Abstract
Membranous nephropathy (MN) is an immune-mediated glomerular disease characterized by podocyte injury and immune complex deposition. The phosphatidylinositol 3-kinase/protein kinase-B (PI3K/protein kinase B [AKT]) pathway plays an important role in renal cell survival and inflammation. Quercetin (QUE), a natural flavonoid with antioxidant and anti-inflammatory properties, has shown potential renal protective effects. This study aimed to investigate the therapeutic effect of QUE on MN and its modulation of the PI3K/AKT signaling pathway. A cationic bovine serum albumin-induced MN rat model was established and divided into blank control, model control, and QUE groups. QUE (50 mg/kg/d) was administered orally for 10 weeks. Proteinuria, glomerular immunoglobulin G and complement 3 deposition, inflammatory cytokines, and PI3K/AKT pathway activity were examined. QUE treatment significantly reduced 24-h proteinuria compared with the model control group (P < .05). The intense granular deposition of immunoglobulin G and complement 3 observed in MN rats was notably alleviated after QUE administration. Furthermore, QUE downregulated the overexpression of PI3K and phosphorylated AKT proteins in renal tissue and improved the imbalance of serum inflammatory cytokines. QUE alleviated proteinuria, reduced immune complex deposition, and suppressed abnormal PI3K/AKT pathway activation in MN rats, suggesting that QUE confers renal protection through anti-inflammatory and signal-modulatory mechanisms.