AUTHOR=Lin Shinn-Zong , Kuo Wei-Wen , Tsai Bruce Chi-Kang , Paul Catherine Reena , Kuo Chia-Hua , Hsieh Dennis Jine-Yuan , Kao Shih-Wen , Pai Pei-Ying , Chen Shan-Jun , Huang Chih-Yang , Lin Kuan-Ho 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1562116

DOI=10.3389/fphar.2025.1562116

ISSN=1663-9812

ABSTRACT=BackgroundDiabetic 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.ObjectiveThis 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).ResultsTreatment 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.ConclusionThese 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.