Mechanisms of Liancao Xueniao Capsules in Treating Hematuria Associated with IgA Nephropathy: Network Pharmacology and Experimental Validation.

IgA nephropathy (IgAN) is a prevalent primary glomerular disease characterized by hematuria, proteinuria, and progressive renal dysfunction. Hematuria, a key clinical manifestation, is closely associated with podocyte injury and inflammatory activation. Emerging evidence indicates that the TNF signaling pathway plays a central role in mediating renal inflammation and podocyte damage. Liancao Xueniao Capsule, a traditional Chinese medicine formulation, has shown therapeutic potential in reducing hematuria and protecting renal function; however, its underlying mechanisms remain unclear. In this study, network pharmacology analysis was combined with experimental validation in an IgAN rat model to investigate the therapeutic mechanisms of Liancao Xueniao Capsule. After 8 weeks of treatment, renal function indices, histopathological alterations, podocyte-associated protein expression, and inflammatory pathway-related factors were systematically evaluated. The results showed that the capsule significantly reduced urinary erythrocytes, 24 h urinary albumin, serum creatinine (Scr), and blood urea nitrogen (BUN), while improving renal pathological injury and fibrosis. Furthermore, it restored the expression of podocyte-specific proteins CD2AP and WT-1 and markedly decreased the levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Mechanistic studies revealed that these effects were associated with inhibition of the TNF signaling pathway and its downstream mediators. In conclusion, Liancao Xueniao Capsule alleviates podocyte injury and improves hematuria in IgAN by suppressing TNF-mediated inflammatory responses, providing experimental evidence for its therapeutic application in IgAN.