Genipin induces cyclooxygenase-2 expression via NADPH oxidase, MAPKs, AP-1, and NF-kappa B in RAW 264.7 cells

Title
Genipin induces cyclooxygenase-2 expression via NADPH oxidase, MAPKs, AP-1, and NF-kappa B in RAW 264.7 cells
Author(s)
정태천T Khanal[T Khanal]김형균[김형균]MT Do[MT Do]정영철[정영철]김희숙[김희숙]박윤준[박윤준]정혜광[정혜광]최재호[최재호]
Keywords
ACTIVATED PROTEIN-KINASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; JUN NH2-TERMINAL KINASE; REACTIVE OXYGEN; SIGNAL-TRANSDUCTION; MEDIATED INDUCTION; PROSTAGLANDIN E-2; COX-2 EXPRESSION; NOX FAMILY; P38 MAPK
Issue Date
201402
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.64, pp.126 - 134
Abstract
Genipin is a compound found in gardenia fruit extract with diverse pharmacological activities. However, the mechanism underlying genipin-induced cyclooxygenase-2 (COX-2) expression remains unknown. In this study, we investigated the effects of genipin on COX-2 expression and determined that exposure to genipin dose-dependently enhanced the production of prostaglandin E-2 (PGE(2)), a major COX-2 metabolite, in RAW 264.7 cells. These effects were mediated by genipin-induced activation of the COX-2 promoter, as well as AP-1 and NF-kappa B luciferase constructs. Phosphatidylinositol-3-kinase/Akt and MAPKs were also significantly activated by genipin, and Akt and MAPKs inhibitors (PD98059, SB20358, SP600125, and LY294002) inhibited genipin-induced COX-2 expression. Moreover, genipin increased production of the ROS and the ROS-producing NAPDH-oxidase (NOX) family oxidases, NOX2 and NOX3. Inhibition of NADPH with diphenyleneiodonium attenuated ROS production, COX-2 expression and NF-kappa B and AP-1 activation. These results suggest that the molecular mechanism mediating ROS-dependent COX-2 up-regulation and PGE(2) production by genipin involves activation of Akt, MAPKs and AP-1/NF-kappa B. (C) 2013 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/33313http://dx.doi.org/10.1016/j.fct.2013.11.035
ISSN
0278-6915
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약학대학 > 약학부 > Articles
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