Curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation

Biomedicine & Pharmacotherapy, Vol. 137 (2021)

Mots clés
Auteurs
  • Lin Ye
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Xueting Hu
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Xiang Hu
  • Department of Endocrinology and Central Lab, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Sihui Yin
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Jianqiang Chen
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Hanghui He
  • Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
  • Shanshan Hong
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Bin Yang
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China
  • Krishna K. Singh
  • Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Ontario N6A5C1, Canada
  • Jianpeng Feng
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Yi Wang
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
  • Wu Luo
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Endocrinology and Central Lab, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Corresponding authors at: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • Guang Liang
  • Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China; Corresponding authors at: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.

Résumé

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-κB/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro-fibrotic mechanisms, apoptosis, inflammatory response, and NF-κB and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-κB and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations.

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