Wu WB, Tao Y, Xu NJ, Shao QQ, Yuan F, Dong H, Lu FE, Zheng CH, Wu F. Ginsenoside Rd promote the contact between mitochondria and lipid droplets through Plin1/Mfn2 to treat diabetic kidney disease. World J Diabetes 2026; 17(9): 123886 [DOI: 10.4239/wjd.123886]
Corresponding Author of This Article
Fan Wu, Physician, Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, Hubei Province, China. 18202729109@163.com
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Wu WB, Tao Y, Xu NJ, Shao QQ, Yuan F, Dong H, Lu FE, Zheng CH, Wu F. Ginsenoside Rd promote the contact between mitochondria and lipid droplets through Plin1/Mfn2 to treat diabetic kidney disease. World J Diabetes 2026; 17(9): 123886 [DOI: 10.4239/wjd.123886]
World J Diabetes. Sep 15, 2026; 17(9): 123886 Published online Sep 15, 2026. doi: 10.4239/wjd.123886
Ginsenoside Rd promote the contact between mitochondria and lipid droplets through Plin1/Mfn2 to treat diabetic kidney disease
Wen-Bin Wu, Yi Tao, Nai-Jia Xu, Qing-Qing Shao, Fen Yuan, Hui Dong, Fu-Er Lu, Cheng-Hong Zheng, Fan Wu
Wen-Bin Wu, Yi Tao, Nai-Jia Xu, Cheng-Hong Zheng, Wuhan Hospital of Traditional Medicine, Wuhan 430014, Hubei Province, China
Qing-Qing Shao, Department of Dermatology, Wuhan No. 1 Hospital, Wuhan 430022, Hubei Province, China
Fen Yuan, Hui Dong, Fu-Er Lu, Fan Wu, Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Co-first authors: Wen-Bin Wu and Yi Tao.
Co-corresponding authors: Cheng-Hong Zheng and Fan Wu.
Author contributions: Wu WB and Tao Y completed the experiment as co-first authors; Xu NJ and Shao QQ participated in the experiment and provided technical guidance for the experiment; Yuan F, Dong H and Lu FE provided guidance for the experimental scheme; Zheng CH and Wu F provided financial support and detailed arrangement for the experimental plan as co-corresponding authors; all authors have read and approved the final manuscript.
AI contribution statement: No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions.
Supported by National Natural Science Foundation of China, No. 82405337; Natural Science Foundation of Hubei Province of China, No. 2024AFB489; Wuhan Natural Science Foundation Exploration Program (Chenguang Program), No. 2025020701020243.
Institutional animal care and use committee statement: All protocols were approved by the Animal Ethics Committee of Tongji Hospital (IACUC number: TJH-202502035).
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data supporting this study are available from the corresponding author upon reasonable request, subject to privacy and ethical restrictions.
Corresponding author: Fan Wu, Physician, Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, Hubei Province, China. 18202729109@163.com
Received: June 30, 2026 Revised: July 17, 2026 Accepted: August 25, 2026 Published online: September 15, 2026 Processing time: 91 Days and 17.5 Hours
Abstract
BACKGROUND
Diabetic kidney disease (DKD) is one of the most severe microvascular complications of diabetes, characterized by pathological changes such as glomerulosclerosis and renal interstitial fibrosis. Recent studies indicate that abnormal renal lipid metabolism and lipotoxicity are key drivers of DKD progression, where dysfunctional coupling between lipid droplets and mitochondria leads to insufficient fatty acid (FA) oxidation, exacerbating lipid deposition and fibrosis. Although ginsenoside Rd, a primary active component of Panax ginseng, has shown potential in alleviating DKD, its specific mechanism particularly whether it acts by regulating lipid droplet-mitochondria interactions and related signaling pathways remains unclear.
AIM
To investigate the protective effect of ginsenoside Rd against DKD and its underlying mechanism via the protein kinase A/perilipin (Plin) 1/mitofusin (Mfn) 2-mediated lipid droplet-mitochondria interaction.
METHODS
Db/db mouse DKD model was used and treated with different doses of ginsenoside Rd. Renal function and lipid levels were assessed biochemically; fibrosis was evaluated via histochemical staining; lipid droplet-mitochondria interaction was examined by electron microscopy and immunofluorescence. Using Plin1 deficient models, we examined the Plin1/Mfn2 signaling pathway and related molecules by polymerase chain reaction and western blotting.
RESULTS
Ginsenoside Rd significantly improved glycemic control, renal function, and attenuated renal fibrosis in db/db mice. This was associated with reduced renal lipid deposition and enhanced FA oxidation. Further studies showed that ginsenoside Rd promoted lipid droplet-mitochondria contact and activated the Plin1/Mfn2 pathway. These protective effects were abolished in Plin1 knockout or knockdown models.
CONCLUSION
This study demonstrates that ginsenoside Rd alleviates DKD by activating protein kinase A, which enhances Plin1/Mfn2-mediated lipid droplet-mitochondria contact, thereby accelerating FA oxidation, reducing lipotoxicity and renal fibrosis.
Core Tip: This study identifies the protein kinase A/perilipin (Plin) 1/mitofusin 2 axis as a novel therapeutic target for diabetic kidney disease. Ginsenoside Rd activates protein kinase A, promotes Plin1-mitofusin 2 interaction, enhances lipid droplet-mitochondria contact, and stimulates fatty acid oxidation, thereby attenuating renal lipid accumulation and fibrosis. Using in vivo and in vitro lossoffunction models, we demonstrate that Plin1 is essential for ginsenoside Rd induced organelle tethering and metabolic benefit, providing a mechanistic framework for diabetic kidney disease intervention.
