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

Autor: Dong Q; CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, China.; Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Xining 810008, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Hu N; CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, China.; Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Xining 810008, China., Yue H; CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, China.; Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Xining 810008, China., Wang H; CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, China.; Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Xining 810008, China.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2021 Jul 28; Vol. 26 (15). Date of Electronic Publication: 2021 Jul 28.
DOI: 10.3390/molecules26154566
Abstrakt: α -glucosidase is a major enzyme that is involved in starch digestion and type 2 diabetes mellitus. In this study, the inhibition of hypericin by α-glucosidase and its mechanism were firstly investigated using enzyme kinetics analysis, real-time interaction analysis between hypericin and α -glucosidase by surface plasmon resonance (SPR), and molecular docking simulation. The results showed that hypericin was a high potential reversible and competitive α-glucosidase inhibitor, with a maximum half inhibitory concentration (IC 50 ) of 4.66 ± 0.27 mg/L. The binding affinities of hypericin with α -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 × 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 α -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 α-glucosidase enzymes were altered, which led to a decrease in α-glucosidase activity. This research identified that hypericin, an anthracene ketone compound, could be a novel α-glucosidase inhibitor and further applied to the development of potential anti-diabetic drugs.
Databáze: MEDLINE
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