Aromadendrin Inhibits Lipopolysaccharide-Induced Nuclear Translocation of NF-kappaB and Phosphorylation of JNK in RAW 264.7 Macrophage Cells

ABSTRACT

Aromadendrin, a flavonol, has been reported to possess a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-diabetic properties. However, the underlying mechanism by which aromadendrin exerts its biological activity has not been extensively demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of aromadedrin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Aromadendrin significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2. In accordance, aromadendrin attenuated LPS-induced overexpression iNOS and COX-2. In addition, aromadendrin significantly suppressed LPS-induced degradation of IkappaB, which sequesters NF-kappaB in cytoplasm, consequently inhibiting the nuclear translocation of pro-inflammatory transcription factor NF-kappaB. To elucidate the underlying signaling mechanism of anti-inflammatory activity of aromadendrin, MAPK signaling pathway was examined. Aromadendrin significantly attenuated LPS-induced activation of JNK, but not ERK and p38, in a concentration-dependent manner. Taken together, the present study clearly demonstrates that aromadendrin exhibits anti-inflammatory activity through the suppression of nuclear translocation of NF-kappaB and phosphorylation of JNK in LPS-stimulated RAW 264.7 macrophage cells.