Huangkui Capsule Effects in IgAN Through TLR4-Mediated Inflammatory Signaling

Globally, immunoglobulin A (IgA) nephropathy (IgAN) is diagnosed more frequently than any other primary glomerular disorder and contributes substantially to the development of chronic kidney disease and end-stage renal disease. Although the Huangkui capsule, derived from Abelmoschus manihot, has demonstrated renoprotective effects across various kidney diseases, its molecular mechanisms in IgAN remain poorly elucidated. In this study, an experimental IgAN rat model was established and treated with the Huangkui capsule for 8 weeks. A comprehensive evaluation was performed using renal function assessment, histopathological examination, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and western blot (WB) analysis to investigate renal injury, inflammatory responses, and activation of the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. Huangkui capsule significantly reduced proteinuria, hematuria, serum creatinine, and blood urea nitrogen levels, alleviated glomerular pathological injury and fibrosis, and decreased mesangial IgA and complement component 3 (C3) deposition. In addition, the Huangkui capsule restored the expression of the podocyte-associated proteins nephrin, CD2-associated protein (CD2AP), and Wilms' tumor protein 1 (WT-1), while suppressing the expression of TLR4, MyD88, phosphorylated inhibitor of NF-κB alpha (IκBα), phosphorylated NF-κB, and downstream pro-inflammatory cytokines. These findings suggest that Huangkui capsule ameliorates renal injury and preserves podocyte integrity in experimental IgAN. Its renoprotective effects may be associated with modulation of the TLR4/MyD88/NF-κB signaling pathway. This study provides reproducible experimental evidence supporting further mechanistic investigation and the potential clinical application of the Huangkui capsule for IgAN.