Protective effect of morin by targeting mitochondrial reactive oxygen species induced by hydrogen peroxide demonstrated at a molecular level in MDCK epithelial cells

Abstract

Background: The development of diabetic nephropathy is aided by the presence of oxidative stress. Morin, a natural flavonoid molecule, has been shown to have antioxidant and anti-diabetic properties. However, little is known about the mechanism of its protective effect in diabetic nephropathy pathogenesis caused by oxidative stress.

Methods: Using Madin-Darby canine kidney (MDCK) cells as a working model, the current study investigates the detailed mechanism of morin's beneficial action. In hydrogen peroxide-induced oxidative stressed MDCK cells, there was a considerable rise in intracellular ROS and decreased antioxidant enzyme levels.

Results: Morin has a higher binding affinity for the antioxidant receptor; according to in silico study using molecular docking and ADMET, it is predicted to be an orally active molecule. While morin administration increased SOD and CAT activity in oxidative stress-induced MDCK cells, it also reduced mitochondrial oxidative stress and apoptosis. Furthermore, the present study discovered the molecular mechanism through which morin reduced oxidative stress in MDCK cells by upregulating antioxidant enzyme molecules including GST, GPx, and GCS.

Conclusion: These findings suggest that morin reduces H₂O₂-induced oxidative stress, reduces DNA oxidative damage, and prevents the depletion of antioxidant genes in MDCK cells.

Keywords: Antioxidant; MDCK cells; Morin; Oxidative stress; Reactive oxygen species.