title: Baicalin attenuates proinflammatory cytokine production in oxygen-glucose deprived challenged rat microglial cells by inhibiting TLR4 signaling pathway.
abstract: Baicalin, a flavonoid compound isolated from Scutellariae radix, has been shown to possess a number of pharmacological effects. The aim of the present study was to observe the inhibitory effects of baicalin on the activation of microglial cells induced by oxygen-glucose deprivation (OGD) and the specific mechanisms by which these effects are mediated. Cultured rat primary microglial cells were exposed to baicalin at final concentrations of 10 μg/ml, 20 μg/ml and 40 μg/ml during 4h of OGD. The effects of baicalin on (i) cell viability; (ii) secretion of proinflammatory cytokines; (iii) Tlr4 mRNA expression; (iv) p-c-jun, p-ERK1/2, p-JNK, p-p38, TRAF6 and p-IκB-α levels; and (v) co-localization of TLR4 and MyD88 were evaluated using the Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assays (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), western blot and double-labeled immunofluorescence staining, respectively. OGD increased cell viability and release of TNF-α, IL-1β, IL-6 and IL-8, these effects were suppressed by baicalin. Baicalin also attenuated the OGD-induced increases in Tlr4 mRNA expression. In addition, high dose of baicalin reduced TRAF6 levels remarkably. Furthermore, baicalin also downregulated phosphorylation of IκB-α, c-jun, ERK1/2, JNK, p38 and inhibited the OGD-induced transfer of MyD88 from cytoplasm to membrane in microglial cells. The results show that baicalin can inhibit OGD-induced production of inflammatory factors in microglial cells by attenuating inflammatory factors and regulating the TLR4 signaling pathways.
authors.affiliation: Xiyuan Hospital of China Academy of Chinese Medical Sciences, 1 Xiyuan Caochang, Hai Dian District, Beijing 100091, China.
authors.forename: Jincai
authors.initials: J
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Cuixiang
authors.initials: C
authors.lastname: Zhang
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fu
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Jianxun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D005419:Flavonoids; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C038044:baicalin; D005947:Glucose; D010100:Oxygen