2. Academic Validation
  3. Jujuboside A ameliorates glomerular podocytes lipotoxicity in diabetic mice by YY1-mediated promotion of intracellular cholesterol transport and efflux

Jujuboside A ameliorates glomerular podocytes lipotoxicity in diabetic mice by YY1-mediated promotion of intracellular cholesterol transport and efflux

  • J Nutr Biochem. 2025 Dec 13:150:110231. doi: 10.1016/j.jnutbio.2025.110231.
Ying Liu 1,  Dandan Pan 1,  Pinyan Zhang 1,  Yuting Shao 1,  Yinhua Kong 1,  Zhenzhou Jiang 2,  Wenjing Zhu 1,  Houwen Wang 1,  Xinghan Liu 3,  Sitong Qian 1,  Tao Wang 4,  Xia Zhu 5,  Tingting Yang 6,  Qian Lu 7
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
  • 2 New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China.
  • 3 Department of Clinical Medicine, Kangda College of Nanjing Medicine University, Lianyungang, China.
  • 4 Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 5 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. Electronic address: [email protected].
  • 6 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. Electronic address: [email protected].
  • 7 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. Electronic address: [email protected].
PMID: 41397601 DOI: 10.1016/j.jnutbio.2025.110231
Abstract

Glomerular podocytes injury represents a critical pathological hallmark of diabetic kidney disease (DKD), in which lipotoxicity plays a central pathogenic role. Our previous investigations in type 2 diabetes mellitus (T2DM) have demonstrated that Jujuboside A (Ju A), a triterpene saponin isolated from Semen Ziziphi Spinosae (SZS), exerted dual therapeutic effects in T2DM by ameliorating hepatic steatosis and renal dysfunction. However, the role of podocytes lipid metabolism in Ju A-mediated protection against DKD remain undefined prior to the present study. In this work, we reported that Ju A significantly attenuated glomerular podocytes injury and lipotoxicity in DKD, while concurrently improving renal function and preserving glomerular morphology. Mechanistically, Yin Yang 1 (YY1)-mediated alleviation of lipotoxicity contributed to the protective effect of Ju A against glomerular podocytes injury, primarily by promoting intracellular Cholesterol transport and efflux. In conclusion, our findings demonstrated that Ju A mitigated lipid overload in glomerular podocytes by modulating Cholesterol homeostasis via YY1, which not only intercepted the pathological progression of DKD but also provided a potential therapeutic target (YY1) and candidate agent (Ju A) for DKD intervention.

Keywords

Cholesterol homeostasis; Diabetic kidney disease; Glomerular podocytes injury; Jujuboside A; Lipotoxicity; YY1.

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