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Int. J. Mol. Sci. 2016, 17(4), 529; doi:10.3390/ijms17040529

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

1
Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea
2
College of Medical and Life Sciences, Silla University, Busan 46958, Korea
3
Korea Polar Research Institute, KORDI, Yeonsu-gu, Incheon 21990, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Katalin Prokai-Tatrai
Received: 29 February 2016 / Revised: 18 March 2016 / Accepted: 25 March 2016 / Published: 8 April 2016
(This article belongs to the Special Issue Neuroprotective Strategies 2016)
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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. View Full-Text
Keywords: TMC-256C1; Aspergillus; marine fungus; neuroprotective effect; anti-neuroinflammatory effect; heme oxygenase-1 (HO-1) TMC-256C1; Aspergillus; marine fungus; neuroprotective effect; anti-neuroinflammatory effect; heme oxygenase-1 (HO-1)
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Kim, D.-C.; Cho, K.-H.; Ko, W.; Yoon, C.-S.; Sohn, J.H.; Yim, J.H.; Kim, Y.-C.; Oh, H. 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. Int. J. Mol. Sci. 2016, 17, 529.

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