Anti-Inflammatory Activity of Angelica keiskei Through Suppression of Mitogen-Activated Protein Kinases and Nuclear Factor-kappa B Activation Pathways

Abstract

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 kappa B (NF-kappa B). 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-kappa B 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-kappa B.