title: Molecular dynamics simulation integrating the inhibition kinetics of hydroxysafflor yellow A on α-glucosidase.
abstract: Inhibition of α-glucosidase has attracted the attention of researchers due to its connection to type-2 diabetes. Hydroxysafflor yellow A (HSYA) extracted from Carthamus tinctorius L. is a natural antioxidant used in traditional Chinese medicine. In this study, the effect of HSYA on α-glucosidase was evaluated using inhibitory kinetics based on the antioxidant properties of HSYA and by performing computational simulation integration methods. HSYA reversibly inhibited α-glucosidase in a competitive inhibition manner and the evaluated kinetic parameters were IC50= 1.1 ± 0.22 mM and Ki= 1.04 ± 0.23 mM, respectively. The results of spectrofluorimetry showed that the inner hydrophobic regions of α-glucosidase, which are mostly in the active site, were exposed to the surface with increasing HSYA concentrations, indicating that the inactivation of α-glucosidase by HSYA was accompanied by regional unfolding. The molecular dynamics simulations indicated that the four rings of HSYA interact with four residues such as G217, A278, H279, and G280 at the entrance of the active site. Our study provides insight into the inhibition of α-glucosidase and the accompanying structural changes by HSYA. Based on its α-glucosidase-inhibiting effect and its potential as a natural antioxidant, HSYA is a potential agent for treating α-glucosidase-associated type-2 diabetes.
authors.affiliation: a College of Chemistry , Beijing Normal University , Beijing 100875 , China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: b Korean Bioinformation Center (KOBIC) , Korea Research Institute of Bioscience and Biotechnology , Daejeon 305-806 , Korea.|c Department of Nanobiotechnology and Bioinformatics , University of Sciences and Technology , Daejeon 305-350 , Korea.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: d Zhejiang Provincial Key Laboratory of Applied Enzymology , Yangtze Delta Region Institute of Tsinghua University , Jiaxing 314006 , P.R. China.
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
authors.affiliation: e Department of Dermatology , Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul 135-710 , Korea.
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.affiliation: a College of Chemistry , Beijing Normal University , Beijing 100875 , China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Zheng
authors.affiliation: f School of Preclinical Medicine , Beijing University of Chinese Medicine , Beijing 100029 , P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D031178:Carthamus / Q000737:chemistry; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008516:Medicine, Chinese Traditional; D056004:Molecular Dynamics Simulation; D011809:Quinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D065089:Glycoside Hydrolase Inhibitors; D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone; D000520:alpha-Glucosidases
keywords: competitive inhibitor; hydroxysafflor yellow A; inhibition kinetics; molecular dynamics; α-glucosidase