Swertiamarin mitigates nephropathy in high-fat diet/streptozotocin-induced diabetic rats by inhibiting the formation of advanced glycation end products

Abstract

Context: The molecular mechanism by which Swertiamarin (SM) prevents advanced glycation end products (AGEs) induced diabetic nephropathy (DN) has never been explored. Objective:To evaluate the effect of SM in preventing the progression of DN in high fat diet-streptozotocin-induced diabetic rats. Materials and methods: After 1?week of acclimatisation, the rats were divided randomly into five groups as follows: (1) Control group, which received normal chow diet; (2) High-fat diet (HFD) group which was fed diet comprising of 58.7% fat, 27.5% carbohydrate and 14.4% protein); (3) Aminoguanidine (AG) group which received HFD + 100?mg/k.b.w.AG (intraperitoneal); (4) Metformin (Met) group which received HFD + 70?mg/k.b.w. the oral dose of Met and (5) SM group which was supplemented orally with 50?mg/k.b.w.SM along with HFD. After 12?weeks all HFD fed animals were given a single 35?mg/k.b.w. dose of streptozotocin with continuous HFD feeding for additional 18?weeks. Later, various biochemical assays, urine analyses, histopathological analysis of kidneys, levels of AGEs, expression of various makers, and in-silico analysis were performed. Results: The diabetic group demonstrated oxidative stress, increased levels of AGEs, decreased renal function, fibrosis in the renal tissue, higher expression of the receptor for advanced glycation end products (RAGE), which were ameliorated in the SM treated group. In-silico analysis suggests that SM can prevent the binding of AGEs with RAGE. Conclusions:SM ameliorated DN by inhibiting the oxidative stress induced by AGEs.