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

• Published in: International journal of molecular sciences Vol. 17; no. 4; p. 529
• Main Authors: Kim, Dong-Cheol, Cho, Kwang-Ho, Ko, Wonmin, Yoon, Chi-Su, Sohn, Jae Hak, Yim, Joung Han, Kim, Youn-Chul, Oh, Hyuncheol
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.04.2016; MDPI
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; anti-neuroinflammatory effect; Aspergillus; Aspergillus - chemistry; Cell Line; Cell Survival - drug effects; Cells; Chromones - chemistry; Chromones - isolation & purification; Chromones - pharmacology; Fungi; heme oxygenase-1 (HO-1); Heme Oxygenase-1 - analysis; Heme Oxygenase-1 - immunology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - immunology; Inflammatory diseases; Lipopolysaccharides - immunology; Marine biology; marine fungus; Mice; Microglia - cytology; Microglia - drug effects; Microglia - immunology; Neuroprotective Agents - chemistry; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; neuroprotective effect; NF-E2-Related Factor 2 - immunology; Oxygen; p38 Mitogen-Activated Protein Kinases - immunology; Phosphatidylinositol 3-Kinases - immunology; Proto-Oncogene Proteins c-akt - immunology; Reactive Oxygen Species - immunology; Signal Transduction - drug effects; TMC-256C1; Up-Regulation - drug effects; heme oxygenase-1 (HO-1); Aspergillus; TMC-256C1; marine fungus; neuroprotective effect; anti-neuroinflammatory effect
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms17040529

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.