Zxtps Alleviate Nafl Induced by High-Fat Diet in Mice Through Improving Intestinal Microbiota Imbalance and Liver Metabolic Dysfunction

Abstract

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 (Alisma orientale) and Baizhu (Atractylodes macrocephala). And its extractions have demonstrated hepatoprotective properties. We hypothesize that the polysaccharides in Zexie Tang might have therapeutic effects on NAFLD. In this study, we isolated a novel homogeneous polysaccharide, 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.

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Funding declaration: This study completed with the support of the National Natural Science Foundation of China (Grant No. 32102659, 32102729) and China Postdoctoral Science Foundation (Grant No. 2022TQ0098 and 2024M760844). Natural Science Foundation of Henan 852 Provaince (242300421296). Science and technology in Henan Province (242102310082). Central Plains science and technology innovation leading talent project (254000510005); Henan Provincial Science and Technology Tackling Key Problems Project (252102231013). Thank to Jiangsu Sanshu Biotechnology Co., Ltd. for the technical support of this experiment: polysaccharide structure analysis, intestinal 33 857 microbial detection

Conflict of Interests: No competing interest

Ethical Approval: The Ethics Committee at Henan University of Chinese Medicine’s Experimental Animal Center granted approval for this animal investigation (Approval Number: DWLL 20230028).

Keywords: Polysaccharides, ZXTPs, Fatty liver, Autophage, Lipid metabolism