Cited by 160Pain Mechanisms and TreatmentsPhytochemistry and Biological ActivitiesInflammatory mediators and NSAID effects

(-)-Linalool inhibits in vitro NO formation. Probable involvement in the antinociceptive activity of this monoterpene compound

Peana, Alessandra T., Marzocco, Stefania, Popolo, Ada, Pinto, Aldo·2006·Life Sciences

Abstract

Recent studies performed in our laboratory have shown that (-)-linalool, the natural occurring enantiomer in essential oils, possesses anti-inflammatory, antihyperalgesic and antinociceptive effects in different animal models. The antinociceptive and antihyperalgesic effect of (-)-linalool has been ascribed to the stimulation of the cholinergic, opioidergic and dopaminergic systems, to its local anaesthetic activity and to the blockade of N-Methyl-d-aspartate receptors (NMDA). Since nitric oxide (NO) and prostaglandin E(2) (PGE(2)) play an important role in oedema formation and hyperalgesia and nociception development, to investigate the mechanism of these actions of the (-)-linalool, we examined the effects of this compound on lipopolysaccharide (LPS)-induced responses in macrophage cell line J774.A1. Exposure of LPS-stimulated cells to (-)-linalool significantly inhibited nitrite accumulation in the culture medium without inhibiting the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression, suggesting that the inhibitory activity of (-)-linalool is mainly due to the iNOS enzyme activity. In contrast, exposure of LPS-stimulated cells to (-)-linalool failed, if not at the highest concentration, both in inhibiting PGE(2) release and in inhibiting increase of inducible cyclooxygenase-2 (COX(2)) expression in the culture medium. Collectively, these results indicate that the reduction of NO production/release is responsible, at least partially, for the molecular mechanisms of (-)-linalool antinociceptive effect, probably through mechanisms where cholinergic and glutamatergic systems are involved.

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Crossref · 10.1016/j.lfs.2005.05.065

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  • PGE2 and COX-2 expression are inhibited in LPS-stimulated J774.A1 macrophages only when treated with high concentrations of (-)-linalool; linalool inhibits NO release but not iNOS expression, indicating its inhibitory activity is mainly attributed to iNOS enzyme activity.

    “PGE2 was only inhibited by LPS-stimulated macrophages J774.A1 cells when treated with high concentrations of (-)-linalool. The same was observed for the COX-2 expression. The same monoterpene inhibited NO release but did not inhibit the increase of iNOS expression indicating that the inhibitory activity of linalool was mainly attributed to the iNOS enzyme activity [142].”

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Authors
Peana, A. T., Marzocco, S., Popolo, A., & Pinto, A.
Affiliations
  • University of Sassari (IT)
  • University of Salerno (IT)
Corresponding author
Peana, Alessandra T.
Venue
Life Sciences
Publisher
Elsevier BV
Published
2006-01
Volume
78
Issue
7
Pages
719-723
ISSN
0024-3205 (ISSN-L)
OpenAlex
W2073572798
Cited by
160
References
31
Citations by year
2026: 2 · 2025: 4 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 11 · 2020: 14 · 2019: 6 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 9 · 2013: 5 · 2012: 8
FWCI
1.98
Type
journal article
Language
en
Open access
closed
Locations
  • Life Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • UnissResearch (Università degli Studi di Sassari) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
linalool, nitric oxide, inducible nitric oxide synthase, antinociceptive activity, hyperalgesia, prostaglandin E2, cyclooxygenase-2, lipopolysaccharide, macrophages, monoterpenes, cholinergic system, glutamatergic system, anti-inflammatory activity
MeSH terms
Acyclic Monoterpenes, Analgesics, Animals, Cell Line, Dose-Response Relationship, Drug, Drug Combinations, Insecticides, Lipopolysaccharides, Macrophages, Nitric Oxide, Nitrites, Dinoprostone, Culture Media, Conditioned, Monoterpenes, Cyclooxygenase 2, Nitric Oxide Synthase Type II

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