guo
- Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, 250002, China.
- Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.
- Shandong Academy of Eye Disease Prevention and Therapy, No. 48#, Yingxiongshan Road, Jinan, 250002, China.
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Zhang L, Hu Y, Zhang J, Cai M, Lan L, Sun G. Application of chemical pattern recognition and similarity evaluation in electrochemical and HPLC-DAD fingerprints for quality consistency study of herbal medicines. Anal Chim Acta 2025; 1349:343830. [PMID: 40074459 DOI: 10.1016/j.aca.2025.343830] [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: 12/12/2024] [Revised: 02/14/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND Herbal medicines and their preparations play a significant role in healthcare systems, yet concerns remain about their quality consistency. Chemical fingerprinting and multi-component quantitative analysis are the commonly used analytical methods and are widely applied in the quality analysis of herbal medicines. The study uses Gegen Qinlian tablets (GQTs) as a case to propose a comprehensive quality consistency evaluation system. RESULTS Initially, the evaluation system is based on three quality components and three mixtures representing RPL, RS, and RC, categorizing all samples into eight levels. Subsequently, a four-wavelength fusion HPLC profiling (FWFP) method was established, yielding a relative standard deviation (RSD) of 0.43 % for mean relative retention times (RRA) and 21.12 % for relative retention area using the normalized fingerprint method (NFM). The systematically quantified fingerprint method (SQFM) was employed, resulting in qualitative similarity (Sm) and quantitative similarity (Pm) ranges of 0.878-0.978 and 74.9%-120.4 %, respectively. Concurrently, the Electrochemical Fingerprint method (ECFM) was applied for joint evaluation with FWFP, producing SE and projection quantitative similarity (CE) ranges of 0.962-1.000 and 70.6-155.2 %, respectively. Ultimately, the series spectra from FWFP and ECFM were used to comprehensively assess sample quality, with SFW-EC and CEW-EC ranges of 0.891-0.979 and 87.5-120.9 %, leading to the classification of the 22 GQT batches into five grades. SIGNIFICANCE The study first proposes using characteristic parameters of the ECFM combined with SE and CE to evaluate the similarity of electrochemical fingerprints. It also comprehensively describes and uses SQFM to evaluate the quality of herbal medicines, including methodological validation, qualitative similarity (Sm), quantitative similarity (Pm), and reliability assessment. These methods may provide new insights for the similarity evaluation of different types of fingerprints, which can be applied in the quality consistency study of herbal medicines.
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Affiliation(s)
- Liuwei Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Yanlei Hu
- China National Pharmaceutical Industry Corporation Ltd., Beijing, 101301, China
| | - Jianglei Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
| | - Ming Cai
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
| | - Lili Lan
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
| | - Guoxiang Sun
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
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Qiao M, Xue T, Zhu Y, Yang J, Hu J. Polysaccharides from Cistanche deserticola mitigate inflammatory bowel disease via modulating intestinal microbiota and SRC/EGFR/PI3K/AKT signaling pathways. Int J Biol Macromol 2025; 308:142452. [PMID: 40139591 DOI: 10.1016/j.ijbiomac.2025.142452] [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: 12/14/2024] [Revised: 03/10/2025] [Accepted: 03/21/2025] [Indexed: 03/29/2025]
Abstract
Polysaccharides of Cistanche deserticola Ma (CDPS), with high safety and low toxicity have been reported to possess anti-inflammatory, immunomodulatory, antioxidant, anti-aging, anti-osteoporosis, antidepressant, intestinal flora regulatory and hepatoprotective properties. Nevertheless, the effects of CDPS on inflammatory bowel disease (IBD) and its underlying mechanisms have never been reported. To estimate its therapeutic potential on IBD, the extracted CDPS were characterized via utilizing a series of chemical, spectroscopic, and instrumental analyses, and the protective effects and mechanisms of CDPS in colitis mice was investigated. Our results indicated that CDPS were identified as acidic heteropolysaccharides. CDPS alleviated dextran sodium sulfate-induced IBD mice characterized by decreasing disease activity index, improving colon length and body weight, restoring histopathological lesions, inhibiting the expression of pro-inflammatory cytokine (IL-6, IL-1β, TNF-α) and MPO activity, elevating the expression of anti-inflammatory cytokine (IL-10) in colon tissue. The findings manifested CDPS could mitigate the inflammation of colon. Simultaneously, CDPS inhibited the expression of genes and proteins associated with SRC/EGFR/PI3K/AKT signaling pathways, and reduced the diversity and abundance of harmful gut microbiota, including Helicobacter, Bacteroides and Colidextribacter, while descending the relative abundance of Lachnospiraceae_NK4A136_group at genus level. In summary, this work elucidated that CDPS alleviates IBD symptoms via mitigating the inflammation of colon, and modulating intestinal microbiota and SRC/EGFR/PI3K/AKT signaling pathways. It underscores the promise of CDPS as a functional food ingredient or preventive drugs for IBD.
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Affiliation(s)
- Ming Qiao
- Department of Pharmacy, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China; Xinjiang Key Laboratory of Clinical Drug Research, Urumqi 830011, China
| | - Taotao Xue
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China
| | - Yi Zhu
- Department of Pharmacy, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China; Xinjiang Key Laboratory of Clinical Drug Research, Urumqi 830011, China
| | - Jianhua Yang
- Department of Pharmacy, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China; Xinjiang Key Laboratory of Clinical Drug Research, Urumqi 830011, China
| | - Junping Hu
- College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China.
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Lu Y, Zhou R, Zhu R, Wu X, Liu J, Ma Y, Zhang X, Zhang Y, Yang L, Li Y, Zhang Y, Yan Y, Zhang Q. Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway. Neuropharmacology 2025; 267:110296. [PMID: 39798687 DOI: 10.1016/j.neuropharm.2025.110296] [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: 11/26/2024] [Revised: 12/30/2024] [Accepted: 01/04/2025] [Indexed: 01/15/2025]
Abstract
This study aims to elucidate the target and mechanism of baicalin, a clinically utilized drug, in the treatment of neuroinflammatory diseases. Neuroinflammation, characterized by the activation of glial cells and the release of various pro-inflammatory cytokines, plays a critical role in the pathogenesis of various diseases, including spinal cord injury (SCI). The remission of such diseases is significantly dependent on the improvement of inflammatory microenvironment. Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) complex plays an important role in pathogen recognition and innate immune activation. baicalin, a natural flavonoid, is renowned for its potent anti-inflammatory property. In this study, we discovered that baicalin significantly reduced the activation of glial cells and the levels of pro-inflammatory cytokines at the lesion site of SCI mice, thereby mitigating demyelination and neuronal damage. By directly occupying the active pocket of TLR4/MD2 complex on microglia, baicalin inhibited PI3K/AKT/NF-κB pathway, thereby exerting its anti-inflammatory effect. These findings were corroborated in mice induced by lipopolysaccharide, a TLR4 agonist. Furthermore, baicalin indirectly altered phenotype of astrocytes by reducing secretion of TNF-α, IL-1α, and C1q levels from microglia. Our work demonstrated that baicalin effectively alleviated neuroinflammation by directly targeting microglia and indirectly modulating astrocytes phenotype. As a natural flavonoid, baicalin holds significant potential as a therapeutic candidate for diseases characterized by neuroinflammation.
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Affiliation(s)
- Yufang Lu
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Ruiying Zhou
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Ruyi Zhu
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Xue Wu
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an, Xianyang, Shaanxi, 712046, China
| | - Jin Liu
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Yue Ma
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Xin Zhang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Yaling Zhang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Luting Yang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Yanhua Li
- Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases, Medical School, Shanxi Datong University, Datong, Shanxi, 037009, China
| | - Yuan Zhang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China
| | - Yaping Yan
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China.
| | - Qian Zhang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China.
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Liang Z, Li S, Wang H, Tang Z, Zhang B, Wei Y, Huang Y, Li N, Zhang Y. Bioassay-guided and DeepSAT + SMART-driven identification of hepatoprotective phenolics from the fruits of Phyllanthus emblica. Fitoterapia 2025; 182:106475. [PMID: 40081426 DOI: 10.1016/j.fitote.2025.106475] [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: 01/08/2025] [Revised: 03/04/2025] [Accepted: 03/09/2025] [Indexed: 03/16/2025]
Abstract
To explore potential protective effects of natural products against alcohol-induced liver disease, a bioactivity-driven approach and HSQC-based DeepSAT and SMART were employed. Twelve phenolics, including four previously uncharacterized compounds (1-4), were identified from the fruits of Phyllanthus emblica. Their structures were elucidated as gallic acid analogs through comprehensive spectroscopic analysis, including HRESIMS and NMR methods. Network pharmacology predicted that compounds 1-12 may target on AKT1, TNF, and NFKB1, with potential to improve alcohol-induced liver injury, as suggested by Swiss Target Prediction. Compounds 1-4, 6, 8, and 9 exhibited significant protective effects against alcohol-induced liver damage in NCTC-1469 cells at a concentration of 20 μg/mL. Notably, compound 4 was found to exert its anti-alcoholic liver injury effect via the TLR4/NF-κB signaling pathway.
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Affiliation(s)
- Zhenzhen Liang
- School of Traditional Chinese Materia Medica, Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning Province, Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City, Shenyang Pharmaceutical University, Shenyang 110016, China; State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China
| | - Sheng Li
- State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China
| | - Hui Wang
- School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, Hebei, China
| | - Ziyi Tang
- School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, Hebei, China
| | - Bodou Zhang
- State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China
| | - Yinling Wei
- State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China
| | - Yun Huang
- School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, Hebei, China.
| | - Ning Li
- School of Traditional Chinese Materia Medica, Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning Province, Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City, Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Yu Zhang
- State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
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11
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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.
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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
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Shi S, Jiang H, Ma W, Guan Z, Han M, Man S, Wu Z, He S. Preclinical studies of natural flavonoids in inflammatory bowel disease based on macrophages: a systematic review with meta-analysis and network pharmacology. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:2293-2318. [PMID: 39422746 DOI: 10.1007/s00210-024-03501-0] [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: 07/25/2024] [Accepted: 09/30/2024] [Indexed: 10/19/2024]
Abstract
Flavonoid is a category of bioactive polyphenolic compounds that are extensively distributed in plants with specific pharmacological properties, such as anti-inflammatory and anti-oxidant. Importantly, natural flavonoids have shown the protected function on the dextran sulfate sodium (DSS)-induced colitis in animals and lipopolysaccharides (LPS)-induced inflammatory response in macrophages. The purpose of this systematic review is to explore the efficacy of natural flavonoids in animal models of IBD (inflammatory bowel disease) and potential mechanisms in macrophages by meta-analysis and network pharmacology in preclinical studies. Relevant foundation studies were searched from January 2010 to November 2023 in databases like PubMed, Elsevier ScienceDirect, and Web of Science. Then, OriginPro software was used to extract values from images, and the analysis was performed using Review Manager 5.3. The retrieved data was analyzed according to the fixed-effects model and random-effects model. Subsequently, heterogeneity was evaluated using the I2 statistics. Lastly, network pharmacology was applied to confirm mechanisms of natural flavonoids on IBD. According to the results of meta-analysis, we found the natural flavonoids exhibited powerful therapeutic effects against IBD, which not only reversed colonic shortness (WMD = 1.33, 95% CI (1.07, 1.59), P < 0.00001), but also reduced histological score (SMD = - 2.66, 95% CI (- 3.77, - 1.95), P < 0.00001) between natural flavonoid treatment groups compared with the experimental IBD model. Furthermore, treatment with natural flavonoids decreased the levels of tumor necrosis factor-α (TNF-α) in macrophages. Mechanistically, our summarized data substantiate that natural flavonoids alleviate LPS-induced M1 macrophage polarization, anti-oxidant, anti-inflammatory, maintain intestinal barrier, and inhibit the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. Moreover, the results of network pharmacology also support this. This systematic review demonstrated the efficiency of natural flavonoids in treating IBD in preclinical research by meta-analysis and network pharmacology, which offered supporting evidence for clinical trial implementation. However, some limitations remain present, such as technique quality shortage, missed reports on account of negative results, failure to count sample size, and the risk of bias.
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Affiliation(s)
- Shasha Shi
- Pharmacy School, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Hao Jiang
- Pharmacy School, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Wenke Ma
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Zitong Guan
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Mengxue Han
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Shuai Man
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Key Laboratory of Traditional Chinese Medicine for Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
| | - Zhuzhu Wu
- Key Laboratory of Traditional Chinese Medicine for Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
| | - Shan He
- Pharmacy School, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
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Jin Y, Liu H, Wang Y, Zhang R, Wang Q, Wang Y, Cui H, Wang X, Bian Y. Pathogenesis and treatment of colitis-associated colorectal cancer: Insights from Traditional Chinese Medicine. JOURNAL OF ETHNOPHARMACOLOGY 2025; 338:119096. [PMID: 39532222 DOI: 10.1016/j.jep.2024.119096] [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: 06/18/2024] [Revised: 10/11/2024] [Accepted: 11/09/2024] [Indexed: 11/16/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Inflammatory Bowel Disease (IBD) is an inflammatory intestinal disease, and with prolonged illness duration, the annual risk of IBD progressing to colitis-associated colorectal cancer (CAC) gradually increases. In recent years, there has been a noticeable trend towards the application of traditional Chinese medicine (TCM) in the treatment of CAC. AIM OF THIS REVIEW This comprehensive review summarizes the pathogenesis of CAC and details the therapeutic benefits of TCM in treating CAC, including various TCM prescriptions and ingredients, establishing the theoretical foundation for the application of TCM in CAC treatment. METHODS We assessed literature published before March 24, 2024, from several databases, including Web of Science, PubMed, Scopus and Google Scholar. The keywords used include "traditional Chinese medicine", "traditional Chinese medicine prescriptions", "traditional Chinese medicine ingredients", "herbal medicine", "colitis-associated colorectal cancer", "inflammatory bowel disease", "colorectal cancer" and "colitis-cancer transformation". We conducted a comprehensive collection and collation of pertinent scientific articles from various databases, focusing on the efficacy of TCM in the prevention and treatment of "colitis-cancer transformation". RESULTS This paper provides a concise summary and thorough analysis of twenty-eight prescriptions and ingredients of TCM for the prevention and treatment of CAC, based on existing experimental and clinical research. There are positive signs that TCM can effectively prevent and treat the "colitis-cancer transformation" through repairing the intestinal mucosal barrier, correcting intestinal flora imbalance, and regulating intestinal immune responses. CONCLUSION TCM possesses comprehensive regulatory advantages that are multifaceted, multilevel, and multitarget. It has a definite curative effect in the prevention and treatment of CAC. It is essential to enhance the clinical efficacy of TCM in the prevention and treatment of CAC based on syndrome differentiation and treatment, with the assistance of modern medicine.
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Affiliation(s)
- Yutong Jin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Haizhao Liu
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300192, China
| | - Yuhui Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Ruixuan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Qiaochu Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300073, China
| | - Yao Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Huantian Cui
- First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China.
| | - Xiangling Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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Li L, Zhao Y, Ding Y, Guo L, Dai R, Chen A, Duan G. Forsythia suspensa leaf fermented tea extracts attenuated oxidative stress in mice via the Ref-1/HIF-1α signal pathway and modulation of gut microbiota. Sci Rep 2025; 15:4106. [PMID: 39900709 PMCID: PMC11790883 DOI: 10.1038/s41598-025-87182-6] [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: 09/05/2024] [Accepted: 01/16/2025] [Indexed: 02/05/2025] Open
Abstract
Forsythia suspensa leaf fermented tea (FSLFT) is made from tender buds of Forsythia suspensa collected in spring. The main active components of FSLFT include forsythiaside, forsythia ester glycoside, rutin, and forsythia flavonoids, which have antibacterial, antioxidant, liver-protective, and immune-regulatory effects. Oxidative stress can trigger excessive apoptosis in intestinal epithelial cells, leading to dysfunction of the small intestinal mucosa and impaired intestinal absorption. This study focused on Kunming mice as research subjects and used hydrogen peroxide as an inducer to investigate the antioxidant and anti-inflammatory effects of FSLFT in vivo, as well as its regulatory effects on the intestinal microbiota of mice. The aim of this study was to establish a theoretical foundation for the functional study of Forsythia suspensa leaves and provide specific recommendations for their growth and application. The results showed that H2O2 treatment led to an increase in oxidative levels in mice. FSLFT has been shown to have antioxidant effects via the Redox Factor-1(Ref-1)/ hypoxia-inducible factor-1 alpha (HIF-1α) pathway, reduce inflammation caused by hydrogen peroxide through the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway, and protect mouse colons from oxidative stress by repairing gut microbiota imbalance and increasing microbial diversity and abundance. These findings establish a theoretical basis for studying the functional properties of FSLFT.
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Affiliation(s)
- Lijuan Li
- Shanxi Provincial Department, Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi, 046000, Shanxi, China
| | | | - Yuxin Ding
- Shanxi Agriculture University, Taigu, China
| | - Lanze Guo
- Shanxi Agriculture University, Taigu, China
| | - Ruiyao Dai
- Shanxi Agriculture University, Taigu, China
| | - Aixiang Chen
- Shanxi Provincial Department, Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi, 046000, Shanxi, China
| | - Guofeng Duan
- Shanxi Provincial Department, Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi, 046000, Shanxi, China.
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Chong J, Chen Z, Ma J, He L, Zhu Y, Lu Z, Qiu Z, Chen C, Chen Y, Jiang F. Mechanistic investigation and the optimal dose based on baicalin in the treatment of ulcerative colitis-A preclinical systematic review and meta-analysis. BMC Gastroenterol 2025; 25:50. [PMID: 39901089 PMCID: PMC11792396 DOI: 10.1186/s12876-025-03629-0] [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: 09/21/2024] [Accepted: 01/20/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a type of inflammatory bowel disease, and current treatments often fall short, necessitating new therapeutic options. Baicalin shows therapeutic promise in UC animal models, but a systematic review is needed. METHODS A systematic search was conducted across databases including PubMed, EBSCO, Web of Science, and Science Direct, up to March 2024, identifying randomized controlled trials (RCTs) examining baicalin's impact on UC in animal models. Seventeen studies were selected through manual screening. Meta-analyses and subgroup analyses utilized Rev Man 5.3 and Stata 15.0 software to assess symptom improvement. RESULTS From 1304 citations, 17 were analyzed. Baicalin significantly modulated various biomarkers: HCS (SMD = -3.91), DAI (MD = -2.75), spleen index (MD = -12.76), MDA (SMD = -3.88), IL-6 (SMD = -10.59), IL-1β (SMD = -3.98), TNF-α (SMD = -8.05), NF-κB (SMD = -5.46), TLR4 (MD = -0.38), RORγ (MD = -0.89), MCP-1 (MD = -153.25), MPO (SMD = -7.34), Caspase-9 (MD = -0.93), Caspase-3 (MD = -0.45), FasL (MD = -1.20)) and enhanced BWC (MD = 0.06), CL (MD = 1.39), ZO-1 (MD = 0.44), SOD (SMD = 3.04), IL-10 mRNA (MD = 3.14), and FOXP3 (MD = 0.45) levels. Baicalin's actions may involve the PI3K/AKT, TLR4/NF-κB, IKK/IKB, Bcl-2/Bax, Th17/Treg, and TLRs/MyD88 pathways. Optimal therapeutic outcomes were predicted at dosages of 60-150 mg/kg over 10-14 weeks. CONCLUSION Baicalin demonstrates a multifaceted therapeutic potential in UC, attributed to its anti-inflammatory, antioxidant, anti-apoptotic, and intestinal barrier repair properties. While higher doses and longer treatments appear beneficial, further research, particularly human clinical trials, is necessary to verify its effectiveness and safety in people.
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Affiliation(s)
- Jinchen Chong
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Zepeng Chen
- Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China
| | - Jiaze Ma
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Linhai He
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Yijia Zhu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Zhihua Lu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Zhengxi Qiu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
- Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Chen Chen
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China
| | - Yugen Chen
- Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, PR China.
- Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China.
- Jiangsu Collaborative Innovation Center of Chinese Medicine in Prevention and Treatment of Tumor, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China.
| | - Feng Jiang
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China.
- Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, PR China.
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16
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Liao Y, Kong Y, Chen H, Xia J, Zhao J, Zhou Y. Unraveling the priming phase of NLRP3 inflammasome activation: Molecular insights and clinical relevance. Int Immunopharmacol 2025; 146:113821. [PMID: 39674000 DOI: 10.1016/j.intimp.2024.113821] [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: 09/13/2024] [Revised: 11/10/2024] [Accepted: 12/05/2024] [Indexed: 12/16/2024]
Abstract
The NLRP3 inflammasome plays a pivotal role in the innate immune response. Its activation involves a two-step mechanism that consists of priming and activation. The priming of the NLRP3 inflammasome is a vital initial phase necessary for its activation and subsequent involvement in the immune response, though its understanding varies across studies. Recent research has identified key proteins that influence the priming process, revealing a sophisticated regulatory network. This review provides a comprehensive review of the priming phase of NLRP3 inflammasome activation, with a particular focus on the underlying molecular mechanisms, including transcriptional regulation, orchestration of the phosphorylation status, deubiquitination and the relationships with the inflammation-associated diseases. Understanding the intricacies of NLRP3 inflammasome priming not only elucidates fundamental aspects of immune regulation, but also provides potential avenues for therapeutic intervention in inflammatory diseases.
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Affiliation(s)
- Yonghong Liao
- College of Veterinary Medicine, Southwest University, 402460 Chongqing, China; National Center of Technology Innovation for Pigs, 402460, Rongchang, Chongqing, China
| | - Yueyao Kong
- College of Veterinary Medicine, Southwest University, 402460 Chongqing, China
| | - Hongyu Chen
- College of Veterinary Medicine, Southwest University, 402460 Chongqing, China
| | - Jing Xia
- College of Veterinary Medicine, Southwest University, 402460 Chongqing, China
| | - Jianjun Zhao
- College of Animal Science and Technology, Southwest University, 402460 Chongqing, China
| | - Yang Zhou
- College of Veterinary Medicine, Southwest University, 402460 Chongqing, China; National Center of Technology Innovation for Pigs, 402460, Rongchang, Chongqing, China.
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17
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Jia Y, Gengji J, Gong T, Zhang Z, Deng L. An Amorphous Solid Dispersion of Baicalin and its Oral Therapeutic Effect on Ulcerative Colitis. Pharm Res 2024; 41:2377-2389. [PMID: 39668326 DOI: 10.1007/s11095-024-03804-0] [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: 11/03/2024] [Accepted: 12/01/2024] [Indexed: 12/14/2024]
Abstract
OBJECTIVE Ulcerative colitis (UC) treatment currently faces multiple challenges including adverse effects, prolonged therapy durations, and high costs. Baicalin (BA) has demonstrated anti-inflammatory benefits for inflammatory bowel disease, and the objective of this scholarly work is to address the challenges associated with the poor aqueous solubility and diminished oral bioavailability of the compound in question, thereby offering an innovative therapeutic approach for the management of ulcerative colitis. METHODS We developed a baicalin-arginine complex (BA-Arg) by screening for suitable basic compounds and utilizing a freeze-drying method, resulting in an amorphous solid dispersion of BA. RESULTS Our findings revealed that BA·Arg significantly enhances the intestinal absorption and transmembrane transport of BA without inducing toxicity in Caco-2 cells. Pharmacokinetic studies in healthy Wistar rats demonstrated significantly higher plasma concentrations of BA compared to free BA. In a mouse model induced by 3.5% dextran sodium sulfate, BA·Arg treatment markedly alleviated colitis symptoms as evidenced by reduced inflammatory cell infiltration, decreased lymphocyte aggregation in the colon, and better preservation of intestinal mucosa. This improved the overall anti-colitis efficacy of BA. CONCLUSIONS Overall, our study presents a simple, eco-friendly formulation process that enhances BA solubility without the need for organic solvents, offering a practical and sustainable solution for developing BA-based therapies for UC.
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Affiliation(s)
- Yaxin Jia
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Jiajia Gengji
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Tao Gong
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Zhirong Zhang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Li Deng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
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Gao X, Feng X, Hou T, Huang W, Ma Z, Zhang D. The roles of flavonoids in the treatment of inflammatory bowel disease and extraintestinal manifestations: A review. FOOD BIOSCI 2024; 62:105431. [DOI: 10.1016/j.fbio.2024.105431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Han N, Li J, Li Y, Zhao F, Wang J, Ye P, Zeng Z. Xanthohumol ameliorates dextran sodium sulfate-induced colitis in mice by inhibiting of NF-κB signaling pathways and modulating intestinal microbiota. Eur J Nutr 2024; 64:21. [PMID: 39576384 DOI: 10.1007/s00394-024-03525-5] [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: 05/20/2024] [Accepted: 10/18/2024] [Indexed: 11/24/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Xanthohumol (XN), an isoprenylated flavonoid natural product found only in hops, possesses a variety of biological activities such as anticancer, anti-inflammatory, hepatoprotective, and anti-obesity. AIM OF THE STUDY The aim of this study was to investigate the effects and mechanisms of XN on the treatment of colitis. MATERIALS AND METHODS First, acute colitis was induced by using distilled water containing 3% DSS for 10 consecutive days. The therapeutic efficacy of XN was assessed by an established DSS-induced mouse colitis model. Subsequently, disease activity index (DAI) and colon length of mice were assessed. The health of the intestines was assessed by histopathological analysis. Inflammatory factors, IL-1β, IL-6, and TNF-α, were detected in colon tissues by ELISA.Finally, mouse intestinal contents were extracted and subjected to 16 S rRNA Sequencing, and the gut microbiota was analysed for Alpha-diversity and Beta-diversity. RESULTS The results showed that XN ameliorated DSS-induced colitis. Furthermore, XN reduced pro-inflammatory cytokine levels such as IL-1β, IL-6, and TNF-α, as well as inhibited the activation of the TLR4/NF-κB pathway, all of which helped to mitigate the inflammatory response. Finally, we also found that XN alleviated intestinal dysbiosis in colitis mice. CONCLUSION In conclusion, our study demonstrated that XN provides protective effects against colitis, and has the potential to be further explored as a lead compound for the treatment of inflammatory bowel disease (IBD).
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Affiliation(s)
- Ning Han
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
| | - Jie Li
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
| | - Yangyang Li
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
| | - Feiei Zhao
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
| | - Jun Wang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
| | - Peiyu Ye
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
| | - Zhenling Zeng
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
- National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
- National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
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Cao L, Wang X, Ma X, Xu M, Li J. Potential of natural products and gut microbiome in tumor immunotherapy. Chin Med 2024; 19:161. [PMID: 39567970 PMCID: PMC11580227 DOI: 10.1186/s13020-024-01032-7] [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: 06/22/2024] [Accepted: 11/01/2024] [Indexed: 11/22/2024] Open
Abstract
Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies.
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Affiliation(s)
- Luchang Cao
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixian'ge Street, Xicheng District, Beijing, China
| | - Xinmiao Wang
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixian'ge Street, Xicheng District, Beijing, China
| | - Xinyi Ma
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixian'ge Street, Xicheng District, Beijing, China
| | - Manman Xu
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixian'ge Street, Xicheng District, Beijing, China
| | - Jie Li
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixian'ge Street, Xicheng District, Beijing, China.
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Huang J, Zhang J, Wang F, Tang X. Exploring the immune landscape of disulfidptosis in ulcerative colitis and the role of modified gegen qinlian decoction in mediating disulfidptosis to alleviate colitis in mice. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118527. [PMID: 38971342 DOI: 10.1016/j.jep.2024.118527] [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: 04/16/2024] [Revised: 06/22/2024] [Accepted: 07/04/2024] [Indexed: 07/08/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ulcerative colitis (UC), a recurrent inflammatory bowel disease, continues to challenge effective pharmacologic management. Disulfidptosis, a recently identified form of cell death, appears implicated in the progression of various diseases. Scientific studies have demonstrated that Modified Gegen Qinlian decoction (MGQD) alleviates UC symptoms. However, the underlying mechanisms remain inadequately elucidated. AIM OF THE STUDY This study investigated the role of disulfidptosis in UC and explored the potential of MGQD to ameliorate UC by mediating disulfidptosis. METHODS Microarray data were utilized to identify disulfidptosis-related genes stably expressed in UC, and integrated genomic analyses were conducted to elucidate the landscape of disulfidptosis in UC. Subsequently, C57BL/6J mice were administered 3% dextran sodium sulfate (DSS) to induce experimental colitis and treated with MGQD. Quantitative real-time polymerase chain reaction and immunohistochemical analysis of colonic tissues from colitis mice were performed to validate the microarray data findings. Finally, molecular docking was employed to explore the binding interactions between MGQD components and disulfidptosis biomarkers. RESULTS Myosin heavy chain 10 (MYH10) and filamin A (FLNA) were identified as stably expressed in UC, demonstrating high diagnostic value for the disease. Correlation analysis indicated that disulfidptosis-related genes are associated with elevated levels of immune cells in UC. Single gene set enrichment analysis further clarified that these genes might be involved in the pathological processes of UC via immune-related pathways. Subsequent animal experiments revealed that MYH10 and FLNA were significantly upregulated in mice with colitis, a condition reversed by MGQD treatment. Molecular docking results showed that MYH10 and FLNA serve as stable binding targets for the primary components of MGQD. CONCLUSIONS The study identified a connection between the disulfidptosis-related landscape and immune infiltration in UC, suggesting that MGQD may modulate disulfidptosis by inhibiting MYH10 and FLNA, thereby alleviating UC.
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Affiliation(s)
- Jinke Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China; Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaqi Zhang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengyun Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Xudong Tang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
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Qu L, Huang Y, Wu Y, He L, Liu Y, Chen Z, Ma X, Fan D. Ginsenoside Rk3 Treats Corneal Injury Through the HMGB1/TLR4/NF-κB Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:24387-24399. [PMID: 39435975 DOI: 10.1021/acs.jafc.4c04250] [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: 10/23/2024]
Abstract
The cornea serves as a vital protective shield for the eye, safeguarding its intricate internal structures from external threats. Damage to the cornea compromises this protective function, triggering inflammation and potentially causing long-term harm. While ginsenoside Rk3 has demonstrated potential for repairing the corneal barrier and reducing inflammation, its effectiveness in treating corneal damage remains relatively unexplored. This comprehensive study uses both in vivo and in vitro models to investigate the therapeutic capabilities of ginsenoside Rk3. Using two models of corneal damage, a benzalkonium chloride-induced mouse model and a high osmolarity-induced human corneal epithelial cell model, we scrutinized the effects of ginsenoside Rk3 treatment. Our results showed that ginsenoside Rk3-treated mice manifested reduced corneal damage and inflammation compared with their untreated counterparts. Furthermore, mice treated with ginsenoside Rk3 exhibited an organized arrangement of corneal cells and diminished stromal layer thickness, indicating reparative properties of ginsenoside Rk3. Additionally, ginsenoside Rk3 increased the expression of tight junction proteins, suppressed inflammatory factors, and decreased HMGB1 protein expression, thereby modulating downstream signaling pathways. Collectively, our findings present compelling evidence that ginsenoside Rk3 is a promising therapeutic option for corneal injury. By repairing the corneal barrier, mitigating inflammation, and modulating specific protein levels, ginsenoside Rk3 opens new avenues for managing corneal damage.
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Affiliation(s)
- Linlin Qu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
- Xi'an Giant Biotechnology Co., Ltd., Xi'an 710076, China
| | - Yingcong Huang
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
| | - Yuqing Wu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
| | - Lei He
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
| | - Yannan Liu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
| | - Zhiqi Chen
- Shaanxi Giant Biotechnology Co., Ltd., Xi'an 710065, China
| | - Xiaoxuan Ma
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
| | - Daidi Fan
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710127, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710127, China
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Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. JOURNAL OF INTEGRATIVE MEDICINE 2024; 22:621-636. [PMID: 39368944 DOI: 10.1016/j.joim.2024.09.003] [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: 09/23/2023] [Accepted: 09/07/2024] [Indexed: 10/07/2024]
Abstract
Natural product-based antiviral candidates have received significant attention. However, there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance. Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi. They have proven to be effective against a broad range of viruses by directly killing virus particles, protecting infected cells, and targeting viral antigens on their surface, among other mechanisms. As natural products, they both possess the advantage of lower toxicity, enhanced therapeutic efficacy, and even antagonistic effects against drug-resistant viral strains. Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds, demonstrating their antiviral properties. However, to date, no review on the antiviral effects of baicalein and baicalin has been published. This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms. The aim is to provide a basis for the rational development and utilization of baicalein and baicalin, as well as to promote antiviral drug research. Please cite this article as: Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024; 22(6): 621-636.
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Affiliation(s)
- Xin-Yang Liu
- School of Basic Medicine, Naval Medical University, Shanghai 200433, China
| | - Wei Xie
- Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - He-Yang Zhou
- School of Pharmacy, Naval Medical University, Shanghai 200433, China
| | - Hui-Qing Zhang
- Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China.
| | - Yong-Sheng Jin
- School of Pharmacy, Naval Medical University, Shanghai 200433, China.
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24
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Jha D, Bakker ENTP, Kumar R. Mechanistic and therapeutic role of NLRP3 inflammasome in the pathogenesis of Alzheimer's disease. J Neurochem 2024; 168:3574-3598. [PMID: 36802053 DOI: 10.1111/jnc.15788] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/03/2023] [Accepted: 02/13/2023] [Indexed: 02/20/2023]
Abstract
Alzheimer's disease (AD), a progressive neurodegenerative disorder, has emerged as the most common form of dementia in the elderly. Several pathological hallmarks have been identified, including neuroinflammation. A comprehensive insight into the underlying mechanisms that can fuel the development of novel therapeutic approaches is necessary because of the alarmingly rapid increase in the frequency of incidence. Recently, NLRP3 inflammasome was identified as a critical mediator of neuroinflammation. Activation of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome by amyloid, neurofibrillary tangles, impaired autophagy and endoplasmic reticulum stress, triggers the release of pro-inflammatory cytokines such as IL-1β and IL-18. Subsequently, these cytokines can promote neurodegeneration and cognitive impairment. It is well established that genetic or pharmacological ablation of NLRP3 alleviates AD-related pathological features in in vitro and in vivo models. Therefore, several synthetic and natural compounds have been identified that exhibit the potential to inhibit NLRP3 inflammasome and alleviate AD-associated pathology. The current review article will highlight the various mechanisms by which activation of NLRP3 inflammation occurs during Alzheimer's disease, and how it influences neuroinflammation, neurodegeneration and cognitive impairment. Moreover, we will summarise the different small molecules that possess the potential to inhibit NLRP3 and can pave the path for developing novel therapeutic interventions for AD.
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Affiliation(s)
- Dhanshree Jha
- Department of Biotechnology, GITAM School of Sciences, GITAM (Deemed to be) University, Vishakhapatnam, India
| | - Erik N T P Bakker
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centre, Location University of Amsterdam, and Amsterdam Neuroscience Research Institute, Amsterdam, the Netherlands
| | - Rahul Kumar
- Department of Biotechnology, GITAM School of Sciences, GITAM (Deemed to be) University, Vishakhapatnam, India
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centre, Location University of Amsterdam, and Amsterdam Neuroscience Research Institute, Amsterdam, the Netherlands
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Bahaa MM, Hegazy SK, Maher MM, Bahgat MM, El-Haggar SM. Pentoxifylline in patients with ulcerative colitis treated with mesalamine by modulation of IL-6/STAT3, ZO-1, and S1P pathways: a randomized controlled double-blinded study. Inflammopharmacology 2024; 32:3247-3258. [PMID: 39192162 DOI: 10.1007/s10787-024-01560-6] [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: 03/26/2024] [Accepted: 08/14/2024] [Indexed: 08/29/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that lasts a long time and has a variety of causes. AIM The primary aim of this study was to evaluate pentoxifylline's (PTX) essential function in patients with UC. METHODS Fifty-two mild to moderate UC patients who matched the eligibility requirements participated in this clinical study. One gram of mesalamine (t.i.d.) and a placebo were administered to the mesalamine group (n = 26) for a duration of 24 weeks. Mesalamine 1 g t.i.d. and PTX 400 mg two times daily were administered to the PTX group (n = 26) for 24 weeks. A gastroenterologist investigated patients at the start and 6 months after the medication was given to assess disease activity index (DAI) and numeric pain rating scale (NRS). Also, interleukin-6 (IL-6), sphingosine 1 phosphate (S1P), tumor necrosis factor-alpha (TNF-α), and fecal myeloperoxidase (MPO) were measured before and after therapy. Zonula occuldin-1 (ZO-1) and signal transducer and activator of transcription factor-3 (STAT-3) expression was assessed before and after therapy as well as histological assessment. Short Form 36 Health Survey (SF-36), was assessed for each patient before and after 6 months of treatment. RESULTS The PTX group showed statistically lower levels of serum SIP, TNF-α, IL-6, faecal MPO, gene expression of STAT-3, and a significant increase of ZO-1 in comparison with the mesalamine group. DAI and NRS significantly decreased whereas SF-36 significantly increased in the PTX group. CONCLUSION PTX could alleviate inflammation in patients with UC, so it might be promising adjunctive for patients with UC. TRIAL REGISTRATION IDENTIFIER NCT05558761.
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Affiliation(s)
- Mostafa M Bahaa
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
| | - Sahar K Hegazy
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Guiesh Street, El-Gharbia Government, Tanta, 31527, Egypt
| | - Maha M Maher
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Internal Medicine Department, Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Monir M Bahgat
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Internal Medicine Department, Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Sahar M El-Haggar
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Guiesh Street, El-Gharbia Government, Tanta, 31527, Egypt
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Oshima N, Kusamori K, Takasaki R, Takeda M, Katsurada Y, Nose T, Okoshi K, Nishikawa M, Hada N. Scutellaria Root extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content. J Nat Med 2024; 78:978-984. [PMID: 38787459 DOI: 10.1007/s11418-024-01814-1] [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: 09/29/2023] [Accepted: 03/23/2024] [Indexed: 05/25/2024]
Abstract
Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.
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Affiliation(s)
- Naohiro Oshima
- Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan.
- Division of Environmental Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-Ku, Kawasaki, Kanagawa, 210-9501, Japan.
| | - Kosuke Kusamori
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan
| | - Ryo Takasaki
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan
| | - Moe Takeda
- Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan
| | - Yuri Katsurada
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan
| | - Takumi Nose
- Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan
| | - Kazuki Okoshi
- Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan
| | - Makiya Nishikawa
- Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan.
| | - Noriyasu Hada
- Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda City, Chiba, 278-8510, Japan.
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Zhao J, Lu F, Yu H, Cao J, Su Z, Zhao J. Proteomic analysis of baicalin intervention on protein expression and modification in the hippocampus of Alzheimer's disease model rat. Int J Neurosci 2024:1-10. [PMID: 39136404 DOI: 10.1080/00207454.2024.2332963] [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: 02/20/2024] [Revised: 03/11/2024] [Accepted: 03/15/2024] [Indexed: 09/03/2024]
Abstract
OBJECTIVE We aimed to explore the treatment effect and therapeutic mechanisms of baicalin in Alzheimer's disease (AD). METHODS The AD rat model was established by intracerebroventricular injection of Aβ1-40, with rats in the baicalin group receiving baicalin intraventricular injections. Morris Water Maze and Hematoxylin-eosin (H&E) Staining were employed to detect the successful model construction and baicalin treatment effect. The proteins extracted from the hippocampus were subjected to proteomics analysis. Bioinformatics technology was employed for differential protein screening, functional classification, and enrichment. Western Blot was employed to validate the expressions of differentially expressed proteins (DEPs) and the protein modification alternations. RESULTS Water maze test confirmed the successful AD model construction and baicalin can improve learning and memory abilities. A total of 26 DEPs associated with 28 Gene Ontology (GO) functions were identified in the model and 32 DEPs were obtained between the baicalin group and the model. Bioinformatics analysis demonstrated that AD occurrence resulted in neuronal dysfunction and was associated with immune responses. The baicalin therapeutic effect on AD may be associated with metabolic processes, vitamin response, angiogenesis regulation, and fatty acid response. Immunoglobulin heavy constant mu (Ighm) and Immunoglobulin G2a (IgG2a) exhibited significant increases in AD and baicalin attenuated their expressions, while Fatty acid desaturase 1 (Fads1) exhibited a significantly diminished expression and baicalin could reverse the trend. Succinylation detection exhibited the differentially expressed at 35 kD between the model and baicalin group. CONCLUSION Baicalin intervention may ameliorate cognitive impairment in AD rats by modulating the expressions of proteins and the succinylation modifications.
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Affiliation(s)
- Jiwei Zhao
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Fan Lu
- Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong, China
| | - Hongli Yu
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Jingwei Cao
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Zhiqiang Su
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Jingkun Zhao
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
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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.
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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
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Gu T, Kong M, Duan M, Chen L, Tian Y, Xu W, Zeng T, Lu L. Cu exposure induces liver inflammation via regulating gut microbiota/LPS/liver TLR4 signaling axis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 278:116430. [PMID: 38718729 DOI: 10.1016/j.ecoenv.2024.116430] [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: 03/27/2024] [Revised: 04/26/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024]
Abstract
Copper (Cu) serves as an essential cofactor in all organisms, yet excessive Cu exposure is widely recognized for its role in inducing liver inflammation. However, the precise mechanism by which Cu triggers liver inflammation in ducks, particularly in relation to the interplay in gut microbiota regulation, has remained elusive. In this investigation, we sought to elucidate the impact of Cu exposure on liver inflammation through gut-liver axis in ducks. Our findings revealed that Cu exposure markedly elevated liver AST and ALT levels and induced liver inflammation through upregulating pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and triggering the LPS/TLR4/NF-κB signaling pathway. Simultaneously, Cu exposure induced alterations in the composition of intestinal flora communities, notably increasing the relative abundance of Sphingobacterium, Campylobacter, Acinetobacter and reducing the relative abundance of Lactobacillus. Cu exposure significantly decreased the protein expression related to intestinal barrier (Occludin, Claudin-1 and ZO-1) and promoted the secretion of intestinal pro-inflammatory cytokines. Furthermore, correlation analysis was observed that intestinal microbiome and gut barrier induced by Cu were closely related to liver inflammation. Fecal microbiota transplantation (FMT) experiments further demonstrated the microbiota-depleted ducks transplanting fecal samples from Cu-exposed ducks disturbed the intestinal dysfunction, which lead to impaire liver function and activate the liver inflammation. Our study provided insights into the mechanism by which Cu exposure induced liver inflammation in ducks through the regulation of gut-liver axis. These results enhanced our comprehension of the potential mechanisms driving Cu-induced hepatotoxicity in avian species.
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Affiliation(s)
- Tiantian Gu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China
| | - Minghua Kong
- School of Life Sciences, Westlake University, Hangzhou 310024, China
| | - Mingcai Duan
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China
| | - Li Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China
| | - Yong Tian
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China
| | - Wenwu Xu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China
| | - Tao Zeng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China
| | - Lizhi Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs of China, Hangzhou, 310021, China; Zhejiang Key Laboratory of Livestock and Poultry Breeding, Hangzhou 310021, China; Zhejiang Provincial Engineering Research Center for Poultry Breeding Industry and Green Farming Technology, Hangzhou 310021, China.
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Liu S, Wang XX, Wang J, Yang H, Zhang ZM, Zhuang PY, Liu H, Du K. Discovery of sesquiterpenoids from the roots of Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu and their anti-inflammatory activity by IKBα/NF-κB p65 signaling pathway suppression. Bioorg Chem 2024; 147:107420. [PMID: 38718461 DOI: 10.1016/j.bioorg.2024.107420] [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: 02/27/2024] [Revised: 04/28/2024] [Accepted: 04/29/2024] [Indexed: 05/18/2024]
Abstract
Phytochemical analysis of Chloranthus henryi var. hupehensis roots led to the identification of a new eudesmane sesquiterpenoid dimer, 18 new sesquiterpenoids, and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer that is assembled by a unique oxygen bridge (C11-O-C8') of two highly rearranged eudesmane-type sesquiterpenes with the undescribed C16 carbon framework. (+)-2 and (-)-2 were a pair of new skeleton dinorsesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures were elucidated using spectroscopic data, single-crystal X-ray diffraction analysis, and quantum chemical computations. In the LPS-induced BV-2 microglial cell model, 17 suppressed IL-1β and TNF-α expression with EC50 values of 6.81 and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production in a dose dependent manner and without cytotoxicity. In subsequent mechanism studies, compounds 3, 16, and 17 could reduce IL-1β and TNF-α production by inhibiting IKBα/p65 pathway activation.
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Affiliation(s)
- Shuai Liu
- School of Pharmacy, North China University of Science and Technology, Tangshan 063210, Hebei Province, People's Republic of China
| | - Xiao-Xia Wang
- School of Pharmacy, North China University of Science and Technology, Tangshan 063210, Hebei Province, People's Republic of China
| | - Juan Wang
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110112, Liaoning Province, People's Republic of China
| | - Hui Yang
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, People's Republic of China
| | - Zi-Mo Zhang
- School of Pharmacy, North China University of Science and Technology, Tangshan 063210, Hebei Province, People's Republic of China
| | - Peng-Yu Zhuang
- School of Pharmacy, North China University of Science and Technology, Tangshan 063210, Hebei Province, People's Republic of China.
| | - Hang Liu
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, People's Republic of China.
| | - Ke Du
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110112, Liaoning Province, People's Republic of China.
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Luo Y, Fu S, Liu Y, Kong S, Liao Q, Lin L, Li H. Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis. JOURNAL OF ETHNOPHARMACOLOGY 2024; 326:117990. [PMID: 38423412 DOI: 10.1016/j.jep.2024.117990] [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: 12/13/2023] [Revised: 02/18/2024] [Accepted: 02/26/2024] [Indexed: 03/02/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear. AIM OF THE STUDY Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota. MATERIALS AND METHODS The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT). RESULTS BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways. CONCLUSION BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.
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Affiliation(s)
- Yuting Luo
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Sai Fu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Yuling Liu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Shasha Kong
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Qian Liao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Longfei Lin
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Hui Li
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China; Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, 330000, China; Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang, 330000, China.
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Weng L, Zhao M, Zhang Y, Xu R, Zhang J, Wang Y, Xu Y, Zhao C, Wang M. Characteristics of lipid metabolism after treatment of colon cancer mice with American ginseng vesicles. PHYTOCHEMICAL ANALYSIS : PCA 2024. [PMID: 38768606 DOI: 10.1002/pca.3367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 04/02/2024] [Accepted: 04/02/2024] [Indexed: 05/22/2024]
Abstract
INTRODUCTION Lipid molecules are present in tumours and play an important role in the anti-inflammatory response as well as in antiviral protection. Changes in the type and location of lipids in the intestine following exposure to environmental stressors play an important role in several disorders, including ulcerative colitis (UC), inflammatory bowel disease (IBD), and colorectal cancer. OBJECTIVES The aim of this work is to provide a new theoretical basis for tumour initiation and development by accurately measuring the spatial distribution of lipids and metabolites in intestinal tissue. Spatial metabolomics allows the detection of samples with minimal sample volume by label-free imaging of complex samples in their original state. The distribution of lipid molecules in tumours has not been reported, although the distribution of lipid molecules in intestinal tissue has been reported in the literature. METHODS The range of lipid profiles in colon cancer mouse tumour tissue was compiled using a spatial metabolomics: lipid extraction method. The changes in lipid distribution in two regions after oral administration of American Ginseng (Panax quinquefolius L.) vesicles were also compared. Tumour tissue samples were extracted with 80% methanol-20% formic acid in water. RESULTS The resulting spatial metabolic profile allowed the identification of seven lipid classes in mouse tumours. The distribution of fibre tissue cells was 23.2% higher than tumour tissue cells, with the exception of the fatty acid (FA) species.
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Affiliation(s)
- Ling Weng
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Min Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Yumeng Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Ruixiang Xu
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Jiayi Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Yingjie Wang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Yanxue Xu
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Chunjie Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
| | - Miao Wang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China
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Masheghati F, Asgharzadeh MR, Jafari A, Masoudi N, Maleki-Kakelar H. The role of gut microbiota and probiotics in preventing, treating, and boosting the immune system in colorectal cancer. Life Sci 2024; 344:122529. [PMID: 38490297 DOI: 10.1016/j.lfs.2024.122529] [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: 08/24/2023] [Revised: 12/03/2023] [Accepted: 02/21/2024] [Indexed: 03/17/2024]
Abstract
The gut microbiome plays a significant role in developing colorectal cancer (CRC). The gut microbiome usually acts as a protective barrier against harmful pathogens and infections in the intestine, while also regulating inflammation by affecting the human immune system. The gut microbiota and probiotics play a role not only in intestinal inflammation associated with tumor formation but also in regulating anti-cancer immune response. As a result, they associated with tumor progression and the effectiveness of anti-cancer therapies. Research indicates that gut microbiota and probiotics can be used as biomarkers to predict the impact of immunotherapy and enhance its efficacy in treating CRC by regulating it. This review examines the importance of gut microbiota and probiotics in the development and progression of CRC, as well as their synergistic impact on anti-cancer treatments.
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Affiliation(s)
- Forough Masheghati
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | | | - Abbas Jafari
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Naser Masoudi
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of General Surgery, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hadi Maleki-Kakelar
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
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Li M, Gan J, Xu X, Zhang S, Li Y, Bian L, Dong Z. Preparation, characterisation and in vitro anti-inflammatory activity of Baicalin microsponges. Heliyon 2024; 10:e29151. [PMID: 38617936 PMCID: PMC11015413 DOI: 10.1016/j.heliyon.2024.e29151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 03/25/2024] [Accepted: 04/02/2024] [Indexed: 04/16/2024] Open
Abstract
Baicalin, a flavonoid extracted from traditional Chinese medicine, Scutellaria baicalensis has significant anti-inflammatory effects. Microsponges are drug delivery systems that improve drug stability and slow the release rate. The combination of baicalin and the microsponges produced a new and stable system for its delivery, resulting in a novel formulation of baicalin. Baicalin microsponges (BM) were prepared using the quasi-emulsion solvent diffusion method. Effects of the mass ratio of the polymer (ethylcellulose) to baicalin, the concentration of the emulsifier polyvinyl alcohol (PVA), the stirring speed on the encapsulation efficiency (EE), and yield of the microsponges were investigated by combining the one-factor test and Box-Behnken design (BBD). The preparation process was standardised using 2.61:1 mass ratio of ethyl cellulose to baicalin, 2.17% concentration of PVA, with stirring at 794 rpm. Optimised BM formulations were evaluated for the parameters of EE (54.06 ± 3.02)% and yield of (70.37 ± 2.41)%, transmission electron microscopy (TEM), and in vitro cell evaluation. Results of the in vitro anti-inflammatory assay showed that baicalin microsponges-pretreated-lipopolysaccharide (LPS)-induced RAW264.7, mouse macrophages showed reduced inflammatory response, similar to that seen in baicalin-treated macrophages.
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Affiliation(s)
- Miao Li
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Lianyungang, 222005, PR China
| | - Jiajie Gan
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
- Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Lianyungang, 222005, PR China
| | - Xuhui Xu
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Lianyungang, 222005, PR China
| | - Shuai Zhang
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
- Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Lianyungang, 222005, PR China
| | - Yuanyuan Li
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
| | - Le Bian
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
- Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Lianyungang, 222005, PR China
| | - Zibo Dong
- School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, PR China
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Lianyungang, 222005, PR China
- Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Lianyungang, 222005, PR China
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He MT, Park G, Park DH, Choi M, Ku S, Go SH, Lee YG, Song SJ, Ahn CW, Jang YP, Kang KS. So Shiho Tang Reduces Inflammation in Lipopolysaccharide-Induced RAW 264.7 Macrophages and Dextran Sodium Sulfate-Induced Colitis Mice. Biomolecules 2024; 14:451. [PMID: 38672468 PMCID: PMC11047977 DOI: 10.3390/biom14040451] [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: 02/28/2024] [Revised: 04/02/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
So Shiho Tang (SSHT) is a traditional herbal medicine commonly used in Asian countries. This study evaluated the anti-inflammatory effect of SSHT and the associated mechanism using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and murine dextran sodium sulfate (DSS)-induced ulcerative colitis models. Pre-treatment of RAW 264.7 macrophages with SSHT significantly reduced LPS-induced inflammation by decreasing nitrite production and regulating the mitogen-activated protein kinase pathway. Meanwhile, in mice, DSS-induced colitis symptoms, including colon shortening and body weight loss, were attenuated by SSHT. Moreover, representative compounds of SSHT, including glycyrrhizic acid, ginsenoside Rb1, baicalin, saikosaponin A, and saikosaponin B2, were quantified, and their effects on nitrite production were measured. A potential anti-inflammatory effect was detected in LPS-induced RAW 264.7 cells. Our findings suggest that SSHT is a promising anti-inflammatory agent. Its representative components, including saikosaponin B2, ginsenoside Rb1, and baicalin, may represent the key active compounds responsible for eliciting the anti-inflammatory effects and can, therefore, serve as quality control markers in SSHT preparations.
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Affiliation(s)
- Mei Tong He
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (M.T.H.); (D.H.P.)
| | - Geonha Park
- Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;
| | - Do Hwi Park
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (M.T.H.); (D.H.P.)
| | - Minsik Choi
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (M.C.); (S.K.); (S.H.G.); (Y.G.L.); (S.J.S.)
| | - Sejin Ku
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (M.C.); (S.K.); (S.H.G.); (Y.G.L.); (S.J.S.)
| | - Seung Hyeon Go
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (M.C.); (S.K.); (S.H.G.); (Y.G.L.); (S.J.S.)
| | - Yun Gyo Lee
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (M.C.); (S.K.); (S.H.G.); (Y.G.L.); (S.J.S.)
| | - Seok Jun Song
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (M.C.); (S.K.); (S.H.G.); (Y.G.L.); (S.J.S.)
| | - Chang-Wook Ahn
- Dr. Ahn’s Surgery Clinic, Osan 18144, Republic of Korea;
| | - Young Pyo Jang
- Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (M.C.); (S.K.); (S.H.G.); (Y.G.L.); (S.J.S.)
- Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Ki Sung Kang
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (M.T.H.); (D.H.P.)
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Zhang L, Miao C, Wang Z, Guan X, Ma Y, Song J, Shen S, Song H, Li M, Liu C. Preparation and characterisation of baicalin magnesium and its protective effect in ulcerative colitis via gut microbiota-bile acid axis modulation. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 126:155416. [PMID: 38394726 DOI: 10.1016/j.phymed.2024.155416] [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: 11/28/2023] [Revised: 01/23/2024] [Accepted: 02/03/2024] [Indexed: 02/25/2024]
Abstract
BACKGROUND Scutellaria baicalensis Georgi is a well-known herb in traditional Chinese medicine that is frequently prescribed for various gastrointestinal conditions, including ulcerative colitis (UC). Its primary active constituent, baicalin, has poorly water solubility that reduces its efficacy. PURPOSE To enhance the aqueous solubility of baicalin by optimising its extraction process. We compared the modulatory effects of isolated water-soluble baicalin and water-insoluble baicalin on UC, and delved deeper into the potential mechanisms of water-soluble baicalin. METHODS We successfully extracted a more hydrophilic baicalin directly from an aqueous S. baicalensis Georgi extract through the process of recrystallisation following alcoholic precipitation of the aqueous extract obtained from S. baicalensis Georgi, eliminating the need for acid additives. This specific form of baicalin was conclusively identified by UV, IR, atomic absorption spectroscopy, elemental analysis, 1H NMR, 13C NMR, and ESI-HRMS. We subsequently compared the regulatory effects of baicalin on UC before and after optimisation, employing 16S rDNA sequencing, bile acid-targeted metabolomics, and transcriptome analysis to elucidate the potential mechanism of water-soluble baicalin; and the key genes and proteins implicated in this mechanism were verified through RT-PCR and western blotting. RESULTS A new form of baicalin present in the aqueous solution of S. baicalensis Georgi was isolated, and its structural characterisation showed that it was bound to magnesium ions (baicalin magnesium) and exhibited favorable water solubility. Baicalin magnesium offers enhanced therapeutic benefits over baicalin for UC treatment, which alleviated the inflammatory response and oxidative stress levels while improving intestinal mucosal damage. Further investigation of the mechanism revealed that baicalin magnesium could effectively regulate bile acid metabolism and maintain intestinal microecological balance in UC mice, and suppress the activation of the nuclear factor-kappa B and peroxisome proliferator-activated receptor α signalling pathways, thereby playing a therapeutic role. CONCLUSIONS Baicalin magnesium has good water solubility, which solves the bottleneck problem of water insolubility in the practical applications of baicalin. Moreover, baicalin magnesium exhibits therapeutic potential for UC significantly better than baicalin.
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Affiliation(s)
- Lin Zhang
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Ceyu Miao
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Zhixuan Wang
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Xiulu Guan
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Yechao Ma
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Jingyu Song
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Shiyuan Shen
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China
| | - Hongru Song
- Hebei North University, Zhangjiakou 075000, PR China
| | - Mingqian Li
- Cancer Institute of Integrated Tradition Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, PR China.
| | - Cuizhe Liu
- Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, Hebei 067000, PR China.
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Pu G, Li Y, Liu T, Li H, Wang L, Chen G, Cao S, Yin H, Amuda TO, Guo X, Luo X. mmu-miR-374b-5p modulated inflammatory factors via downregulation of C/EBP β/NF-κB signaling in Kupffer cells during Echinococcus multilocularis infection. Parasit Vectors 2024; 17:163. [PMID: 38553755 PMCID: PMC10981327 DOI: 10.1186/s13071-024-06238-0] [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: 10/08/2023] [Accepted: 03/05/2024] [Indexed: 04/01/2024] Open
Abstract
BACKGROUND Alveolar echinococcosis (AE) is an important infectious disease caused by the metacestode larvae of Echinococcus multilocularis, seriously threatening global public health security. Kupffer cells (KCs) play important roles in liver inflammatory response. However, their role in hepatic alveolar echinococcosis has not yet been fully elucidated. METHODS In this study, qRT-PCR was used to detect the expression level of miR-374b-5p in KCs. The target gene of miR-374b-5p was identified through luciferase reporter assays and loss of function and gains. Critical genes involved in NFκB signaling pathway were analyzed by qRT-PCR and western blot. RESULTS This study reported that miR-374b-5p was significantly upregulated in KCs during E. multilocularis infection and further showed that miR-374b-5p was able to bind to the 3'-UTR of the C/EBP β gene and suppressed its expression. The expression levels of NF-κBp65, p-NF-κBp65 and pro-inflammatory factors including iNOS, TNFα and IL6 were attenuated after overexpression of miR-374b-5p while enhanced after suppression of miR-374b-5p. However, the Arg1 expression level was promoted after overexpression of miR-374b-5p while suppressed after downregulation of miR-374b-5p. Additionally, increased protein levels of NF-κBp65 and p-NF-κBp65 were found in the C/EBP β-overexpressed KCs. CONCLUSIONS These results demonstrated that miR-374b-5p probably regulated the expression of inflammatory factors via C/EBP β/NF-κB signaling. This finding is helpful to explore the mechanism of inflammation regulation during E. multilocularis infection.
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Affiliation(s)
- Guiting Pu
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Yanping Li
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Tingli Liu
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Hong Li
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Liqun Wang
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Guoliang Chen
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Shanling Cao
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Hong Yin
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, 225009, People's Republic of China
| | - Tharheer Oluwashola Amuda
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China
| | - Xiaola Guo
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China.
| | - Xuenong Luo
- State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, Gansu Province, People's Republic of China.
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, 225009, People's Republic of China.
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Li F, Yang Y, Ge J, Wang C, Chen Z, Li Q, Yang F. Multi-omics revealed the mechanisms of Codonopsis pilosula aqueous extract in improving UC through blocking abnormal activation of PI3K/Akt signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117220. [PMID: 37820998 DOI: 10.1016/j.jep.2023.117220] [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: 05/31/2023] [Revised: 09/20/2023] [Accepted: 09/21/2023] [Indexed: 10/13/2023]
Abstract
ETHNOPHARMACOLOGICALRELEVANCE Codonopsis pilosula (DS), a traditional Chinese medicine, had been used to regulate the immune, digestive and circulatory systems of the human, as well as protect the gastrointestinal tract, improve lung function. AIM OF THE STUDY The aim of study was to explore the effects and mechanism of Codonopsis pilosula aqueous extract (DS) intervention in improving ulcerative colitis (UC). MATERIALS AND METHODS UC model rats were established using combination of TNBS and ethanol. Tissue samples were collected for transcriptome and metabolomics analysis. Network pharmacology was performed on DS to identify bioactive compounds. Western blot was used to detect the key proteins involved in UC pathogenesis and PI3K/AKT pathways. RESULTS DS exerted the preventive and therapeutic effects in improving UC via inhibiting abnormal inflammatory responses and promoting antioxidant capacity. Levels of intestinal barrier, oxidative stress and inflammatory mediators were improved to nearly normal level in vivo by DS. Metabolome profiles showed that DS could restore the metabolic disorders associated with the UC pathogenesis. Further transcriptome results showed that DS mainly alleviate UC through inhibiting PI3K/Akt signaling pathway, and various related genes that dramatically expressed in UC Model rats were downregulated by DS. Typically, network pharmacology analysis identified that Glycitein was the hub compounds that involved in the mechanism of DS in improving UC. CONCLUSIONS The results show that Codonopsis pilosula (DS) was an potential excellent material in treating of UC depending on its suitable concentration. Possible therapeutic mechanisms of the DS involved in mitigating colonal inflammation, restoring metabolic disorders, promoting antioxidant capacity, and especially blocking the activation of PI3K/Akt pathway.
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Affiliation(s)
- Fang Li
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China.
| | - Yanping Yang
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China; The First Affiliated Hospital of Air Force Medical University, China.
| | - Junli Ge
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China.
| | - Chunxia Wang
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China.
| | - Zhengjun Chen
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China.
| | - Qin Li
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China; Gansu Health Vocational College, Lanzhou, 730030, China.
| | - Fude Yang
- College of pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China.
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Esmaealzadeh N, Ram M, Abdolghaffari A, Marques AM, Bahramsoltani R. Toll-like receptors in inflammatory bowel disease: A review of the role of phytochemicals. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155178. [PMID: 38007993 DOI: 10.1016/j.phymed.2023.155178] [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: 04/06/2023] [Revised: 10/18/2023] [Accepted: 10/31/2023] [Indexed: 11/28/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammation within the gastrointestinal tract with a remarkable impact on patients' quality of life. Toll-like receptors (TLR), as a key contributor of immune system in inflammation, has a critical role in the pathogenesis of IBD and thus, can be a suitable target of therapeutic agents. Medicinal plants have long been considered as a source of bioactive agents for different diseases, including IBD. PURPOSE This review discusses current state of the art on the role of plant-derived compounds for the management of IBD with a focus on TLRs. METHODS Electronic database including PubMed, Web of Science, and Scopus were searched up to January 2023 and all studies in which anticolitis effects of a phytochemical was assessed via modulation of TLRs were considered. RESULTS Different categories of phytochemicals, including flavonoids, lignans, alkaloids, terpenes, saccharides, and saponins have demonstrated modulatory effects on TLR in different animal and cell models of bowel inflammation. Flavonoids were the most studied phytochemicals amongst others. Also, TLR4 was the most important type of TLRs which were modulated by phytochemicals. Other mechanisms such as inhibition of pro-inflammatory cytokines, nuclear factor-κB pathway, nitric oxide synthesis pathway, cyclooxygenase-2, lipid peroxidation, as well as induction of endogenous antioxidant defense mechanisms were also reported for phytochemicals in various IBD models. CONCLUSION Taken together, a growing body of pre-clinical evidence support the efficacy of herbal compounds for the treatment of IBD via modulation of TLRs. Future clinical studies are recommended to assess the safety and efficacy of these compounds in human.
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Affiliation(s)
- Niusha Esmaealzadeh
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahboobe Ram
- Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Amirhossein Abdolghaffari
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - André Mesquita Marques
- Department of Natural Products, Institute of Drug Technology (Farmanguinhos), FIOCRUZ, Rio de Janeiro, Brazil
| | - Roodabeh Bahramsoltani
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran; PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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Zhao M, Wang P, Sun X, Yang D, Zhang S, Meng X, Zhang M, Gao X. Detrimental Impacts of Pharmaceutical Excipient PEG400 on Gut Microbiota and Metabolome in Healthy Mice. Molecules 2023; 28:7562. [PMID: 38005284 PMCID: PMC10673170 DOI: 10.3390/molecules28227562] [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: 09/27/2023] [Revised: 11/02/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.
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Affiliation(s)
- Mei Zhao
- School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China;
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
| | - Pengjiao Wang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
| | - Xiaodong Sun
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
| | - Dan Yang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
| | - Shuo Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
- Experimental Animal Center, Guizhou Medical University, Guiyang 550025, China
| | - Xiaoxia Meng
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
- School of Medicine and Health Management, Guizhou Medical University, Guiyang 550025, China
| | - Min Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
| | - Xiuli Gao
- School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China;
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; (P.W.); (X.S.); (D.Y.); (S.Z.); (X.M.)
- Microbiology and Biochemical Pharmaceutical Engineering Research Center, Guizhou Medical University, Guiyang 550025, China
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Hu Q, Hou S, Xiong B, Wen Y, Wang J, Zeng J, Ma X, Wang F. Therapeutic Effects of Baicalin on Diseases Related to Gut-Brain Axis Dysfunctions. Molecules 2023; 28:6501. [PMID: 37764277 PMCID: PMC10535911 DOI: 10.3390/molecules28186501] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 08/10/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
The gut-brain axis is an active area of research. Several representative diseases, including central nervous system disorders (Alzheimer's disease, Parkinson's disease, and depression), metabolic disorders (obesity-related diseases), and intestinal disorders (inflammatory bowel disease and dysbiosis), are associated with the dysfunctional gut-brain axis. Baicalin, a bioactive flavonoid extracted from Scutellaria baicalensis, is reported to exert various pharmacological effects. This narrative review summarizes the molecular mechanisms and potential targets of baicalin in disorders of the gut-brain axis. Baicalin protects the central nervous system through anti-neuroinflammatory and anti-neuronal apoptotic effects, suppresses obesity through anti-inflammatory and antioxidant effects, and alleviates intestinal disorders through regulatory effects on intestinal microorganisms and short-chain fatty acid production. The bioactivities of baicalin are mediated through the gut-brain axis. This review comprehensively summarizes the regulatory role of baicalin in gut-brain axis disorders, laying a foundation for future research, although further confirmatory basic research is required.
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Affiliation(s)
- Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (Q.H.); (S.H.); (J.W.)
| | - Shuyu Hou
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (Q.H.); (S.H.); (J.W.)
| | - Baoyi Xiong
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Yueqiang Wen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China;
| | - Jundong Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (Q.H.); (S.H.); (J.W.)
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (Q.H.); (S.H.); (J.W.)
| | - Fang Wang
- Department of Pharmacy, Medical Supplies Center of PLA General of PLA General Hospital, Beijing 100039, China
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Zong B, Xiao Y, Ren M, Wang P, Fu S, Qiu Y. Baicalin Weakens the Porcine ExPEC-Induced Inflammatory Response in 3D4/21 Cells by Inhibiting the Expression of NF- κB/MAPK Signaling Pathways and Reducing NLRP3 Inflammasome Activation. Microorganisms 2023; 11:2126. [PMID: 37630686 PMCID: PMC10458126 DOI: 10.3390/microorganisms11082126] [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: 07/20/2023] [Revised: 08/15/2023] [Accepted: 08/18/2023] [Indexed: 08/27/2023] Open
Abstract
Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of death in pigs and has led to considerable economic losses for the pig industry. Porcine ExPEC infections often cause systemic inflammatory responses in pigs, characterized by meningitis, arthritis, pneumonia, and septicemia. Baicalin has been reported to possess potent anti-inflammatory activity, but its function in porcine ExPEC remains unknown. The aim of this study was to explore the protective effect and mechanism of baicalin against the porcine ExPEC-induced inflammatory responses in 3D4/21 cells. After treatment with baicalin, the effects on cell damage, the level of pro-inflammatory cytokines, the expression of nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of NOD-like receptor protein 3 (NLRP3) inflammasomes were examined. Our results show that baicalin significantly reduced the damage to 3D4/21 cells infected with porcine ExPEC PCN033. Further study showed that baicalin significantly reduced the transcription and expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8). Furthermore, baicalin inhibited the phosphorylation of proteins such as P65, nuclear factor κB inhibitor α (IκBα), extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 and reduced the expression levels of proteins such as NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. These results reveal that baicalin reduced the damage to 3D4/21 cells by inhibiting the expression of NF-κB/MAPK signaling pathways and blocking NLRP3 inflammasome activation in 3D4/21 cells infected with porcine ExPEC. Taken together, these results suggest that baicalin may have potential as a medicine for the treatment of porcine ExPEC-infected pigs by regulating inflammatory responses. This study provides a novel potential pharmaco-therapeutic approach to preventing porcine ExPEC infection.
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Affiliation(s)
- Bingbing Zong
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China
- Engineering Research Center of Feed Protein Resources on Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 400023, China
- Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 400023, China
| | - Yong Xiao
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China
- Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 400023, China
| | - Mingxing Ren
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China
- Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 400023, China
| | - Peiyi Wang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China
- Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 400023, China
| | - Shulin Fu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China
- Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 400023, China
| | - Yinsheng Qiu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China
- Engineering Research Center of Feed Protein Resources on Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 400023, China
- Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 400023, China
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Jia B, Jiang Y, Yao Y, Xu Y, Wang Y, Li T. Baicalin attenuates dexamethasone-induced apoptosis of bone marrow mesenchymal stem cells by activating the hedgehog signaling pathway. Chin Med J (Engl) 2023; 136:1839-1847. [PMID: 36804262 PMCID: PMC10406080 DOI: 10.1097/cm9.0000000000002113] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND Perturbations in bone marrow mesenchymal stem cell (BMSC) differentiation play an important role in steroid-induced osteonecrosis of the femoral head (SONFH). At present, studies on SONFH concentrate upon the balance within BMSC osteogenic and adipogenic differentiation. However, BMSC apoptosis as well as proliferation are important prerequisites in their differentiation. The hedgehog (HH) signaling pathway regulates bone cell apoptosis. Baicalin (BA), a well-known compound in traditional Chinese medicine, can affect the proliferation and apoptosis of numerous cell types via HH signaling. However, the potential role and mechanisms of BA on BMSCs are unclear. Thus, we aimed to explore the role of BA in dexamethasone (Dex)-induced BMSC apoptosis in this study. METHODS Primary BMSCs were treated with 10 -6 mol/L Dex alone or with 5.0 μmol/L, 10.0 μmol/L, or 50.0 μmol/L BA for 24 hours followed by co-treatment with 5.0 μmol/L, 10.0 μmol/L, or 50.0 μmol/L BA and 10 -6 mol/L Dex. Cell viability was assayed through the Cell Counting Kit-8 (CCK-8). Cell apoptosis was evaluated using Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining followed by flow cytometry. The imaging and counting, respectively, of Hochest 33342/PI-stained cells were used to assess the morphological characteristics and proportion of apoptotic cells. To quantify the apoptosis-related proteins (e.g., apoptosis regulator BAX [Bax], B-cell lymphoma 2 [Bcl-2], caspase-3, and cleaved caspase-3) and HH signaling pathway proteins, western blotting was used. A HH-signaling pathway inhibitor was used to demonstrate that BA exerts its anti-apoptotic effects via the HH signaling pathway. RESULTS The results of CCK-8, Hoechst 33342/PI-staining, and flow cytometry showed that BA did not significantly promote cell proliferation (CCK-8: 0 μmol/L, 100%; 2.5 μmol/L, 98.58%; 5.0 μmol/L, 95.18%; 10.0 μmol/L, 98.11%; 50.0 μmol/L, 99.38%, F = 2.33, P > 0.05), but it did attenuate the effect of Dex on apoptosis (Hoechst 33342/PI-staining: Dex+ 50.0 μmol/L BA, 12.27% vs. Dex, 39.27%, t = 20.62; flow cytometry: Dex + 50.0 μmol/L BA, 12.68% vs. Dex, 37.43%, t = 11.56; Both P < 0.05). The results of western blotting analysis showed that BA reversed Dex-induced apoptosis by activating the HH signaling pathway, which down-regulated the expression of Bax, cleaved-caspase 3, and suppressor of fused (SUFU) while up-regulating Bcl-2, sonic hedgehog (SHH), and zinc finger protein GLI-1 (GLI-1) expression (Bax/Bcl-2: Dex+ 50.0 μmol/L BA, 1.09 vs. Dex, 2.76, t = 35.12; cleaved caspase-3/caspase-3: Dex + 50.0 μmol/L BA, 0.38 vs . Dex, 0.73, t = 10.62; SHH: Dex + 50.0 μmol/L BA, 0.50 vs . Dex, 0.12, t = 34.01; SUFU: Dex+ 50.0 μmol/L BA, 0.75 vs . Dex, 1.19, t = 10.78; GLI-1: Dex+ 50.0 μmol/L BA, 0.40 vs . Dex, 0.11, t = 30.68. All P < 0.05). CONCLUSIONS BA antagonizes Dex-induced apoptosis of human BMSCs by activating the HH signaling pathway. It is a potential candidate for preventing SONFH.
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Affiliation(s)
- Bin Jia
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
- Medical Department, Qingdao University, Qingdao, Shandong 266071, China
| | - Yaping Jiang
- Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Yao Yao
- Medical Department, Qingdao University, Qingdao, Shandong 266071, China
| | - Yingxing Xu
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
- Medical Department, Qingdao University, Qingdao, Shandong 266071, China
| | - Yingzhen Wang
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Tao Li
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
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44
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Zhang P, Jiang H. Acetyl-11-keto-β-boswellic Acid Confers Protection in DSS-Induced Colitis via the JNK-p38 MAPK and NF-κB Signaling Pathways. Adv Biol (Weinh) 2023; 7:e2200247. [PMID: 36658725 DOI: 10.1002/adbi.202200247] [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: 09/09/2022] [Revised: 12/27/2022] [Indexed: 01/21/2023]
Abstract
The present study aims to explore the effect and mechanism of acetyl-11-keto-β-boswellic acid (AKBA) on inflammatory bowel disease (IBD). The IBD-mouse model is established by replacing normal water intake with 2.5% dextran sulfate sodium salt (DSS) aqueous solution, and 50 mg kg-1 of AKBA treatment is administered. The experimental mice are randomly divided into four groups, including control, AKBA , DSS, and DSS + AKBA groups. AKBA therapy conspicuously ameliorates the adverse symptoms caused by DSS in mice and inhibits the reduction of colon length and the rise of disease activity index score. Hematoxylin-eosin staining results suggest that AKBA strikingly improves the pathological conditions of the colon and small intestine tissues in IBD mice. AKBA prominently inhibits the DSS-induced increase of proinflammatory factor contents and the upregulation of the c-Jun N-terminal kinase (JNK)-p38/mitogen-activated protein kinase (MAPK) and Nuclear factor kappa B (NF-κB) pathways' protein levels in the colon tissues of IBD mice. AKBA alleviates DSS-induced colonic inflammatory injury in IBD mice by repressing the activation of the JNK-p38/MAPK and NF-κB pathways.
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Affiliation(s)
- Peng Zhang
- Department of TCM, The Affiliated Xuzhou Central Hospital of Nanjing University of Chinese Medicine, Xuzhou City, Jiangsu Province, 221000, China
| | - Hua Jiang
- Department of TCM, Workers Hospital of China Coal No. 5 Construction Company, 105 Huaihai West Road, Xuzhou City, Jiangsu Province, 221000, China
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Wen Y, Wang Y, Zhao C, Zhao B, Wang J. The Pharmacological Efficacy of Baicalin in Inflammatory Diseases. Int J Mol Sci 2023; 24:ijms24119317. [PMID: 37298268 DOI: 10.3390/ijms24119317] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/09/2023] [Accepted: 05/15/2023] [Indexed: 06/12/2023] Open
Abstract
Baicalin is one of the most abundant flavonoids found in the dried roots of Scutellaria baicalensis Georgi (SBG) belonging to the genus Scutellaria. While baicalin is demonstrated to have anti-inflammatory, antiviral, antitumor, antibacterial, anticonvulsant, antioxidant, hepatoprotective, and neuroprotective effects, its low hydrophilicity and lipophilicity limit the bioavailability and pharmacological functions. Therefore, an in-depth study of baicalin's bioavailability and pharmacokinetics contributes to laying the theoretical foundation for applied research in disease treatment. In this view, the physicochemical properties and anti-inflammatory activity of baicalin are summarized in terms of bioavailability, drug interaction, and inflammatory conditions.
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Affiliation(s)
- Yongqiang Wen
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
| | - Yazhou Wang
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
| | - Chenxu Zhao
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
| | - Baoyu Zhao
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
| | - Jianguo Wang
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China
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Liu M, Wang Y, Xiang H, Guo M, Li S, Liu M, Yao J. The Tryptophan Metabolite Indole-3-Carboxaldehyde Alleviates Mice with DSS-Induced Ulcerative Colitis by Balancing Amino Acid Metabolism, Inhibiting Intestinal Inflammation, and Improving Intestinal Barrier Function. Molecules 2023; 28:molecules28093704. [PMID: 37175112 PMCID: PMC10180526 DOI: 10.3390/molecules28093704] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/22/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
Ulcerative colitis (UC) has attracted much attention for its negative influence on quality of life and increased risk of colorectal cancer. Chemical and biological drugs are currently the usual treatment for UC. These drugs always induce severe side effects, or patients might become resistant to these therapies. Therefore, new therapeutic options for UC are urgently needed. In this study, we discovered the inhibitory activity of the intestinal tryptophan metabolite indole-3-carboxaldehyde (3-IAld) in dextran sulfate sodium salt (DSS)-induced UC mice by targeting the TLR4/NF-κB/p38 signaling pathway. This compound effectively protected against colon length shortening and damage induced by DSS in the colon, notably reducing the severity of inflammation. The production of inflammatory factors of TNF-α, IL-6, and IL-1β was significantly attenuated when treating with 3-IAld in vivo and vitro. This might be attributed to inhibition of the TLR4/NF-kB/p38 signaling pathway. Moreover, 3-IAld could up-regulate the expression of ZO-1 and Occludin in vivo and vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) results showed that 3-IAld could balance the aspartate and glutamate metabolism and the lysine degradation metabolism in the serum of DSS-induced colitis mice. In conclusion, 3-IAld ameliorated the intestinal barrier dysfunction and inflammatory response in DSS-induced UC mice, balanced amino acid metabolism, and inhibited the activation of the TLR4/NF-kB/p38 signaling pathway, thereby protecting mice with colitis.
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Affiliation(s)
- Mingfei Liu
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Yuxuan Wang
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Haixin Xiang
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Meng Guo
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Shirong Li
- State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi 276005, China
- Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi 276005, China
| | - Ming Liu
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Jingchun Yao
- State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi 276005, China
- Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi 276005, China
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Hot Melt Extrusion as an Effective Process in the Development of Mucoadhesive Tablets Containing Scutellariae baicalensis radix Extract and Chitosan Dedicated to the Treatment of Oral Infections. Int J Mol Sci 2023; 24:ijms24065834. [PMID: 36982908 PMCID: PMC10054152 DOI: 10.3390/ijms24065834] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/15/2023] [Accepted: 03/17/2023] [Indexed: 03/22/2023] Open
Abstract
Hot Melt Extrusion (HME) technology was developed to obtain blends containing lyophilized Scutellariae baicalensis root extract and chitosan in order to improve the rheological properties of the obtained blends, including tableting and compressibility properties. (Hydroxypropyl)methyl cellulose (HPMC) in 3 different ratios was used as amorphous matrix formers. The systems were characterized using X-ray powder diffraction (PXRD), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR), and in vitro release, permeability, and microbiological activity studies. Then, the extrudates were used to prepare tablets in order to give them the appropriate pharmaceutical form. HPMC-based systems released baicalin more slowly, resulting in delayed peaks in the acceptor fluid. This behavior can be explained by the fact that HPMC swells significantly, and the dissolved substance must have diffused through the polymer network before being released. The best tabletability properties are provided by the formulation containing the extrudate with lyophilized extract HPMC 50:50 w/w. These tablets offer a valuable baicalin release profile while maintaining good mucoadhesive properties that condition the tablet’s retention in the application site and the effectiveness of therapy.
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Tan X, Wen Y, Han Z, Su X, Peng J, Chen F, Wang Y, Wang T, Wang C, Ma K. Cinnamaldehyde Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating TLR4/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation. Chem Biodivers 2023; 20:e202200089. [PMID: 36653304 DOI: 10.1002/cbdv.202200089] [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: 01/26/2022] [Revised: 01/16/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease mainly associated with immune dysfunction and microbiota disturbance. Cinnamaldehyde (CIN) is an active ingredient of Cinnamomum cassia with immunomodulatory and anti-inflammatory properties. However, the therapeutic effect and detailed mechanism of CIN on UC remains unclear, and warrant further dissection. In this study, network pharmacology and molecular docking analyses were introduced to predict the potential targets and mechanism of CIN against UC. The therapeutic effect and the predicted targets of CIN on UC were further validated by in vivo and in vitro experiments. Seven intersection targets shared by CIN and UC were obtained, and four hub targets, i. e., toll-like receptor 4 (TLR4), transcription factor p65 (NF-κB), NF-kappa-B inhibitor alpha (IκBα), prostaglandin G/H synthase 2 (COX2) were acquired, which were mainly involved in NF-κB, tumor necrosis factor (TNF), Toll-like receptor and NOD-like receptor signaling pathways. CIN alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis by decreasing the disease active index (DAI), restoring colon length, and relieving colonic pathology. CIN attenuated systemic inflammation by reducing serum myeloperoxidase (MPO), TNF-α, interleukin-6 (IL-6), and interleukin-1β (IL-1β), down-regulating TLR4, phosphorylated-NF-κB (p-NF-κB), phosphorylated-IκBα (p-IκBα), and COX2 expression in colonic tissues, and decreasing NOD-like receptor protein 3 (NLRP3), Caspase-1, and IL-1β protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. These results indicate that CIN alleviates DSS-induced colitis inflammation by modulating TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.
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Affiliation(s)
- Xiaofen Tan
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China
| | - Yifan Wen
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China
| | - Zhijun Han
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China
| | - Xuyang Su
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China
| | - Jing Peng
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China
| | - Feng Chen
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China
| | - Yadong Wang
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China
| | - Tianming Wang
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China.,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China
| | - Changzhong Wang
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China
| | - Kelong Ma
- College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, 230012, P. R. China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, P. R. China
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Jang JY, Im E, Kim ND. Therapeutic Potential of Bioactive Components from Scutellaria baicalensis Georgi in Inflammatory Bowel Disease and Colorectal Cancer: A Review. Int J Mol Sci 2023; 24:1954. [PMID: 36768278 PMCID: PMC9916177 DOI: 10.3390/ijms24031954] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/16/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Scutellaria baicalensis Georgi (SBG), an herbal medicine with various biological activities, including anti-inflammatory, anticancer, antiviral, antibacterial, and antioxidant activities, is effective in treatment of colitis, hepatitis, pneumonia, respiratory infections, and allergic diseases. This herbal medicine consists of major active substances, such as baicalin, baicalein, wogonoside, and wogonin. Inflammatory bowel disease (IBD) comprises a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis being the main types. IBD can lead to serious complications, such as increased risk of colorectal cancer (CRC), one of the most common cancers worldwide. Currently, there is no cure for IBD, and its incidence has been increasing over the past few decades. This review comprehensively summarizes the efficacy of SBG in IBD and CRC and may serve as a reference for future research and development of drugs for IBD and cancer treatment.
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Affiliation(s)
| | - Eunok Im
- Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea
| | - Nam Deuk Kim
- Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea
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50
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Paczkowska-Walendowska M, Cielecka-Piontek J. Chitosan as a Functional Carrier for the Local Delivery Anti-Inflammatory Systems Containing Scutellariae baicalensis radix Extract. Pharmaceutics 2022; 14:2148. [PMID: 36297583 PMCID: PMC9611887 DOI: 10.3390/pharmaceutics14102148] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/06/2022] [Accepted: 10/06/2022] [Indexed: 08/27/2023] Open
Abstract
The aim of the study was to establish the influence of chitosan on the preparation of systems containing Scutellariae baicalensis radix extract and to demonstrate the potential of anti-inflammatory action for the treatment of periodontitis. In the first stage, the impact of the variables (extraction mixture composition, temperature, and the number of extraction cycles) on the extracted samples' biological characteristics was analyzed using the Design of Experiments (DoE) approach. The best conditions for baicalin, baicalein, and wogonin extraction from Scutellariae baicalensis radix were 80% methanol in the extraction mixture, 70 °C, and 4 cycles per 60 min. The DoE approach can be used to choose the best chitosan system parameters with equal success. An increase in the deacetylation degree of chitosan used in the system improved the potential for reducing free radicals and inhibiting the hyaluronidase enzyme. Also, increasing the degree of chitosan deacetylation results in increased resistance of the carrier to biodegradation and an extended baicalin release profile, which is also associated with an increase in the viscosity of the chitosan-based system. In total, the system of a freeze-dried extract with chitosan 90/500 in the ratio of 2:1 (system S9) turns out to be the one with the best physicochemical (high percentage of baicalin release and the highest viscosity conditioning the prolonged stay at the site of administration) and biological properties (the highest antioxidant and anti-inflammatory activities), resulting in the highest potential for use in the treatment of oral inflammatory diseases.
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