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Soyasaponin A 2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline Deficient (MCD) Diet-induced Non-alcoholic Steatohepatitis (NASH) Mice

Scope: Non-alcoholic steatohepatitis (NASH) is a chronic progressive disease with complex pathogenesis of which the bile acids (BAs) and gut microbiota are involved. Soyasaponins (SS) exhibits many health-promoting effects including hepatoprotection but its prevention against NASH is unclear. This study aimed to investigate the preventive bioactivities of SS monomer (SS-A2 ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota.

Methods and results: The methionine and choline deficient (MCD) diet-fed male C57BL/6 mice were intervened with obeticholic acid or SS-A2 for 16 weeks. Hepatic pathology was assessed by hematoxylin-eosin and Masson's trichrome staining. BAs in serum, liver, and colon were measured by UPLC-TQMS. Gut microbiota in caecum were determined by 16S rDNA amplicon sequencing. In the MCD diet-induced NASH mice, SS-A2 significantly reduced hepatic steatosis, lobular inflammation, ballooning, NAS scores and fibrosis, decreased Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increased Desulfovibrionaceae (Desulfovibrio). Moreover, SS-A2 reduced serum BAs accumulation and promoted fecal BAs excretion. SS-A2 changed the BAs profiles in both liver and serum and specifically increased the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum was negatively correlated with serum THDCA.

Conclusion: SS-A2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice.

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