Abstract
BACKGROUND AND OBJECTIVE: Buzhong Yiqi Decoction (BZYQ), a classic Chinese herbal formula, demonstrates clinical efficacy in treating membranous nephropathy (MN), yet its molecular mechanisms remains undefined. This study aims to uncover the therapeutic mechanisms of BZYQ against MN at the molecular level. METHODS: BZYQ components/targets were retrieved from TCMSP and UniProtKB, while MN-related targets were obtained from GeneCards and GEO. Core targets were identified via Protein-Protein Interaction (PPI) analysis and machine learning (ML). Immune cell infiltration was analyzed using CIBERSORT, and diagnostic values were evaluated via Receiver Operating Characteristic (ROC) curves. Molecular docking validated interactions between core targets and BZYQ's active ingredients, with efficacy and mechanisms further verified in a cationic bovine serum albumin-induced mouse MN model. RESULTS: Screening identified MYC and NFKBIA as core targets, primarily enriched in B-cell receptor signaling. Immune infiltration analysis showed their correlation with follicular helper T cell abundance. ROC curves confirmed area under the curve > 0.7 for both targets. Molecular docking revealed strong binding (average energy: -7.13 kcal/mol) between targets and BZYQ components. In vivo, BZYQ significantly reduced 24-h urinary protein (P < 0.001), increased serum albumin (P < 0.05), decreased serum creatinine (P < 0.05), and alleviated renal pathology/immune complex deposition. Mechanistically, immunohistochemistry/Western blotting showed BZYQ downregulated MYC (P < 0.05) and upregulated IκBα (P < 0.05) versus the model group. CONCLUSION: BZYQ emerges as a promising therapeutic for MN. Elucidating its anti-MN mechanisms provides a theoretical basis for clinical translation.