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Comparative study of selective in vitro and in silico BACE1 inhibitory potential of glycyrrhizin together with its metabolites, 18α- and 18β-glycyrrhetinic acid, isolated from Hizikia fusiformis

Archives of Pharmacal Research volume 41, pages 409–418 (2018)Cite this article

Abstract

Hizikia fusiformis (Harvey) Okamura is a brown seaweed widely used in Korea and Japan, and it contains different therapeutically active constituents. In the present study, we investigated the activities of glycyrrhizin isolated from H. fusiformis, including its metabolites, 18α- and 18β-glycyrrhetinic acid against Alzheimer’s disease (AD) via acetyl and butyrylcholinesterase and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibition. Among these three compounds, 18β-glycyrrhetinic acid (IC50 = 8.93 ± 0.69 µM) demonstrated two fold potent activity against BACE1 compared to the positive control, quercetin (IC50 = 20.18 ± 0.79 µM). Additionally, glycyrrhizin with an IC50 value of 20.12 ± 1.87 µM showed similarity to quercetin, while 18α-glycyrrhetinic acid showed moderate activity (IC50 = 104.35 ± 2.84 µM). A kinetic study revealed that glycyrrhizin and 18β-glycyrrhetinic acid were non-competitive and competitive inhibitiors of BACE1, demonstrated via Ki values of 16.92 and 10.91 µM, respectively. Molecular docking simulation studies evidently revealed strong binding energy of these compounds for BACE1, indicating their high affinity and capacity for tighter binding to the active site of the enzyme. These data suggest that glycyrrhizin isolated from the edible seaweed, H. fusiformis and its metabolite, 18β-glycyrrhetinic acid demonstrated selective inhibitory activity against BACE1 to alleviate AD.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2012R1A6A1028677).

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Author notes

  1. Aditi Wagle and Su Hui Seong have contributed equally to this work.

Affiliations

  1. Department of Food and Life Science, Pukyong National University, Busan, 48513, Republic of Korea

    Aditi Wagle, Su Hui Seong & Jae Sue Choi

  2. College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongsan, 38430, Republic of Korea

    Bing Tian Zhao & Mi Hee Woo

  3. Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 54896, Republic of Korea

    Hyun Ah Jung

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  1. Aditi Wagle
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  2. Su Hui Seong
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Correspondence to Hyun Ah Jung or Jae Sue Choi.

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Wagle, A., Seong, S.H., Zhao, B.T. et al. Comparative study of selective in vitro and in silico BACE1 inhibitory potential of glycyrrhizin together with its metabolites, 18α- and 18β-glycyrrhetinic acid, isolated from Hizikia fusiformis. Arch. Pharm. Res. 41, 409–418 (2018). https://doi.org/10.1007/s12272-018-1018-2

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  • DOI: https://doi.org/10.1007/s12272-018-1018-2

Keywords

  • Hizikia fusiformis
  • 18β-glycyrrhetinic acid
  • glycyrrhizin
  • 18α-glycyrrhetinic acid
  • BACE1