This study aimed to ascertain the potential benefits of green radish polysaccharide (GRP) in treating alcoholic liver disease (ALD) in mice and explore its mechanism of action. Using biochemical analysis, high-throughput sequencing of gut microbiota, and gas chromatography-mass spectrometry to measure short-chain fatty acids (SCFAs) in feces, we found that GRP intervention significantly improved lipid metabolism and hepatic function in mice subjected to excessive alcohol intake. The GRP intervention reduced malondialdehyde levels by 66% and increased total superoxide dismutase levels by 22%, thereby mitigating alcohol-induced oxidative stress. Furthermore, GRP intervention in mice with alcohol consumption resulted in a reduction in tumor necrosis factor, interleukin 6, and lipopolysaccharide levels by 12%, 9%, and 25%, respectively, effectively attenuating alcoholic liver inflammation. 16S rRNA amplicon sequencing demonstrated that excessive alcohol consumption markedly altered the gut microbiota composition in mice. The GRP treatment resulted in a significant reduction in the number of beneficial bacteria (Lactobacillus and Lachnospiraceae_NK4A136_group) and an increase in the proportion of harmful bacteria (Muribaculaceae and Verrucomicrobiota). The metabolomic analyses of the SCFAs demonstrated an increase in the contents of SCFAs, acetic acid, propionic acid, and butyric acid, following GRP supplementation. Furthermore, the metabolic levels of cholinergic synapses and glycolysis/gluconeogenesis were found to be modulated. In conclusion, these findings suggest that GRP may attenuate alcohol-induced oxidative damage in the liver by modulating the gut microbiota and hepatic metabolic pathways. This may position GRP as a potential functional component for ALD prevention.
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