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
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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.
KeywordsHizikia fusiformis 18β-glycyrrhetinic acid glycyrrhizin 18α-glycyrrhetinic acid BACE1
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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Conflict of interest
The authors declare no conflicts of interest.
- Damle M (2014) Glycyrrhiza glabra (Liquorice)—a potent medicinal herb. Int J Herb Med 2:132–136Google Scholar
- Jung BM, Ahn CB, Kang SJ, Park JH, Chung DH (2001) Effects of Hijikia fusiforme extracts on lipid metabolism and liver antioxidative enzyme activities in triton-induced hyperlipidemic rats. J Korean Soc Food Sci Nutr 30:1184–1189Google Scholar
- Kim KI (1998) Studies on the blood anticoagulant polysaccharide isolated from hot water extracts of Hizikia fusiforme. J Food Sci Nutr 27:1204–1210Google Scholar
- Koo JG, Choi YS, Kwak JK (2001) Blood-Anticoagulant Activity of Fucoidans from Sporophylls of Undaria pinnatifida, Laminaria religiosa, Hizikia fusiforme and Sargassum fulvellum in Korea. J Koreran Fish Soc 34:511–520Google Scholar
- Park KE, Jang MS, Lim CW, Kim YK, Seo YW, Park HY (2005) Antioxidant activity on ethanol extract from boiled-water of Hizikia fusiformis. J Korean Soc Appl Biol Chem 48:435–439Google Scholar