A Mechanistic Approach to the In Vivo Anti-Inflammatory Activity of Sesquiterpenoid Compounds Isolated from Inula viscosa

Abstract

The present study was designed to examine the anti-inflammatory activity of the sesquiterpenoids ilicic acid and inuviscolide, isolated from Inula viscosa, on cell degranulation, leukotriene biosynthesis, neurogenic drive and glucocorticoid-like interactions. Swiss female mice were used to measure the ear oedema induced by phorbol esters or ethyl phenylpropiolate (EPP), and the paw oedema induced by phospholipase A₂ (PLA₂) or serotonin. Drug treatment consisted of one topically-applied dose in the ear models and a subcutaneous or intraperitoneal injection in the paw models. Quantitative analysis of leukotriene B₄ (LTB₄) formation was performed on rat peritoneal neutrophils by high performance liquid chromatography (HPLC). The lactone inuviscolide reduced the PLA₂-induced oedema (ID₅₀: 98 μmol/kg). The effect on serotonin-induced oedema was not changed by modifiers of the glucocorticoid response. Ilicic acid showed minor in vivo effects, but was slightly more potent than inuviscolide on the 12-O-tetradecanoylphorbol 13-acetate (TPA) acute oedema test (ID₅₀: 0.650 μmol per ear). Inuviscolide reduced LTB₄ generation in intact cells, with an IC₅₀ value of 94 μM. On the basis of the reported results, inuviscolide is the main anti-inflammatory sesquiterpenoid from Inula viscosa, and may act by interfering with leukotriene synthesis and PLA₂-induced mastocyte release of inflammatory mediators.

Abbreviations

COX:cyclooxygenase

DMSO:dimethyl sulphoxide

DPP:12-deoxyphorbol 13-phenylacetate

EPP:ethyl phenylpropiolate

HPLC:high performance liquid chromatography

ID₅₀:50 % inhibitory dose

5-HT:serotonin

LOX:lipoxygenase

LTB₄:leukotriene B₄

MTT:3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium

PGB₂:prostaglandin B₂

PKC:protein kinase C

PLA₂:phospholipase A₂

TPA:12-O-tetradecanoylphorbol 13-acetate

Ilicic acid - Inula viscosa - Asteraceae - inuviscolide - leukotriene B₄ - phospholipase A₂ - serotonin

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