Dehydroeburicoic Acid, a Dual Inhibitor against Oxidative Stress in Alcoholic Liver Disease
Alcoholic liver disease (ALD) is a complicated disease which can lead to hepatocellular carcinoma; however, there is a lack of satisfactory therapeutics. Dehydroeburicoic acid (DEA) (<b>1</b>), a triterpenoid isolated from <i>Antrodia cinnamomea</i>, has been reported to act...
Сохранить в:
| Главные авторы: | , , , , , , , , |
|---|---|
| Формат: | |
| Опубликовано: |
MDPI AG,
2022-12-01T00:00:00Z.
|
| Предметы: | |
| Online-ссылка: | Connect to this object online. |
| Метки: |
Добавить метку
Нет меток, Требуется 1-ая метка записи!
|
| Итог: | Alcoholic liver disease (ALD) is a complicated disease which can lead to hepatocellular carcinoma; however, there is a lack of satisfactory therapeutics. Dehydroeburicoic acid (DEA) (<b>1</b>), a triterpenoid isolated from <i>Antrodia cinnamomea</i>, has been reported to act against ALD, but its mechanisms of action are still not clear. In this study, we report for the first time the use of DEA (<b>1</b>) as a dual inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) and GSK3β in an in vitro ALD cell model. DEA (<b>1</b>) engages Keap1 to disrupt the Keap1-Nrf2 PPI and inhibits GSK3β to restore Nrf2 activity in a Keap1-independent fashion. DEA (<b>1</b>) promotes Nrf2 nuclear translocation to activate downstream antioxidant genes. Importantly, DEA (<b>1</b>) restores the mitochondrial dysfunction induced by ethanol and generates antioxidant activity in the ALD cell model with minimal toxicity. We anticipate that DEA (<b>1</b>) could be a potential scaffold for the further development of clinical agents for treating ALD. |
|---|---|
| Примечание: | 10.3390/ph16010014 1424-8247 |