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 α-amylase and α-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 α-amylase and α-glucosidase. In this study, the interaction of Lxn with α-amylase and α-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 α-amylase and α-glucosidase compared to their synthetic inhibitors, acarbose (-0.21 kcal mol-1) and miglitol (-2.78 kcal mol-1), respectively. In vitro α-amylase and α-glucosidase inhibition assays revealed that Lxn had IC50values of 435.5 μg mL-1and 1.84 mg mL-1, but acarbose has values of 2.5 and 16.19 μg mL-1. The in vivo results showed an increased activity for α-amylase and α-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 α-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 α-amylase and α-glucosidase and could be of medical and nutritional relevance in the treatment of diabetes.
Department of Molecular Nutrition; CSIR-Central Food Technological Research Institute, Mysuru 570 020, Karnataka, India.
Sowmya Shree
SS
Gopal
Department of Molecular Nutrition; CSIR-Central Food Technological Research Institute, Mysuru 570 020, Karnataka, India.
Magisetty Jhansi
MJ
Lakshmi
Department of Biochemistry; CSIR-Central Food Technological Research Institute, Mysuru 570 020, Karnataka, India. baskaranv@cftri.res.in.
Gurunathan
G
Sharavana
Department of Biochemistry; CSIR-Central Food Technological Research Institute, Mysuru 570 020, Karnataka, India. baskaranv@cftri.res.in.
Gunaseelan
G
Sathaiah
Department of Grain Science and Technology, CSIR-Central Food Technological Research Institute, Mysuru 570 020, Karnataka, India.
Yadahally N
YN
Sreerama
Department of Biochemistry; CSIR-Central Food Technological Research Institute, Mysuru 570 020, Karnataka, India. baskaranv@cftri.res.in.
Vallikannan
http://orcid.org/0000-0001-9817-7282
V
Baskaran
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002338:Carotenoids / Q000008:administration & dosage* / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D018545:Lactuca / Q000737:chemistry*; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D002338:Carotenoids; D000516:alpha-Amylases; D000520:alpha-Glucosidases