Over-activated microglia during stroke has been documented to aggravate brain damage. Our previous studies showed that senkyunolide I (SEI) exerted anti-inflammatory effects against endotoxin insult in vitro and ameliorative effects on cerebral ischemia/reperfusion (I/R) injury in vivo. Using oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic stroke, we here investigated the anti-inflammatory effect of SEI on microglial cells and explored the underlying mechanisms. OGD for 3 h followed by reoxygenation for 12 h significantly enhanced the release of pro-inflammatory cytokines and expressions of inflammation-related enzymes in BV-2 cells, which was inhibited by pretreatment with SEI. To elucidate the mechanisms, we studied its effect on upstream signaling pathways. It was found that SEI suppressed the activation of NE-kappa B pathway induced by OGD/R and the MAPK pathway was shown not to be involved. Furthermore, SEI significantly down-regulated TLR4/MyD88 pathway with specifically improving inducible Hsp70 level through increasing HSF-1/DNA binding activity, and these regulations responsive to SEI were attenuated by transfecting Hsp70 siRNA and HSF-1 decoy ODNs. Additionally, SEI exerted similar influence on Hsp70/TLR4/NF-kappa B pathway in rat primary microglial cells. The results suggested that SEI had a potent effect against stroke-induced neuroinflammation through suppressing the TLR4/NE-kappa B pathway by up-regulating Hsp70 dependent on HSF-1. (C) 2016 Elsevier B.V. All rights reserved.
[1]Shanghai Univ Tradit Chinese Med, Engn Res Ctr Modern Preparat TCM, Minist Educ, Shanghai, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, TCM Syndrome & Syst Biol Res Ctr, Shanghai, Peoples R China.
[3]Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China.
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