Therapeutic potential of Cordyceps militaris cultivated with Ginkgo biloba seeds for alleviating western diet-induced type 2 diabetes and diabetic nephropathy

Background: Diabetic nephropathy (DN), a leading cause of chronic kidney disease and end-stage renal disease, is a serious complication of type 2 diabetes mellitus (T2DM). Current therapies primarily slow disease progression but are unable to reverse kidney damage, highlighting the need for novel therapy to treat DN. Objective: This study evaluated the therapeutic potential of Cordyceps militaris (C. militaris) cultivated on Ginkgo biloba (G. biloba) seeds in ameliorating T2DM and its complications, especially DN. A T2DM mouse model was established using ApoE knockout mice fed a Western diet (WD). Results: Treatment with the specially cultivated C. militaris ameliorated hyperglycemia, dyslipidemia and hepatic dysfunction, while mitigating T2DM-induced renal damage. Key biochemical markers, including blood glucose, triglycerides, cholesterol, blood urea nitrogen (BUN), and creatinine, were significantly improved after treatment. Histopathologic analysis revealed restored renal morphology, reduced fibrosis and decreased amyloid deposition. Mechanistic studies showed downregulation of fibrosis-related proteins such as α-SMA, COL1, TIMP-1, CTGF, TGFβ1 and fibronectin, and upregulation of E-cadherin, Smad7 and Klotho, proteins with anti-fibrotic and renoprotective properties. Conclusion: These results suggest that the specially cultivated C. militaris enhances metabolic regulation and renal repair mechanisms, effectively attenuating T2DM-induced renal damage. This unique cultivation approach enriches the bioactive properties of C. militaris and offers a promising natural therapeutic strategy for T2DM and DN. Further studies are needed to validate these results in clinical settings and to explore long-term efficacy and safety.