Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke
Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from <i>Terminalia chebula</i> has been found to have various biological...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/24/5390 |
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| author | Rong Zhou Kuan Lin Changlong Leng Mei Zhou Jing Zhang Youwei Li Yujing Liu Xiansheng Ye Xiaoli Xu Binlian Sun Xiji Shu Wei Liu |
| author_facet | Rong Zhou Kuan Lin Changlong Leng Mei Zhou Jing Zhang Youwei Li Yujing Liu Xiansheng Ye Xiaoli Xu Binlian Sun Xiji Shu Wei Liu |
| author_sort | Rong Zhou |
| collection | DOAJ |
| description | Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from <i>Terminalia chebula</i> has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans. |
| first_indexed | 2024-03-09T15:59:56Z |
| format | Article |
| id | doaj.art-07408ea6407a4cc1a6cf04f5bd48cab7 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T15:59:56Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-07408ea6407a4cc1a6cf04f5bd48cab72023-11-24T17:10:29ZengMDPI AGNutrients2072-66432022-12-011424539010.3390/nu14245390Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic StrokeRong Zhou0Kuan Lin1Changlong Leng2Mei Zhou3Jing Zhang4Youwei Li5Yujing Liu6Xiansheng Ye7Xiaoli Xu8Binlian Sun9Xiji Shu10Wei Liu11Wuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaWuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, ChinaExcessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from <i>Terminalia chebula</i> has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans.https://www.mdpi.com/2072-6643/14/24/5390ischemic strokeChebulic acidNrf2neuroprotectionantioxidants |
| spellingShingle | Rong Zhou Kuan Lin Changlong Leng Mei Zhou Jing Zhang Youwei Li Yujing Liu Xiansheng Ye Xiaoli Xu Binlian Sun Xiji Shu Wei Liu Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke Nutrients ischemic stroke Chebulic acid Nrf2 neuroprotection antioxidants |
| title | Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke |
| title_full | Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke |
| title_fullStr | Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke |
| title_full_unstemmed | Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke |
| title_short | Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke |
| title_sort | chebulic acid prevents hypoxia insult via nrf2 are pathway in ischemic stroke |
| topic | ischemic stroke Chebulic acid Nrf2 neuroprotection antioxidants |
| url | https://www.mdpi.com/2072-6643/14/24/5390 |
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