Damião Pergentino de Sousa

A Review on Anti-Inflammatory Activity of Monoterpenes

Faced with the need to find new anti-inflammatory agents, great effort has been expended on the development of drugs for the treatment of inflammation. This disorder reduces the quality of life and overall average productivity, causing huge financial losses. In this review the anti-inflammatory activity of 32 bioactive monoterpenes found in essential oils is discussed. The data demonstrate the pharmacological potential of this group of natural chemicals to act as anti-inflammatory drugs.

Analgesic-like Activity of Essential Oils Constituents

Research on neuroactive drugs is a pharmaceutical sector of high interest and growth. The discovery of efficient drugs that can relieve pain is a subject of research in the pharmaceutical industry and academic field because pain is a symptom of many diseases. This review will summarize results on the discovery of essential oil constituents with analgesic-like activity from the chemical and pharmacological perspectives. Overall, 43 bioactive compounds were selected in nociception models. Among them, 62.8% were monoterpenes, 18.6% sesquiterpenes and other constituents represented 18.6%. The data show the potential of this group of natural product chemicals as analgesic drugs that may be useful for therapeutic purposes.

Antinociceptive Effect of the Monoterpene R -(+)-Limonene in Mice

In the present study were studied the antinociceptives properties of monoterpene R-(+)-limonene (LM) in chemical and thermal models of nociception in mice. The R-(+)-limonene was administered, intraperitoneally (i.p.), at doses of 25 and 50 mg/kg. The results showed significant inhibition produced on chemical nociception induced by intraperitoneal acetic-acid and in the second phase of subplantar formalin test, but did not manifest a significant effect in hot-plate test. The R-(+)-limonene-induced antinociception in second phase of formalin test was insensitive to naloxone (1 mg/kg, s.c.). It was also demonstrated that R-(+)-limonene (25, 50 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor impaired the motor performance in rota-rod test, indicating that the observed antinociception is unlikely to be due to sedation or motor abnormality. In conclusion it may be suggested that the R-(+)-limonene presented antinociceptive activity and that, probably, this action can be related with peripheral analgesia, but, not with the stimulation of opioids receptors.

Study of anticonvulsant effect of citronellol, a monoterpene alcohol, in rodents

Citronellol is one monoterpene alcohol, which is present in the essential oils of various aromatic plant species. This study evaluated the neuroprotective activity of citronellol on pentylenetetrazol- and picrotoxin-induced convulsions and maximal electroshock-induced seizures in mice. Administration of citronellol significantly reduced the number of animals of convulsion induced by pentylenetetrazol and eliminated the extensor reflex of maximal electroshock-induced seizures test in about 80% of the experimental animals. In addition, administration of citronellol showed protection in the pentylenetetrazol and picrotoxin tests by increasing the latency of clonic seizures. We also investigated the effect of citronellol in the rat isolated nerve using the single sucrose-gap technique. We showed that the amplitude of the compound action potential decreased more than 90% when the monoterpene was incubated for 30 min at 6.4 mM and we did not verify any effect on the repolarization of the compound action potential. Taken together, our results demonstrated an anticonvulsant activity of the citronellol that could be, at least in part, explained by the diminution of the action potential amplitude.

Central nervous system activity of acute administration of isopulegol in mice

Isopulegol is a monoterpene alcohol intermediate in the preparation of (-)-menthol and it is present in the essential oils of various plants. This work presents behavioral effects of isopulegol in animal models of open field, elevated plus maze (EPM), rota rod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Isopulegol was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg, while diazepam 1 or 2 mg/kg and imipramine 10 or 30 mg/kg were used as standard drugs. The results showed that, similar to diazepam (1 mg/kg), both doses of isopulegol significantly modified all the observed parameters in the EPM test, without alter the general motor activity in the open field test. In the same way, both doses of isopulegol increased the number of head dips in the hole-board test. Forced swimming and tail suspension tests showed that isopulegol (25 and 50 mg/kg) was able to induce a significant increase in the immobility time, in opposite to imipramine, a recognized antidepressant drug. There was a decrease in the sleep latency time and prolongation of the pentobarbital-induced sleeping time with both doses of Isopulegol. Different from diazepam (2 mg/kg), isopulegol (25 e 50 mg/kg) had no effect on the motor coordination of animals in the rota rod test. These results showed that isopulegol presented depressant- and anxiolytic-like effects.

Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models.

The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P < 0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P < 0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.

Essential Oils and Their Constituents: Anticonvulsant Activity

A literature-based survey of plants species and their essential oils with anticonvulsant activity was carried out. As results, 30 species belonging to 13 families and 23 genera were identified for their activities in the experimental models used for anticonvulsant drug screening. Thirty chemical constituents of essential oils with anticonvulsant properties were described. Information on these 30 species is presented together with isolated bioactive compound studies.

Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission.

Carvacrol (5‐isopropyl‐2‐methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate‐induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open‐field test. However, CVC decreased the number of groomings in the open‐field test. In the plus maze test, CVC, at three doses significantly increased all the observed parameters in the EPM test and flumazenil was able to reverse the effects of diazepam and CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate‐induced sleeping time test. These results show that CVC presents anxiolytic effects in the plus maze test which are not influenced by the locomotor activity in the open‐field test.

Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action

The aim of the study is to determine the acute toxicity and anxiolytic-like effects of a mixture of cis and trans of (+)-limonene epoxide in animal models of anxiety. After acute treatment with (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg (i.p.) no mortality was noted during 14 days of observation. In general, behavior, food and water consumption showed no significant changes. In open field test, (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg, after intraperitoneal administration, significantly decreased the number of crossings, grooming and rearing (p<0.001). All these effects were reversed by the pre-treatment with flumazenil (25 mg/kg, i.p.), similar to those observed with diazepam used as a positive standard. In the elevated-plus-maze test, (+)-limonene epoxide increased the time of permanence and the number of entrances in the open arms. All these effects were reversed by flumazenil, an antagonist of benzodiazepine receptors. In addition, (+)-limonene epoxide (75 mg/kg) also produced a significant inhibition of the motor coordination (p<0.01), that was reversed by flumazenil. In conclusion, the present work evidenced sedative and anxiolytic-like effects of (+)-limonene epoxide, which might involve an action on benzodiazepine-type receptors. These results indicate that the properties of (+)-limonene epoxide should be more thoroughly examined in order to achieve newer tools for management and/or treatment of central nervous system diseases and anxiolytic-like effects. The LD50 obtained for the acute toxicity studies using intraperitoneal route of administration was 4.0 g/kg. These findings suggest that acute administration of the (+)-limonene epoxide exerts an anxiolytic-like effect on mice, and it could serve as a new approach for the treatment anxiety, since it practically does not produce toxic effects.

A Review on Anti-Inflammatory Activity of Phenylpropanoids Found in Essential Oils

The search for alternative drugs capable of disrupting the inflammatory process has become an important issue in scientific research, especially with reference to the use of natural substances and the reduction of undesirable side effects. Essential oils represent an important source of such substances, since their active constituents often exhibit an array of pharmacological properties, including anti-inflammatory activity. This review presents an overview of the anti-inflammatory action exerted by phenylpropanoids from essential oils and discusses possible mechanisms of action involved in the anti-inflammatory response, assessed through specific experimental models.