BACKGROUND: Pueraria lobata (Willd.) Ohwi (PL) has been used in China to detoxify alcohol and protect the liver for millennia, though its mechanism of liver protection has not been elucidated. However, fermentation is considered to be one of the effective ways to enhance the efficacy of traditional Chinese medicine. The aim of this study was to investigate the hepatoprotective mechanism of probiotic-fermented PL (FPL). Sprague Dawley rats were administered with FPL followed by gavage of alcohol for seven consecutive days; following that, liver injury levels were evaluated in rats.RESULTS: FPL ameliorated lipid accumulation and inflammation levels in rats. Meanwhile, the levels of ethanol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P4502E1 were elevated by FPL treatment. It was observed that the levels of catalase, superoxide dismutase, and glutathione peroxidase were elevated, and the expression of nuclear transcriptional factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 genes and proteins were increased by FPL treatment, demonstrating that the Nrf2-mediated signal pathway was activated. Furthermore, FPL restored the composition of the gut microbiota with an increase in the abundances of Firmicutes and Lactobacillus and a decrease in the abundances of Bacteroidota and Akkermansia. Additionally, a strong correlation was found between the gut microbiota and the antioxidant parameters. CONCLUSION:The results indicate that FPL possesses an excellent protective effect in alcoholic liver injury. Our findings are beneficial to the development of hepatoprotective nutraceuticals for alcoholics.

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