Salvinorin A, a neoclerodane diterpene isolated from Salvia 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 LTC4 production 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.

Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization / Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, MARIA ANTONIETTA; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Zjawiony, Jordan K; Izzo, ANGELO ANTONIO; Capasso, Raffaele; Roviezzo, Fiorentina. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 7:13(2017), p. 525. [10.3389/fphar.2016.00525]

Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

ROSSI, ANTONIETTA
Primo
;
CAIAZZO, ELISABETTA
Secondo
;
Bilancia, Rossella;RIEMMA, MARIA ANTONIETTA;PAGANO, ESTER;CICALA, CARLA;IALENTI, ARMANDO;IZZO, ANGELO ANTONIO;CAPASSO, RAFFAELE
Penultimo
;
ROVIEZZO, FIORENTINA
Ultimo
2017

Abstract

Salvinorin A, a neoclerodane diterpene isolated from Salvia 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 LTC4 production 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.
2017
Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization / Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, MARIA ANTONIETTA; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Zjawiony, Jordan K; Izzo, ANGELO ANTONIO; Capasso, Raffaele; Roviezzo, Fiorentina. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 7:13(2017), p. 525. [10.3389/fphar.2016.00525]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/667018
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