期刊
FRONTIERS IN ENDOCRINOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.646720
关键词
Biochanin A; endoplasmic reticulum stress; apoptosis; p38MAPK; cerebral ischemia/reperfusion; oxygen-glucose deprivation/reoxygenation
资金
- National Natural Science Foundation of China [81560378, 81860231]
- Guangxi Natural Science Foundation [2018GXNSFAA050054, 2018GXNSFAA294138]
- Independent Research Project of Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation [203030301806]
- Scientific Research Ability Enhancement Project for Young and Middle-aged Faculty of GuilinMedical University [20502018006]
Our study demonstrates that biochanin A can alleviate cerebral I/R-induced damage by suppressing apoptosis, ER stress, and p38 MAPK signaling.
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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