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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)891-902
Number of pages12
JournalJournal of Molecular Medicine
Volume89
Issue number9
Early online date16 Apr 2011
DOIs
Publication statusPublished - Sep 2011

Fingerprint

salvinorin A
Salvia
Lipopolysaccharides
Anti-Inflammatory Agents
Macrophages
rimonabant
Cannabinoid Receptor CB1
Nitrites
Narcotic Antagonists
Carrageenan
Opioid Receptors
Naloxone
Interleukin-1
Interleukin-10
Formaldehyde

Keywords

  • Animals
  • Anti-Inflammatory Agents
  • Cells, Cultured
  • Cyclooxygenase 2
  • Diterpenes, Clerodane
  • Edema
  • Inflammation
  • Inflammation Mediators
  • Lipopolysaccharides
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Receptor, Cannabinoid, CB1
  • Receptors, Opioid, kappa
  • Salvia
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo. / Aviello, Gabriella; Borrelli, Francesca; Guida, Francesca; Romano, Barbara; Lewellyn, Kevin; De Chiaro, Maria; Luongo, Livio; Zjawiony, Jordan K; Maione, Sabatino; Izzo, Angelo A; Capasso, Raffaele.

In: Journal of Molecular Medicine, Vol. 89, No. 9, 09.2011, p. 891-902.

Research output: Contribution to journalArticle

Aviello, G, Borrelli, F, Guida, F, Romano, B, Lewellyn, K, De Chiaro, M, Luongo, L, Zjawiony, JK, Maione, S, Izzo, AA & Capasso, R 2011, 'Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo', Journal of Molecular Medicine, vol. 89, no. 9, pp. 891-902. https://doi.org/10.1007/s00109-011-0752-4
Aviello, Gabriella ; Borrelli, Francesca ; Guida, Francesca ; Romano, Barbara ; Lewellyn, Kevin ; De Chiaro, Maria ; Luongo, Livio ; Zjawiony, Jordan K ; Maione, Sabatino ; Izzo, Angelo A ; Capasso, Raffaele. / Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo. In: Journal of Molecular Medicine. 2011 ; Vol. 89, No. 9. pp. 891-902.
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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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T1 - Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo

AU - Aviello, Gabriella

AU - Borrelli, Francesca

AU - Guida, Francesca

AU - Romano, Barbara

AU - Lewellyn, Kevin

AU - De Chiaro, Maria

AU - Luongo, Livio

AU - Zjawiony, Jordan K

AU - Maione, Sabatino

AU - Izzo, Angelo A

AU - Capasso, Raffaele

N1 - This work was, in part, supported by “Fondazione Enrico & Enrica Sovena”.

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

KW - Animals

KW - Anti-Inflammatory Agents

KW - Cells, Cultured

KW - Cyclooxygenase 2

KW - Diterpenes, Clerodane

KW - Edema

KW - Inflammation

KW - Inflammation Mediators

KW - Lipopolysaccharides

KW - Macrophages

KW - Male

KW - Mice

KW - Mice, Inbred ICR

KW - Nitric Oxide

KW - Nitric Oxide Synthase Type II

KW - Receptor, Cannabinoid, CB1

KW - Receptors, Opioid, kappa

KW - Salvia

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00109-011-0752-4

DO - 10.1007/s00109-011-0752-4

M3 - Article

VL - 89

SP - 891

EP - 902

JO - Journal of Molecular Medicine

JF - Journal of Molecular Medicine

SN - 0946-2716

IS - 9

ER -