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Anti-neuroinflammatory Effect of a Novel Caffeamide Derivative, KS370G, in Microglial cells

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Abstract

Accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in several neurodegenerative disorders. Therefore, development of methods for microglial inhibition is considered an important strategy in the search for neuroprotective agents. Caffeic acid phenethyl ester (CAPE) is distributed wildly in nature, but rapid decomposition by esterase leads to its low bioavailability. In this study, we investigated the effects of KS370G, a novel caffeic acid phenylethyl amide, on microglial activation. KS370G significantly inhibited the release of nitric oxide (NO) and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Treatment with KS370G also induced heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS)-3 expression in the microglia. Furthermore, the anti-inflammatory effects of KS370G were found to be regulated by phosphorylated adenosine monophosphate-activated protein kinase-α (AMPK-α) translocated to the nucleus. Moreover, KS370G showed significant anti-neuroinflammatory effects on microglial activation in vivo and on motor behavior as well. The protective effect of KS370G was weakened by an AMPK inhibitor Compound C. This study focuses on the importance of key molecular determinants of inflammatory homeostasis, AMPK, HO-1, and SOCS-3, and their possible involvement in anti-neuroinflammatory responses.

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Acknowledgments

This work was supported by grants from the National Science Council (NSC 101-2320-B-039-048-MY2) and Taichung Tzu Chi General Hospital (TTCRD 101–03). The authors thank Ms Y. R. Chen for technical support.

Conflict of interest

The authors report no biomedical financial interests or potential conflicts of interest.

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Authors and Affiliations

  1. Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan

    Dah-Yuu Lu & Yu-Shu Liu

  2. Department of Neurosurgery, Taichung Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taichung, Taiwan

    Bor-Ren Huang

  3. Cancer Research Center, Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan

    Wei-Lan Yeh

  4. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan

    Hsiao-Yun Lin

  5. Department of Pharmacology and Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Shiang-Suo Huang

  6. Tsuzuki Institute for Traditional Medicine, China Medical University, Taichung, Taiwan

    Yueh-Hsiung Kuo

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  1. Dah-Yuu Lu
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  2. Bor-Ren Huang
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  3. Wei-Lan Yeh
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  4. Hsiao-Yun Lin
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  5. Shiang-Suo Huang
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  6. Yu-Shu Liu
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  7. Yueh-Hsiung Kuo
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Corresponding authors

Correspondence to Dah-Yuu Lu or Yueh-Hsiung Kuo.

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Lu, DY., Huang, BR., Yeh, WL. et al. Anti-neuroinflammatory Effect of a Novel Caffeamide Derivative, KS370G, in Microglial cells. Mol Neurobiol 48, 863–874 (2013). https://doi.org/10.1007/s12035-013-8474-y

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  • DOI: https://doi.org/10.1007/s12035-013-8474-y

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