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- Publisher Website: 10.1016/j.freeradbiomed.2020.06.034
- Scopus: eid_2-s2.0-85090409669
- PMID: 32784031
- WOS: WOS:000594647200001
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Article: Rehmapicroside ameliorates cerebral ischemia-reperfusion injury via attenuating peroxynitrite-mediated mitophagy activation
Title | Rehmapicroside ameliorates cerebral ischemia-reperfusion injury via attenuating peroxynitrite-mediated mitophagy activation |
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Authors | |
Keywords | Rehmapicroside Ischemic stroke Peroxynitrite Drp1 Mitophagy |
Issue Date | 2020 |
Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed |
Citation | Free Radical Biology & Medicine, 2020, v. 160, p. 526-539 How to Cite? |
Abstract | Peroxynitrite (ONOO−)-mediated mitophagy activation represents a vital pathogenic mechanism in ischemic stroke. Our previous study suggests that ONOO− mediates Drp1 recruitment to the damaged mitochondria for excessive mitophagy, aggravating cerebral ischemia/reperfusion injury and the ONOO−-mediated mitophagy activation could be a crucial therapeutic target for improving outcome of ischemic stroke. In the present study, we tested the neuroprotective effects of rehmapicroside, a natural compound from a medicinal plant, on inhibiting ONOO−-mediated mitophagy activation, attenuating infarct size and improving neurological functions by using the in vitro cultured PC12 cells exposed to oxygen glucose deprivation with reoxygenation (OGD/RO) condition and the in vivo rat model of middle cerebral artery occlusion (MCAO) for 2 h of transient cerebral ischemia plus 22 h of reperfusion. The major discoveries include following aspects: (1) Rehmapicroside reacted with ONOO− directly to scavenge ONOO−; (2) Rehmapicroside decreased O2− and ONOO−, up-regulated Bcl-2 but down-regulated Bax, Caspase-3 and cleaved Caspase-3, and down-regulated PINK1, Parkin, p62 and the ratio of LC3-II to LC3-I in the OGD/RO-treated PC12 cells; (3) Rehmapicroside suppressed 3-nitrotyrosine formation, Drp1 nitration as well as NADPH oxidases and iNOS expression in the ischemia-reperfused rat brains; (4) Rehmapicroside prevented the translocations of PINK1, Parkin and Drp1 into the mitochondria for mitophagy activation in the ischemia-reperfused rat brains; (5) Rehmapicroside ameliorated infarct sizes and improved neurological deficit scores in the rats with transient MCAO cerebral ischemia. Taken together, rehmapicroside could be a potential drug candidate against cerebral ischemia-reperfusion injury, and its neuroprotective mechanisms could be attributed to inhibiting the ONOO−-mediated mitophagy activation. |
Persistent Identifier | http://hdl.handle.net/10722/293741 |
ISSN | 2023 Impact Factor: 7.1 2023 SCImago Journal Rankings: 1.752 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhang, Y | - |
dc.contributor.author | HE, Y | - |
dc.contributor.author | WU, M | - |
dc.contributor.author | Chen, H | - |
dc.contributor.author | ZHANG, L | - |
dc.contributor.author | Yang, D | - |
dc.contributor.author | Wang, Q | - |
dc.contributor.author | Shen, J | - |
dc.date.accessioned | 2020-11-23T08:21:09Z | - |
dc.date.available | 2020-11-23T08:21:09Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Free Radical Biology & Medicine, 2020, v. 160, p. 526-539 | - |
dc.identifier.issn | 0891-5849 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293741 | - |
dc.description.abstract | Peroxynitrite (ONOO−)-mediated mitophagy activation represents a vital pathogenic mechanism in ischemic stroke. Our previous study suggests that ONOO− mediates Drp1 recruitment to the damaged mitochondria for excessive mitophagy, aggravating cerebral ischemia/reperfusion injury and the ONOO−-mediated mitophagy activation could be a crucial therapeutic target for improving outcome of ischemic stroke. In the present study, we tested the neuroprotective effects of rehmapicroside, a natural compound from a medicinal plant, on inhibiting ONOO−-mediated mitophagy activation, attenuating infarct size and improving neurological functions by using the in vitro cultured PC12 cells exposed to oxygen glucose deprivation with reoxygenation (OGD/RO) condition and the in vivo rat model of middle cerebral artery occlusion (MCAO) for 2 h of transient cerebral ischemia plus 22 h of reperfusion. The major discoveries include following aspects: (1) Rehmapicroside reacted with ONOO− directly to scavenge ONOO−; (2) Rehmapicroside decreased O2− and ONOO−, up-regulated Bcl-2 but down-regulated Bax, Caspase-3 and cleaved Caspase-3, and down-regulated PINK1, Parkin, p62 and the ratio of LC3-II to LC3-I in the OGD/RO-treated PC12 cells; (3) Rehmapicroside suppressed 3-nitrotyrosine formation, Drp1 nitration as well as NADPH oxidases and iNOS expression in the ischemia-reperfused rat brains; (4) Rehmapicroside prevented the translocations of PINK1, Parkin and Drp1 into the mitochondria for mitophagy activation in the ischemia-reperfused rat brains; (5) Rehmapicroside ameliorated infarct sizes and improved neurological deficit scores in the rats with transient MCAO cerebral ischemia. Taken together, rehmapicroside could be a potential drug candidate against cerebral ischemia-reperfusion injury, and its neuroprotective mechanisms could be attributed to inhibiting the ONOO−-mediated mitophagy activation. | - |
dc.language | eng | - |
dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed | - |
dc.relation.ispartof | Free Radical Biology & Medicine | - |
dc.subject | Rehmapicroside | - |
dc.subject | Ischemic stroke | - |
dc.subject | Peroxynitrite | - |
dc.subject | Drp1 | - |
dc.subject | Mitophagy | - |
dc.title | Rehmapicroside ameliorates cerebral ischemia-reperfusion injury via attenuating peroxynitrite-mediated mitophagy activation | - |
dc.type | Article | - |
dc.identifier.email | Yang, D: yangdan@hku.hk | - |
dc.identifier.email | Shen, J: shenjg@hku.hk | - |
dc.identifier.authority | Yang, D=rp00825 | - |
dc.identifier.authority | Shen, J=rp00487 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.freeradbiomed.2020.06.034 | - |
dc.identifier.pmid | 32784031 | - |
dc.identifier.scopus | eid_2-s2.0-85090409669 | - |
dc.identifier.hkuros | 319907 | - |
dc.identifier.volume | 160 | - |
dc.identifier.spage | 526 | - |
dc.identifier.epage | 539 | - |
dc.identifier.isi | WOS:000594647200001 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0891-5849 | - |