Angelica sinensis polysaccharide could alleviate the gastrointestinal damage in alcoholic fatty liver disease mice: Regulation of alcohol metabolism and enhancement of short-chain fatty acids utilization

J Ethnopharmacol. 2024 Nov 15:119117. doi: 10.1016/j.jep.2024.119117. Online ahead of print.

Abstract

Ethnopharmacological relevance: Dysfunction of the intestinal barrier was an important trigger for alcoholic liver damage and alcohol had brought about intestinal damage before causing liver damage. The root of Angelica sinensis (Oliv.) Diels, crucial traditional medicinal material, was widely utilized for its blood-invigorating, intestinal-lubricating and gynecological benefits. Angelica sinensis polysaccharide (ASP) was an essential natural active ingredient of Angelica sinensis and exhibited considerable potential for gastrointestinal protection. Nevertheless, the systematic research of ASP on the gastrointestinal tract remained insufficient.

Aim of this study: To systematically explore the protective effect and underlying mechanisms of ASP against alcohol-induced gastrointestinal injury, including the stomach, ileum and colon.

Materials and methods: The AFLD mice model was established via the intragastric administration of alcohol twice a day for one week. The protective effect of ASP on the representative segments of the gastrointestinal tract (stomach, ileum and colon) was subsequently studied after confirming its hepatoprotective activity. The impact of ASP on gastrointestinal alcohol metabolism was examined to explain its antioxidant and antiapoptotic activities. Furthermore, the effect of ASP on short-chain fatty acids (SCFA) in the colon and colonic contents was investigated to further enhance the understanding of the underlying mechanisms.

Results: ASP could reduce oxidative stress and apoptosis in the gastrointestinal tract via regulating CYP2E1-mediated alcohol metabolism. Additionally, ASP could significantly increase the levels of FFAR2, FFAR3 and HCAR2 in colon, thereby promoting the utilization of SCFA.

Conclusion: ASP was proven for the first time to improve gastrointestinal damage caused by alcohol, indicating its enormous potential as a candidate medicine for the treatment of alcohol related gastrointestinal injury.

Keywords: Alcohol metabolism; Angelica sinensis polysaccharide; Gastrointestinal protection; Short-chain fatty acids.