Linalool and linalyl acetate are the principal components of many essential oils known to possess several biological activities, attributable to these monoterpene compounds. In this work, we evaluated individually the anti-inflammatory properties of (-) linalool, that is, the natural occurring enantiomer, and its racemate form, present in various amounts in distilled or extracted essential oils. Because in the linalool-containing essential oils, linalyl acetate, is frequently present, we also examined the anti-inflammatory action of this monoterpene ester. Carrageenin-induced edema in rats was used as a model of inflammation.
The experimental data indicate that both the pure enantiomer and its racemate induced, after systemic administration, a reduction of edema. Moreover, the pure enantiomer, at a dose of 25 mg/kg, elicited a delayed and more prolonged effect, while the racemate form induced a significant reduction of the edema only one hour after carrageenin administration. At higher doses, no differences were observed between the (-) enantiomer and the racemate; a further increase in the dose of both forms did not result in an increased effect at any time of observation.
The effects of equi-molar doses of linalyl acetate on local edema were less relevant and more delayed than that of the corresponding alcohol. These finding suggest a typical pro-drug behavior of linalyl acetate.
The results obtained indicate that linalool and the corresponding acetate play a major role in the anti-inflammatory activity displayed by the essential oils containing them, and provide further evidence suggesting that linalool and linalyl acetate-producing species are potentially anti-inflammatory agents.
Key words: (-) Linalool, ([+ or -]) linalool, linalyl acetate, essential oil, anti-inflammatory activity
Linalool and linalyl acetate are monoterpene compounds reported to be major volatile components of the essential oils of several aromatic species. A number of linalool- and linalyl acetate-producing species are used in traditional medicin systems to relieve symptoms and cure a variety of ailments, both acute and chronic. Their pharmacological activities are attributable to the content of alcohols like linalool and its corresponding ester (linalyl acetate) (Peana and Moretti, 2002). Linalool was evaluated recently for its psychopharmacological activity in mice, revealing marked dose-dependent sedative effects on the central nervous system (CNS) (Jirovetz et al. 1991; Buchbauer et al. 1991), including protection against pentylenetetrazol (PTZ), picrotoxin and transcorneal electroshock-induced convulsions, hypnotic and hypothermic properties (Elisabetsky et al. 1995; Elisabetsky et al. 1999). It has also been reported that linalool modulates glutamate activation expression in vitro (competitive antagonism of L-[ [H.sup.3]]glutamate binding) and in vivo (delayed subcutaneous N-methyl-D-aspartate-induced convulsions and blockade of intracerebroventricular quinolinic acid-induced convulsions) (Silva Brum et al. 2001; Brum et al. 2001). Anesthetic activity related to its effects on the nicotinic receptor-ion channel (Ghelardini et al. 1999; Re et al. 2000) and a spasmolytic effect (Lis-Balchin and Hart, 1999) were also reported, as well as antimicrobial activity against several bacteria and fungi (Carson and Riley, 1995; Pattnaik et al. 1997; Peana et al. 1999). Moreover, linalool, as well as some terpenes and terpenoids, could enhance the permeability of a number of drugs through biological...