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(-)-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

DOI 10.1016/j.lfs.2005.05.065

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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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Authors: Peana, A. T., Marzocco, S., Popolo, A., & Pinto, A.
Affiliations: University of Sassari (IT)
University of Salerno (IT)
Corresponding author: Peana, Alessandra T.
ORCID: Peana, Alessandra T.
Marzocco, Stefania
Popolo, Ada
Venue: Life Sciences
Publisher: Elsevier BV
Published: 2006-01
Volume: 78
Issue: 7
Pages: 719-723
ISSN: 0024-3205 (ISSN-L)
DOI: 10.1016/j.lfs.2005.05.065
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Life Sciences (publishedVersion)
PubMed (publishedVersion)
UnissResearch (Università degli Studi di Sassari) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
Health Sciences › Medicine › Pharmacology (medical) › 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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(-)-Linalool inhibits in vitro NO formation. Probable involvement in the antinociceptive activity of this monoterpene compound

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