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Article: Neuroprotective effect of cajaninstilbene acid against cerebral ischemia and reperfusion damages by activating AMPK/Nrf2 pathway
Title | Neuroprotective effect of cajaninstilbene acid against cerebral ischemia and reperfusion damages by activating AMPK/Nrf2 pathway |
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Authors | |
Keywords | Neuroprotection Cajaninstilbene acid Nrf2 AMP-activated protein kinase Ischemic stroke |
Issue Date | 2020 |
Publisher | Elsevier: Open Access Journals. The Journal's web site is located at https://www.journals.elsevier.com/journal-of-advanced-research/ |
Citation | Journal of Advanced Research, 2020, Epub 2020-07-23 How to Cite? |
Abstract | Introduction and Objectives:
Neuroprotection is an important strategy for ischemic stroke treatment. Cajaninstilbene acid (CSA), a unique stilbenoid with a styryl group, is a potential neuroprotective agent. Hence, t his study aimed to evaluate the neuroprotective effect and molecular mechanism of CSA against cerebral ischemia/reperfusion (I/R) damages.
Methods:
Cerebral ischemia was modeled by oxygen and glucose deprivation (OGD) in SH-SY5Y cells or transient intraluminal suture middle cerebral artery occlusion (MCAO) in rats, and tert-butyl hydroperoxide (t-BHP) was used to induce oxidative stress in SH-SY5Y cells. CSA (2.5, 5 mg/kg) was intraperitoneally given upon reperfusion after 2 h of MCAO. The signaling pathways were analyzed by Western blotting and inhibitor blocking.
Results:
CSA possessed significant neuroprotective activity, as evidenced by the reduced cell death in OGD/R or t-BHP injured SH-SY5Y cells, and decreased infarct volume and neurological deficits in MCAO/R rats. Further studies indicated that the protective effect was achieved via the antioxidant activity of CSA, which decreased the oxidative stress and its related mitochondrial dysfunction in SH-SY5Y cells. Notably, Nrf2 was activated in SH-SY5Y cells and MCAO/R rats by CSA, and the inhibition of Nrf2 by brusatol weakened CSA-mediated neuroprotection . Furthermore, after applying a series of kinase inhibitors, CSA-induced Nrf2 activation was markedly inhibited by BML-275 (an AMPK inhibitor) , implying that AMPK was the dominant kinase to regulate the Nrf2 pathway for CSA’s neuroprotective effects with enhanced AMPK phosphorylation observed both in vivo and in vitro.
Conclusion:
CSA exerted neuroprotection via activating the AMPK/Nrf2 pathway to reduce I/R-induced cellular oxidative stress and mitochondrial disfunction. CSA could be a potential neuroprotective drug candidate for the treatment of ischemic stroke. |
Persistent Identifier | http://hdl.handle.net/10722/293626 |
ISSN | 2023 Impact Factor: 11.4 2023 SCImago Journal Rankings: 1.905 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | XU, H | - |
dc.contributor.author | Shen, J | - |
dc.contributor.author | Xiao, J | - |
dc.contributor.author | Chen, F | - |
dc.contributor.author | Wang, M | - |
dc.date.accessioned | 2020-11-23T08:19:30Z | - |
dc.date.available | 2020-11-23T08:19:30Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Journal of Advanced Research, 2020, Epub 2020-07-23 | - |
dc.identifier.issn | 2090-1232 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293626 | - |
dc.description.abstract | Introduction and Objectives: Neuroprotection is an important strategy for ischemic stroke treatment. Cajaninstilbene acid (CSA), a unique stilbenoid with a styryl group, is a potential neuroprotective agent. Hence, t his study aimed to evaluate the neuroprotective effect and molecular mechanism of CSA against cerebral ischemia/reperfusion (I/R) damages. Methods: Cerebral ischemia was modeled by oxygen and glucose deprivation (OGD) in SH-SY5Y cells or transient intraluminal suture middle cerebral artery occlusion (MCAO) in rats, and tert-butyl hydroperoxide (t-BHP) was used to induce oxidative stress in SH-SY5Y cells. CSA (2.5, 5 mg/kg) was intraperitoneally given upon reperfusion after 2 h of MCAO. The signaling pathways were analyzed by Western blotting and inhibitor blocking. Results: CSA possessed significant neuroprotective activity, as evidenced by the reduced cell death in OGD/R or t-BHP injured SH-SY5Y cells, and decreased infarct volume and neurological deficits in MCAO/R rats. Further studies indicated that the protective effect was achieved via the antioxidant activity of CSA, which decreased the oxidative stress and its related mitochondrial dysfunction in SH-SY5Y cells. Notably, Nrf2 was activated in SH-SY5Y cells and MCAO/R rats by CSA, and the inhibition of Nrf2 by brusatol weakened CSA-mediated neuroprotection . Furthermore, after applying a series of kinase inhibitors, CSA-induced Nrf2 activation was markedly inhibited by BML-275 (an AMPK inhibitor) , implying that AMPK was the dominant kinase to regulate the Nrf2 pathway for CSA’s neuroprotective effects with enhanced AMPK phosphorylation observed both in vivo and in vitro. Conclusion: CSA exerted neuroprotection via activating the AMPK/Nrf2 pathway to reduce I/R-induced cellular oxidative stress and mitochondrial disfunction. CSA could be a potential neuroprotective drug candidate for the treatment of ischemic stroke. | - |
dc.language | eng | - |
dc.publisher | Elsevier: Open Access Journals. The Journal's web site is located at https://www.journals.elsevier.com/journal-of-advanced-research/ | - |
dc.relation.ispartof | Journal of Advanced Research | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Neuroprotection | - |
dc.subject | Cajaninstilbene acid | - |
dc.subject | Nrf2 | - |
dc.subject | AMP-activated protein kinase | - |
dc.subject | Ischemic stroke | - |
dc.title | Neuroprotective effect of cajaninstilbene acid against cerebral ischemia and reperfusion damages by activating AMPK/Nrf2 pathway | - |
dc.type | Article | - |
dc.identifier.email | Shen, J: shenjg@hku.hk | - |
dc.identifier.email | Wang, M: mfwang@hku.hk | - |
dc.identifier.authority | Shen, J=rp00487 | - |
dc.identifier.authority | Wang, M=rp00800 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.jare.2020.07.011 | - |
dc.identifier.scopus | eid_2-s2.0-85089259679 | - |
dc.identifier.hkuros | 319921 | - |
dc.identifier.volume | Epub 2020-07-23 | - |
dc.identifier.isi | WOS:000728551300004 | - |
dc.publisher.place | Netherlands | - |