Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner. (August 2021)

• Record Type: Journal Article
• Authors: Li, Qinmei; Cui, Yao; Xu, Baichang; Wang, Yuhan; Lv, Feifei; Li, Zheng; Li, Huan; Chen, Xiaogang; Peng, Xiaomin; Chen, Yating; Wu, Enyun; Qu, Dongshuai; Jian, Yichen; Si, Hongbin
• Is Part Of: Pharmacological research. Volume 170(2021)
• Publication Date: 2021-08
• Subjects: IBD inflammatory bowel disease -- UC ulcerative colitis -- GQD Gegen Qinlian decoction -- FMT fecal microbiota transplantation -- SCFA Short-chain fatty acids -- TLR4 toll-like receptor 4 -- NF-κB nuclear factor kappa-B -- DSS dextran sodium sulfate -- SD Sprague-Dawley -- M-LCFA medium and long-chain fatty acid -- AA amino acid -- BA bile acid -- DAI disease activity index -- CMDI colon mucosal damage index -- DAO diamine oxidase -- MPO myeloperoxidase -- MDA malondialdehyde -- SOD superoxide dismutase -- NO nitric oxide -- CK creatine kinase -- CAT catalase -- GSH reduced glutathione -- GST glutathione S transferase -- ELISA enzyme-linked immunosorbent assay -- TG triglyceride -- HDL-C high-density lipoprotein-cholesterol -- LDL_C low-density lipoprotein-cholesterol -- GLU glucose -- CHOL cholesterol -- ALP alkaline phosphatase -- LDH lactic dehydrogenase -- ALT alanine transaminase -- AST aspartate transaminase -- ZO-1 zonula occludens -- CXCL1 Chemokine CXCL1 -- IFN-γ Interferon-γ -- IL-17A Interleukin-17A -- IL-1β Interleukin-1β -- IL-6 Interleukin-6 -- IL-10 interleukin-10 -- MIP-1α Macrophage inflammatory protein-1α -- MIP-1β Macrophage inflammatory protein-1β -- TNF-α Tumor necrosis factor-α -- H&E hematoxylin and eosin -- Treg regulatory T -- Th17 T helper type 17 -- ROS reactive oxygen species -- RNS reactive nitrogen species -- PCA principal component analysis -- PcoA Principal coordinates analysis -- OTUs observed taxonomic units -- LefSe linear discriminant analysis of effect size -- NADPH nicotinamide adenine dinucleotide phosphate -- ATP adenosine triphosphate -- CDCA chenodeoxycholic acid -- DCA deoxycholic acid -- TMCA tauro-muricholic acid -- BCAA branched chain aminoacids -- BCFA branched fatty acid -- TBA total bile acid -- PSC primary sclerosing cholangitis -- CSE cystathionine-γ-lyase enzyme -- DNBS dinitro benzene sulfonic acid -- CA cholic acid; Puerarin (PubChem CID: 5281807) -- Baicalein (PubChem CID: 5281605) -- Berberine (PubChem CID: 2353) -- Glycyrrhiic acid (PubChem CID: 14982) -- Magnolol (PubChem CID: 72300); PBM -- DSS-induced colitis -- Gut microbiota -- Targeted metabolomics -- Intestinal barrier; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105694
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy. Graphical Abstract: ga1