Cargando…

Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natur...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Fang, Chen, Ze-Ran, Yang, Xu-Hong, Xu, Yue, Ran, Ning-Jing, Liu, Mei-Jun, Jin, Shuo-Guo, Jia, Hua-Nan, Zhang, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606694/
https://www.ncbi.nlm.nih.gov/pubmed/36313310
http://dx.doi.org/10.3389/fphar.2022.1024439
_version_ 1784818353661018112
author Yang, Fang
Chen, Ze-Ran
Yang, Xu-Hong
Xu, Yue
Ran, Ning-Jing
Liu, Mei-Jun
Jin, Shuo-Guo
Jia, Hua-Nan
Zhang, Yang
author_facet Yang, Fang
Chen, Ze-Ran
Yang, Xu-Hong
Xu, Yue
Ran, Ning-Jing
Liu, Mei-Jun
Jin, Shuo-Guo
Jia, Hua-Nan
Zhang, Yang
author_sort Yang, Fang
collection PubMed
description Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines’ prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.
format Online
Article
Text
id pubmed-9606694
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96066942022-10-28 Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling Yang, Fang Chen, Ze-Ran Yang, Xu-Hong Xu, Yue Ran, Ning-Jing Liu, Mei-Jun Jin, Shuo-Guo Jia, Hua-Nan Zhang, Yang Front Pharmacol Pharmacology Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines’ prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9606694/ /pubmed/36313310 http://dx.doi.org/10.3389/fphar.2022.1024439 Text en Copyright © 2022 Yang, Chen, Yang, Xu, Ran, Liu, Jin, Jia and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yang, Fang
Chen, Ze-Ran
Yang, Xu-Hong
Xu, Yue
Ran, Ning-Jing
Liu, Mei-Jun
Jin, Shuo-Guo
Jia, Hua-Nan
Zhang, Yang
Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
title Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
title_full Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
title_fullStr Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
title_full_unstemmed Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
title_short Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
title_sort monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced shsy-5y cells in vitro via activation of pi3k/akt signaling
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606694/
https://www.ncbi.nlm.nih.gov/pubmed/36313310
http://dx.doi.org/10.3389/fphar.2022.1024439
work_keys_str_mv AT yangfang monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT chenzeran monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT yangxuhong monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT xuyue monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT ranningjing monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT liumeijun monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT jinshuoguo monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT jiahuanan monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling
AT zhangyang monomethyllithospermatealleviatesischemicstrokeinjuryinmiddlecerebralarteryocclusionmiceinvivoandprotectsoxygenglucosedeprivationreoxygenationinducedshsy5ycellsinvitroviaactivationofpi3kaktsignaling