The comparison of neuroprotective effects of isoliquiritigenin and its Phase I metabolites against glutamate-induced HT22 cell death.
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.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea.
Eun-Ju
EJ
Yang
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea.
Minjun
M
Kim
Gham BioPharm, Co. Ltd., #401, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea.
Ji Eun
JE
Woo
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Sankyuk-dong, Daegu 41566, Republic of Korea.
Taeho
T
Lee
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.
Jong-Wha
JW
Jung
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.
Kyung-Sik
KS
Song
D000818:Animals; D001572:Benzofurans / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D047188:Chalcones / Q000378:metabolism / Q000494:pharmacology*; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*
D001572:Benzofurans; D047188:Chalcones; D005419:Flavonoids; D018696:Neuroprotective Agents; C553221:davidigenin; D018698:Glutamic Acid; C040918:butein; D002599:Chalcone; C040920:isoliquiritigenin; C054989:sulfuretin
Butein; Glutamate; HT22; Isoliquiritigenin; Neuroprotection; Phase I metabolites