Lactucaxanthin - a potential anti- diabetic carotenoid from lettuce (Lactuca sativa) inhibits α-amylase and α-glucosidase activity in vitro and in diabetic rats

Intestinal and pancreatic alpha-amylase and alpha-glucosidase inhibitors offer an approach to lower the levels of post-prandial hyperglycemia through the control of dietary starch breakdown in digestion. This study hypothesized that lactucaxanthin (Lxn) in lettuce (Lactuca sativa) inhibits the activity of a-amylase and a-glucosidase. In this study, the interaction of Lxn with alpha-amylase and alpha-glucosidase in silico and its inhibitory effect on these enzymes were studied using in vitro and STZ-induced diabetic rat models. Lxn was isolated from lettuce with 96% purity confirmed by HPLC and LCMS. The in silico analysis showed that Lxn has a lower binding energy (-6.05 and -6.34 kcal mol(-1)) with alpha-amylase and alpha-glucosidase compared to their synthetic inhibitors, acarbose (-0.21 kcal mol(-1)) and miglitol (-2.78 kcal mol(-1)), respectively. In vitro alpha-amylase and alpha-glucosidase inhibition assays revealed that Lxn had IC50 values of 435.5 ae g mL-1 and 1.84 mg mL-1, but acarbose has values of 2.5 and 16.19 ae g mL(-1). The in vivo results showed an increased activity for alpha-amylase and alpha-glucosidase in the intestine (4.7 and 1.30 fold, p < 0.05) and pancreas (1.3 and 1.48 fold, p < 0.05) of STZ induced diabetic rats compared to normal rats. Whereas the activity decreased (p < 0.05) in the Lxn fed diabetic rats, except for the intestinal alpha-glucosidase activity (1.69 +/- 0.12 PNP per min per mg protein). This was confirmed by the low blood glucose level (239.4 +/- 18.2 mg dL(-1)) in diabetic rats fed Lxn compared to the diabetic group (572.2 +/- 30.5 mg dL(-1), p < 0.05). Lxn significantly inhibited (p < 0.05) the activity of alpha-amylase and alpha-glucosidase and could be of medical and nutritional relevance in the treatment of diabetes.