Abstract: The present study was aimed to discover novel inhibitors of CaN-NFAT pathway from herbal extracts.The luciferase reporter assay was applied to screen the effective inhibitors of CaN-NFAT pathway from herbal extracts using K562 cells stably transfected with NFAT-driven luciferase reporter.CCK-8 assay was used to evaluate their cytotoxicity.The results of luciferase reporter assay and CCK8 cytotoxicity assay on a variety of herbal extracts showed that the herbal extracts of propolis, Crataegus pinnatifida Bunge, Carthamus tinctorius L., Forsythia suspensa (Thunb.) Vahl, Radix ranunculi ternati, Taraxacum mongolicum, Leonurus sibiricus L., Herba epimedii  effectively inhibited the activation of CaN-NFAT pathway in PMA/A23187-stimulated K562 cells at the concentration of 1 mg/mL without significant cytotoxicity.Dose-dependency study indicated that extracts of  Colla Apis, Crataegus pinnatifida Bunge, Carthamus tinctorius L., Artemisia carvifolia and Forsythia suspensa (Thunb.) Vahl inhibited the activation of CaN-NAFT signal pathway dose-dependently within the concentrations of 0.25-1 mg/mL.These results suggested that CaN-NFAT pathway might be one of the targets by which these herbs exert anti-inflammatory and immune-modulating effects,and that there might be inhibitors of CaN-NFAT pathway in these extracts.

Key words: calcineurin, NFAT, signal transduction, cytokine, herbal extract, inflammation, eczema