Inhibition of Inflammatory Cytokine Secretion by Plant-DerivedCompounds Inuviscolide and Tomentosin: The Role of NFκB and STAT1

The plant Inula viscosa has been shown to possess many important medicinal benefits, including anti-inflammatory, anti-oxidant, anti-bacterial, and anti-fungal activities, but the plant metabolites that mediate these effects and their mechanism of action are poorly understood. In a previous study, we demonstrated a reduced expression of the p65 subunit of nuclear factor kappa B (NFκB) in melanoma cells treated with the purified sesquiterpene lactone compounds, Inuviscolide (Inv) and Tomentosin (Tom), extracted from Inula viscosa leaves. In this study, we tested the invitro effect of these purified compounds on the secretion of pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) upon stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). Their possible mechanism of action was also studied. The results showed that both agents caused decreased production of IL-2, IL-1β, IFNγ, and slightly increased secretion of TNFα, whereas secretion of IL-6 was not affected. The elevated levels of TNFα did not appear to affect the viability of human PBMCs. Western blot analysis revealed a reduction in the protein level of both the transcription factor component p65/RelA of nuclear factor-κB (NFκB) and the signal transducer and activator of transcription 1 (STAT1) through proteosomal degradation. However, no change was observed in the expression level of the nuclear factor-κB component, p50 (NFκB), or the signal transducer and activator of transcription 3 (STAT3). Taken together, our results indicate the possible future use of these agents as an anti-inflammatory treatment in cases where overstimulation of cytokine secretion is the basis for the pathological symptoms.