Biochanin A Alleviates Cerebral Ischemia/Reperfusion Injury by Suppressing Endoplasmic Reticulum Stress-Induced Apoptosis and p38MAPK Signaling Pathway In Vivo and In Vitro.
Biochanin A Alleviates Cerebral Ischemia/Reperfusion Injury by Suppressing Endoplasmic Reticulum Stress-Induced Apoptosis and p38MAPK Signaling Pathway In Vivo and In Vitro.
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Biochanin A 通过抑制体内外内质网应激诱导的细胞凋亡和 p38MAPK 信号通路减轻脑缺血/再灌注损伤
DOI：
10.3389/fendo.2021.646720
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发表时间：
2021
影响因子：
5.2
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Guo MM;Qu SB;Lu HL;Wang WB;He ML;Su JL;Chen J;Wang Y
我们以前已经表明鹰嘴豆芽素A在脑缺血/再灌注（I/R）损伤的背景下表现出神经保护特性。然而，这些性质的机械基础仍然知之甚少。因此，本研究的目的是探讨鹰嘴豆芽素A控制内质网（ER）的压力，细胞凋亡，并在胎鼠原代皮层神经元内的炎症反应的氧-葡萄糖剥夺/复氧（OGD/R）损伤的方式，并在大脑中动脉闭塞和再灌注（MCAO/R）损伤的大鼠模型。对于OGD/R体外模型系统，在24 h复氧期后2 h OGD后评价细胞，而在2 h缺血和24 h再灌注后评价体内神经功能缺损。在这些样品中评估与细胞凋亡、ER应激（ERS）和p38 MAPK磷酸化相关的蛋白质的表达。在MCAO/R损伤后，用鹰嘴豆芽素A治疗的大鼠相对于对照大鼠表现出减少的神经功能缺损。此外，GRP 78和CHOP水平在体外和体内I/R建模后升高，而鹰嘴豆芽素A治疗与CHOP水平降低但GRP 78水平进一步升高相关。此外，OGD/R或MCAO/R与显著增强的p38 MAPK磷酸化相关，而鹰嘴豆芽素A治疗可减轻p38 MAPK磷酸化。类似地，OGD/R或MCAO/R损伤导致caspase-3、caspase-12和Bax水平增加以及Bcl-2水平降低，而鹰嘴豆芽素A处理足以逆转这些表型。总之，这些发现表明鹰嘴豆芽素A可以减轻脑I/R诱导的损伤，至少部分通过抑制细胞凋亡，ER应激，和p38 MAPK信号，从而作为一个有效的神经保护剂。
We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R in vitro model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas in vivo neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both in vitro and in vivo, whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part via suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.
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影响因子：
4.8
作者：
Morishima, N;Nakanishi, K;Yasuhiko, Y
通讯作者：
Yasuhiko, Y
内质网应激在人类病理学中的作用。
DOI：
10.1146/annurev-pathol-012513-104649
发表时间：
2015
期刊：
Annual review of pathology
影响因子：
--
作者：
Oakes SA;Papa FR
通讯作者：
Papa FR
影响因子：
7.2
作者：
Garcia de la Cadena, Selene;Hernandez-Fonseca, Karla;Massieu, Lourdes
通讯作者：
Massieu, Lourdes
影响因子：
5.8
作者：
Kalogeris T;Baines CP;Krenz M;Korthuis RJ
通讯作者：
Korthuis RJ
影响因子：
4.3
作者：
Casas C
通讯作者：
Casas C