title: Pistagremic acid, a glucosidase inhibitor from Pistacia integerrima.
abstract: Pistacia integerrima Stewart in traditionally used as folk remedy for various pathological conditions including diabetes. In order to identify the bioactive compound responsible for its folk use in diabetes, a phytochemical and biological study was conducted. Pistagremic acid (PA) was isolated from the dried galls extract of P. integerrima. Strong α-glucosidase inhibitory potential of PA was predicted using its molecular docking simulations against yeast α-glucosidase as a therapeutic target. Significant experimental α-glucosidase inhibitory activity of PA confirmed the computational predictions. PA showed potent enzyme inhibitory activity both against yeast (IC(50): 89.12±0.12μM) and rat intestinal (IC(50): 62.47±0.09μM) α-glucosidases. Interestingly, acarbose was found to be more than 12 times more potent an inhibitor against mammalian (rat intestinal) enzyme (having IC(50) value 62.47±0.09μM), as compared to the microbial (yeast) enzyme (with IC(50) value 780.21μM). Molecular binding mode was explored via molecular docking simulations, which revealed hydrogen bonding interactions between PA and important amino acid residues (Asp60, Arg69 and Asp 70 (3.11Å)), surrounding the catalytic site of the α-glucosidase. These interactions could be mainly responsible for their role in potent inhibitory activity of PA. PA has a strong potential to be further investigated as a new lead compound for better management of diabetes.
authors.affiliation: Institute of Chemical Sciences, Centre for Phytomedicine & Medicinal Organic Chemistry, University of Peshawar, Peshawar 25120, Pakistan.
authors.forename: Ghias
authors.initials: G
authors.lastname: Uddin
authors.forename: Abdur
authors.initials: A
authors.lastname: Rauf
authors.forename: Abdulaziz M
authors.initials: AM
authors.lastname: Al-Othman
authors.forename: Simona
authors.initials: S
authors.lastname: Collina
authors.forename: Muhammad
authors.initials: M
authors.lastname: Arfan
authors.forename: Gowhar
authors.initials: G
authors.lastname: Ali
authors.forename: Inamullah
authors.initials: I
authors.lastname: Khan
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D065089:Glycoside Hydrolase Inhibitors; D007422:Intestines / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D027927:Pistacia / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D014315:Triterpenes; C581170:pistagremic acid; D000520:alpha-Glucosidases