Src and Syk are targeted to an anti-inflammatory ethanol extract of Aralia continentalis.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia continentalis Kitagawa (Araliaceae) is a representative ethnomedicinal herbal plant traditionally prescribed in Korea to relieve various inflammatory symptoms. However, the exact molecular mechanism of its anti-inflammatory activity has not been fully investigated. MATERIALS AND METHODS: The effect of the ethanol extract from the roots of this plant (Ac-EE) on the production of the inflammatory mediator nitric oxide (NO) was studied in RAW264.7 cells. Its effect on inflammatory symptoms (gastritis and hepatitis) in mice was also examined. In particular, the molecular inhibitory mechanism was analysed by measuring the activation of transcription factors and their upstream signalling and the kinase activity of target enzymes. RESULTS: Ac-EE dose-dependently suppressed NO production in lipopolysaccharide (LPS)-activated RAW264.7 cells. This extract also displayed curative activity against EtOH/HCl-induced gastritis and LPS-induced hepatitis in mice. Ac-EE-mediated anti-inflammatory activity was found to be at the transcriptional level, as it blocked the activation of the nuclear factor (NF)-κB pathway composed of Syk and Src, according to immunoblotting and immunoprecipitation analyses and a kinase assay with whole and nucleus lysates from RAW264.7 cells and mice. CONCLUSION: Ac-EE may be developed as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future work using pre-clinical studies will be needed to investigate this possibility.