Baicalein attenuates caspase-independent cells death via inhibiting PARP-1 activation and AIF nuclear translocation in cerebral ischemia/reperfusion rats

Cerebral ischemia-reperfusion injury (CIRI) refers to the phenomenon that the ischemic injury of brain leads to the injury of brain cells, and ischemic injury is further aggravated after the recovery of blood reperfusion. In this study, we first constructed Oxygen and glucose deprivation/reoxygenation (OGD/R) injury model of PC12 cells, we found that the expression of LncRNA AK139328 in model cells was significantly increased through RT-qPCR. Subsequently, we interfered LncRNA AK139328 in model cells by plasmid transfection and found that interfering LncRNA AK139328 could significantly reduce the expression of inflammatory factors, including TNF a, IL-1β, IL-6, McP-1, and oxidative stress-related factors, including ROS, MDA, LDH, while the expressions of SOD and GSHPx were significantly increased. Flow cytometry was used to detect cell apoptosis, and apoptosisrelated proteins bcl-2, Bax, cleaved-caspase3 and cleaved PARP-1 were detected by western blot. Results show that interfering LncRNA AK139328 could reduce the apoptosis rate of OGD/R cells and the expression of Bax, cleaved caspase3 and cleaved PARP-1, while increasing the expression of bcl-2. Meanwhile, we found that after interfering LncRNA AK139328, the expressions of Nrf2, HO-1, NQO-1 and phosphorylated-P65 increased, while P65 showed no significant changes. This may be related to Nrf2/HO-1 and NF-κB signaling pathways. In a word, our study showed that interfering with LncRNA AK139328 can reduce cell inflammation and apoptosis in CIRI.

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Modulation of Preactivation of PPAR-βon Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion

PPAR Research ◽

10.1155/2012/209794 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Ge Kuang ◽

Qin He ◽

Yunmei Zhang ◽

Ruichun Zhuang ◽

Anling Xiang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Hippocampal Neurons ◽

Nuclear Translocation ◽

Ischemia Reperfusion Injury ◽

Neuroprotective Effect ◽

Ischemia Reperfusion ◽

Global Cerebral Ischemia ◽

Dependent Manner ◽

Neuroprotective Effects ◽

Cerebral Ischemia Reperfusion

The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-αwere increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-βwere significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-βagonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-βactivation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus.

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Inhibition of SENP6 restrains cerebral ischemia-reperfusion injury by regulating Annexin-A1 nuclear translocation-associated neuronal apoptosis

Theranostics ◽

10.7150/thno.60277 ◽

2021 ◽

Vol 11 (15) ◽

pp. 7450-7470

Author(s):

Qian Xia ◽

Meng Mao ◽

Zhen Zeng ◽

Zhenzhao Luo ◽

Yin Zhao ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Neuronal Apoptosis ◽

Nuclear Translocation ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Annexin A1 ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

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Baicalein ameliorated cerebral ischemia-reperfusion injury dependent on calpain 1/AIF pathway

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab222 ◽

2021 ◽

Author(s):

Shanshan Li ◽

Yaoshuai Zhang ◽

Lili Fei ◽

Yuhan Zhang ◽

Jinlong Pang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Nuclear Translocation ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Neurological Deficits ◽

Neuroprotective Activity ◽

Scutellaria Baicalensis Georgi ◽

Cerebral Ischemia Reperfusion

Abstract Cerebral ischemia-reperfusion (CIR) has become the leading cause of death and disability. Baicalein is a natural bioactive ingredient extracted from Scutellaria baicalensis Georgi and has neuroprotective activity. In our work, baicalein was found to reduce neurological deficits, brain water content, infarct area and neuronal death of rats induced by middle cerebral artery occlusion/reperfusion. In vitro, oxygen-glucose deprivation/reperfusion induced inordinate ROS production and apoptosis that could be reversed by baicalein. Our study revealed for the first time that baicalein has the potential to binds and inhibits the activity of calpain 1, thereby inhibiting AIF nuclear translocation. These findings demonstrated that baicalein protected against CIR injury via inhibiting AIF nuclear translocation by inhibiting calpain 1 activity.

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Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway

BioMed Research International ◽

10.1155/2016/2816056 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 39

Author(s):

Jia Liu ◽

Qianxue Chen ◽

Zhihong Jian ◽

Xiaoxing Xiong ◽

Lingmin Shao ◽

...

Keyword(s):

Cerebral Ischemia ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Coumarin Derivative ◽

Neural Cells ◽

Cerebral Ischemia Reperfusion ◽

Anti Inflammatory

Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R injury is not yet clear. Recent studies have demonstrated that TLR4/NF-κB signaling pathway takes part in the damaging inflammatory process of cerebral I/R injury. The present study aimed to investigate the effect of DAP on cerebral I/R injury in vivo and its possible mechanisms. DAP was administered before middle cerebral artery occlusion and reperfusion in mice. The neurological scores, cerebral infarct sizes, the levels of inflammatory cytokines, apoptotic neural cells, and the levels of TLR4, NF-κB p65, and IκBα were estimated. The results showed that an obvious improvement of neurological scores and infarct sizes was observed in DAP-treated mice after MCAO/R. DAP treatment decreased the overexpression of TNF-α, IL-1β, and IL-6 and attenuated neural cells apoptosis. Moreover, DAP treatment decreased the TLR4 expression, IκB-α degradation, and nuclear translocation of NF-κB. Taken together, our results suggested that DAP exerted neuroprotective and anti-inflammatory effects on cerebral I/R injury. The potential mechanism was involved in the inhibition of TLR4/NF-κB mediated inflammatory signaling pathway.

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12/15-Lipoxygenase inhibitor baicalein suppresses PPARγ expression and nuclear translocation induced by cerebral ischemia/reperfusion

Brain Research ◽

10.1016/j.brainres.2009.10.038 ◽

2010 ◽

Vol 1307 ◽

pp. 149-157 ◽

Cited By ~ 27

Author(s):

Yan-Wei Xu ◽

Li Sun ◽

Hao Liang ◽

Guo-Min Sun ◽

Yan Cheng

Keyword(s):

Cerebral Ischemia ◽

Nuclear Translocation ◽

Ischemia Reperfusion ◽

Lipoxygenase Inhibitor ◽

Cerebral Ischemia Reperfusion ◽

Pparγ Expression

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Electroacupuncture Could Regulate the NF-κB Signaling Pathway to Ameliorate the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/924541 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 12

Author(s):

Wen-yi Qin ◽

Yong Luo ◽

Ling Chen ◽

Tao Tao ◽

Yang Li ◽

...

Keyword(s):

Cerebral Ischemia ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Critical Role ◽

Artery Occlusion ◽

Sprague Dawley ◽

Inflammatory Injury ◽

Cerebral Ischemia Reperfusion

The activated nuclear factor-KappaB signaling pathway plays a critical role in inducing inflammatory injury. It has been reported that electroacupuncture could be an effective anti-inflammatory treatment. We aimed to explore the complex mechanism by which EA inhibits the activation of the NF-κB signal pathway and ameliorate inflammatory injury in the short term; the effects of NEMO Binding Domain peptide for this purpose were compared. Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats are in the study. The neurobehavioral scores, infarction volumes, and the levels of IL-1βand IL-13 were detected. NF-κB p65, IκBα, IKKα, and IKKβwere analyzed and the ability of NF-κB binding DNA was investigated. The EA treatment and the NBD peptide treatment both reduced infarct size, improved neurological scores, and regulated the levels of IL-1βand IL-13. The treatment reduced the expression of IKKαand IKKβand altered the expression of NF-κB p65 and IκBαin the cytoplasm and nucleus; the activity of NF-κB was effectively reduced. We conclude that EA treatment might interfere with the process of NF-κB nuclear translocation. And it also could suppress the activity of NF-κB signaling pathway to ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion.

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