title: Inhibitory evaluation of oligonol on α-glucosidase, protein tyrosine phosphatase 1B, cholinesterase, and β-secretase 1 related to diabetes and Alzheimer's disease.
abstract: Oligonol is a low-molecular-weight form of polyphenol that is derived from lychee fruit extract and contains catechin-type monomers and oligomers of proanthocyanidins. This study investigates the anti-diabetic activities of oligonol via α-glucosidase and human recombinant protein tyrosine phosphatase 1B (PTP1B) assays, as well as its anti-Alzheimer activities by evaluating the ability of this compound to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Oligonol exhibited potent concentration-dependent anti-diabetic activities by inhibiting α-glucosidase and PTP1B with IC50 values of 23.14 µg/mL and 1.02 µg/mL, respectively. Moreover, a kinetics study revealed that oligonol inhibited α-glucosidase (K i = 22.36) and PTP1B (K i = 8.51) with characteristics typical of a mixed inhibitor. Oligonol also displayed potent concentration-dependent inhibitory activity against AChE and BChE with IC50 values of 4.34 µg/mL and 2.07 µg/mL, respectively. However, oligonol exhibited only marginal concentration-dependent BACE1 inhibitory activity with an IC50 value of 130.45 µg/mL. A kinetics study revealed mixed-type inhibition against AChE (K i = 4.65) and BACE1 (K i = 58.80), and noncompetitive-type inhibition against BChE (K i = 9.80). Furthermore, oligonol exhibited dose-dependent inhibitory activity against peroxynitrite (ONOO(-))-mediated protein tyrosine nitration. These results indicate that oligonol has strong preventative potential in diabetes mellitus and in Alzheimer's disease.
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea. choijs@pknu.ac.kr.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Himanshu Kumar
authors.initials: HK
authors.lastname: Bhakta
authors.affiliation: Amino Up Chemical Company, Ltd., Sapporo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujii
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Republic of Korea.
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Republic of Korea.
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.affiliation: Graduate School of Science and Engineering for Research, University of Toyama, Toyama, 930-8555, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea. jungha@jbnu.ac.kr.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000201:enzymology; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors; D010636:Phenols / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*
chemical_list: D002800:Cholinesterase Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010636:Phenols; C514283:oligonol; D030421:Peroxynitrous Acid; D002392:Catechin; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Anti-Alzheimer activity; Anti-diabetic activity; Kinetics; Oligonol