Gancao Xiexin Decoction Ameliorates Ulcerative Colitis in Mice via Modulating Gut Microbiota and Metabolites

Abstract

Purpose Ulcerative colitis (UC) is a chronic inflammatory bowel disease that starts with mucosal inflammation of the rectum and extends proximally in the colon in a continuous manner over a variable distance. Although it is more common in North America and Western Europe, its incidence is also increasing in Asia. Despite the introduction of several different classes of medications, the treatment options for UC may be insufficiently effective and burdened with significant side effects. In the present study, the therapeutic effects of Gancao Xiexin decoction (GCXX) were investigated on mice with dextran sulfate sodium (DSS)-induced colitis with exploration of the underlying mechanisms. Methods Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 7 days. GCXX and (or) the standard of care anti-inflammatory drug, mesalazine (5-aminosalicylic acid) were then administered for 7 days. The gut microbiota was characterized by 16S rDNA high-throughput gene sequencing and gut metabolites were detected by untargeted metabolomics. Germ-free mice were subsequently used to determine whether GCXX ameliorated UC principally through modulation of the gut microbiota. Results GCXX treatment was demonstrated to significantly reduce disease activity index (DAI) scores, prevent colonic shortening, ameliorate colonic tissue damage and reduce the levels of pro-inflammatory cytokines. Furthermore, analysis of the gut microbiota showed that GCXX-treated mice had higher relative quantity of Dubosiella (P<0.05) and lower relative quantity of Escherichia-Shigella (P<0.05). Metabolomics analysis indicated that GCXX could reduce the level of linoleic acid (P<0.05) and regulate its metabolism pathway. Moreover, in germ-free mice, GCXX failed to increase body weight, reduce DAI scores, or alleviate either colonic shortening or colonic damage. Conclusion The present study demonstrated that GCXX ameliorated DSS-induced colitis principally through modulating the gut microbiota and metabolites. This information should be integrated into the overall mechanisms of GCXX treatment of UC.

Pharmacological and molecular analysis of the effects of Huangqi Jianzhong decoction on proliferation and apoptosis in GES-1 cells infected with H. pylori

“…Radix Astragali is a monarch drug in a formula that is able to enhance the phagocytic function of the human immune system, scavenge free radicals, inhibit the growth of H. pylori , promote gastric mucosal repair, and produce anti-tumor effects ( Wu et al, 2022 ). Paeoniae Radix Alba , Ramulus Cinnamomi , and Radix Glycyrrhizae are minister drugs, of which Glycyrrhiza uralensis can reduce gastric acid concentration and inhibit bacteria ( Luo et al, 2022 ); and Ramulus Cinnamomi , combined with Paeoniae Radix Alba and Fructus Jujube , can invigorate qi, warm the center of the body and dissipate cold. It can tranquilize the mind and nourish the blood, and even improve edema and relieve pain ( Nöst et al, 2019 ).…”

Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored

“…Dahuang mudan decoction ameliorated colitis in mice by restoring the Th17/Treg balance, recovering the α-diversity, increasing the abundance of Firmicutes and Actinobacteria , decreasing the abundance of Proteobacteria and Bacteroidetes , increasing the number of butyrate-producing bacteria (namely, Butyricicoccus baumannii ), and restoring intestinal SCFA content [ 144 ]. Gancao xiexin decoction exerts therapeutic effects on IBD dependent on gut microbiota, which fails to reduce DAI scores or alleviate either colonic shortening or colonic damage in germ-free mice [ 145 ]. Other formulas include Gegen Qinlian decoction, Lizhong decoction, etc., as shown in Table 3 .…”

Banxia Xiexin decoction combined with 5‐ASA protects against CPT‐11‐induced intestinal dysfunction in rats via inhibiting TLR4/NF‐κB signaling pathway

“… 12 , 13 , 14 Of them, BXD is a classic prescription for the treatment of diarrhea caused by gastrointestinal diseases. In the previous studies, Banxia ( Pinelliae Rhizoma ) and Gancao ( Glycyrrhizae Radix et Rhizoma ) in BXD have been proven to alleviate dextran sulfate sodium‐induced chronic ulcerative colitis in mice 15 , 16 and Huangqin ( Scutellariae Radix ) can regulate intestinal flora in colitis mice, 17 while Renshen ( Ginseng Radix et Rhizoma ) is a promising herb for treating inflammatory bowel disease. 18 It has also reported that BXD reduces prostaglandin E2 production in the rat colon, increases water absorption, and decreases spontaneous contraction of the colon terminal by releasing nitric oxide (NO) 19 as well as protects rats from weight loss, enterocyte damage, anorexia, and delayed diarrhea caused by CPT‐11.…”