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

• Published in: Molecular nutrition & food research 2021-07, Vol.65 (14), p.e2100067
• Main Authors: Xiong, Fei, Zheng, Zhongdaixi, Xiao, Lingyu, Su, Chuhong, Chen, Junbin, Gu, Xiangfu, Tang, Jiaqi, Zhao, Yue, Luo, Huiyu, Zha, Longying
• Format: Article
• Language: English
• Subjects: Animals; Bile Acids and Salts - metabolism; Chenodeoxycholic Acid - analogs & derivatives; Choline Deficiency; Colon - metabolism; Diet; Disease Models, Animal; Gastrointestinal Microbiome - drug effects; Inflammation; Liver - drug effects; Liver - metabolism; Male; Methionine - deficiency; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - drug therapy; Saponins - pharmacology
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202100067

Nonalcoholic 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 aims to investigate the preventive bioactivities of SS monomer (SS-A ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota. The methionine and choline deficient (MCD) diet-fed male C57BL/6 mice were intervened with obeticholic acid or SS-A for 16 weeks. Hepatic pathology is assessed by hematoxylin-eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet-induced NASH mice, SS-A significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increases Desulfovibrionaceae (Desulfovibrio). Moreover, SS-A reduces serum BAs accumulation and promotes fecal BAs excretion. SS-A changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA. SS-A alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice.