title: Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus Aspergillus sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines.
abstract: In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus Aspergillus sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea. kimman07@hanmail.net.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea. zxzxguild@gmail.com.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea. rabis815@naver.com.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea. ycs1991@naver.com.
authors.forename: Chi-Su
authors.initials: CS
authors.lastname: Yoon
authors.affiliation: College of Medical and Life Sciences, Silla University, Busan 46958, Korea. jhsohn@silla.ac.kr.
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Korea Polar Research Institute, KORDI, Yeonsu-gu, Incheon 21990, Korea. jhyim@kopri.re.kr.
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea. yckim@wku.ac.kr.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea. hoh@wonkwang.ac.kr.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001230:Aspergillus / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000276:immunology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051267:NF-E2-Related Factor 2 / Q000276:immunology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D002867:Chromones; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C467210:TMC 256C1; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Aspergillus; TMC-256C1; anti-neuroinflammatory effect; heme oxygenase-1 (HO-1); marine fungus; neuroprotective effect