Molecular immunopharmacology of traditional Chinese medicine–derived compounds in membranous nephropathy: mechanistic insights into immune aging and kidney essence deficiency

Membranous nephropathy (MN) is a prototypical immune-mediated glomerular disease characterized by the formation of autoantibodies targeting podocyte antigens, deposition of subepithelial immune complexes, and activation of complement pathways leading to podocyte injury and proteinuria. The discovery of target antigens such as the M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) has substantially advanced the understanding of MN immunopathogenesis. Despite these advances, current therapeutic approaches remain limited by incomplete response rates, treatment-related toxicity, and the lack of personalized treatment strategies. Recent studies have highlighted the immunomodulatory potential of bioactive compounds derived from traditional medicinal plants. Several compounds with well-defined molecular structures including icariin, astragaloside IV, catalpol, cordycepin, and Lycium barbarum polysaccharides have demonstrated experimentally validated mechanisms affecting key molecular pathways involved in inflammation and immune regulation. These compounds modulate intracellular signaling networks such as NF-κB, PI3K-Akt signaling, NLRP3 inflammasome activation, AMPK signaling, and oxidative stress pathways, which are closely associated with immune dysregulation and podocyte injury in MN. In parallel, advances in systems biology and precision medicine are transforming the investigation of immune-mediated kidney diseases. Multi-omics technologies, biomarker discovery, artificial intelligence-assisted disease classification, and network pharmacology approaches provide integrative tools for identifying disease mechanisms and therapeutic targets. These analytical frameworks enable the systematic exploration of compound-target interactions and may facilitate the development of personalized treatment strategies for MN. This review integrates current knowledge on the immunopathogenesis of membranous nephropathy with emerging insights into bioactive compounds derived from traditional Chinese medicine (TCM) and modern systems biology approaches. By linking experimentally supported molecular mechanisms with computational and translational research strategies, this work highlights potential avenues for developing innovative immunomodulatory therapies and advancing precision medicine in immune-mediated kidney diseases.