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Bioorg Med Chem Lett. 2016 Dec 1;26(23):5639-5643. doi: 10.1016/j.bmcl.2016.10.072. Epub 2016 Oct 26.

The comparison of neuroprotective effects of isoliquiritigenin and its Phase I metabolites against glutamate-induced HT22 cell death.

Author information

1
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea.
2
Gham BioPharm, Co. Ltd., #401, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea.
3
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea. Electronic address: jungj@knu.ac.kr.
4
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea; Gham BioPharm, Co. Ltd., #401, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea. Electronic address: kssong@knu.ac.kr.

Abstract

It is becoming increasingly important to investigate drug metabolites to evaluate their toxic or preventive effects after administration of the parent compound. In our previous study, isoliquiritigenin isolated from Glycyrrhizae Radix effectively protected mouse-derived hippocampal neuronal cells (HT22) against 5mM glutamate-induced oxidative stress. However, there is little information on the protective effects of the metabolites of isoliquiritigenin on HT22 cells. In this study, isoliquiritigenin and its Phase I metabolites were prepared and their neuroprotective activities on glutamate-treated HT22 cells were compared. The prepared metabolites were liquiritigenin (1), 2',4,4',5'-tetrahydroxychalcone (2), sulfuretin (3), butein (4), davidigenin (5), and cis-6,4'-dihydroxyaurone (6). Among the six metabolites, 4 showed better neuroprotective effects than the parent compound, isoliquiritigenin. Our study suggests that the neuroprotective effect of isoliquiritigenin could be elevated by its active metabolite 4, which is a chalcone containing a catechol group in the B ring.

KEYWORDS:

Butein; Glutamate; HT22; Isoliquiritigenin; Neuroprotection; Phase I metabolites

PMID:
27815122
DOI:
10.1016/j.bmcl.2016.10.072
[Indexed for MEDLINE]

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