Paeoniflorin (PF) and astragaloside IV (AS-IV) have protective effects on cerebral ischemia. We aimed to test the effects of combined use of PF and AS-IV on ischemic brain edema and investigate whether the effects were dependent on connexin43 (Cx43). We detected the expression of Cx43 induced by PF and AS-IV after cerebral ischemia. We also examined the effects of combined use of PF and AS-IV on ischemic edema and further investigated the related pathways. We demonstrated PF and AS-IV decreased Cx43 and aquaporin4 (AQP4) associating with reduction of brain edema by dry-wet weight and brain-specific gravity methods after cerebral ischemia. Administration of PF and AS-IV displayed a further attenuation of brain edema with lower Cx43 levels. Meanwhile, Cx43 blockade inhibited AQP4 down-regulation by the two drugs. Moreover, phosphorylation of C-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) were increased by PF and AS-IV, respectively. The effects of PF and AS-IV to down-regulate Cx43 were suppressed by JNK and ERK inhibitors, respectively. Our data indicate that PF and AS-IV alleviate ischemic brain edema, which has close relation to Cx43 down-regulation causing decrease of AQP4 via JNK and ERK pathways activation, respectively. Combined administration elicits synergistic effects on brain edema reduction. Copyright (c) 2017 John Wiley & Sons, Ltd.
基金:
National Basic Research Program (973 Program) of ChinaNational Basic Research Program of China [2012CB518602]; Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [16140903200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81171129, 81500998]
第一作者机构:[1]Fudan Univ, Huashan Hosp, Dept Neurol, State Key Lab Med Neurobiol, 12 Mid Wulumuqi Rd, Shanghai 200040, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Fudan Univ, Huashan Hosp, Dept Neurol, State Key Lab Med Neurobiol, 12 Mid Wulumuqi Rd, Shanghai 200040, Peoples R China[*1]Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai 200040, China.
推荐引用方式(GB/T 7714):
Chu Heling,Huang Chuyi,Gao Zidan,et al.Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down-Regulating Connexin 43[J].PHYTOTHERAPY RESEARCH.2017,31(9):1410-1418.doi:10.1002/ptr.5868.
APA:
Chu, Heling,Huang, Chuyi,Gao, Zidan,Dong, Jing,Tang, Yuping&Dong, Qiang.(2017).Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down-Regulating Connexin 43.PHYTOTHERAPY RESEARCH,31,(9)
MLA:
Chu, Heling,et al."Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down-Regulating Connexin 43".PHYTOTHERAPY RESEARCH 31..9(2017):1410-1418