In vitro and in vivo inhibition effect of capsaicin and pyridoxamine combination on advanced glycation end products in streptozotocin-induced experimental diabetes in rats

Glycation causes the formation of advanced glycation end products (AGE), which play an important role in the pathogenesis of diabetic complications, which alter changes the structure and functional properties of proteins that negatively affect cellular metabolism. In the current study, we investigated beneficial effects of red chili pepper extract (RC) and capsaicin (CAPS), the main bitter ingredient in red peppers and pyridoxamine (PM), a vitamin B6, one by one or in combination on glycation and AGEs damage in STZ-induced diabetic rats. The total amount of capcaicin in RC was found to be 3.51 mg/gDW by HPLC. 96 Male Sprague Dawley rats (8 wk old), each weighing 200-300 grams, were divided into 12 groups of 8 rats each. A single dose of STZ (50 mg/kg body weight) was administered to induce experimental diabetes in rats. Group 1 was normal control, group 2 was diabetic control. Groups 3 and 4, 200 and 400 mg/kg RC, groups 5 and 6, 6 and 8 mg/kg CAPS and group 7, 4 mg/mL PM and group 8 were receiving 300 mg/kg metformin (MF). Groups 9 and 10, 200 and 400 mg/kg RC+ 4 mg/mL PM and groups 11 and 12 were diabetic rats treated with 6 and 8 mg/kg CAPS + 4 mg/mL PM. Oral treatment with intragastric tube was administered every day for 28 days. At the end of the experiment, subjects in all groups were given anesthesia once and the rib cage was performed by intracardiac intervention and blood was collected. Immediately, the liver and kidneys were grossly removed for histological examination. The results of our study showed that the combined doses of RC+PM and CAPS+PM significantly reduced blood glucose levels, serum uric acid, urea, creatinine, AST, ALT, ALP, LDH, total cholesterol, fructosamine, HbA1c levels and significantly increased serum HDL and insulin levels. Moreover, the inhibitory effects of BSA/fructose system and RC and CAPS on AGE formation were investigated in vitro. Antiglycation activity was determined using the formation of AGE fluorescence intensity, the level of fructosamine, α-dicarbonyl compounds and protein carbonyl content. The results showed that different concentrations (50-400 µM) of significantly inhibited AGE formation, fructosamine level, α-dicarbonyl compounds and protein carbonyl oxidation in glycated BSA during 4 weeks of study.