Characterization of nimbidiol as a potent intestinal disaccharidase and glucoamylase inhibitor present in Azadirachta indica (neem) useful for the treatment of diabetes.
Azadirachta indica, used in antidiabetic herbal drugs, was reported to contain α-glucosidase inhibitor. Bioassay guided purification characterized the inhibitor as nimbidiol (a diterpenoid), present in root and stem-bark of the tree. Nimbidiol inhibited intestinal (mammalian) maltase-glucoamylase, sucrase-isomaltase, lactase, trehalase and fungal α-glucosidases. Nimbidiol showed a mixed competitive inhibition on intestinal carbohydrases. IC50, Ki and Ki' (µM) were 1.35 ± 0.12, 0.08 ± 0.01, 0.25 ± 0.11, respectively, for maltase-glucoamylase (maltotetraose as substrate). Nimbidiol was more potent inhibitor of isomaltase (IC50 0.85 ± 0.035 µM), lactase (IC50 20 ± 1.33 µM) and trehalase (IC50 30 ± 1.75 µM) than acarbose, voglibose, salacinol, kotalanol and mangiferin. Ki and Ki' values (µM) for intestinal sucrase were 0.7 ± 0.12 and 1.44 ± 0.65, respectively. Development of nimbidiol as an antidiabetic drug appears to be promising because of broad inhibition spectrum of intestinal glucosidases and easy synthesis of the molecule.
Department of Biotechnology, Heritage Institute of Technology , Kolkata , India.
Abhishek
A
Mukherjee
Subhabrata
S
Sengupta
D000818:Animals; D031601:Azadirachta / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D004186:Disaccharidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007422:Intestines / Q000201:enzymology*; D007700:Kinetics; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship
D004224:Diterpenes; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C496111:nimbidiol; D004186:Disaccharidases; D005087:Glucan 1,4-alpha-Glucosidase