Caffeic acid phenethyl ester-mediated Nrf2 activation and I kappa B kinase inhibition are involved in NF kappa B inhibitory effect: Structural analysis for NF kappa B inhibition

Title
Caffeic acid phenethyl ester-mediated Nrf2 activation and I kappa B kinase inhibition are involved in NF kappa B inhibitory effect: Structural analysis for NF kappa B inhibition
Author(s)
곽미경Youna Lee[Youna Lee]신동하[신동하]Ji-Hye Kim[Ji-Hye Kim]Sungchae Hong[Sungchae Hong]Daekyu Choi[Daekyu Choi]Yung-Jin Kim[Yung-Jin Kim]정연진[정연진]
Keywords
EPITHELIAL-CELLS; INFLAMMATORY RESPONSES; SIGNALING PATHWAY; ALPHA; EXPRESSION; REGULATOR; CAPE; INDUCTION; APOPTOSIS; COMPLEX
Issue Date
201009
Publisher
ELSEVIER SCIENCE BV
Citation
EUROPEAN JOURNAL OF PHARMACOLOGY, v.643, no.1, pp.21 - 28
Abstract
Caffeic acid phenethyl ester (CAPE) is an active component of propolis from honeybee. We investigated potential molecular mechanisms underlying CAPE-mediated nuclear factor kappa beta (NF kappa B) inhibition and analyzed structure of CAPE for its biological effect. CAPE attenuated expression of NF kappa B dependent luciferase stimulated with TNF-alpha or LPS and suppressed LPS-mediated induction of iNOS, a target gene product of NF kappa B. In HCT116 cells, CAPE interfered with TNF-alpha dependent I kappa B alpha degradation and subsequent nuclear accumulation of p65, which occurred by direct inhibition of inhibitory protein kappaB kinase (IKK). CAPE increased the expression of Nrf2-dependent luciferase and heme oxygenase-1, a target gene of Nrf2, and elevated the nuclear level of Nrf2 protein, indicating that CAPE activated the Nrf2 pathway. In HCT116 cells with stable expression of Nrf2 shRNA, CAPE elicited a reduced inhibitory effect on TNF-alpha-activated NF kappa B compared to scramble RNA expressing control cells. On the other hand, the NF kappa B inhibitory effect of CAPE was diminished by removal or modification of the Michael reaction acceptor, catechol or phenethyl moiety in CAPE. These data suggest that CAPE inhibits TNF-alpha-dependent NF kappa B activation via direct inhibition of IKK as well as activation of Nrf2 pathway, in which the functional groups in CAPE may be involved. (C) 2010 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/23696http://dx.doi.org/10.1016/j.ejphar.2010.06.016
ISSN
0014-2999
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약학대학 > 약학부 > Articles
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