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Zheng M, Liu H, Zhang R, Guo X, Shao Q, Zhang J, Li L, Wang J, Miao S, Shi X, Ma S. Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation. JOURNAL OF ETHNOPHARMACOLOGY 2025; 347:119696. [PMID: 40157401 DOI: 10.1016/j.jep.2025.119696] [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: 12/18/2024] [Revised: 03/19/2025] [Accepted: 03/23/2025] [Indexed: 04/01/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE SiniSan (SNS), a traditional formula from the Treatise on Typhoid Fever, has been shown in modern clinical practice to effectively treat both ulcerative colitis (UC) and depression, although the underlying mechanisms remain incompletely understood. AIM OF THE STUDY This study employed UPLC-Q-Orbitrap-MS, network pharmacology, molecular docking, and experimental validation to investigate SNS's mechanism in treating UC with comorbid depression. MATERIALS AND METHODS UPLC-Q-Orbitrap-MS, in conjunction with network pharmacology and molecular docking, identified active constituents and potential targets of SNS. A UC model induced by a 3 % dextran sulfate sodium (DSS) solution was used for experimental validation. Therapeutic efficacy was assessed through behavioral tests, ELISA, routine blood tests, histopathology, immunofluorescence, Western blot, and qRT-PCR. RESULTS SNS alleviated weight loss and inflammation in DSS-induced colitis in mice while exhibiting antidepressant effects in the open field test, forced swim test, and tail suspension test. Furthermore, SNS improved intestinal mucosal barrier function and restored hippocampal blood-brain barrier integrity. It inhibited microglial proliferation and neuroinflammation in the Hippocampus Cornu Ammonis 1 and dentate gyrus regions. Mechanistic analysis revealed that SNS mediates its effects on UC by modulating targets in the PI3K/AKT signaling pathway. CONCLUSIONS SNS ameliorates UC with comorbid depression by restoring the integrity of both the intestinal mucosal barrier and the blood-brain barrier, alleviating DSS-induced colitis and neuroinflammation.
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Affiliation(s)
- Meiling Zheng
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China; Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, PR China
| | - Huilin Liu
- Department of Rehabilitation Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China
| | - Rui Zhang
- Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China
| | - Xiaodi Guo
- The College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, PR China
| | - Qi Shao
- Department of Pharmacy, Tongchuan Mining Bureau Central Hospital, Tongchuan, Shaanxi, 27000, PR China
| | - Jing Zhang
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China
| | - Long Li
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China
| | - Jin Wang
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China
| | - Shan Miao
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
| | - Xiaopeng Shi
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
| | - Shanbo Ma
- Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China; Innovation Research Institute, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
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Zheng T, Huang KY, Tang XD, Wang FY, Lv L. Endoplasmic reticulum stress in gut inflammation: Implications for ulcerative colitis and Crohn's disease. World J Gastroenterol 2025; 31:104671. [PMID: 40248056 PMCID: PMC12001174 DOI: 10.3748/wjg.v31.i13.104671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 02/20/2025] [Accepted: 03/13/2025] [Indexed: 04/02/2025] Open
Abstract
Eukaryotic cells contain the endoplasmic reticulum (ER), a prevalent and intricate membranous structural system. During the development of inflammatory bowel disease (IBD), the stress on the ER and the start of the unfolded protein response are very important. Some chemicals, including 4μ8C, small molecule agonists of X-box binding protein 1, and ISRIB, work on the inositol-requiring enzyme 1, turn on transcription factor 6, and activate protein kinase RNA-like ER kinase pathways. This may help ease the symptoms of IBD. Researchers investigating the gut microbiota have discovered a correlation between ER stress and it. This suggests that changing the gut microbiota could help make new medicines for IBD. This study looks at how ER stress works and how it contributes to the emergence of IBD. It also talks about its possible clinical importance as a therapeutic target and looks into new ways to treat this condition.
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Affiliation(s)
- Ting Zheng
- Graduate School, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Kai-Yue Huang
- Graduate School, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Xu-Dong Tang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Feng-Yun Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Lin Lv
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
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Tang H, Gao X, Wu Z, Chen J, Chen L, Du X. Expression and role of CTHRC1 in inflammatory bowel disease in children. Cytotechnology 2025; 77:44. [PMID: 39867826 PMCID: PMC11759733 DOI: 10.1007/s10616-025-00705-x] [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: 11/12/2024] [Accepted: 01/07/2025] [Indexed: 01/28/2025] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, progressive, immune-mediated, gastrointestinal inflammatory disease with increasing occurrences in children. Collagen triple helix repeat containing 1 (CTHRC1), a migration-promoting protein, acts as a tumor-promoting factor in malignant tumors. However, functions and mechanisms of CTHRC1 in children with IBD remain unclear. This study aimed to determine the effects and mechanisms of CTHRC1 on dextran sodium sulfate (DSS)-treated HT-29 cells. HT-29 control cells were exposed to 2% DSS to develop an in vitro IBD model. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to assess CTHRC1 expression in serum of children with IBD and HT-29 cells. Cell viability and apoptosis were assessed using MTT and flow cytometry (FCM). Expressions of cleaved-Caspase3 and Caspase3 were determined by western blotting. The cytokine production (TNF-α, IL-1β and IL-6) in HT-29 cells was measured by ELISA assay. Activation or inactivation of NF-κB signaling pathway was confirmed by western blot assay. Results showed that CTHRC1 expression was upregulated in the IBD serum and HT-29 control cells. The level of CTHRC1 was lower in CTHRC1-siRNA transfected cells than in control siRNA-treated cells. Notably, silence of CTHRC1 markedly enhanced HT-29 cells viability, decreased apoptotic cells, suppressed cleaved-Caspase3 expression, inhibited cleaved-Caspase3/Caspase3 ratio, reduced the production of inflammatory cytokines, and blocked NF-κB signaling pathway induced by DSS. However, these effects were reversed following diprovocim treatment. Thus, that knockdown of CTHRC1 alleviated DSS-induced HT-29 cell injury by inhibiting the NF-κB signaling pathway in vitro, providing a new therapeutic target for IBD in children. Supplementary Information The online version contains supplementary material available at 10.1007/s10616-025-00705-x.
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Affiliation(s)
- Heng Tang
- Radiology Department, Hubei NO.3 People’s Hospital of Jianghan University, Wuhan, China
| | - Xiang Gao
- Radiology Department, Hubei NO.3 People’s Hospital of Jianghan University, Wuhan, China
| | - Zhaofang Wu
- Child Rehabilitation Department, Hubei NO.3 People’s Hospital of Jianghan University, No. 26 Zhongshan Avenue, Qiaokou District, Wuhan, 430033 China
| | - Jia Chen
- Child Rehabilitation Department, Hubei NO.3 People’s Hospital of Jianghan University, No. 26 Zhongshan Avenue, Qiaokou District, Wuhan, 430033 China
| | - Li Chen
- Child Rehabilitation Department, Hubei NO.3 People’s Hospital of Jianghan University, No. 26 Zhongshan Avenue, Qiaokou District, Wuhan, 430033 China
| | - Xiang Du
- Child Rehabilitation Department, Hubei NO.3 People’s Hospital of Jianghan University, No. 26 Zhongshan Avenue, Qiaokou District, Wuhan, 430033 China
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Gao G, Su X, Liu S, Wang P, Chen JJ, Liu T, Xu J, Zhang Z, Zhang X, Xie Z. Cornuside as a promising therapeutic agent for diabetic kidney disease: Targeting regulation of Ca 2+ disorder-mediated renal tubular epithelial cells apoptosis. Int Immunopharmacol 2025; 149:114190. [PMID: 39904045 DOI: 10.1016/j.intimp.2025.114190] [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: 01/05/2025] [Revised: 01/20/2025] [Accepted: 01/27/2025] [Indexed: 02/06/2025]
Abstract
Renal tubular epithelial cells (RTECs) apoptosis is the key factor in the development of diabetic kidney disease (DKD). Endoplasmic reticulum stress (ERS) leading to mitochondrial Ca2+ overload is one of the causes of apoptosis in RTECs. Corni Fructus (CF) is an herbal medicine, developed and applied as a functional food, and it is commonly used to treat DKD. Cornuside (Cor) is one of the main chemical components in CF. This research seeks to investigate the function of Cor in DKD and delve into its possible mechanisms. Cor significantly improved renal function and ameliorated renal pathological changes of db/db mice. Bioinformatics analyses suggested that the modulation of endoplasmic reticulum-induced intrinsic apoptosis pathway was a primary mechanism by which Cor ameliorated DKD. TUNEL assays and flow cytometry assays indicated that Cor effectively inhibited RTECs apoptosis in db/db mice and AGE-induced HK-2 cells. Further experimental studies showed that Cor mitigated ERS by inhibiting the activation of PERK/ATF4/CHOP signal pathway and down-regulation of VDAC1 protein expression, thus alleviating mitochondrial Ca2+ overload. More importantly, Cor directly targeted NEDD4 to facilitate VDAC1 degradation. Notably, the silencing of NEDD4 nearly abolished Cor's inhibitory effects on mitochondrial Ca2+ overload and apoptosis. In conclusion, Cor modulated Ca2+ homeostasis by alleviating ERS and targeting NEDD4, thus mitigating apoptosis of RTECs in DKD. These findings indicate that Cor has the potential for the treatment and drug development of DKD.
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Affiliation(s)
- Gai Gao
- School of Pharmacy, Minzu University of China, Beijing, 100081, China; Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China
| | - Xuan Su
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China
| | - Shuyan Liu
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China
| | - Pan Wang
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China
| | - Jenny Jie Chen
- International Academic Affairs Department, Management and Science University, University Drive, Off Persiaran Olahraga, Section 13, 40100, Shah Alam, Selangor Darul Ehsan, Malaysia
| | - Tongxiang Liu
- School of Pharmacy, Minzu University of China, Beijing, 100081, China
| | - Jiangyan Xu
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China
| | - Zhenqiang Zhang
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China.
| | - Xiaowei Zhang
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China.
| | - Zhishen Xie
- Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, 450046, China.
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Long D, Mao C, Zhang W, Zhu Y, Xu Y. Natural products for the treatment of ulcerative colitis: focus on the JAK/STAT pathway. Front Immunol 2025; 16:1538302. [PMID: 40078988 PMCID: PMC11897526 DOI: 10.3389/fimmu.2025.1538302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
Ulcerative colitis (UC) is an autoimmune disease with an incompletely understood pathogenesis. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway plays a key role in immune response and inflammation. More and more studies demonstrated that JAK/STAT signaling pathway is associated with the pathogenesis of UC. The JAK/STAT pathway affects UC in multiple ways by regulating intestinal inflammatory response, affecting intestinal mucosal barrier, modulating T cell homeostasis, and regulating macrophages. Encouragingly, natural products are promising candidates for the treatment of UC. Natural products have the advantage of being multi-targeted and rich in therapeutic modalities. This review summarized the research progress of JAK/STAT pathway-mediated UC. Furthermore, the latest studies on natural products targeting the JAK/STAT pathway for the treatment of UC were systematically summarized, including active ingredients such as arbutin, aloe polysaccharide, berberine, matrine, curcumin, Ginsenoside Rh2, and so on. The aim of this paper is to provide new ideas for drug development to regulate JAK/STAT signaling for treating UC.
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Affiliation(s)
- Dan Long
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Chenhan Mao
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Wei Zhang
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Ying Zhu
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yin Xu
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
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Liu L, Chen Y, Han Y, Zhang X, Wu Y, Lin J, Cao L, Wu M, Zheng H, Fang Y, Wei L, Sferra TJ, Jafri A, Ke X, Peng J, Shen A. Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway. PHARMACEUTICAL BIOLOGY 2024; 62:607-620. [PMID: 39034914 PMCID: PMC11265301 DOI: 10.1080/13880209.2024.2378012] [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: 10/12/2023] [Accepted: 07/02/2024] [Indexed: 07/23/2024]
Abstract
CONTEXT Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted. OBJECTIVE To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms. MATERIALS AND METHODS A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining. RESULTS Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1β and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues. DISCUSSION AND CONCLUSIONS The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.
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Affiliation(s)
- Liya Liu
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Youqin Chen
- Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA
| | - Yuying Han
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Xinran Zhang
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Yulun Wu
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Jing Lin
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Liujing Cao
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Meizhu Wu
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Huifang Zheng
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Yi Fang
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Lihui Wei
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Thomas J. Sferra
- Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA
| | - Anjum Jafri
- Department of Genetics and Genome Sciences, Histology Core, Case Western Reserve University, Cleveland, OH, USA
| | - Xiao Ke
- Department of Gastroenterology, The Second People’s Hospital affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Clinical Medical Research Centre of Chinese Medicine for Spleen and Stomach, Fuzhou, China
| | - Jun Peng
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
| | - Aling Shen
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Clinical Research Institute, The Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, China
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Lee S, Jung SY, Yoo D, Go D, Park JY, Lee JM, Um W. Alternatives of mesenchymal stem cell-derived exosomes as potential therapeutic platforms. Front Bioeng Biotechnol 2024; 12:1478517. [PMID: 39315312 PMCID: PMC11417005 DOI: 10.3389/fbioe.2024.1478517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 08/26/2024] [Indexed: 09/25/2024] Open
Abstract
With outstanding therapeutic potential in the tissue regeneration and anti-inflammation, mesenchymal stem cell-derived exosomes (MSC-EXOs) have emerged as a prominent therapeutic in recent. However, poor production yield and reproducibility have remained as significant challenges of their practical applications. To surmount these challenges, various alternative materials with stem cell-like functions, have been recently investigated, however, there has been no comprehensive analysis in these alternatives so far. Here, we discuss the recent progress of alternatives of MSC-EXOs, including exosomes and exosome-like nanovesicles from various biological sources such as plants, milk, microbes, and body fluids. Moreover, we extensively compare each alternative by summarizing their unique functions and mode of actions to suggest the expected therapeutic target and future directions for developing alternatives for MSC-EXOs.
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Affiliation(s)
| | | | | | | | | | - Jong Min Lee
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea
| | - Wooram Um
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea
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Ma Z, Du X, Sun Y, Jia Y, Liang X, Gao Y. Attenuation of PM2.5-Induced Lung Injury by 4-Phenylbutyric Acid: Maintenance of [Ca 2+]i Stability between Endoplasmic Reticulum and Mitochondria. Biomolecules 2024; 14:1135. [PMID: 39334901 PMCID: PMC11430257 DOI: 10.3390/biom14091135] [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: 08/01/2024] [Revised: 09/03/2024] [Accepted: 09/06/2024] [Indexed: 09/30/2024] Open
Abstract
Fine particulate matter (PM2.5) is a significant cause of respiratory diseases and associated cellular damage. The mechanisms behind this damage have not been fully explained. This study investigated two types of cellular damage (inflammation and pyroptosis) induced by PM2.5, focusing on their relationship with two organelles (the endoplasmic reticulum and mitochondria). Animal models have demonstrated that PM2.5 induces excessive endoplasmic reticulum stress (ER stress), which is a significant cause of lung damage in rats. This was confirmed by pretreatment with an ER stress inhibitor (4-Phenylbutyric acid, 4-PBA). We found that, in vitro, the intracellular Ca2+ ([Ca2+]i) dysregulation induced by PM2.5 in rat alveolar macrophages was associated with ER stress. Changes in mitochondria-associated membranes (MAMs) result in abnormal mitochondrial function. This further induced the massive expression of NLRP3 and GSDMD-N, which was detrimental to cell survival. In conclusion, our findings provide valuable insights into the relationship between [Ca2+]i dysregulation, mitochondrial damage, inflammation and pyroptosis under PM2.5-induced ER stress conditions. Their interactions ultimately have an impact on respiratory health.
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Affiliation(s)
- Zhenhua Ma
- College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
- Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan 750002, China
| | - Xiaohui Du
- College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Yize Sun
- College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Yunna Jia
- College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Xiaojun Liang
- Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan 750002, China
| | - Yunhang Gao
- College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, 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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Zhou X, Wang H, Huang M, Chen J, Chen J, Cheng H, Ye X, Wang W, Liu D. Role of bitter contributors and bitter taste receptors: a comprehensive review of their sources, functions and future development. FOOD SCIENCE AND HUMAN WELLNESS 2024; 13:1806-1824. [DOI: 10.26599/fshw.2022.9250151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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11
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Zhang X, Huang C, Hou Y, Jiang S, Zhang Y, Wang S, Chen J, Lai J, Wu L, Duan H, He S, Liu X, Yu S, Cai Y. Research progress on the role and mechanism of Sirtuin family in doxorubicin cardiotoxicity. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 129:155673. [PMID: 38677274 DOI: 10.1016/j.phymed.2024.155673] [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: 12/23/2023] [Revised: 04/16/2024] [Accepted: 04/21/2024] [Indexed: 04/29/2024]
Abstract
BACKGROUND Doxorubicin (DOX) is a widely utilized anthracycline chemotherapy drug in cancer treatment, yet its efficacy is hindered by both short-term and long-term cardiotoxicity. Although oxidative stress, inflammation and mitochondrial dysfunction are established factors in DOX-induced cardiotoxicity, the precise molecular pathways remain elusive. Further exploration of the pathogenesis and identification of novel molecular targets are imperative. Recent studies have implicated the Sirtuins family in various physiological and pathological processes, suggesting their potential in ameliorating DOX-induced cardiotoxicity. Moreover, research on Sirtuins has discovered small-molecule compounds or medicinal plants with regulatory effects, representing a notable advancement in preventing and treating DOX-induced cardiac injury. PURPOSE In this review, we delve into the pathogenesis of DOX-induced cardiotoxicity and explore the therapeutic effects of Sirtuins in mitigating this condition, along with the associated molecular mechanisms. Furthermore, we delineate the roles and mechanisms of small-molecule regulators of Sirtuins in the prevention and treatment of DOX-induced cardiotoxicity. STUDY-DESIGN/METHODS Data for this review were sourced from various scientific databases (such as Web of Science, PubMed and Science Direct) up to March 2024. Search terms included "Sirtuins," "DOX-induced cardiotoxicity," "DOX," "Sirtuins regulators," "histone deacetylation," among others, as well as several combinations thereof. RESULTS Members of the Sirtuins family regulate both the onset and progression of DOX-induced cardiotoxicity through anti-inflammatory, antioxidative stress and anti-apoptotic mechanisms, as well as by maintaining mitochondrial stability. Moreover, natural plant-derived active compounds such as Resveratrol (RES), curcumin, berberine, along with synthetic small-molecule compounds like EX527, modulate the expression and activity of Sirtuins. CONCLUSION The therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity represents a potential molecular target. However, further research is urgently needed to elucidate the relevant molecular mechanisms and to assess the safety and biological activity of Sirtuins regulators. This review offers an in-depth understanding of the therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity, providing a preliminary basis for the clinical application of Sirtuins regulators in this condition.
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Affiliation(s)
- Xuan Zhang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Chaoming Huang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Yanhong Hou
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Shisheng Jiang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Yu Zhang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Shulin Wang
- The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, Qingyuan 511500, China
| | - Jiamin Chen
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Jianmei Lai
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Lifeng Wu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Huiying Duan
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Shuwen He
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Xinyi Liu
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
| | - Shanshan Yu
- Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
| | - Yi Cai
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
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12
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Zhang B, Cheng Y, Jian Q, Xiang S, Xu Q, Wang C, Yang C, Lin J, Zheng C. Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview. Front Pharmacol 2024; 15:1375585. [PMID: 38650627 PMCID: PMC11033398 DOI: 10.3389/fphar.2024.1375585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 03/21/2024] [Indexed: 04/25/2024] Open
Abstract
The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.
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Affiliation(s)
- Boxun Zhang
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yingying Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qin Jian
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Sirui Xiang
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qi Xu
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuchu Wang
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuan Yang
- Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuan Zheng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Sichuan Provincial Engineering Research Center of Innovative Re-development of Famous Classical Formulas, Tianfu TCM Innovation Harbour, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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13
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Chen L, Zhong XL, Cao WY, Mao ML, Liu DD, Liu WJ, Zu XY, Liu JH. IGF2/IGF2R/Sting signaling as a therapeutic target in DSS-induced ulcerative colitis. Eur J Pharmacol 2023; 960:176122. [PMID: 37863414 DOI: 10.1016/j.ejphar.2023.176122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 10/12/2023] [Accepted: 10/13/2023] [Indexed: 10/22/2023]
Abstract
Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS.
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Affiliation(s)
- Ling Chen
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Xiao-Lin Zhong
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Wen-Yu Cao
- Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Ming-Li Mao
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Dan-Dan Liu
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Wen-Jia Liu
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Xu-Yu Zu
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China; Department of Tumor Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
| | - Jiang-Hua Liu
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
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Chen R, Li F, Zhou K, Xing M, Zhang X, Zhao X, Wu C, Han Z, Zhou Y, Yan L, Xia D. Component identification of modified sanmiao pills by UPLC-Xevo G2-XS QTOF and its anti-gouty arthritis mechanism based on network pharmacology and experimental verification. JOURNAL OF ETHNOPHARMACOLOGY 2023; 311:116394. [PMID: 36940736 DOI: 10.1016/j.jep.2023.116394] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/01/2023] [Accepted: 03/13/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Modified sanmiao pills (MSMP), a traditional Chinese medicine (TCM) formula, is consisted of rhizome of Smilax glabra Roxb., Cortexes of Phellodendron chinensis Schneid., rhizome of Atractylodes chinensis (DC.) Koidz., and roots of Cyathula officinalis Kuan. in a ratio of 3:3:2:1. This formula has been broadly applied to treat gouty arthritis (GA) in China. AIMS OF THE STUDY To elaborate the pharmacodynamic material basis and pharmacological mechanism of MSMP against GA. MATERIALS AND METHODS UPLC-Xevo G2-XS QTOF combined with UNIFI platform was applied to qualitatively assess the chemical compounds of MSMP. Network pharmacology and molecular docking were used to identify the active compounds, core targets and key pathways of MSMP against GA. The GA mice model was established by MSU suspension injecting into ankle joint. The swelling index of ankle joint, expressions of inflammatory cytokines, and histopathological changes in mice ankle joints were determined to validate the therapeutic effect of MSMP against GA. The protein expressions of TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome in vivo was detected by Western blotting. RESULTS In total, 34 chemical compounds and 302 potential targets of MSMP were ascertained, of which 28 were overlapping targets pertaining to GA. 143 KEGG enrichment pathway were obtained, of which the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and NF-κB signaling pathway were strongly associated with GA. In silico study indicated that the active compounds had excellent binding affinity to core targets. In vivo study confirmed that MSMP observably decreased swelling index and alleviated pathological damage to ankle joints in acute GA mice. Besides, MSMP significantly inhibited the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by MSU, as well as the expression levels of key proteins involved in TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome. CONCLUSION MSMP possessed a pronounced therapeutic effect on acute GA. Results from network pharmacology and molecular docking showed that obaculactone, oxyberberine, and neoisoastilbin might treat gouty arthritis by down-regulating TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.
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Affiliation(s)
- Ruyi Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Fenfen Li
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Kai Zhou
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Mengyu Xing
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Xiaoxi Zhang
- Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Xinyu Zhao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Chenxi Wu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Ziwei Han
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Yixuan Zhou
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Li Yan
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Daozong Xia
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
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Jin R, Juventus Aweya J, Lin R, Weng W, Shang J, Wang D, Fan Y, Yang S. The bioactive peptide VLATSGPG regulates the abnormal lipid accumulation and inflammation induced by free fatty acids in HepG2 cells via the PERK signaling pathway. J Funct Foods 2023. [DOI: 10.1016/j.jff.2023.105515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2023] Open
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16
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Li J, Zou S, Yang W, Peng M, Chen B, Deng J, Wei M, Zheng G. Identification of volatile and nonvolatile compounds in Citri Reticulatae Pericarpium Viride using GC-MS, UPLC-Q-Exactive Orbitrap-MS, and HPLC-PDA. Food Sci Nutr 2023; 11:1415-1425. [PMID: 36911822 PMCID: PMC10002908 DOI: 10.1002/fsn3.3181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 01/05/2023] Open
Abstract
Gas chromatograph-mass spectrometer (GC-MS), ultra-high-performance liquid chromatograph-Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS), and high-performance liquid chromatography-photodiode array detection (HPLC-PDA) were used to qualitatively and quantitatively analyze the chemical component of Citri Reticulatae Pericarpium Viride "Geqingpi" (GQP). First of all, the volatile components of GQP are identified by GC-MS. Totally 56 volatile components were determined, and γ-Terpinene (33.39%) and D-Limonene (22.95%) were the main terpenes. Secondly, UHPLC-Q-Exactive Orbitrap-MS was used for identifying nonvolatile compositions and 42 compositions were identified totally, including 23 flavonoids, nine organic acids, three coumarins, two alkaloids compounds, and five other compounds, among which nine of the determined constituents were detected for the first time in GQP. Thirdly, the content of seven main constituents in GQP was quantitatively analyzed via HPLC-PDA, which were synephrine, hesperidin, limonin, nobiletin, HMF, tangeretin, and 5-HPMF. Further investigation for quantitative analysis of seven bioactive compounds suggested that the concentration of hesperidin in GQP approximately was 16.0% (160.78 ± 0.95 mg·g-1), which was far higher than the standard for identification and quality control of CRPV in Chinese Pharmacopoeia (2020 edition) that "the content of hesperidin shall not be less than 5.0%." The phytochemicals of GQP were elucidated in this study, which might be supporting information for identification between GQP and Citri Reticulatae Pericarpium Viride "Sihuaqingpi" (SHQP) and provided a scientific basis for the further active ingredient for pharmacological research and development prospects of GQP.
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Affiliation(s)
- Jingxuan Li
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
| | - Shiqi Zou
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
| | - Wanling Yang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
| | - Mengdie Peng
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
| | - Baizhong Chen
- Guangdong Xinbaotang Biological Technology Co., LtdJiangmenChina
| | - Jinji Deng
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
| | - Minyan Wei
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
| | - Guodong Zheng
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
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Jia B, Zhao L, Liu P, Li M, Tian Z. Limonin ameliorates indomethacin-induced intestinal damage and ulcers through Nrf2/ARE pathway. Immun Inflamm Dis 2023; 11:e787. [PMID: 36840501 PMCID: PMC9958512 DOI: 10.1002/iid3.787] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 01/31/2023] [Accepted: 02/01/2023] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause intestinal damage and ulcers and the incidence is increasing. Limonin plays an important role in the regulation of inflammatory diseases, but it has not been reported in the treatment of intestinal injury and ulcers. METHODS Indomethacin (INDO) induced intestinal injury and ulcer model in rats. The indexes related to intestinal injury were detected. Western blot and molecular docking techniques were used to detect the docking between Limonin and Nrf2. Next, ML385, an inhibitor of Nrf2/ARE signaling pathway, was applied to treat intestinal epithelial IEC-6 cells induced by INDO. And CCK8, Western blot, TUNEL, ELISA, DCFH-DA assay, kits, and immunofluorescence were conducted to detect cell activity, apoptosis, inflammatory response, oxidative stress, and tight junction again. RESULTS INDO can significantly induce intestinal ulcerative lesions in rats. Limonin could improve intestinal ulcerative lesions induced by INDO in rats. Limonin could reduce INDO-induced inflammatory response and oxidative stress in the small intestine of rats, and improve the intestinal barrier dysfunction induced by INDO. Limonin could dock with Nrf2 structure and activate Nrf2/ARE signaling pathway. ML385 could reverse the protective effect of Limonin against INDO-induced cell damage. CONCLUSION Limonin ameliorates INDO-induced intestinal damage and ulcers through Nrf2/ARE pathway.
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Affiliation(s)
- Bo Jia
- Department of Spleen and Stomach Diseases, Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
| | - Leyi Zhao
- Qihuang CollegeBeijing University of Chinese MedicineBeijingChina
| | - Pengpeng Liu
- School of PharmacyLiaoning University of Traditional Chinese MedicineDalianChina
| | - Meng Li
- Department of Spleen and Stomach Diseases, Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
| | - Zhilei Tian
- Department of GastroenterologyAir Force Specialty Medical CenterBeijingChina
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Zhou Z, He W, Tian H, Zhan P, Liu J. Thyme ( Thymus vulgaris L.) polyphenols ameliorate DSS-induced ulcerative colitis of mice by mitigating intestinal barrier damage, regulating gut microbiota, and suppressing TLR4/NF-κB-NLRP3 inflammasome pathways. Food Funct 2023; 14:1113-1132. [PMID: 36594593 DOI: 10.1039/d2fo02523j] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Thyme (Thymus vulgaris L.) is an important medicinal and edible homologous plant, and the composition and bioactivity of its polyphenol extracts have attracted widespread attention from researchers. In this study, the polyphenols in thyme were separated and identified by UPLC/MS-MS and UPLC-DAD, and the intervention effect and mechanism of thyme polyphenols (TP) on ulcerative colitis (UC) were analyzed in combination with dextran sulfate sodium salt (DSS)-induced mice colitis model. It was found that the main substances of TP were scutellarin (160.68 ± 2.09 mg g-1), rosmarinic acid (80.33 ± 1.74 mg g-1), scutellarein (56.53 ± 1.32 mg g-1), apigenin-7-O-glucuronide (21.06 ± 0.68 mg g-1), gallic acid (13.80 ± 0.73 mg g-1), and ferulic acid (12.00 ± 0.20 mg g-1). TP and sulfasalazine, which were respectively supplemented to these experimental mice at 200 mg per kg bw and 100 mg per kg bw, showed similar effects on alleviating intestinal inflammation, as indicated by the consistency of the decreased NLRP3 and TLR4 proteins and inhibited pro-inflammatory cytokine secretion in NF-κB inflammatory signaling pathway. Furthermore, the treatment with TP at doses of 200 and 400 mg per kg bw both effectively upregulated tight junction protein expression and enhanced intestinal epithelial cell integrity. Consistently, the abundany of probiotics including Blautia, Bacteroides, Romboutsia, and Faecalibaculum associated with the synthesis of short chain fatty acids (SCFAs) were elevated, whereas harmful bacteria including Escherichia Shigella, Muribaculum, and Clostridium sensu stricto 1 associated with the inflammatory process were significantly inhibited. Notably, TP supplemented at the dose of 100 mg per kg bw showed weak mitigated effects on the above symptoms, while the other two TP experimental groups showed similar promising therapeutic potential, suggesting that such beneficial effects required a certain dose of TP to be achieved. These results indicated that TP could suppress the TLR4/NLRP3-NF-κB inflammasome pathways, protect the intestinal epithelial barrier, and remodel the disordered gut microbiota, which suggested that TP might be a promising dietary strategy for UC.
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Affiliation(s)
- Zuman Zhou
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710100, China.
| | - Wanying He
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710100, China.
| | - Honglei Tian
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710100, China.
| | - Ping Zhan
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710100, China.
| | - Jianshu Liu
- Shaanxi Provincial Research Center of Functional Food Engineering Technology, Xi'an 710100, China
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19
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Zhang T, Huang Q, Gan K, Zhou K, Hu K, Ding W, Jin J, Li J. Effects of limonin treatment on the survival of random skin flaps in mice. Front Surg 2023; 9:1043239. [PMID: 36684359 PMCID: PMC9852612 DOI: 10.3389/fsurg.2022.1043239] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/21/2022] [Indexed: 01/09/2023] Open
Abstract
Random skin flap is commonly used in plastic and reconstructive surgery, however, distal part of skin flap often occurs ischemia and necrosis. Limonin, with bioactivities of anti-inflammation, anti-apoptosis and anti-oxidative stress, may be effective for skin flap survival. In our study, random flap model was performed in mice to explore the role of limonin in the survival of skin flap. On postoperative day 7, the necrosis of skin flaps was observed, while visualization of blood flow below the tissue surface was detected through Laser Doppler blood flow imaging (LDBFI). Then flap tissues were acquired to assess and levels of angiogenesis, apoptosis and oxidative stress. The results showed that limonin decreased necrosis and edema of skin flaps compared with the control group, with more blood flow in the flap under LDBFI detection. Limonin treatment also increased the mean vessels density, elevated the expression levels of angiogenic proteins (matrix metallopeptidase 9, vascular endothelial growth factor, Cadherin5) and antioxidant proteins [superoxide dismutase 1 (SOD1), endothelial nitric oxide synthase, heme oxygenase], and reduced the expression of apoptotic factors (BAX, CYC, Caspase3). In summary, limonin could effectively enhance the survival of random skin flap, the potential mechanism may attribute to the induction of angiogenesis, and inhibition of apoptosis and oxidative stress.
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Affiliation(s)
- Ting Zhang
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China
| | - Qing Huang
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China
| | - Kaifeng Gan
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China
| | - Ke Zhou
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China
| | - Keqi Hu
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China
| | - Wei Ding
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China
| | - Jiale Jin
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, China,Correspondence: Jiale Jin Jin Li
| | - Jin Li
- Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China,Correspondence: Jiale Jin Jin Li
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20
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Zhang M, Zheng Y, Li X, Wu H, Liu P, Zhang K, Shi Z, Lv M, Wang F, Tang X. Tong-Xie-Yao-Fang alleviates diarrhea-predominant irritable bowel syndrome in rats via the GCN2/PERK-eIF2α-ATF4 signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 107:154350. [PMID: 36194974 DOI: 10.1016/j.phymed.2022.154350] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 07/01/2022] [Accepted: 07/19/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disease. Tong-Xie-Yao-Fang (TXYF), the traditional Chinese herbal medicine prescription, is a classic and effective prescription for the treatment of IBS-D, but its mechanism of action is not fully clarified. OBJECTIVE To evaluate the efficacy of TXYF in the treatment of IBS-D and to explore its potential mechanism of action. METHODS Changes in the serum levels of 50 free amino acids were targeted for detection by high-performance liquid chromatography (HPLC), and the expression of glucose-regulated protein 78 (GRP78), general control nonderepressible 2 (GCN2), and endoplasmic reticulum-resident kinase (PERK) was detected by immunohistochemistry examinations in healthy volunteers and IBS-D patients. The IBS-D rat was constructed by the three-factor superposition method of neonatal maternal separation, 2,4,6-trinitrobenzene sulfonic acid enema, and chronic unpredictable stress stimulation. The treatment effect of TXYF on IBS-D rats was observed by recording the body weight, grasp force, fecal water content (FWC), and abdominal withdrawal reflex (AWR) of rats before and after treatment. The effects of GCN2/PERK-eukaryotic initiation factor-2 (eIF2α) -activating transcription Factor 4 (ATF4) pathway proteins and gene expression were analyzed by western blotting, reverse transcription-polymerase chain reaction (RT-qPCR), and immunohistochemistry evaluations. RESULTS Compared with healthy volunteers, IBS-D patients exhibited lower levels of cysteine, γ-aminoacetic acid (GABA), homoproline, and lysine, and immunohistochemistry showed strong activation of GRP78, a marker of endoplasmic reticulum stress. Differential expression of GCN2 and PERK proteins was detected in IBS-D patients and rat colons. In the IBS-D rats, TXYF improved the body weight and grasp force, reduced the FWC, and improved the AWR score. TXYF increased the levels of p-GCN2 and GCN2 and reduced the levels of GRP78, p-PERK, PERK, p-eIF2α, and eIF2α, thereby affecting the expression of the apoptosis-related transcription factors ATF4, CHOP, Caspase-3, and Bcl-2. CONCLUSION Our study showed that TXYF improved IBS-D by inhibiting apoptosis. The anti-apoptosis effects were potentially mediated by regulating the GCN2/PERK-eIF2a-ATF4 signaling pathway.
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Affiliation(s)
- Min Zhang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yijun Zheng
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xia Li
- Beijing University of Chinese Medicine, Beijing, China
| | - Haomeng Wu
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ping Liu
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Kunli Zhang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhongfei Shi
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Mi Lv
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengyun Wang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Xudong Tang
- China Academy of Chinese Medical Sciences, Beijing, China.
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21
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Raimondo S, Urzì O, Meraviglia S, Di Simone M, Corsale AM, Rabienezhad Ganji N, Palumbo Piccionello A, Polito G, Lo Presti E, Dieli F, Conigliaro A, Alessandro R. Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways. J Cell Mol Med 2022; 26:4195-4209. [PMID: 35789531 PMCID: PMC9344827 DOI: 10.1111/jcmm.17404] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/20/2022] [Accepted: 05/08/2022] [Indexed: 12/13/2022] Open
Abstract
Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine and primary human macrophages were pre-treated with LEVs for 24 h and then were stimulated with lipopolysaccharide (LPS). We found that pre-treatment with LEVs decreased gene and protein expression of pro-inflammatory cytokines, such as IL-6, IL1-β and TNF-α, and reduced the nuclear translocation and phosphorylation of NF-κB in LPS-stimulated murine macrophages. The inhibition of NF-κB activation was associated with the reduction in ERK1-2 phosphorylation. Furthermore, the ability of LEVs to decrease pro-inflammatory cytokines and increase anti-inflammatory molecules was confirmed ex vivo in human primary T lymphocytes. In conclusion, we demonstrated that LEVs exert anti-inflammatory effects both in vitro and ex vivo by inhibiting the ERK1-2/NF-κB signalling pathway.
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Affiliation(s)
- Stefania Raimondo
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
| | - Ornella Urzì
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
| | - Serena Meraviglia
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
- Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR)AOUP Paolo GiacconePalermoItaly
| | - Marta Di Simone
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
- Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR)AOUP Paolo GiacconePalermoItaly
| | - Anna Maria Corsale
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
- Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR)AOUP Paolo GiacconePalermoItaly
| | - Nima Rabienezhad Ganji
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
| | - Antonio Palumbo Piccionello
- Dipartimento di Scienze e Tecnologie Biologiche Chimiche e FarmaceuticheUniversità degli Studi di PalermoPalermoItaly
| | - Giulia Polito
- Dipartimento di Scienze e Tecnologie Biologiche Chimiche e FarmaceuticheUniversità degli Studi di PalermoPalermoItaly
| | - Elena Lo Presti
- Institute for Biomedical Research and Innovation (IRIB)National Research Council (CNR)PalermoItaly
| | - Francesco Dieli
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
- Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR)AOUP Paolo GiacconePalermoItaly
| | - Alice Conigliaro
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
| | - Riccardo Alessandro
- Dipartimento di Biomedicina, Neuroscienze e Diagnostica AvanzataUniversità degli Studi di PalermoPalermoItaly
- Institute for Biomedical Research and Innovation (IRIB)National Research Council (CNR)PalermoItaly
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22
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Tang S, Meng J, Tan J, Liu X, Zhou H, Li N, Hou S. N6-methyladenosine demethylase FTO regulates inflammatory cytokine secretion and tight junctions in retinal pigment epithelium cells. Clin Immunol 2022; 241:109080. [PMID: 35878734 DOI: 10.1016/j.clim.2022.109080] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 07/03/2022] [Accepted: 07/19/2022] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Uveitis is an intraocular inflammatory disease. Epigenetics has been associated with its pathogenesis. However, the role of N6-methyladenosine (m6A) in uveitis has not been reported. We aimed to examine the role of m6A and its regulatory mechanism in experimental autoimmune uveitis (EAU). METHODS The mRNA expression of m6A-related methylase and demethylase of retinal pigment epithelium (RPE) between mice with EAU and control mice was detected by RT-qPCR. The overall m6A level of ARPE-19 cells was detected by an m6A quantitative detection kit. Cell proliferation was observed by CCK-8 assays, and ELISA was used to test the secretion of inflammatory factors. The expression of tight junction proteins and the target genes of FTO were examined by western blotting and MeRIP-PCR. RESULTS A decreased expression of FTO in RPE cells was found in mice with EAU. Increased overall m6A%, proliferation of cells and secretion of IL-6, IL-8 and MCP-1 were found after FTO knockdown in ARPE-19 cells. However, ZO-1 and occludin protein expression was decreased. ATF4 protein expression was decreased in the FTO knockdown (shFTO) group as compared with the control (shNC) group. In contrast, the m6A level of ATF4 was elevated, as shown by MeRIP-PCR. Functional analysis showed that p-STAT3 expression was increased in the shFTO group, and the change in occludin expression was reversed in ATF4 rescue experiment. CONCLUSION FTO may affect the translation of ATF4 by regulating its m6A level, resulting in the increased expression of p-STAT3 and inflammatory factors, and leading to uveitis.
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Affiliation(s)
- Shiyun Tang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Ophthalmology, Chongqing, China; Chongqing Eye Institute, Chongqing, China; Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Jiayu Meng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Ophthalmology, Chongqing, China; Chongqing Eye Institute, Chongqing, China; Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Jun Tan
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Ophthalmology, Chongqing, China; Chongqing Eye Institute, Chongqing, China; Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Xianyang Liu
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Ophthalmology, Chongqing, China; Chongqing Eye Institute, Chongqing, China; Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Hongxiu Zhou
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Ophthalmology, Chongqing, China; Chongqing Eye Institute, Chongqing, China; Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Na Li
- College of Basic Medicine, Chongqing Medical University, Chongqing, China.
| | - Shengping Hou
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Ophthalmology, Chongqing, China; Chongqing Eye Institute, Chongqing, China; Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.
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23
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Ying H, Ruan Y, Zeng Z, Bai Y, Xu J, Chen S. Iron oxide nanoparticles size-dependently activate mouse primary macrophages via oxidative stress and endoplasmic reticulum stress. Int Immunopharmacol 2022; 105:108533. [DOI: 10.1016/j.intimp.2022.108533] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 01/01/2022] [Accepted: 01/06/2022] [Indexed: 12/12/2022]
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24
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Yuan Z, Xiao-Wei L, Juan W, Xiu-Juan L, Nian-Yun Z, Lei S. HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway. J Physiol Biochem 2022; 78:641-652. [PMID: 35315506 PMCID: PMC9381492 DOI: 10.1007/s13105-022-00884-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 02/18/2022] [Indexed: 01/06/2023]
Abstract
Fatty liver can be induced by dietary habits and lifestyle and is directly related to obesity. Although the benefits of exercise interventions for reduction of liver fat have recently been acknowledged, the underlying mechanisms remain unclear. Thus, our present study investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on high-fat diet-induced hepatic lipid accumulation, and explored the role of endoplasmic reticulum (ER) stress signaling pathways. To establish an obesity model, rats were fed with a normal standard diet or a high-fat diet (45% kcal as fat). Then, both lean and obese rats were divided into three subgroups: sedentary control (LC, OC) groups, high-intensity interval training (LHI, OHI) groups, and moderated-intensity continuous training (LMI, OMI) groups (n = 10). Rats in the exercise group underwent a swimming training protocol for 8 weeks. After the experimental period, serum and liver tissues from different groups were dissected for morphological and biochemical analyses. The results showed that with HIIT and MICT interventions, body weight and serum inflammatory markers (e.g., MCP-1, IL-1β, and TNF-α) were reduced in obese rats. Interestingly, HIIT was more effective in ameliorating liver triglyceride content and enhancing mitochondrial metabolic-enzymatic activity than was MICT in obese rats. Both HIIT and MICT conferred beneficial properties through upregulating Nrf2 expression, improving antioxidant enzyme activities and reduction of hepatic ER stress, which may have been regulated by the Bip-mediated PERK-ATF4-CHOP pathway. In conclusion, our findings confirmed the effectiveness of HIIT and MICT, particularly HIIT, in mitigating hepatic lipid accumulation.
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Affiliation(s)
- Zhang Yuan
- The Key Laboratory of Systems Biomedicine, Ministry of Education, and The Exercise Translational Medicine Centre, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.,School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China.,Jiangsu Collaborative Innovation Center for Sport and Health Project, Nanjing, 210014, China
| | - Liu Xiao-Wei
- School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China.,Huishan District Rehabilitation Hospital, Wuxi, 214100, China
| | - Wei Juan
- School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China.,Jiangsu Collaborative Innovation Center for Sport and Health Project, Nanjing, 210014, China
| | - Liu Xiu-Juan
- School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China.,Jiangsu Collaborative Innovation Center for Sport and Health Project, Nanjing, 210014, China
| | - Zhang Nian-Yun
- School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China
| | - Sheng Lei
- School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China. .,Jiangsu Collaborative Innovation Center for Sport and Health Project, Nanjing, 210014, China.
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25
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Liu C, Zeng Y, Wen Y, Huang X, Liu Y. Natural Products Modulate Cell Apoptosis: A Promising Way for the Treatment of Ulcerative Colitis. Front Pharmacol 2022; 13:806148. [PMID: 35173617 PMCID: PMC8841338 DOI: 10.3389/fphar.2022.806148] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 01/10/2022] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease impacting patients’ quality of life and imposing heavy societal and economic burdens. Apoptosis of intestinal epithelial cells (IECs) has been considered an early event during the onset of UC and plays a crucial role in disease development. Thus, effectively inhibiting apoptosis of IECs is of critical significance for the clinical management of UC, presenting a potential direction for the research and development of pharmacotherapeutic agents. In recent years, research on the ameliorative effects of natural products on UC through inhibiting IECs apoptosis has attracted increasing attention and made remarkable achievements in ameliorating UC. In this review, we summarized the currently available research about the anti-apoptotic effects of natural products on UC and its mechanisms involving the death-receptor mediated pathway, mitochondrial-dependent pathway, ERS-mediated pathway, MAPK-mediated pathway, NF-κB mediated pathway, P13k/Akt pathway, JAK/STAT3 pathway, and NLRP3/ASC/Caspase-1 pathway. Hopefully, this review may yield useful information about the anti-apoptotic effects of natural products on UC and their potential molecular mechanisms and provide helpful insights for further investigations.
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Affiliation(s)
- Chenhao Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yiwei Zeng
- School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yulong Wen
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xinggui Huang
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yi Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Yi Liu,
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26
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Wang X, Liang Z, Xiang H, Li Y, Chen S, Lu H. LKB1 Regulates Vascular Macrophage Functions in Atherosclerosis. Front Pharmacol 2021; 12:810224. [PMID: 34975507 PMCID: PMC8714937 DOI: 10.3389/fphar.2021.810224] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 11/29/2021] [Indexed: 11/13/2022] Open
Abstract
Liver kinase B1 (LKB1) is known to shape the regulation of macrophage function by participating in multiple processes including cell metabolism, growth, and polarization. However, whether LKB1 also affects the functional plasticity of macrophages in atherosclerosis has not attracted much attention. Abnormal macrophage function is a pathophysiological hallmark of atherosclerosis, characterized by the formation of foam cells and the maintenance of vascular inflammation. Mounting evidence supports that LKB1 plays a vital role in the regulation of macrophage function in atherosclerosis, including affecting lipid metabolism reprogramming, inflammation, endoplasmic reticulum stress, and autophagy in macrophages. Thus, decreased expression of LKB1 in atherosclerosis aggravates vascular injury by inducing excessive lipid deposition in macrophages and the formation of foam cells. To systematically understand the role and potential mechanism of LKB1 in regulating macrophage functions in atherosclerosis, this review summarizes the relevant data in this regard, hoping to provide new ideas for the prevention and treatment of atherosclerosis.
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Affiliation(s)
- Xuewen Wang
- Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, China
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Ziwei Liang
- Department of Clinical Laboratory, Yueyang people’s Hospital, Yueyang, China
| | - Hong Xiang
- Center for Experimental Medicine, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yanqiu Li
- Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Shuhua Chen
- Department of Biochemistry, School of Life Sciences of Central South University, Changsha, China
- Correspondence: Hongwei Lu, ; Shuhua Chen,
| | - Hongwei Lu
- Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, China
- Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, China
- Center for Experimental Medicine, The Third Xiangya Hospital of Central South University, Changsha, China
- Correspondence: Hongwei Lu, ; Shuhua Chen,
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27
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Xia T, Gu Y, Shen J, Zheng L, Xu C. Limonin ameliorates acute pancreatitis by suppressing JAK2/STAT3 signaling pathway. ENVIRONMENTAL TOXICOLOGY 2021; 36:2392-2403. [PMID: 34423886 DOI: 10.1002/tox.23352] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/10/2021] [Accepted: 08/15/2021] [Indexed: 06/13/2023]
Abstract
Acute pancreatitis (AP) is one of the most common acute abdomen of digestive system and has the characteristics of dangerous condition and rapid development. Limonin has been confirmed to hold anti-inflammatory and antioxidant effects in various diseases. However, its potential beneficial effect on AP and the concrete mechanisms have never been revealed. Here, two mouse models were used to investigate the protective effects of limonin on AP, the caerulein-induced mild acute pancreatitis (MAP) model and L-arginine-induced severe AP (SAP) model. Firstly, it was found that limonin administration attenuated lipase and serum amylase levels and ameliorated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Additionally, the amelioration of AP by limonin was associated with reduced levels of inflammation initiators (IL-6, IL-1β, CCL2, and TNF-α). Mechanistically, we found that limonin suppressed the Janus Activating Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway, as evident by the decreased levels of JAK2 and p-STAT3. And activation of JAK2 using JAK2 activator rescued the protective effects of limonin on AP. Thus, our results demonstrate that limonin can ameliorate AP in two mice models via suppressing JAK2/STAT3 signaling pathway.
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Affiliation(s)
- Tingting Xia
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yijie Gu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiaqing Shen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Lu Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chunfang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Deng J, Huang M, Wu H. Protective effect of limonin against doxorubicin-induced cardiotoxicity via activating nuclear factor - like 2 and Sirtuin 2 signaling pathways. Bioengineered 2021; 12:7975-7984. [PMID: 34565300 PMCID: PMC8806972 DOI: 10.1080/21655979.2021.1985299] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The anti-tumor and anti-inflammatory effects of limonin have been established, here, we aim to explore whether limonin can induce protective effects against doxorubicin (DOX)-mediated cardiotoxicity which limits its clinical application. We found that limonin attenuated DOX-mediated cytoxicology of myocardial cell line H9C2 by measuring cell viability and reactive oxygen species (ROS) level. Additionally, limonin ameliorates DOX-induced cardiac injury in rat by examining the activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) concentration, and histopathological changes. Mechanistically, it was shown that limonin partially abrogated the inhibition of Nuclear factor – like 2 and Sirtuin 2 signaling induced by DOX. Furthermore, limonin-mediated protective effects on DOX-mediated cytoxicology of H9C2 were rescued by a Sirt2-specific inhibitor or siRNA against Sirt2. Thus, this work reveals that limonin can suppress DOX-mediated cardiotoxicity by activating Nrf2 and Sirt2 signaling.
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Affiliation(s)
- Jie Deng
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China
| | - Min Huang
- Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China
| | - Hao Wu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China
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Zhou JP, Yang XN, Song Y, Zhou F, Liu JJ, Hu YQ, Chen LG. Rosiglitazone alleviates lipopolysaccharide-induced inflammation in RAW264.7 cells via inhibition of NF-κB and in a PPARγ-dependent manner. Exp Ther Med 2021; 22:743. [PMID: 34055059 PMCID: PMC8138265 DOI: 10.3892/etm.2021.10175] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 04/15/2021] [Indexed: 12/14/2022] Open
Abstract
Rosiglitazone is a synthetic peroxisome proliferator-activated receptor (PPAR)γ agonist widely used for the treatment of type 2 diabetes. Recent studies have demonstrated that rosiglitazone displays anti-inflammatory effects. The present study aimed to investigate whether rosiglitazone alleviates decreases in RAW264.7 cell viability resulting from lipopolysaccharide (LPS)-induced inflammation, as well as exploring the underlying mechanism. A macrophage inflammatory injury model was established by treating RAW264.7 cells with 100 ng/ml LPS. Cells were divided into LPS and rosiglitazone groups with different concentrations. Cell viability was assessed by performing an MTT assay. The expression of inflammatory cytokines was detected by conducting enzyme-linked immunosorbent assays and reverse transcription-quantitative PCR. Nitric oxidesecretion was assessed using the Griess reagent system. The expression levels of key nuclear factor-κB pathway-associated proteins were detected via western blotting. Rosiglitazone alleviated LPS-induced decrease in RAW264.7 cell viability and inhibited inflammatory cytokine expression in a concentration-dependent manner. Rosiglitazone significantly inhibited LPS-induced upregulation of p65 phosphorylation levels and downregulated IκBα expression levels. However, rosiglitazone-mediated inhibitory effects were reversed by PPARγ knockdown. The results of the present study demonstrated that rosiglitazone significantly inhibited LPS-induced inflammatory responses in RAW264.7 macrophage cells, which was dependent on PPARγ activation and NF-κB suppression.
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Affiliation(s)
- Jing-Ping Zhou
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Xiao-Ning Yang
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Yang Song
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Fei Zhou
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Jing-Jing Liu
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Yi-Qun Hu
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
| | - Li-Gang Chen
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China
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