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(-)-Linalool inhibits in vitro NO formation. Probable involvement in the antinociceptive activity of this monoterpene compound
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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“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].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [142]
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Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review
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“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] .”
BackgroundLinalool: a review on a key odorant molecule with valuable biological properties
Aprotosoaie, A. C., Hăncianu, M., Costache, I. I., & Miron, A. (2014) · Flavour and Fragrance Journal · doi:10.1002/ffj.3197 · Cited by 343
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Linalool bioactive properties and potential applicability in drug delivery systems
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Metadata
- 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 (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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