2. Academic Validation
  3. DKS26 Alleviates Ischemia-Reperfusion Injury-Induced Acute Kidney Injury by Stabilizing Vitamin D Receptors to Inhibit the Inflammatory Pathway of NF-κB P65

DKS26 Alleviates Ischemia-Reperfusion Injury-Induced Acute Kidney Injury by Stabilizing Vitamin D Receptors to Inhibit the Inflammatory Pathway of NF-κB P65

  • Int J Mol Sci. 2025 Mar 25;26(7):2985. doi: 10.3390/ijms26072985.
Luqun Liang 1 2,  Yuanyuan Ruan 1 2,  Xiong Yu 1 2,  Wanlin Tan 1 2,  Xiaoxiao Xu 1 2,  Jing Jia 1 2,  Jin Peng 1 2,  Fangfang Wang 1 2,  Yulin Peng 1 2,  Yuting Chen 1 2,  Lingling Liu 1 2,  Bing Guo 1 2,  Jiquan Zhang 3,  Yuanyuan Wang 1 2
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Guizhou Medical University, No. 6 Ankang Road, Guiyang 561113, China.
  • 2 Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, No. 6 Ankang Road, Guiyang 561113, China.
  • 3 State Key Laboratory of Functions and Applications of Medicinal Plants, College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, No. 6 Ankang Road, Guiyang 561113, China.
PMID: 40243616 DOI: 10.3390/ijms26072985
Abstract

Acute kidney injury (AKI) is a common critical clinical disease with high morbidity and mortality rates. Ischemia-reperfusion (IR) is the main cause of AKI, and there is no effective treatment or prevention. Therefore, it is critical to screen for effective therapeutic agents and to find therapeutic targets. DKS26 is a derivative of oleanolic acid (OA) optimized for bioavailability while retaining the anti-inflammatory, antioxidant, and anti-apoptotic properties of OA. This study aimed to investigate the therapeutic effects of DKS26 on AKI and its underlying molecular mechanisms. We established an AKI model in vivo and in vitro and observed that DKS26 had an ameliorative effect on IR or H/R-induced renal tubular epithelial cell injury and reduced oxidative stress, inflammation, and Apoptosis. Meanwhile, Swiss TargetPrediction and AutoDock Vina analysis revealed that DKS26 may interact with vitamin D receptors (VDR) through hydrogen bonding, suggesting that DKS26 may exert effects through VDR. In this study, we found that DKS26 treatment enhanced the stability of the VDR protein, promoted the binding of VDR to p-NF-κB P65Ser311, reduced the entry of p-NF-κB P65Ser311 into the nucleus, and inhibited the transcription of downstream inflammatory genes as well as their own expression, thus exerting its protective effect. In summary, these findings suggest that DKS26 may be a promising preventive strategy and provide a theoretical and experimental basis for AKI treatment.

Keywords

DKS26; NF-κB P65; VDR; acute kidney injury; ischemia reperfusion.

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