Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo.
Gabriella Aviello, Francesca Borrelli, Francesca Guida, Barbara Romano, Kevin Lewellyn, Maria De Chiaro, Livio Luongo, Jordan K Zjawiony, Sabatino Maione, Angelo A Izzo, Raffaele Capasso
Journal of molecular medicine (Berlin, Germany) September 1, 2011 DOI: 10.1007/s00109-011-0752-4 via PubMed
Summary
Salvinorin A, a hallucinogenic compound, reduces inflammation in immune cells and in animal models of inflammation. At extremely low concentrations (0.1-10 pM), it lowers levels of inflammatory markers nitrite, TNF-α, and IL-10 (but not IL-1β) and reduces expression of iNOS (but not COX-2) in stimulated macrophages. These effects are blocked by antagonists of both κ-opioid receptors (KOR) and cannabinoid CB1 receptors, and salvinorin A prevents the overproduction of these receptors induced by inflammation. In living animals, salvinorin A reduces paw swelling caused by LPS or carrageenan and pain from formalin injection, with these effects also blocked by KOR and CB1 antagonists. The compound acts through both KOR and CB1 receptors to produce potent anti-inflammatory actions on macrophages and moderate anti-inflammatory effects in vivo.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Macrophages and mice |
| Citations | 70 |
| Key finding | Salvinorin A exerts ultrapotent anti-inflammatory effects on macrophages and moderate anti-inflammatory effects in vivo via both κ-opioid and cannabinoid CB1 receptors. |
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.