Ginkgolide B alleviates renal and podocyte injury in membranous nephropathy by inhibiting ferroptosis

This study investigated whether ginkgolide B alleviates renal and podocyte injury in membranous nephropathy by inhibiting ferroptosis. Rats with passive Heymann nephritis received ginkgolide B (7.5 mg/kg/day) or vehicle. Ginkgolide B significantly ameliorated nephrotic syndrome, reducing 24-hour urinary protein excretion, and improving serum albumin levels. It also normalized lipid profiles and enhanced renal function, with all changes achieving statistical significance at p<0.05. Histopathological analysis revealed reduced glomerular immune deposits, preserved podocyte density indicated by improved WT-1 nuclear expression/distribution, and restored slit diaphragm integrity shown by increased CD2AP expression. Mechanistically, ginkgolide B suppressed ferroptosis by significantly decreasing reactive oxy-gen species and lipid peroxides, reducing iron deposition, downregulating ferroptosis drivers NCOA4, ACSL4, and LPCAT3, and restoring glutathione peroxidase 4 activity (p<0.05 for all). These findings demonstrate that ginkgolide B mitigates membranous nephropathy-associated renal and podocyte injury by inhibiting ferroptosis.