Network Pharmacology and Molecular Dynamics Simulation Study on the Mechanism of Wuda Jiangjun Ointment in Treating Chronic Lumbar Muscle Strain

Abstract

Objective: To investigate the mechanism of Wuda Jiangjun Ointment in treating chronic lumbar muscle strain based on network pharmacology and molecular dynamics simulation. Methods: Active components of Wuda Jiangjun Ointment were identified using the TCMSP database, HERB database, and a review of relevant literature. SwissTarget Prediction, GeneCards, and OMIM databases were employed to predict targets related to chronic lumbar muscle strain. The intersection of drug and disease targets was obtained using the bioinformatics platform and imported into the STRING database to construct a protein-protein interaction (PPI) network. Cytoscape 3.10.2 software was used to visualize the PPI network and perform topological analysis to screen core targets. Functional enrichment analysis of GO and KEGG pathways for the intersecting targets was conducted using the DAVID database. A "drug-active component-disease-target" network diagram was constructed using Cytoscape 3.10.2. Molecular docking was performed using AutoDock software to simulate the binding of active components to target proteins. Furthermore, the Amber 24 software package was utilized to evaluate the binding stability between target proteins and active components. Results: A total of 75 active components and 350 corresponding potential targets of Wuda Jiangjun Ointment were screened, along with 2,159 disease targets for chronic lumbar muscle strain. There were 192 intersecting targets between the active components and the disease. Topological analysis of the PPI network identified TP53, AKT1, STAT3, etc., as core targets. Topological analysis of the "drug-active component-disease-target" network identified quercetin, dehydropipernonaline, tomentosin A, etc., as key components. GO and KEGG enrichment analyses indicated that the key pathways were primarily involved in the IL-17 signaling pathway, the AGE-RAGE signaling pathway in diabetic complications, and cellular senescence. Thus, the therapeutic mechanism was predicted to be related to inflammatory responses, among others. Molecular docking and molecular dynamics simulations verified that the core target proteins and active components exhibited good binding affinity. Conclusion: Wuda Jiangjun Ointment exerts anti-inflammatory effects and treats chronic lumbar muscle strain by participating in biological processes such as inflammatory responses through multiple components, targets, and pathways. This study provides a basis for further research into the molecular mechanisms.