Integrating proteomics and network pharmacology to explore the relevant mechanism of Huangkui capsule in the treatment of chronic glomerulonephritis.

Introduction: Chronic glomerulonephritis (CGN) is a common glomerular disease with multifactorial pathogenesis. Huangkui capsule (HKC), a traditional Chinese herbal formulation, demonstrates therapeutic potential in CGN; however, its molecular mechanisms remain insufficiently characterized. This study aimed to clarify the therapeutic mechanisms of HKC in CGN by integrating proteomic analysis with network pharmacology. Methods: We employed liquid chromatography-mass spectrometry (LC-MS) to identify the active components of HKC. A CGN rat model was established and treated with HKC. Renal function parameters and serum inflammatory cytokines were assessed. Histopathological alterations and IgG deposition in kidney tissues were examined using hematoxylin-eosin (HE) staining and immunofluorescence, respectively. Proteomic profiling of renal tissue was conducted, and network pharmacology analysis was applied to identify potential therapeutic targets of HKC. Results: A total of 39 active compounds were identified in HKC. HKC administration significantly improved renal function and mitigated glomerular injury in CGN rats. Proteomic analysis revealed 2,079 differentially expressed proteins, predominantly associated with oxidoreductase activity. Network pharmacology identified 462 targets related to HKC and 1,835 targets associated with CGN, with 13 overlapping targets, including STAT3, PIK3R1, AKT1, HIF-1α, and VEGF, which were downregulated following HKC treatment. Conclusion: HKC exerts renoprotective effects in CGN by regulating multiple signaling pathways, notably HIF-1, VEGF, PI3K-Akt, MAPK, and PPAR. Through attenuation of inflammatory and oxidative responses, HKC alleviates renal pathological damage and supports kidney function, offering mechanistic insight into its multi-target therapeutic potential.