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

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.

• Authors: R Capasso, F Borrelli, J Zjawiony, L Kutrzeba, G Aviello, G Sarnelli, F Capasso, A A Izzo
• Journal: Neurogastroenterology and motility (Neurogastroenterol Motil) Vol. 20 Issue 2 Pg. 142-8 (Feb 2008) ISSN: 1350-1925 [Print] England
• PMID: 17931335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Diterpenes
• Diterpenes, Clerodane
• Hallucinogens
• Plant Extracts
• Receptors, Opioid, kappa
• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
• salvinorin A

Topics

• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer (pharmacology)
• Analgesics, Non-Narcotic (pharmacology)
• Animals
• Diterpenes (pharmacology)
• Diterpenes, Clerodane
• Gastrointestinal Motility (drug effects)
• Hallucinogens (pharmacology)
• Inflammation (physiopathology)
• Male
• Mice
• Mice, Inbred ICR
• Plant Extracts (pharmacology)
• Plant Leaves (chemistry)
• Receptors, Opioid, kappa (drug effects)
• Salvia (chemistry)