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Integrating Network Analysis and Experimental Validation to Reveal the Autophagy-Associated Mechanism of Danggui Shaoya San (DSS) Prescription in the Treatment of Non-Alcoholic Simple Fatty Liver

Abstract

Background: This study explores the mechanism of Danggui Shaoyao San regulating liver autophagy function in the treatment of Non-Alcoholic Simple Fatty Liver (NAFL). The clinical efficacy of Danggui Shaoyao San in treating NAFL was evaluated and analyzed using a combination of network pharmacology and experimental validation. Methods: The chemical constituents of DSS were detected by HighPerformance Liquid Chromatography Q-Extractive Mass Spectrometry (HPLCQ-Exactive-MS). Related compounds and targets were screened from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP); genes associated with NAFL were identified in GeneCards and OMIM. Cytoscape 3.8.2 was used to construct the active componentspotential therapeutic target network. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) of potential therapeutic targets were carried out on the Metascape platform. A Protein-Protein Interaction (PPI) network was generated using STRING. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. Finally, the predicted results were preliminarily verified with experiments. Results: Network pharmacology analysis expounded the active components of DSS mand revealed the autophagy-associated mechanism of DSS treating NAFL. Molecular-docking data also supported the hypothesis that the core components of DSS, Lauric Acid, Atractylenolide III, and Catechin interacted well with Beclin1 and LC3. Experiments results indicate that DSS improved serum liver function parameters, lipid parameters, and alleviated hepatic steatosis in rats with NAFL. RT-PCR experiments showed that DSS increased the mRNA expression levels of the autophagy-associated targets Beclin1 and LC3. Conclusions: DSS can reduce liver damage, serum lipid levels, and hepatic steatosis in NAFL rats by increasing the mRNA and protein expression of Beclin1 and LC3, restoring liver cell autophagy function. This provides a basis for the therapeutic mechanism of DSS in treating NAFL.D.

Zheng Luo, Luyun Xia, Wenying Huai, Huan Xu, Haiyan Zhu, Zhiyan Fang, Lili Huang, Yunhui Chen, Ruocong Yang, Tian-e Zhang

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