Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with a pharmacophoric conjugated diene.
ABSTRACT Sesquiterpene acids are natural products that, in contrast with the thoroughly studied sesquiterpene lactones, have received little pharmacological attention. A good source of this class of compounds is Inula viscosa (Asteraceae), a plant with documented anti-inflammatory effects. The present paper gives the results of our investigations on the biochemical mechanisms involved in the anti-inflammatory activity of one such compound, dehydrocostic acid. The most salient findings were that in vitro dehydrocostic acid inhibits leukotriene B(4) production (IC(50)=22 microM), elastase activity (IC(50)=43 microM) and bee venom phospholipase A(2) activity (IC(50)=17 microM). Furthermore, this sesquiterpenoid was effective on some models of acute edema induced by PLA(2) and 12-O-tetradecanoylphorbol 13-acetate (TPA) Comparison of these data with that known for ilicic acid firmly suggests that the presence of a semiplanar ring A is essential for an improved inhibitory activity on inflammatory mediators.
Article: Inhibition of Inflammatory Cytokine Secretion by Plant-Derived Compounds Inuviscolide and Tomentosin: The Role of NF B and STAT1[show abstract] [hide abstract]
ABSTRACT: 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 (NFB) 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 in-vitro 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-1, IFN, and slightly increased secretion of TNF, whereas secretion of IL-6 was not affected. The elevated levels of TNF 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-B (NFB) 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-B component, p50 (NFB), 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.The Open Pharmacology Journal 01/2010; 4:36-44.
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ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). The anti-inflammatory effects of IFE against nitric oxide (NO), PGE(2), TNF-α, and IL-6 release, as well as NF-κB and MAP kinase activation were evaluated in RAW 264.7 cells. IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-α and IL-6. Furthermore, IFE inhibited the NF-κB activation induced by LPS, which was associated with the abrogation of IκB-α degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-κB activation via suppression of IκBα and MAP kinase phosphorylation in macrophages.Immune Network 10/2010; 10(5):145-52.