A series of cinnamic acid derivatives and their inhibitory activity on intestinal alpha-glucosidase.
Inhibition of alpha-glucosidase and alpha-amylase delays the digestion of starch and disaccharides to absorbable monosaccharides, resulting in a reduction of postprandial hyperglycemia. Finding effective mammalian alpha-glucosidase inhibitors from natural sources can be beneficial in the prevention and treatment of diabetes mellitus. We investigated the inhibitory activity of cinnamic acid derivatives against rat intestinal alpha-glucosidase and porcine pancreatic alpha-amylase in vitro. Among 11 cinnamic acid derivatives, caffeic acid, ferulic acid, and isoferulic acid were the most potent inhibitors against intestinal maltase with IC(50) values of 0.74 +/- 0.01, 0.79 +/- 0.04, and 0.76 +/- 0.03 mM, respectively, whereas ferulic acid (IC(50) = 0.45 +/- 0.01 mM) and isoferulic acid (IC(50) = 0.45 +/- 0.01 mM) were effective intestinal sucrase inhibitors. However, all cinnamic acid derivatives were found to be inactive in pancreatic alpha-amylase inhibition. Kinetic analysis revealed that intestinal maltase was inhibited by caffeic acid, ferulic acid, and isoferulic acid in a mixed-inhibition manner. In addition, ferulic acid and isoferulic acid inhibited intestinal sucrase in a mixed type manner, whereas caffeic acid was a non-competitive inhibitor. The combination of isoferulic acid and acarbose showed an additive inhibition on intestinal sucrase. This study could provide a new insight into naturally occurring intestinal alpha-glucosidase inhibitors that could be useful for treatment of diabetes and its complications.
Adisakwattana
Sirichai
S
Department of Transfusion Medicine, Faculty of Allied Health Sciences, The Medical Food Research and Development Center, Chulalongkorn University, Bangkok, Thailand. adisakwattana_siri@yahoo.com
Chantarasinlapin
Praew
P
Thammarat
Haruthai
H
Yibchok-Anun
Sirintorn
S
D000818:Animals; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D065089:Glycoside Hydrolase Inhibitors; D007422:Intestines / Q000201:enzymology*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013552:Swine
D002934:Cinnamates; D065089:Glycoside Hydrolase Inhibitors; C029010:cinnamic acid