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Phytother Res. 2017 Sep;31(9):1410-1418. doi: 10.1002/ptr.5868. Epub 2017 Jul 28.

Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down-Regulating Connexin 43.

Author information

1
Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, No.12 Mid. Wulumuqi Road, Shanghai, 200040, China.
2
Department of Neurology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200336, China.

Abstract

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.

KEYWORDS:

aquaporin4; astragaloside IV; brain edema; cerebral ischemia; connexin43; paeoniflorin

PMID:
28752625
DOI:
10.1002/ptr.5868
[Indexed for MEDLINE]

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