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

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• 作者：Tilak Khanal ; Hyung Gyun Kim ; Minh Truong Do ; Jae Ho Choi ; Young Chul Chung ; Hee Suk Kim ; Youn-Joon Park ; Tae Cheon Jeong ; Hye Gwang Jeong
• 关键词：Genipin ; COX-2 ; NF-魏B ; AP-1 ; NOX
• 刊名：Food and Chemical Toxicology
• 出版年：February, 2014
• 年：2014
• 卷：64
• 期：Complete
• 页码：126-134
• 全文大小：897 K

文摘

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 E₂ (PGE₂), 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-魏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-魏B and AP-1 activation. These results suggest that the molecular mechanism mediating ROS-dependent COX-2 up-regulation and PGE₂ production by genipin involves activation of Akt, MAPKs and AP-1/NF-魏B.