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 A 2 (PLA 2 ) 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 B 4 (LTB 4 ) formation was performed on rat peritoneal neutrophils by high performance liquid chromatography (HPLC). The lactone inuviscolide reduced the PLA 2 -induced oedema (ID 50 : 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 (ID 50 : 0.650 μmol per ear). Inuviscolide reduced LTB 4 generation in intact cells, with an IC 50 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 PLA 2 -induced mastocyte release of inflammatory mediators.