Mechanistic Study of Guan’s Liushangyin for Fall Injury via Network Pharmacology and Molecular Docking

Abstract

Introduction: The study aimed to investigate the potential molecular mechanisms of Guan’s Liushangyin, a classical prescription from Guan’s Commonly Used Prescriptions, in the treatment of fall-related injuries and to provide mechanistic evidence supporting its therapeutic relevance. Methods: Active compounds and their putative targets of Guan’s Liushangyin (Liu Jinu, Rhizoma Drynariae, and Rhizoma Corydalis) were retrieved from the TCMSP database. Fall injury–related targets were collected from GeneCards, PharmGKB, OMIM, TTD, and DrugBank. Protein–protein interaction (PPI) networks were constructed using the STRING database and visualized with Cytoscape. Key targets were identified through topological analysis using NetworkAnalyzer and core modules were extracted via the MCODE plugin. Gene Ontology (GO) functional annotation and KEGG pathway enrichment analyses were performed using R software. Molecular docking was conducted to evaluate binding affinities between representative active compounds and core targets using Chem3D, AutoDock 1.5.6, SYBYL 2.0, and PyMOL 2.4. Results: A total of 66 active compounds were identified, with β-sitosterol, luteolin, quercetin, corydine, curcumenol, and dehydrocorydalis bulbus alkaloids emerging as key constituents. Core therapeutic targets included PTGS2, CASP3, VEGFA, JUN, MAPK1, AKT1, and TP53. Molecular docking analysis demonstrated favorable binding interactions between β-sitosterol and CASP3/PTGS2; luteolin and quercetin with CASP3, JUN, and TP53; Corydalis-related alkaloids with PTGS2; and curcumenol and dehydrocorydalis bulbus alkaloids with MAPK1. GO enrichment analysis indicated that the therapeutic effects of Guan’s Liushangyin are mainly associated with biological processes related to cell cycle regulation, inflammatory response, apoptosis, and signal transduction. KEGG pathway analysis highlighted the PI3K–Akt, TNF, IL-17, and MAPK signaling pathways as key pathways involved in its anti-injury effects. Conclusions: Guan’s Liushangyin may exert therapeutic effects on fall injuries through a multi-component, multi-target, and multi-pathway regulatory mechanism, particularly involving PTGS2, CASP3, VEGFA, JUN, MAPK1, AKT1, and TP53, and pathways related to inflammation, apoptosis, and tissue repair. These findings provide mechanistic support for its traditional use and offer a theoretical basis for future experimental validation and clinical investigation