Study on the mechanism of Xiongshi Shiwei Wendan decoction promoting RCT and treat AS based on network pharmacology, molecular docking and in vitro experiment

doi:10.12092/j.issn.1009-2501.2025.08.003

Abstract

Abstract: AIM: Xiongshi Shiwei Wendan decoction (SWD) comes from Xiong Jibai, a master of traditional Chinese medicine, and has been widely used in the treatment of AS. ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS. The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacology, molecular docking and in vitro experiments, and explore the pathway mechanism of promoting reverse cholesterol transport (RCT). METHODS: The active components of SWD drugs were screened by TCMSP and HERB databases, RCT targets were predicted, the component-target network map was constructed, the PPI network was constructed and the GO and KEGG pathways were enriched and analyzed by STRING database, and the key active components of SWD were selected for molecular docking with ABCA1 protein and miR-33 by AutoDockVina. In vitro, RAW264.7 was used to establish foam cell model, oil red O staining, NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells. Western blotting was used to detect the expression of ABCA1. RESULTS: According to network pharmacology, 336 active components of SWD, 267 targets of RCT and 46 targets of intersection of RCT and SWD were obtained, which involved multiple signal pathways such as lipid and atherosclerosis. Molecular docking showed that the main active components had stable conformation with ABCA1 and miR-33. In vitro experiment, it was found that the lipid content was significantly decreased (P<0.01), the cholesterol outflow rate was significantly increased (P<0.01) and the expression of ABCA1 protein was up-regulated in SWD group (P<0.01), but the expression of ABCA1 in miR-33 overexpression group was significantly decreased (P<0.01). CONCLUSION: SWD has the characteristics of multi-components and multi-targets, which can promote RCT and treat AS through miRNA-33-ABCA1 pathway.

Key words: Xiongshi Shiwei Wendan decoction, atherosclerosis, reverse cholesterol transport, ABCA1, miR-33

CLC Number:

R965.2

MA Xingyu^{1, 2}, XIE Xuejiao², LI Chunqiao¹, ZHANG Zheng¹. Study on the mechanism of Xiongshi Shiwei Wendan decoction promoting RCT and treat AS based on network pharmacology, molecular docking and in vitro experiment[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(8): 1026-1036.

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