title: Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo.
abstract: The hallucinogenic compound, salvinorin A, is a potent κ-opioid receptor (KOR) agonist. However, other target(s) than the KOR, such as the cannabinoid CB1 receptor, have been proposed to explain its multiple pharmacological actions. Here, we have evaluated the effect of salvinorin A in lipopolysaccharide (LPS)-stimulated macrophages as well as in models of inflammation in vivo. Salvinorin A (0.1-10 pM) reduced LPS-stimulated nitrite, TNF-α and IL-10 (but not IL-1β) levels as well as iNOS (but not COX-2) LPS-induced hyperexpression. The effect of salvinorin A on nitrite levels was reverted by the opioid antagonist naloxone, the KOR antagonist nor-binaltorphimine and by the CB1 antagonist rimonabant Salvinorin A also prevented KOR and CB1 hyperexpression induced by LPS. In vivo, salvinorin A reduced the LPS- and the carrageenan-induced paw oedema and formalin-induced inflammatory pain, in a nor-binaltorphimine and rimonabant-sensitive manner. It is concluded that salvinorin A-via KORs and CB1 receptors-exerts ultrapotent actions on macrophages and also shows moderate antinflammatory effects in vivo.
authors.affiliation: Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aviello
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Guida
authors.forename: Barbara
authors.initials: B
authors.lastname: Romano
authors.forename: Kevin
authors.initials: K
authors.lastname: Lewellyn
authors.forename: Maria
authors.initials: M
authors.lastname: De Chiaro
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D045785:Diterpenes, Clerodane / Q000494:pharmacology* / Q000633:toxicity; D004487:Edema / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D027544:Salvia / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D045785:Diterpenes, Clerodane; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D043884:Receptor, Cannabinoid, CB1; D017473:Receptors, Opioid, kappa; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C090499:salvinorin A