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Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites
Jing, Wanghui1,2; Dong, Sijing1,2; Luo, Xialin3; Liu, Jingjing3; Wei, Bin4; Du, Wei5; Yang, Lin1,6; Luo, Hua6; Wang, Yitao6; Wang, Sicen1,2; Lu, Haitao3
2021-02-01
Source PublicationPharmacological Research
ISSN1043-6618
Volume164
Abstract

Inflammatory bowel diseases (IBD) are kind of recurrent inflammatory issues that occur in the gastrointestinal tract, and currently clinical treatment is still unideal due to the complex pathogenesis of IBD. Basically, gut barrier dysfunction is triggered by gut microbiota dysbiosis that is closely associated with the development of IBD, we thus investigated the therapeutic capacity of berberine (BBR) to improve the dysregulated gut microbiota, against IBD in rats, using a combinational strategy of targeted metabolomics and 16 s rDNA amplicon sequencing technology. Expectedly, our data revealed that BBR administration could greatly improve the pathological phenotype, gut barrier disruption, and the colon inflammation in rats with dextran sulfate sodium (DSS)-induced colitis. In addition, 16S rDNA-based microbiota analysis demonstrated that BBR could alleviate gut dysbiosis in rats. Furthermore, our targeted metabolomics analysis illustrated that the levels of microbial tryptophan catabolites in the gastrointestinal tract were significantly changed during the development of the colitis in rats, and BBR treatment can significantly restore such changes of the tryptophan catabolites accordingly. At last, our in vitro mechanism exploration was implemented with a Caco-2 cell monolayer model, which verified that the modulation of the dysregulated gut microbiota to change microbial metabolites coordinated the improvement effect of BBR on gut barrier disruption in the colitis, and we also confirmed that the activation of AhR induced by microbial metabolites is indispensable to the improvement of gut barrier disruption by BBR. Collectively, BBR has the capacity to treat DSS-induced colitis in rats through the regulation of gut microbiota associated tryptophan metabolite to activate AhR, which can greatly improve the disrupted gut barrier function. Importantly, our finding elucidated a novel mechanism of BBR to improve gut barrier function, which holds the expected capacity to promote the BBR derived drug discovery and development against the colitis in clinic setting.

KeywordAhr Activation Berberine Gut Barrier Function Inflammatory Bowel Disease Microbial Tryptophan Catabolites
DOI10.1016/j.phrs.2020.105358
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000615153300018
Scopus ID2-s2.0-85097867642
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Cited Times [WOS]:39   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang, Sicen; Lu, Haitao
Affiliation1.School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
2.Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis, Xi'an, 710061, China
3.Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
4.College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, China
5.Shaanxi Institute for Food and Drug Control, Xi'an, 710065, China
6.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, China
Recommended Citation
GB/T 7714
Jing, Wanghui,Dong, Sijing,Luo, Xialin,et al. Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites[J]. Pharmacological Research,2021,164.
APA Jing, Wanghui,Dong, Sijing,Luo, Xialin,Liu, Jingjing,Wei, Bin,Du, Wei,Yang, Lin,Luo, Hua,Wang, Yitao,Wang, Sicen,&Lu, Haitao.(2021).Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites.Pharmacological Research,164.
MLA Jing, Wanghui,et al."Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites".Pharmacological Research 164(2021).
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