Leech granules inhibit ferroptosis and alleviate renal injury in mice with diabetic kidney disease

Abstract

Ethnopharmacological relevanceThe underlying mechanisms of diabetic kidney disease (DKD) and effective treatment strategies remain unclear. DKD progression is closely associated with abnormal iron metabolism and ferroptosis in vivo. Leeches, used in traditional Chinese medicine for promoting blood circulation and resolving blood stasis, are utilized to treat diabetes and its associated complications. Leeches effectively antagonize oxidative stress injury and exert protective effects on renal function. However, whether leeches can inhibit ferroptosis by modulating oxidative stress and iron metabolism remains unclear. Aim of the studyTo investigate the therapeutic potential of leech granules in DKD and, specifically, their effects on ferroptosis. Materials and methodsWe used a mouse model of DKD. The mice were treated with leech granules via gavage. Component identification and analysis of leech granules were performed using UPLC-MS, and efficacy was assessed by histopathology and analysis of blood glucose, lipids, and renal function. Additionally, the pharmacological mechanisms of leech granules were explored via proteomics, immunohistochemical staining, western blotting, and cell culture. ResultsProteomic analysis showed that iron metabolism was dysregulated and ferroptosis increased in DKD mice. Leech granules significantly reduced iron accumulation and renal pathological damage, decreased ROS levels, upregulated GSH levels, and inhibited ferroptosis in the kidneys of DKD mice. Furthermore, in vitro cellular experiments demonstrated that leech granules could inhibit erastin-induced ferroptosis and protect renal cells. ConclusionsThe regulation of renal iron metabolism and inhibition of ferroptosis mediates the therapeutic effect of leech granules on DKD. Leech granules represent a promising approach for DKD treatment.