Ginsenoside Rb1 reduced ischemic stroke-induced apoptosis through endoplasmic reticulum stress-associated IRE1/TRAF2/JNK pathway

被引:0
|
作者
Wei, Liangli [1 ]
Yuan, Yuqi [1 ]
Yang, Ziteng [2 ]
Li, Yuqing [1 ]
Wang, Tingting [2 ]
Hu, Shenglin [1 ]
Cai, Biao [1 ]
Wang, Guangyun [1 ]
机构
[1] Anhui Univ Chinese Med, Coll Integrated Chinese & Western Med, Coll Life Sci, Hefei 230012, Peoples R China
[2] Anhui Univ Chinese Med, Dept Pharm, Hefei 230012, Peoples R China
基金
中国国家自然科学基金;
关键词
Ginsenoside Rb1 (GRb1); IRE1/TRAF2/JNK pathway; Cerebral ischemia reperfusion; ER stress; Apoptosis; TRANSIENT CEREBRAL-ISCHEMIA; ISCHEMIA/REPERFUSION INJURY; BRAIN; NEUROPROTECTION; INHIBITION; PROTECTION; PROMOTION; AUTOPHAGY; DAMAGE; CELLS;
D O I
10.1007/s00210-024-03292-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The neuroprotective function of ginsenoside Rb1 (GRb1) in cerebral ischemia-reperfusion (I/R) was lately emphasized. However, whether GRb1 plays a regulatory role on endoplasmic reticulum (ER) stress-associated pathway in cerebral I/R damage is still unclear. The aim of this study is to explore the function of GRb1 in cerebral ischemia-induced ER stress and the underlying mechanism related to IRE1/TRAF2/JNK pathway. Longa method, cerebral infarct volume, and HE staining were used to evaluate the efficacy of GRb1 in mice with a mouse model of middle cerebral artery occlusion reperfusion (MCAO/R). We also investigated the effect and mechanism of GRb1 against ischemic stroke using in vitro oxygen-glucose deprivation reperfusion (OGD/R) model. We found that GRb1 could improve neurological scores, infarct volume, and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis and ER stress, and this effect was attenuated by GRb1. In addition, GRb1 significantly reduced I/R-induced IRE1-TRAF2 interaction, IRE1, and JNK phosphorylation. The present study also confirmed that GRb1 significantly improved OGD/R-induced PC12 cells injury. GRb1 could decrease ER stress in OGD/R-injured PC12 cells, which was reflected by the decreased expression of GRP78 and CHOP. The ER stress inducer tunicamycin partially prevented the effects of GRb1 on cell viability, ER stress, and apoptosis after OGD/R, whereas the ER stress inhibitor 4-PBA exerted the opposite effect. Moreover, GRb1 markedly decreased IRE1-TRAF2 interaction, IRE1, and JNK phosphorylation in the presence of OGD/R insult. Furthermore, JNK inhibitor SP600125 and IRE1 inhibitor DBSA pretreatment further promoted the inhibition of GRb1 on ER stress induction and cell damage induced by OGD/R. Molecular docking further elucidated that the mechanism by which GRb1 improves cerebral ischemia maybe related to its direct binding to the kinase domain of IRE1, which in turn inhibited the phosphorylation of IRE1. Collectively, these results demonstrated that GRb1 reduced ischemic stroke-induced apoptosis through the ER stress-associated IRE1/TRAF2/JNK pathway and GRb1 has the potential as a protective drug for the treatment of cerebral ischemia.
引用
收藏
页码:747 / 764
页数:18
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