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Inhibitory evaluation of oligonol on α-glucosidase, protein tyrosine phosphatase 1B, cholinesterase, and β-secretase 1 related to diabetes and Alzheimer’s disease

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Abstract

Oligonol is a low-molecular-weight form of polyphenol that is derived from lychee fruit extract and contains catechin-type monomers and oligomers of proanthocyanidins. This study investigates the anti-diabetic activities of oligonol via α-glucosidase and human recombinant protein tyrosine phosphatase 1B (PTP1B) assays, as well as its anti-Alzheimer activities by evaluating the ability of this compound to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Oligonol exhibited potent concentration-dependent anti-diabetic activities by inhibiting α-glucosidase and PTP1B with IC50 values of 23.14 µg/mL and 1.02 µg/mL, respectively. Moreover, a kinetics study revealed that oligonol inhibited α-glucosidase (K i = 22.36) and PTP1B (K i = 8.51) with characteristics typical of a mixed inhibitor. Oligonol also displayed potent concentration-dependent inhibitory activity against AChE and BChE with IC50 values of 4.34 µg/mL and 2.07 µg/mL, respectively. However, oligonol exhibited only marginal concentration-dependent BACE1 inhibitory activity with an IC50 value of 130.45 µg/mL. A kinetics study revealed mixed-type inhibition against AChE (K i = 4.65) and BACE1 (K i = 58.80), and noncompetitive-type inhibition against BChE (K i = 9.80). Furthermore, oligonol exhibited dose-dependent inhibitory activity against peroxynitrite (ONOO−)-mediated protein tyrosine nitration. These results indicate that oligonol has strong preventative potential in diabetes mellitus and in Alzheimer’s disease.

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Acknowledgments

This work was supported by a Research Grant of Pukyong National University (Granted in 2016).

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Authors and Affiliations

  1. Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea

    Jae Sue Choi & Himanshu Kumar Bhakta

  2. Amino Up Chemical Company, Ltd., Sapporo, Japan

    Hajime Fujii

  3. College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Republic of Korea

    Byung-Sun Min & Chan Hum Park

  4. Graduate School of Science and Engineering for Research, University of Toyama, Toyama, 930-8555, Japan

    Takako Yokozawa

  5. Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea

    Hyun Ah Jung

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  1. Jae Sue Choi
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Correspondence to Jae Sue Choi or Hyun Ah Jung.

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Choi, J.S., Bhakta, H.K., Fujii, H. et al. Inhibitory evaluation of oligonol on α-glucosidase, protein tyrosine phosphatase 1B, cholinesterase, and β-secretase 1 related to diabetes and Alzheimer’s disease. Arch. Pharm. Res. 39, 409–420 (2016). https://doi.org/10.1007/s12272-015-0682-8

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