Ligand docking suggests isomer specific catechin induced SIRT‐1 activation

Abstract

Cinnamon has been proposed to have multiple metabolic effects ranging from anti‐hyperglycemic effects to regulation of basal metabolic rates. Polyphenols such as resveratrol, caffeic acid, aspalathin, and quercetin have been shown to have similar effects through various pathways. Cinnamon extract contains many polyphenolic compounds with structural similarities to the studied polyphenols and as such may exhibit effects via the same biochemical pathways. Cinnamon extract contains a number of catechin isomers, polyphenolic molecules closely related to those stated previously. Due to these similarities, we propose that catechin may act through the pathways proposed for other polyphenols. Resveratrol has been shown to exert effects through modulation of SIRT‐1, a deacetylase enzyme involved in chromatin remodeling and control of gene expression. Our research primarily involved docking of the four catechin isomers into the allosteric binding site of the SIRT‐1 enzyme that resveratrol has been shown to act through. The two R isomers, (−)‐epicatechin (2R,3R) and (+)‐catechin (2R,3S), did not align with our assigned baseline values. However, these molecules cannot be ruled out for biological activity. The two S isomers of catechin, (−)‐catechin (2S,3R) and (+)‐epicatechin (2S,3S), showed favorable scores and positioning similarity to resveratrol. It was also observed through cooperative binding studies that (+)‐epicatechin (2S,3S) has the potential to be an activator of SIRT‐1. Other possible mechanisms of catechin include those of the other polyphenolic compounds. Quercetin has been shown to have effects via two major mechanisms. The first is by promoting glucose uptake in liver cells via upregulation of GLUT‐2 and GLUT‐4 gene expression. The other pathway involves down‐regulation of GLUT‐2 in intestinal microvilli to decrease absorption. Finally the effects of aspalathin have been shown to regulate GLUT‐4 translocation to the plasma membrane in L6 myocytes.Support or Funding InformationDepartment of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.