Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection
Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia m...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.748568/full |
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| author | Xiao-Di Fan Xiao-Di Fan Ming-Jiang Yao Ming-Jiang Yao Bin Yang Xiao Han Xiao Han Ye-Hao Zhang Ye-Hao Zhang Guang-Rui Wang Guang-Rui Wang Peng Li Peng Li Li Xu Li Xu Jian-Xun Liu Jian-Xun Liu |
| author_facet | Xiao-Di Fan Xiao-Di Fan Ming-Jiang Yao Ming-Jiang Yao Bin Yang Xiao Han Xiao Han Ye-Hao Zhang Ye-Hao Zhang Guang-Rui Wang Guang-Rui Wang Peng Li Peng Li Li Xu Li Xu Jian-Xun Liu Jian-Xun Liu |
| author_sort | Xiao-Di Fan |
| collection | DOAJ |
| description | Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT’s anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT’s therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection. |
| first_indexed | 2024-12-22T05:34:50Z |
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| language | English |
| last_indexed | 2024-12-22T05:34:50Z |
| publishDate | 2021-11-01 |
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| spelling | doaj.art-d1a0c168cb0644cd8fe7b74121a094d22022-12-21T18:37:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.748568748568Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular ProtectionXiao-Di Fan0Xiao-Di Fan1Ming-Jiang Yao2Ming-Jiang Yao3Bin Yang4Xiao Han5Xiao Han6Ye-Hao Zhang7Ye-Hao Zhang8Guang-Rui Wang9Guang-Rui Wang10Peng Li11Peng Li12Li Xu13Li Xu14Jian-Xun Liu15Jian-Xun Liu16Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaThe Department of Pathology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaInstitute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Pharmacology of Chinese Materia Medica, Beijing, ChinaStroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT’s anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT’s therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection.https://www.frontiersin.org/articles/10.3389/fphar.2021.748568/fullcerebral ischemiaSaiLuoTong capsulebrain microvascular endothelial cellsanti-oxidationnuclear factor–E2–related factor 2 |
| spellingShingle | Xiao-Di Fan Xiao-Di Fan Ming-Jiang Yao Ming-Jiang Yao Bin Yang Xiao Han Xiao Han Ye-Hao Zhang Ye-Hao Zhang Guang-Rui Wang Guang-Rui Wang Peng Li Peng Li Li Xu Li Xu Jian-Xun Liu Jian-Xun Liu Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection Frontiers in Pharmacology cerebral ischemia SaiLuoTong capsule brain microvascular endothelial cells anti-oxidation nuclear factor–E2–related factor 2 |
| title | Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection |
| title_full | Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection |
| title_fullStr | Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection |
| title_full_unstemmed | Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection |
| title_short | Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway–Dependent Cerebral Microvascular Protection |
| title_sort | chinese herbal preparation sailuotong alleviates brain ischemia via nrf2 antioxidation pathway dependent cerebral microvascular protection |
| topic | cerebral ischemia SaiLuoTong capsule brain microvascular endothelial cells anti-oxidation nuclear factor–E2–related factor 2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.748568/full |
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