Anti-Inflammatory activity of Angelica keiskei through suppression of mitogen-activated protein kinases and nuclear factor-kappaB activation pathways.
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 E(2) production and tumor necrosis factor-alpha 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 kappaB (NF-kappaB). HAK suppressed LPS-induced c-Jun NH(2)-terminal kinase, p38, and p44/p42 MAPK activation. We also found that the cell-based assay system showed that HAK suppressed LPS-induced NF-kappaB 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-kappaB.
Department of Oriental Pathology, College of Oriental Medicine, Kyung Hee University, Gangneung, Republic of Korea.
Hyoung Joo
HJ
Lee
Tae Won
TW
Choi
Hyun Jung
HJ
Kim
Dongwoo
D
Nam
Sang Hoon
SH
Jung
Eun Ha
EH
Lee
Hee Ju
HJ
Lee
Eun Myoung
EM
Shin
Hyeung-Jin
HJ
Jang
Kyoo Seok
KS
Ahn
Bum Sang
BS
Shim
Seung-Hoon
SH
Choi
Sung-Hoon
SH
Kim
Gautam
G
Sethi
Kwang Seok
KS
Ahn
D029969:Angelica / Q000737:chemistry* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000276:immunology; D015536:Down-Regulation; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D010936:Plant Extracts / Q000276:immunology* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D010936:Plant Extracts; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases