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Insights into the α-amylase and α-glucosidase inhibition mechanism of 4-(4-hydroxyphenyl)-but-3-en-2-one from Scutellaria barbata D. Don: enzymatic kinetics, fluorescence spectroscopy and computational simulation

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Abstract

Diabetes mellitus has become a pandemic in modern society. Regulation of carbohydrate hydrolysis by inhibition of key-digestive enzymes is currently used to control hyperglycaemia. Therefore, characterization of safe and efficient alternative therapeutic agents has become essential. Herein, the mechanism of α-amylase and α-glucosidase inhibition of 4-(4-hydroxyphenyl)-but-3-en-2-one (4) isolated from Scutellaria barbata D. Don was investigated by in vitro enzymatic kinetics, conformation analysis and molecular docking. The results demonstrated that 4-(4-hydroxyphenyl)-but-3-en-2-one (4) reversibly inhibited α-amylase and α-glucosidase in a mixed-type and competitive manner with IC50 values of 81.2 ± 5.3 and 54.8 ± 2.4 µM, respectively. Analysis of fluorescence spectroscopy showed that the interaction of the compound with both enzymes was primarily influenced by hydrogen bonding and van der Waals forces, and was a spontaneous process. Moreover, computer modelling indicated that the amino acid residues of the enzymes were bound to the compound mainly by hydrogen bonds. The results indicated that the substituents in the molecular structure of the compounds play a crucial role in the inhibition activity of the compounds. 4-(4-Hydroxyphenyl)-but-3-en-2-one (4) with methyl vinyl ketone substitution on the benzene ring was the most potent inhibitor for both enzymes.

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The NMR and MS spectra of the compounds are available as supplementary material.

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Acknowledgements

This work was supported by the Ministry of Science and Technology of Taiwan (Grants MOST 109-2320-B-020-001 and 109-2622-B-020-003). We acknowledge Ms Lih-Mei Sheu and Ms Shu-Chi Lin, Instrumentation Centre of the College of Science, National Chung Hsing University and National Tsing Hua University for MS measurements. The nuclear magnetic resonance spectrometer (NMR) was performed in the Precision Instruments Centre of National Pingtung University of Science and Technology.

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Authors and Affiliations

  1. Department of Tropical Agriculture and International Cooperation, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Bongani S. Dlamini

  2. Department of Life Science, National Taitung University, Taitung, 95002, Taiwan

    Chiy-Rong Chen

  3. Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Wen-Ling Shih, Jue-Liang Hsu & Chi-I Chang

  4. Department of Food Science, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Yu-Kuo Chen

  5. Research Centre for Austronesian Medicine and Agriculture, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Jue-Liang Hsu

  6. Research Centre for Tropic Agriculture, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Jue-Liang Hsu

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  1. Bongani S. Dlamini
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Dlamini, B.S., Chen, CR., Shih, WL. et al. Insights into the α-amylase and α-glucosidase inhibition mechanism of 4-(4-hydroxyphenyl)-but-3-en-2-one from Scutellaria barbata D. Don: enzymatic kinetics, fluorescence spectroscopy and computational simulation. Med Chem Res 31, 2007–2020 (2022). https://doi.org/10.1007/s00044-022-02966-z

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