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: Dong-Cheol Kim, Kwang-Ho Cho, Wonmin Ko, Chi-Su Yoon, Jae Hak Sohn, Joung Han Yim, Youn-Chul Kim, Hyuncheol Oh
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 17 Issue 4 Pg. 529 (Apr 08 2016) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 27070586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Chromones
• Lipopolysaccharides
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Reactive Oxygen Species
• TMC 256C1
• Heme Oxygenase-1
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, isolation & purification, pharmacology)
• Aspergillus (chemistry)
• Cell Line
• Cell Survival (drug effects)
• Chromones (chemistry, isolation & purification, pharmacology)
• Heme Oxygenase-1 (analysis, immunology)
• Hippocampus (cytology, drug effects, immunology)
• Lipopolysaccharides (immunology)
• Mice
• Microglia (cytology, drug effects, immunology)
• NF-E2-Related Factor 2 (immunology)
• Neuroprotective Agents (chemistry, isolation & purification, pharmacology)
• Phosphatidylinositol 3-Kinases (immunology)
• Proto-Oncogene Proteins c-akt (immunology)
• Reactive Oxygen Species (immunology)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)
• p38 Mitogen-Activated Protein Kinases (immunology)