Ginsenoside Rg1 Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Microbial Tryptophan Metabolism

Abstract

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism.

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

“…Recent studies showed that Trp metabolism in the gut microbiota can be regulated by multiple factors such as natural substances and chemical drugs ( Figure 1 ). Ginsenoside Rg1 could increase the levels of Trp metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid and niacinamide [ 43 ]. In mice with high-fat diet-induced obesity, ginsenoside Rb1 significantly altered the gut microbiota composition and serum Trp [ 44 ].…”

“…The blockade of the kyn–AhR axis can ameliorate colitis-associated colon cancer through inhibiting the immune tolerance [ 169 ]. Multiple natural substances such as ginsenoside Rg1 [ 43 ], fucose [ 45 ], fuzhuan brick tea polysaccharide [ 48 ] and shenling baizhu san [ 51 ] could alleviate ulcerative colitis by modulating the gut microbiota and microbial Trp metabolism.…”

Treatment Effects of Natural Products on Inflammatory Bowel Disease In Vivo and Their Mechanisms: Based on Animal Experiments

“…In two IBD mouse models (DSS-induced and TNBS-induced), ginsenoside Rb1 could improve colitis by activating the endoplasmic reticulum-resident E3 ubiquitin ligase Hrd1 signaling pathway [ 16 ]. Not only that, ginsenoside Rg1 in ginseng can also regulate the intestinal microbiota of IBD mice to alleviate UC through microbial tryptophan metabolism [ 169 ]. Besides, ginsenoside Rh2 and ginsenoside Rk3 in ginseng have the same therapeutic and alleviating effects on experimental IBD [ 170 , 171 ].…”

“…For example, the polyphenolic compound Salvianolic acid B could reduce the degree of inflammation in colitis by inhibiting the increase of Bacteroides and Akkermansia in the intestine of IBD mice [ 198 ]. Ginsenoside Rg1 significantly reversed the DSS-induced imbalance of intestinal microbiota in mice and attenuated acute UC symptoms through microbial tryptophan metabolism [ 169 ]. Juglone, a quinone, can increase the ratio of Firmicutes and Bacteroidota , increase the abundance of Actinobacteriota , and decrease the abundance of Verrucomicrobiota to alter the diversity and composition of intestinal microbes in UC mice [ 18 ].The coumarin-like compound daphnetin significantly increased the abundance of short-chain fatty acid-producing intestinal microbiota [ 253 ].…”

Gut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke

“…AIS can cause disruption of the gut microbiota, which is an important cause of poor prognosis in AIS, and Traditional Chinese herbs can correct this microbiota disorder. It was found that the use of Chinese herbal preparations (both formulae and compounds) could restore the diversity of the gut microbiota to varying degrees, increase the abundance of probiotic bacteria, reduce the abundance of conditionally pathogenic bacteria, and bring the gut microbiota closer to that of healthy populations after AIS( Cai et al, 2019 ; Zhang et al, 2020 ; Fu et al, 2021 ; Lin et al, 2021 ; Wang et al, 2022b ; Cheng et al, 2022 ; Xu et al, 2022 ). To investigate how TCM regulates gut microbiota and how it exerts therapeutic effects, we searched for recently published studies on the regulation of gut microbiota by TCM in the treatment of AIS, including Chinese herbal formulae ( Table 1 ) and herbal compounds ( Table 2 ).…”