The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A reduce inflammation-induced hypermotility in mice

R Capasso, F Borrelli, J Zjawiony, L Kutrzeba, G Aviello, G Sarnelli, F Capasso, A A Izzo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The hallucinogenic plant Salvia divinorum has been used for medical treatments of gastrointestinal disorders. Here, we evaluated the effect of a standardized extract from the leaves of Salvia divinorum (SDE) and of its active ingredient salvinorin A on motility in vivo, both in physiological states and during croton oil-induced intestinal inflammation. SDE (1-100 mg kg(-1)) significantly inhibited motility only in inflamed, but not in control, mice. In control mice, salvinorin A (0.01-10 mg kg(-1)) significantly inhibited motility only at the highest doses tested (3 and 10 mg kg(-1)) and this effect was not counteracted by naloxone or by the kappa-opioid receptor (KOR) antagonist nor-binaltorphimine. Inflammation significantly increased the potency of salvinorin A (but not of the KOR agonist U-50488) in reducing motility. The inhibitory effects of both salvinorin A and U-50488 in inflamed mice were counteracted by naloxone or by nor-binaltorphimine. We conclude that salvinorin A may reduce motility through activation of different targets. In physiological states, salvinorin A, at high doses, inhibited motility through a non-KOR mediated mechanism. Gut inflammation increased the potency of salvinorin A; this effect was mediated by KOR, but it was not shared by U-50488, thus suggesting that salvinorin A may have target(s) other than KOR in the inflamed gut.

Original languageEnglish
Pages (from-to)142-148
Number of pages7
JournalNeurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
Volume20
Issue number2
Early online date4 Sep 2007
DOIs
Publication statusPublished - Feb 2008

Keywords

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics, Non-Narcotic
  • Animals
  • Diterpenes
  • Diterpenes, Clerodane
  • Gastrointestinal Motility
  • Hallucinogens
  • Inflammation
  • Male
  • Mice
  • Mice, Inbred ICR
  • Plant Extracts
  • Plant Leaves
  • Receptors, Opioid, kappa
  • Salvia
  • Journal Article
  • Research Support, Non-U.S. Gov't

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