Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1
The beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the ap...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.946668/full |
| _version_ | 1797995341700661248 |
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| author | Qing Gao Hao Deng Zhengfei Yang Qiuyue Yang Yilin Zhang Xiaopeng Yuan Miao Zeng Maojuan Guo Wenyun Zeng Xijuan Jiang Bin Yu |
| author_facet | Qing Gao Hao Deng Zhengfei Yang Qiuyue Yang Yilin Zhang Xiaopeng Yuan Miao Zeng Maojuan Guo Wenyun Zeng Xijuan Jiang Bin Yu |
| author_sort | Qing Gao |
| collection | DOAJ |
| description | The beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the apoptosis rate following exposure to an oxygen-glucose deprivation/reoxygenation (OGD) environment. In addition, the results of a HuprotTM human protein microarray and network pharmacology indicated that AKT1 is one of the main targets of SDSS. Moreover, functional experiments showed that SDSS intervention markedly increased the phosphorylation level of AKT1 and its downstream regulator, mTOR. The binding sites of SDSS to AKT1 protein were confirmed by Autodock software and a surface plasmon resonance experiment, the result of which imply that SDSS targets to the PH domain of AKT1 at ASN-53, ARG-86, and LYS-14 residues. Furthermore, knockdown of AKT1 significantly abolished the role of SDSS in protecting cells from apoptosis and necrosis. Finally, we investigated the curative effect of SDSS in a rat model of CIRI. The results suggest that administration of SDSS significantly reduces CIRI-induced necrosis and apoptosis in brain samples by activating AKT1 protein. In conclusion, SDSS exerts its positive role in alleviating CIRI by binding to the PH domain of AKT1 protein, further resulting in AKT1 activation. |
| first_indexed | 2024-04-11T10:00:05Z |
| format | Article |
| id | doaj.art-ec76b24ce8bd4789abd77479c5e8f4b8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T10:00:05Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ec76b24ce8bd4789abd77479c5e8f4b82022-12-22T04:30:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.946668946668Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1Qing Gao0Hao Deng1Zhengfei Yang2Qiuyue Yang3Yilin Zhang4Xiaopeng Yuan5Miao Zeng6Maojuan Guo7Wenyun Zeng8Xijuan Jiang9Bin Yu10School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaTianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCollege of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaShenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInternational Exchanges Department and International Education College, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaThe beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the apoptosis rate following exposure to an oxygen-glucose deprivation/reoxygenation (OGD) environment. In addition, the results of a HuprotTM human protein microarray and network pharmacology indicated that AKT1 is one of the main targets of SDSS. Moreover, functional experiments showed that SDSS intervention markedly increased the phosphorylation level of AKT1 and its downstream regulator, mTOR. The binding sites of SDSS to AKT1 protein were confirmed by Autodock software and a surface plasmon resonance experiment, the result of which imply that SDSS targets to the PH domain of AKT1 at ASN-53, ARG-86, and LYS-14 residues. Furthermore, knockdown of AKT1 significantly abolished the role of SDSS in protecting cells from apoptosis and necrosis. Finally, we investigated the curative effect of SDSS in a rat model of CIRI. The results suggest that administration of SDSS significantly reduces CIRI-induced necrosis and apoptosis in brain samples by activating AKT1 protein. In conclusion, SDSS exerts its positive role in alleviating CIRI by binding to the PH domain of AKT1 protein, further resulting in AKT1 activation.https://www.frontiersin.org/articles/10.3389/fphar.2022.946668/fullsodium danshensucerebral ischemic reperfusion injuryAKT1drug targetprotein array analysis |
| spellingShingle | Qing Gao Hao Deng Zhengfei Yang Qiuyue Yang Yilin Zhang Xiaopeng Yuan Miao Zeng Maojuan Guo Wenyun Zeng Xijuan Jiang Bin Yu Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 Frontiers in Pharmacology sodium danshensu cerebral ischemic reperfusion injury AKT1 drug target protein array analysis |
| title | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
| title_full | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
| title_fullStr | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
| title_full_unstemmed | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
| title_short | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
| title_sort | sodium danshensu attenuates cerebral ischemia reperfusion injury by targeting akt1 |
| topic | sodium danshensu cerebral ischemic reperfusion injury AKT1 drug target protein array analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.946668/full |
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