Soyasaponin A₂ Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline‐Deficient (MCD) Diet‐induced Nonalcoholic Steatohepatitis (NASH) Mice

Abstract

Scope: 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 2 ) 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-A 2 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 2 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 2 reduces serum BAs accumulation and promotes fecal BAs excretion. SS-A 2 changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA. Conclusion: SS-A 2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice.

Astragalus mongholicus polysaccharides ameliorate hepatic lipid accumulation and inflammation as well as modulate gut microbiota in NAFLD rats

“…The increased abundances of Bacteroidetes , Proteobacteria and Verrucomicrobia after mAPS administration agreed with the findings of a previous study. 43 In addition, the Desulfovibrionaceae were increased by mAPS, studies have shown that the alleviating effect of Soyasaponins A2 against methionine and choline deficient (MCD) diet-induced steatohepatitis is accompanied by increased abundance of Desulfovibrionaceae , 44 which is an anti-inflammatory bacteria and sulfate-reducing bacteria. 45 Similar finding was also demonstrated in the mitigating effect of Val-Val-Tyr-Pro (VVYP) peptide against non-alcoholic steatohepatitis, in which the abundance of Desulfovibrionaceae was also increased.…”

Ilexsaponin A1 Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism in Mice

“…Accumulating evidence suggests that BA metabolism is associated with liver disease and may be a potential target for its treatment ( Jung et al, 2021 ). Many natural products have been shown to alleviate or prevent NAFLD by regulating BA metabolism ( Huang et al, 2019 ; Xiong et al, 2021 ). In the present study, IsA effectively ameliorated hepatic steatosis and related metabolic dysfunctions in HFD-induced NAFLD mice.…”

Advances in the Bioactivities of Phytochemical Saponins in the Prevention and Treatment of Atherosclerosis

“…Soyasaponins are a family of phytochemical saponins that are present mainly in soybeans and other legumes (e.g., lentils and green peas) [ 52 ]. On average, soybean and its products contain soyasaponins at a content of about 0.17~6.16% [ 53 ]. Soyasaponins are amphiphilic oleanane triterpenoid glycosides with sugar moieties (polar side chains) attached to aglycone (a nonpolar pentacyclic ring).…”

“…Second, soyasaponins can ameliorate inflammation, which is another key mediator in the pathogenesis of AS. In recent years, the anti-inflammatory activities of soyasaponins have been intensively investigated in different inflammatory models of cells and animals [ 11 , 53 , 54 , 62 ] and well reviewed [ 52 , 57 ]. The evidence regarding soyasaponins’ anti-inflammatory activities in macrophages can to a great extent support that soyasaponins may have potentials in the prevention of AS, because macrophages are one of the major players in the pathogenesis of AS.…”