Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel alpha-Glucosidase Inhibitor

NWIPB OpenIR

	Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel alpha-Glucosidase Inhibitor
	Dong, Qi; Hu, Na; Yue, Huilan; Wang, Honglun
	2021
发表期刊	MOLECULES
卷号	26 期号:15
摘要	alpha-glucosidase is a major enzyme that is involved in starch digestion and type 2 diabetes mellitus. In this study, the inhibition of hypericin by alpha-glucosidase and its mechanism were firstly investigated using enzyme kinetics analysis, real-time interaction analysis between hypericin and alpha-glucosidase by surface plasmon resonance (SPR), and molecular docking simulation. The results showed that hypericin was a high potential reversible and competitive alpha-glucosidase inhibitor, with a maximum half inhibitory concentration (IC50) of 4.66 +/- 0.27 mg/L. The binding affinities of hypericin with alpha-glucosidase were assessed using an SPR detection system, which indicated that these were strong and fast, with balances dissociation constant (KD) values of 6.56 x 10(-5) M and exhibited a slow dissociation reaction. Analysis by molecular docking further revealed that hydrophobic forces are generated by interactions between hypericin and amino acid residues Arg-315 and Tyr-316. In addition, hydrogen bonding occurred between hypericin and alpha-glucosidase amino acid residues Lys-156, Ser-157, Gly-160, Ser-240, His-280, Asp-242, and Asp-307. The structure and micro-environment of alpha-glucosidase enzymes were altered, which led to a decrease in alpha-glucosidase activity. This research identified that hypericin, an anthracene ketone compound, could be a novel alpha-glucosidase inhibitor and further applied to the development of potential anti-diabetic drugs.
关键词	hypericin alpha-glucosidase inhibitor mechanism
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/60759
专题	中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Dong, Qi,Hu, Na,Yue, Huilan,et al. Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel alpha-Glucosidase Inhibitor[J]. MOLECULES,2021,26(15).
APA	Dong, Qi,Hu, Na,Yue, Huilan,&Wang, Honglun.(2021).Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel alpha-Glucosidase Inhibitor.MOLECULES,26(15).
MLA	Dong, Qi,et al."Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel alpha-Glucosidase Inhibitor".MOLECULES 26.15(2021).