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KMID : 1161420100130030691
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Journal of Medicinal Food
2010 Volume.13 No. 3 p.691 ~ p.699
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Anti-Inflammatory Activity of Angelica keiskei Through Suppression of Mitogen-Activated Protein Kinases and Nuclear Factor-κB Activation Pathways
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Lee Hyoung-Joo
Choi Tae-Won
Kim Hyun-Jung
Nam Dong-Woo
Jung Sang-Hoon
Lee Eun-Ha
Lee Hee-Ju
Shin Eun-Myoung
Jang Hyeung-Jin
Ahn Kyoo-Seok
Shim Bum-Sang
Choi Seung-Hoon
Kim Sung-Hoon
Sethi Gautam
Ahn Kwang-Seok
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Abstract
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Angelica keiskei has been shown to exhibit antitumor, antioxidant, and antidiabetic activities, and the fresh leaves and dry powder are used for health food. In spite of several beneficial effects, however, the molecular mechanism or mechanisms behind anti-inflammatory activities of A. keiskei remain unclear. Thus, we investigated the effects of A. keiskei on the activities of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We found that the n-hexane fraction of A. keiskei (HAK) significantly inhibited LPS-induced NO and prostaglandin E2 production and tumor necrosis factor-α secretion. HAK also inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNA levels. Furthermore, we hypothesize that anti-inflammatory effects by HAK can be linked to interference with the signaling pathway of mitogen-activated protein kinases (MAPKs) and the activation pathway of nuclear factor κB (NF-κB). HAK suppressed LPS-induced c-Jun NH2-terminal kinase, p38, and p44/p42 MAPK activation. We also found that the cell-based assay system showed that HAK suppressed LPS-induced NF-κB activity in transfectant RAW 264.7 cells. In addition, the electrophoretic mobility shift assay showed the same result as in the cell-based assay system. Our data suggest that the anti-inflammatory effect of HAK is mediated through down-modulation of iNOS and COX-2 gene products by blocking the signaling pathways of MAPKs and NF-κB.
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KEYWORD
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Angelica keiskei, cyclooxygenase-2, mitogen-activated protein kinases, nitric oxide, nuclear factor κB
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