Network pharmacology-integrated molecular docking and experimental validation: Unveiling the protective mechanism of sanhuang guben zhike formula in chronic obstructive pulmonary disease

Abstract

Introduction

SanHuang Guben Zhike Formula (SHGBZKF) is a classical herbal prescription for pulmonary diseases, but its material basis and mechanisms in chronic obstructive pulmonary disease (COPD) are poorly understood. This study investigated its active ingredients and therapeutic mechanisms in COPD via network pharmacology, molecular docking, kinetic simulation, and in vitro experiments.

Methods

Active ingredients of SHGBZKF were screened using TCMSP and SwissADME. COPD-related targets were retrieved from DisGeNET and others, with overlapping targets identified. Core targets were screened via Cytoscape-constructed PPI networks; GO/KEGG analyses used Metascape. Ligand-receptor binding was evaluated by AutoDock Vina 1.1.2, and complex stability verified via GROMACS. β-sitosterol’s effects were validated in CSE-induced COPD cells.

Results

A total of 120 active ingredients and 208 common targets with COPD were identified, including core targets STAT3, AKT1, EGFR. KEGG showed activated PI3K-AKT and EGFR pathways. β-sitosterol had optimal binding energies with AKT1 (ΔG=-10.8 kcal/mol) and EGFR (ΔG= -9.7 kcal/mol), with stable complexes confirmed. It inhibited EGFR, AKT, MAPK pathways, exerting therapeutic effects in CSE-induced cells.

Discussion

SHGBZKF may alleviate COPD progression by synergistically regulating EGFR, AKT, and MAPK signaling pathways through components such as β-sitosterol. Our research first uncovered the molecular mechanism underlying the therapeutic effect of SHGBZKF on respiratory diseases, and this finding is anticipated to lay a theoretical foundation for the clinical use of SHGBZKF.