title: Okanin, effective constituent of the flower tea Coreopsis tinctoria, attenuates LPS-induced microglial activation through inhibition of the TLR4/NF-κB signaling pathways.
abstract: The EtOAc extract of Coreopsis tinctoria Nutt. significantly inhibited LPS-induced nitric oxide (NO) production, as judged by the Griess reaction, and attenuated the LPS-induced elevation in iNOS, COX-2, IL-1β, IL-6 and TNF-α mRNA levels, as determined by quantitative real-time PCR, when incubated with BV-2 microglial cells. Immunohistochemical results showed that the EtOAc extract significantly decreased the number of Iba-1-positive cells in the hippocampal region of LPS-treated mouse brains. The major effective constituent of the EtOAc extract, okanin, was further investigated. Okanin significantly suppressed LPS-induced iNOS expression and also inhibited IL-6 and TNF-α production and mRNA expression in LPS-stimulated BV-2 cells. Western blot analysis indicated that okanin suppressed LPS-induced activation of the NF-κB signaling pathway by inhibiting the phosphorylation of IκBα and decreasing the level of nuclear NF-κB p65 after LPS treatment. Immunofluorescence staining results showed that okanin inhibited the translocation of the NF-κB p65 subunit from the cytosol to the nucleus. Moreover, okanin significantly inhibited LPS-induced TLR4 expression in BV-2 cells. In summary, okanin attenuates LPS-induced activation of microglia. This effect may be associated with its capacity to inhibit the TLR4/NF-κB signaling pathways. These results suggest that okanin may have potential as a nutritional preventive strategy for neurodegenerative disorders.
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hou
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
authors.forename: Guoxun
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, China.
authors.forename: Yingni
authors.initials: Y
authors.lastname: Pan
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jiao
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D031945:Coreopsis / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D047188:Chalcones; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C550307:okanin; D052247:Nitric Oxide Synthase Type II