Capsaicin, an active ingredient from chilli peppers, attenuates glycative stress and restores sRAGE levels in diabetic rats

• Capsaicin retards the late stages of protein glycation and crosslinking in vitro.
• Capsaicin inhibits glycotoxin accumulation and restores the sRAGE levels in diabetic rats.
• This is the first study to demonstrate that capsaicin can reduce the burden of glycotoxin, relieving glycative stress in diabetics.

The effects of capsaicin (CAPS) on protein glycation and the subsequent formation of advanced glycation endproducts (AGEs) were assessed. In vitro glycation assays showed that CAPS retards the late stages of glycation and crosslinking reaction. The dual mechanisms of action involving antioxidant and dicarbonyl trapping activities may contribute to the antiglycation effects. In a rat model of streptozotocin-induced permanent hyperglycaemia, 12 weeks of CAPS administration led to a reduction in the levels of circulating and tissue AGEs, as well as activation of the receptor for AGEs (RAGE). The levels of oxidative biomarkers, evaluated by assessing 8-isoprostane and lymphocyte DNA damage, were also decreased in the CAPS-treated groups compared with the diabetic group. Intriguingly, the reduction of serum and renal soluble RAGE (sRAGE) observed in diabetic rats was restored by CAPS administration. This study is the first to demonstrate that CAPS can reduce the burden of AGEs, thus relieving glycative stress in diabetics.