Zexie Tang Polysaccharides (ZXTPs) alleviate high-fat diet-induced NAFL in mice through improving intestinal microbiota imbalance and liver metabolic dysfunction

Zexie Tang (Alisma Decoction, ZXT), derived from “Jin-Guiyaolue” (Synopsis of Prescriptions from the Golden Chamber), is composed of two kinds of herbs, namely Zexie (Atractylodes macrocephala) and Baizhu (Atractylodes macrocephala). And Baizhu (Atractylodes macrocephala), and its extractions have demonstrated hepatoprotective properties. We hypothesize that the polysaccharides in Zexie Tang might have therapeutic effects on Non-Alcoholic Fatty Liver Disease (NAFLD). In this study, we isolated a novel homogeneous polysaccharide, Zexie Tang Polysaccharides (ZXTPs), and its structure was elucidated by monosaccharide composition, methylation analysis, partial acid hydrolysis, and NMR spectra. The main chain of the polysaccharide is →1-β-D-Fruf-2 → 1-β-D-Fruf-2 →, and the structural formula of the polysaccharide can be deduced as follows: α-D-Glcp-1 → [1-β-D-Fruf-2]₁₁ → 1-β-D-Fru. In vivo experiments indicated that ZXTPs could significantly reduce hepatic steatosis, fasting triglyceride, and cholesterol levels in NAFLD mice. Cell proliferation and Oil Red O staining results showed that ZXTPs concentration-dependently increased cell viability and significantly improved lipid metabolism in vitro. Mechanistically, ZXTPs markedly inhibited the formation of lipid both in vitro and in vivo through activating Autophage and AMPK/PPAR-α pathways. In this study, ZXTPs exert beneficial effects against NAFLD through dual mechanisms involving metabolic regulation and intestinal microbiome modification.