Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and induces anti-oxidative stress and anti-inflammatory effects via the MAPK pathway

Esculin is a derivative of coumarin, which is also an active ingredient of ash bark, and has antibacterial, anti-inflammatory, anti-allergy and skin protective effects. The underlying mechanism and protective effects of esculin on cognitive impairment in experimental diabetic nephropathy (DN) was investigated in the present study. Male C57BL/6J 6-week-old mice were injected intravenously with a single dose of streptozotocin (STZ; 30 mg/kg). At 2 weeks after the STZ injection, mice received intravenous injection with 5, 10 or 20 mg/kg esculin for 2 weeks. In the present study, the results of the Morris water maze test demonstrated that esculin significantly improved behavior and recognition memory in STZ-induced diabetic rats. Furthermore, treatment of STZ-induced diabetic rats with esculin significantly inhibited tumor necrosis factor-alpha, interleukin-6, malondialdehyde, monocyte chemoattractant protein-1 and intracellular adhesion molecule-1 activity levels, and increased the activity of superoxide dismutase, in the kidney, which was determined by ELISA. In addition, esculin treatment significantly suppressed the renal protein expression of activator protein 1, phosphorylated (p)-p38 mitogen activated protein kinase (MAPK) and p-c-Jun N-terminal kinase, and increased p-extracellular signal regulated kinase 1/2 protein expression, in STZ-induced diabetic rats, as determined by western blotting. These results indicate that esculin may ameliorate cognitive impairment in experimental DN, and exert anti-oxidative stress and anti-inflammatory effects, via the MAPK signaling pathway. Thus, it may serve as a potential target for cognitive impairment of DN in the future.