title: Senkyunolide I attenuates oxygen-glucose deprivation/reoxygenation-induced inflammation in microglial cells.
abstract: 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 3h followed by reoxygenation for 12h 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 NF-κB 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-κB pathway in rat primary microglial cells. The results suggested that SEI had a potent effect against stroke-induced neuroinflammation through suppressing the TLR4/NF-κB pathway by up-regulating Hsp70 dependent on HSF-1.
authors.affiliation: Engineering Research Center of Modern Preparation of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China; TCM syndrome and System Biology Research Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yang-Ye
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Engineering Research Center of Modern Preparation of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Engineering Research Center of Modern Preparation of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai, China.
authors.forename: Xue-Li
authors.initials: XL
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai, China. Electronic address: lyfeng@simm.ac.cn.
authors.forename: Lin-Yin
authors.initials: LY
authors.lastname: Feng
authors.affiliation: Engineering Research Center of Modern Preparation of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: fyi_shutcm@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
keywords: HSF-1/Hsp70; Microglial cells; Oxygen-glucose deprivation/reoxygenation; Senkyunolide I; TLR4/NF-κB pathway