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Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo

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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.

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Acknowledgements

This work was, in part, supported by “Fondazione Enrico & Enrica Sovena”.

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The authors state that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy

    Gabriella Aviello, Francesca Borrelli, Barbara Romano, Angelo A Izzo & Raffaele Capasso

  2. Department of Experimental Medicine, Section of Pharmacology, The Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy

    Francesca Guida, Maria De Chiaro, Livio Luongo & Sabatino Maione

  3. Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS, 38677–1848, USA

    Kevin Lewellyn & Jordan K Zjawiony

  4. Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677–1848, USA

    Jordan K Zjawiony

  5. Endocannabinoid Research Group, Pozzuoli, Italy

    Gabriella Aviello, Francesca Borrelli, Barbara Romano, Sabatino Maione, Angelo A Izzo & Raffaele Capasso

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  1. Gabriella Aviello
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  2. Francesca Borrelli
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Correspondence to Angelo A Izzo or Raffaele Capasso.

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Fig. 1

Effect of dexamethasone (DEX, 0.5–2 mg/kg, i.p.) on paw oedema induced by lipopolysaccharide (LPS) (a) or carrageenan (b) as well as on the formalin test (c). Results are mean ± SEM (n = 6–8 for each group). * P < 0.05 vs. vehicle plus LPS (or carrageenan), and #P < 0.05 vs. vehicle. In Fig. 1C, filled symbols denote statistically (P < 0.01) significant differences vs. formalin. (PDF 40 kb)

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Aviello, G., Borrelli, F., Guida, F. et al. Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo. J Mol Med 89, 891–902 (2011). https://doi.org/10.1007/s00109-011-0752-4

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  • DOI: https://doi.org/10.1007/s00109-011-0752-4

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