A chalcone derivative AD-021 inhibits kidney fibrosis in a mouse model of high fat diet/streptozotocin -induced diabetic nephropathy

Authors

  • Wanangkan Poolsri
  • Suchada Kaewin
  • Ade Danova
  • Warinthorn Chavasiri
  • Chatchai Muanprasat

Keywords:

Diabetic nephropathy, chalcone derivatives, kidney fibrosis, diabetic mellitus

Abstract

Diabetic nephropathy (DN) is the most prevalent microvascular disorder in diabetes mellitus and plays an integral role in the aggravation of renal injury and fibrosis, which currently lacks effective treatments. The chalcone derivative AD-021 is a small synthetic molecule recently identified for treating kidney disease. In this study, we evaluated effects of AD-021 on kidney function and kidney fibrosis in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced DN in mice. Mice were treated with intraperitoneal administration of AD-021 (50 mg/kg/day) for 12 weeks. Determination of fasting blood glucose (FBG), renal function-related albumin/creatinine ratio, and urine volume in mice and histopathological section analysis of collagen deposition in kidney tissue were performed. Moreover, western blot analysis was used to investigate the expressions of TGF-β1 and profibrotic-related proteins. We found that administration of AD-021 (50 mg/kg/day) reduced FBG, albumin/creatinine ratio, urine volume and collagen deposition in kidney tissue of DN mice. Furthermore, AD-021 significantly inhibited expression of TGF-β1 and fibronectin, and alleviated loss of E-cadherin protein expression in HFD/STZ-induced DN mice. These data suggest that AD-021 has the potential as a nephroprotective agent in DN patients.

Author Biographies

Wanangkan Poolsri

Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok, Thailand, 10400

Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, Thailand, 10540

Suchada Kaewin

Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, Thailand, 10540

Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, Thailand, 10400

Ade Danova

Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand, 10330

Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural

16 Sciences, Institut Teknologi Bandung, Ganesa No.10, West Java, Indonesia

Warinthorn Chavasiri

Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand, 10330

Chatchai Muanprasat

Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, Thailand, 10540

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Published

2024-05-23

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Invited Article