Integrative analysis of Zidan Yinxie capsules for psoriasis treatment: Insights from network pharmacology, molecular dynamics simulation, and GEO database analysis

The therapeutic efficacy of Zidan Yinxie capsules (ZDYXC) in psoriasis (PSO) has been clinically confirmed, yet its underlying molecular mechanisms remain unclear. We aimed to explore the mechanisms of ZDYXC in the treatment of PSO. To elucidate the mechanisms by which ZDYXC exerts its effects in PSO, active ingredients and their potential targets were first identified using the TCMSP database, while PSO-related genes were collected from several comprehensive databases, including GeneCards, Online Mendelian Inheritance in Man, Pharmacogenetics and Pharmacogenomics Knowledge Base, Therapeutic Target Database, and DrugBank. Common genes between ZDYXC targets and PSO-related genes were then screened, and an integrated network of these targets and active compounds was constructed with Cytoscape 3.10.1 software The Cytoscape Consortium; The Scripps Research Institute, La Jolla). Further analysis of protein-protein interactions among these intersection genes was performed using the STRING 12.0 platform (https://cn.string-db.org/), and hub targets were identified via the CytoNCA 2.1.6 plugin (The Cytoscape Consortium, The Scripps Research Institute, La Jolla). Functional enrichment analysis highlighted the involvement of these genes in immune and inflammation-related pathways. To validate these findings, molecular docking analyses were employed to assess the interactions between key compounds and hub targets, using AutoDock Vina 1.1.2 (The Scripps Research Institute, La Jolla) for binding affinity evaluation and visualization of optimal binding conformations. Additionally, Gromacs 2020 (Royal Institute of Technology, Stockholm, Sweden) was utilized for molecular dynamics simulations to verify the stability of compound-target complexes with the highest binding affinities. The expression and relevance of hub targets were further confirmed through mining GEO datasets, while receiver operating characteristic curve analysis assessed their diagnostic significance in PSO. The study identified 189 active ingredients and 227 targets for ZDYXC, with 148 intersection genes being primarily associated with immune regulation and inflammatory processes. Molecular docking revealed strong affinities between core ZDYXC ingredients, such as vestitol, formononetin, isorhamnetin, kaempferol, luteolin, quercetin, and tanshinone IIA, and hub targets including AKT1, STAT3, ESR1, and TP53. Molecular dynamics confirmed the stability of these interactions. Differential expression and receiver operating characteristic analysis further pointed to STAT3 and ESR1 as hub genes in PSO. This study demonstrates that ZDYXC may treat PSO through multiple ingredients, targets, and pathways, providing a valuable foundation for further mechanistic studies and clinical applications.