title: Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization.
abstract: Salvinorin A, a neoclerodane diterpene isolated fromSalvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma.
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caiazzo
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Bilancia
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Riemma
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Pagano
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cicala
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Ialenti
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy and the Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi University, MS, USA.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.affiliation: Department of Pharmacy, University of Naples Federico IINaples, Italy; Department of Agricultural Sciences, University of Naples Federico IIPortici, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.affiliation: Department of Pharmacy, University of Naples Federico II Naples, Italy.
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
keywords: Salvinorin A; airway hyperreactivity; asthma; leukotrienes; mast cells