A series of cinnamic acid derivatives and their inhibitory activity on intestinal alpha-glucosidase.

• Abstract: 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.
• Authors: Sirichai Adisakwattana, Praew Chantarasinlapin, Haruthai Thammarat, Sirintorn Yibchok-Anun (Affiliation: Department of Transfusion Medicine, Faculty of Allied Health Sciences, The Medical Food Research and Development Center, Chulalongkorn University, Bangkok, Thailand. adisakwattana_siri at yahoo.com)
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 24 Issue 5 Pg. 1194-200 (Oct 2009) ISSN: 1475-6374 [Electronic] England
• PMID: 19772492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cinnamates
• cinnamic acid
• alpha-Glucosidases

Topics

• Animals
• Cinnamates (chemistry, pharmacology)
• Enzyme Activation (drug effects)
• Intestines (enzymology)
• Quantitative Structure-Activity Relationship
• Rats
• Swine
• alpha-Glucosidases (antagonists & inhibitors)