A chalcone derivative AD-021 inhibits kidney fibrosis in a mouse model of high fat diet/streptozotocin -induced diabetic nephropathy
Keywords:
Diabetic nephropathy, chalcone derivatives, kidney fibrosis, diabetic mellitusAbstract
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.
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