Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8879692 | Industrial Crops and Products | 2018 | 7 Pages |
Abstract
Aldose reductase, the pivotal enzyme in the polyol pathway, has been widely investigated as an enzyme critically involved in the onset and progression of various pathologies associated with diabetes mellitus. Investigation of the inhibitory effect of tara [Caesalpinia spinosa (Molina) Kuntze] pods extract on aldose reductase revealed that its n-butanol fraction exhibits excellent aldose reductase inhibitory activity in vitro and ex vivo. Methyl gallate and pistafolin B were isolated from the n-butanol fraction of the tara pod methanolic extract as the main contributors for its aldose reductase inhibition, guided by affinity-based ultrafiltration-high performance liquid chromatography, with pistafolin B being the more potent inhibitor of the two. In vitro and in silico results demonstrated that pistafolin B is a mixed-type inhibitor that can bind to the aldose reductase active site rapidly, preventing substrate access and product formation (IC50, 0.198â¯mM; Ki, 0.34â¯mM). Ex vivo experiments indicated that pistafolin B can penetrate the eye lens and successfully inhibit aldose reductase under hyperglycaemic conditions, thus preventing the accumulation of sorbitol and the subsequent osmotic stress.
Keywords
CH2Cl2VmaxARITFANADPHEtOAcn-BuOHN-butanolFBSEI-MSHRARRLARIACUCrat lens aldose reductase1H NMRP/SROSAldose reductaseEthyl acetateTrifluoroacetic acidUltrafiltrationANOVAone-way analysis of varianceMichaelis-Menten constantInstitutional Animal Care and Use Committeemaximal velocityfoetal bovine serumElectron ionization mass spectrometrymethylene chlorideAldose reductase inhibitorproton nuclear magnetic resonancePenicillin/streptomycinhigh performance liquid chromatographyHPLCReactive oxygen species
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Authors
Zhiqiang Wang, Yanymee N. Guillen Quispe, Seung Hwan Hwang, Guanglei Zuo, Soon Sung Lim,