2020年
Protective Effect of 2',3'-Dihydroxy-4',6'-dimethoxychalcone on Glutamate-Induced Neurotoxicity in Primary Cortical Cultures.
Biological & pharmaceutical bulletin
- ,
- ,
- ,
- ,
- 巻
- 43
- 号
- 1
- 開始ページ
- 184
- 終了ページ
- 187
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1248/bpb.b19-00718
We have previously isolated 2',3'-dihydroxy-4',6'-dimethoxychalcone (DDC) from green perilla leaves as the activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. This study aims to evaluate the effects of DDC against glutamate neurotoxicity using rat primary cortical cultures. Treatment of cultures with DDC for 24 h before glutamate exposure significantly inhibited glutamate neurotoxicity in a concentration-dependent manner. The involvement of hemeoxygenase-1 (HO-1) and reduced glutathione (GSH) in the protective effects of DDC on cortical cultures was also evaluated. While an HO-1 inhibitor did not have a significant effect on DDC-induced neuroprotection, a γ-glutamylcystein synthetase (γ-GCS) inhibitor significantly suppressed the protective effect of DDC. In an astrocyte culture, DDC induced a marked increase in the levels of intracellular reduced GSH. These results suggest that DDC mainly activates the Nrf2-ARE pathway of astrocytes, resulting in the increased extracellular release of reduced GSH, protecting neurons from glutamate neurotoxicity.
- ID情報
-
- DOI : 10.1248/bpb.b19-00718
- PubMed ID : 31902924