Astragalus polysaccharide attenuates nonalcoholic fatty liver disease through THDCA in high-fat diet-fed mice

Astragalus polysaccharide (APS) extracted from Astragalus membranaceus (Fisch.) Bunge was proven to be effective in preventing high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD). However, the exact mechanisms were not completely elucidated.The aim was to reveal the mechanisms of APS on preventing NAFLD from the aspects of regulating bile acids (BAs) homeostasis.Serum and liver BAs in HFD fed mice with or without APS intervention were quantified with an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. The effect of APS on hepatic proteins involved in BAs synthesis were analyzed with Western blot. Finally, the effect of identified taurohyodeoxycholic acid (THDCA) that was significantly increased by APS on hepatic triglyceride (TG) accumulation was explored in vivo and in vitro.APS regulated serum and liver BA profiles in HFD fed mice, especially increased serum THDCA. The levels of hepatic cholesterol 7a-hydroxylase (CYP7A1) and sterol 12a-hydroxylase (CYP8B1) which catalyzed the classical BAs synthesis pathway were significantly decreased by APS, while oxysterol 7a-hydroxylase (CYP7B1) which catalyzed the alternative BAs synthesis pathway was significantly increased by APS. THDCA reduced HFD-induced hepatic lipid accumulation and improved glucose homeostasis in mice, and decreased TG level in palmitic acid/oleic acid treated alpha mouse liver 12 (AML-12) cells. THDCA significantly downregulated the protein level of cluster of differentiation 36 (CD36) involved in fatty acid transport into the liver. Importantly, THDCA showed similar effect with APS in upregulating hepatic CYP7B1 and downregulating CYP7A1.This study revealed the protective effect of APS on NAFLD was associated with the regulation on BA profiles, and proved the potential anti-NAFLD effect of THDCA, highlighting the involvement of BA metabolism in efficacy of herb-derived polysaccharides on metabolism.