Exploring the mechanism of Kemofang in treating idiopathic membranous nephropathy based on LC–MS/MS combined with network pharmacology, molecular docking, and molecular dynamics simulation

Idiopathic membranous nephropathy (IMN), an autoimmune glomerular disease, arises from in situ immune complex deposition in the glomerular subepithelial spaces, triggering complement activation and podocyte injury. Although the Kemo Formula shows therapeutic potential for IMN, its mechanisms remain unclear. This study employed LC-MS/MS, network pharmacology, molecular docking, and dynamic simulations to elucidate the mechanism of action. LC-MS/MS and the TCMSP database identified 83 bioactive components from 267 chemicals detected in the Kemo Formula. Using PubChem, Swiss Target Prediction, and GeneCards, 827 drug targets and 2581 IMN-related targets were screened, yielding 336 overlapping targets linked to 81 components. Network analysis prioritized 15 key components ( baicalein and quercetin) and 36 core targets (TP53, IL6, and AKT1). Functional enrichment revealed involvement in hormone response, MAPK cascade regulation, and kinase binding with pathways including lipid metabolism, PI3K/Akt, and MAPK signaling. Molecular docking indicated strong binding affinities between the active components and targets, while dynamic simulations predicted the stability of the galangin-AKT1 complex. The Kemo Formula likely mitigates IMN by multi-target modulation, ameliorating lipid dysregulation, suppressing podocyte apoptosis, and attenuating immune-inflammatory and oxidative stress via PI3K/Akt and MAPK pathways. This integrative approach highlights its multicomponent, multitarget therapeutic strategy against IMN, providing a foundation for further mechanistic and clinical exploration.