Piperine inhibits PMA-induced cyclooxygenase-2 expression through downregulating NF-魏B, C/EBP and AP-1 signaling pathways in murine macrophages

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• 作者：Hyung Gyun Kim^a ; ¹ ; Eun Hee Han^a ; ¹ ; Woo-Seok Jang^a ; Jae Ho Choi^a ; Tilak Khanal^a ; Bong Hwan Park^a ; Thu Phuong Tran^a ; Young Chul Chung^b ; Hye Gwang Jeong^a ; ^{hgjeong@cnu.ac.kr}
• 关键词：PMA ; phorbol 12-myristate 13-acetate ; Cox-2 ; cyclooxygenase-2 ; NF-魏B ; nuclear factor-魏B ; C/EBP ; CCAAT/enhancer binding protein (C/EBP) ; AP-1 ; activator protein-1 ; PVDF ; polyvinylidene difluoride ; DMSO ; dimethyl sulfoxide ; SDS&ndash ; PAGE ; sodium dodecyl
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：July, 2012
• 卷：50
• 期：7
• 页码：2342-2348
• 文件大小：486 K

摘要

Piperine is a major component of black (Piper nigrum Linn) and long (Piper longum Linn) peppers, and is widely used as a traditional food and medicine. It also exhibits a variety of biological activities, which include antioxidant, anti-tumor and anti-pyretic properties. In the present study, we investigated the inhibitory effects of piperine on phorbol 12-myristate 13-acetate (PMA)-induced cyclooxygenase-2 (COX-2) gene expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. Piperine dose-dependently decreased PMA-induced COX-2 expression and PGE₂ production, as well as COX-2 promoter-driven luciferase activity. Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, revealed that the nuclear factor-魏B (NF-魏B), CCAAT/enhancer binding protein (C/EBP) and activator protein-1 (AP-1), were the predominant contributors to the effects of piperine. In addition, piperine inhibited PMA-induced NF-魏B, C/EBP and c-Jun nuclear translocation. Furthermore, piperine significantly inhibited PMA-induced activation of the Akt and ERK. These findings demonstrate that piperine effectively attenuates COX-2 production, and provide further insight into the signal transduction pathways involved in the anti-inflammatory effects of piperine.