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

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 © 2017 John Wiley & Sons, Ltd.