title: Anti-neuroinflammatory effects of citreohybridonol involving TLR4-MyD88-mediated inhibition of NF-кB and MAPK signaling pathways in lipopolysaccharide-stimulated BV2 cells.
abstract: In the course of searching for anti-neuroinflammatory metabolites from marine fungi, citreohybridonol was isolated from marine-derived fungal strain Toxicocladosporium sp. SF-5699. Citreohybridonol inhibited production of nitric oxide (NO) and prostaglandin E2 (PGE2) in BV2 cells stimulated by lipopolysaccharide (LPS). Citreohybridonol also suppressed the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and other pro-inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the LPS-stimulated cells. In the further study, citreohybridonol disturbed nuclear translocation of nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells by inhibiting the phosphorylation of the inhibitor kappa B-α (IκB-α). Citreohybridonol also had inhibitory effect on the LPS-stimulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Finally, citreohybridonol suppressed the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS-induced BV2 cells. These results suggest that citreohybridonol has anti-neuroinflammatory effect in LPS-stimulated BV2 cells by modulating TLR4-mediated several inflammatory pathways such as NF-κB and p38 MAPK pathways.
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Chi-Su
authors.initials: CS
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Won Min
authors.initials: WM
authors.lastname: Ko
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: College of Medical and Life Sciences, Silla University, Busan, 617-736, Republic of Korea.
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongwon, Republic of Korea.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongwon, Republic of Korea.
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea; Hanbang Body-Fluid Research Center, Wonkwang University, Iksan, 570-749, Republic of Korea. Electronic address: yckim@wonkwang.ac.kr.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 570-749, Republic of Korea; Hanbang Body-Fluid Research Center, Wonkwang University, Iksan, 570-749, Republic of Korea. Electronic address: hoh@wonkwang.ac.kr.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000730:Androstadienes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C000607874:citreohybridonol
keywords: Anti-neuroinflammation; Citreohybridonol; Marine-derived fungus; Mitogen-activated protein kinase (MAPK); Nuclear factor-kappa B (NF-κB)