Anti-neuroinflammatory effect of a novel caffeamide derivative, KS370G, in microglial cells.

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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Lu DY,Huang BR,Yeh WL,Lin HY,Huang SS,Liu YS,Kuo YH

doi

10.1007/s12035-013-8474-y

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

863-74

issue

3

eissn

0893-7648

issn

1559-1182

journal_volume

48

pub_type

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