Hippophae rhamnoides L. leaf extracts alleviate diabetic nephropathy via attenuation of advanced glycation end product-induced oxidative stress in db/db mice

Abstract

Diabetes mellitus leads to chronic complications, such as nephropathy. Diabetic complications are closely related to advanced glycation end products (AGEs). Excessive formation and accumulation of AGEs in diabetic renal diseases lead to excessive oxidative stress, resulting in chronic renal failure. The leaves of Hippophae rhamnoides L. (sea buckthorn leaves; SBL) show biological benefits, including antioxidant effects. This study aimed to evaluate the effect of SBL on kidney damage in db/db mice. The SBL extract was orally administered at 100 and 200 mg kg⁻¹ for 12 weeks to db/db mice. Histological changes and the urine albumin/creatinine ratio were relieved, and the accumulation of AGEs in kidney glomeruli decreased following SBL treatment. Moreover, the SBL extract reduced the expression of AGEs, the receptor for AGEs, and NADPH oxidase 4, but upregulated glyoxalase 1 in the diabetic renal tissue. Urinary excretion levels and expression of 8-hydroxy-2′-deoxyguanosine as a biomarker of oxidative stress decreased after SBL treatment in the renal tissue. Furthermore, SBL attenuated oxidative stress in diabetic kidneys by reducing AGE accumulation, thereby ameliorating renal damage. Therefore, from these results, we infer that the SBL extract can act as a potential therapeutic agent for diabetic renal complications caused by AGEs.