Morin hydrate promotes nephrin expression through modulation of Notch1-Snail signalling pathway in diabetic rats

Abstract

Reduction in nephrin expression is usually observed in patients with diabetic nephropathy, and there is evidence that Notch1/Snail signalling pathway is essential for the expression of nephrin. This study investigated the role of morin hydrate (MH) on Notch1/Snail signalling pathway in the kidney of type-2 diabetic rats (T2D) exposed to diesel exhaust particles (DEP). The male wistar rats (n ​= ​40) were group into 8 groups: Group 1-Control; Group 2-DEP (0.5 ​mg/kg); Group 3-type-2 diabetic rat (T2D); Group 4-T2D ​+ ​DEP (0.5 ​mg/kg); Group 5-DEP (0.5 ​mg/kg) ​+ ​MH (30 ​mg/kg); Group 6-T2D ​+ ​MH (30 ​mg/kg); Group 7-T2D ​+ ​DEP 0.5 ​mg/kg ​+ ​MH 30 ​mg/kg; and Group 8-MH (30 ​mg/kg) only. Type-2 diabetes was induced in the rats through a one-time administration of STZ at 45 ​mg/kg after 14 days treatment with fructose solution at 20% w/v. The type-2 diabetic and non-diabetic rats were exposed to DEP at 0.5 ​mg/kg through nasal instillation every 48 ​h for 14 days. MH (30 ​mg/kg) was given orally every 24 ​h for 15 days. MH is a naturally occurring flavonoid chemical found in a variety of plants, and has been discovered to have a number of biological actions, including antioxidant, anti-inflammatory, and anticancer effects. The effect of MH on kidney function indices and electrolytes, and its modulatory role on Notch1/Snail signalling pathway were determined. In silico studies on binding affinity of MH with some proteins in this pathway was conducted and the electronic behavior of MH was predicted using DFT calculation. The results show that MH oral therapy ameliorates nephrotoxicity and protects the podocytes in T2D rats and T2D rats exposed to DEP. It decreased the serum levels of creatinine, urea and total protein, while also decreasing the levels of renal sodium and potassium ions and bicarbonate. MH increased mRNA expression of nephrin by modulating Notch1/Snail signalling pathway, and these results were supported by the molecular docking studies. This study suggests that MH promote glomerular filtration in T2D exposed to DEP.