Network pharmacology and molecular docking approach to investigate the mechanism of a Chinese herbal formulation Yougui pills against steroid-related osteonecrosis of the femoral head

Abstract

Yougui pills (YGPs) is a classical prescription formula for treating steroid-related osteonecrosis of the femoral head (SONFH) in traditional Chinese medicine (TCM). However, its key ingredients and mechanisms of action are still unknown. In the study, we used molecular docking and network pharmacology to comprehensively investigate the mechanism by YGPs impact on SONFH. TCMSP was used to identify the effective active components of YGPs. Targets associated with SONFH were extracted from GEO datasets in conjunction with GeneCards, OMIM, and DisGeNET databases. Protein-protein interaction (PPI) networks were built using the intersection targets by importing them into the STRING database. Furthermore, DAVID was used to conduct a pathway enrichment analysis for both GO and KEGG. Finally, molecular docking and molecular dynamics simulation was performed to verify the binding ability between key targets and active compound. Screening using relevant databases revealed 126 active compounds with 1078 targets in YGPs, mainly including helenalin, quercetin, stigmasterol, sesamin, etc. The topological analysis of the PPI network revealed that key targets included VEGFA, IL6, IL1B, TNF, ALB, and TP53. According to the findings of the GO enrichment analysis, genes were most significantly enriched in the inflammatory response, response to hypoxia, and positive regulation of angiogenesis. The effects of YGPs have been mostly linked to the HIF-1 signaling pathway and the PI3K-Akt signaling pathway, according to a KEGG pathway enrichment analysis. In addition, the results of molecular docking and molecular dynamics simulations demonstrated that the active chemicals in YGPs have high affinity with the relevant targets. This investigation integrates molecular docking and network pharmacology to identify the effective compounds, related targets, and potential mechanism of YGPs in the treatment of SONFH. This research may provide an integrative strategy to clarify the pharmacological mechanisms of traditional Chinese medicines.