DA-9601 inhibits activation of the human mast cell line HMC-1 through inhibition of NF-κB

Abstract

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.

DA-9601 suppresses 2, 4-dinitrochlorobenzene and dust mite extract-induced atopic dermatitis-like skin lesions

“…DA-9601 is known to exert anti-inflammatory activity [25,26]. We also previously showed that the expression of TNF-α was inhibited by DA-9601 in activated human mast cells [13]. Therefore, we speculate that the inhibitory effect of DA-9601 on leukocyte infiltration in our AD model might be mediated by blocking TNF-α expression and downstream chemokines/adhesion molecules.…”

“…In the present report, we clearly showed the effect of DA-9601 on the AD; however, the molecular target of this effect is still unknown. We previously reported the anti-allergic inflammatory effect of DA-9601 through the inhibition of immediate-type hypersensitivity, histamine release and serum IgE, and pro-inflammatory cytokines by the attenuation of NF-κB [13,30]. The intracellular calcium and cAMP are the most important signaling pathways to the degranulation of mast cells and downstream histamine release [17].…”

“…Artemisia asiatica is widely used in traditional Asian medicine for the treatment of inflammation, cancer and microbial infection [11]. DA-9601 has been reported as having antioxidative, anti-allergic, and anti-inflammatory effects [11][12][13][14]. From the chemical analysis, DA-9601 contains flavonoids and essential oils such as eupatilin, 1,8-cineole, and terpinen-4-ol.…”

Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages

“…A. asiatica has been widely used for centuries in traditional Asian diets and medications without any serious side effects. We previously reported that the anti-allergic and anti-tumor properties of eupatilin in gastric epithelial cells and mast cells (Choi et al, 2008(Choi et al, , 2009Lee et al, 2007Lee et al, , 2008. In addition, the standardized ethanol extract of A. asiatica, DA-9601, has been shown to have strong anti-oxidative effects in experimental animal models, such as esophageal mucosal damage (Choi et al, 2006).…”

Assessing medicinal plants from South-Eastern Spain for potential anti-inflammatory effects targeting nuclear factor-Kappa B and other pro-inflammatory mediators

“…This assay nonetheless gave a clear indication of toxicity against HeLa cells through indications of cell shrinkage or cells floating following exposure to the extracts (carrier solvent controls did not show any of these indicators of toxicity). The active species from this set, for which previous studies exist, include Turkish (Yesilada et al, 1997;Yesilada and Kupeli, 2007), East Asian (Suh et al, 2006;Park et al, 2006a) and Australian species of Clematis ; species of Artemisia from China (Jin et al, 2004;Lee et al, 2007) and Tibet (Sun et al, 2006). As identified in Jin et al (2004) sesquiterpene lactones are the likely NF-B inhibitors found in extracts of Artemisia spp.…”