Inhibitory effect of hesperetin on α-glucosidase: Molecular dynamics simulation integrating inhibition kinetics.
The α-glucosidase inhibitor is of interest to researchers due to its association with type-2 diabetes treatment. Hesperetin is a flavonoid with natural antioxidant properties. This paper presents an evaluation on the effects of hesperetin on α-glucosidase via inhibitory kinetics using a Molecular Dynamics (MD) simulation integration method. Due to the antioxidant properties of hesperetin, it reversibly inhibits α-glucosidase in a slope-parabolic mixed-type manner (IC50=0.38±0.05mM; Kslope=0.23±0.01mM), accompanied by tertiary structural changes. Based on computational MD and docking simulations, two hesperetin rings interact with several residues near the active site on the α-glucosidase, such as Lys155, Asn241, Glu304, Pro309, Phe311 and Arg312. This study provides insight into the inhibition of α-glucosidase by binding hesperetin onto active site residues and accompanying structural changes. Hesperetin presents as a potential agent for treating α-glucosidase-associated type-2 diabetes based on its α-glucosidase-inhibiting effect and its potential as a natural antioxidant.
School of Materials Science & Engineering, Beijing Institute of Fashion Technology, Beijing 100029, PR China.
Yan
Y
Gong
School of Materials Science & Engineering, Beijing Institute of Fashion Technology, Beijing 100029, PR China.
Xiu-Yuan
XY
Qin
School of Materials Science & Engineering, Beijing Institute of Fashion Technology, Beijing 100029, PR China.
Yuan-Yuan
YY
Zhai
Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, PR China.
Hao
H
Hao
Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Nanobiotechnology and Bioinformatics, University of Sciences and Technology, Daejeon 305-350, Republic of Korea. Electronic address: jinhyuk@kribb.re.kr.
Jinhyuk
J
Lee
Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, PR China. Electronic address: parkyd@hotmail.com.
Yong-Doo
YD
Park
D065089:Glycoside Hydrolase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006569:Hesperidin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism*
D065089:Glycoside Hydrolase Inhibitors; D006569:Hesperidin; D000520:alpha-Glucosidases; C013015:hesperetin
Hesperetin; Inhibition; Kinetics; Molecular dynamics; α-Glucosidase