Antidepressant-Like Effect of Lippia sidoides CHAM (Verbenaceae) Essential Oil and Its Major Compound Thymol in Mice.

Depression is a common disease affecting more than 300 million people worldwide. Since Lippia sidoides has shown central nervous system effects in previous works, we aimed to investigate the effect of L. sidoides essential oil and its major compound, thymol on a corticosterone-induced depression model in mice. Male mice (20⁻25 g) received corticosterone (20 mg/kg, subcutaneously), once a day for 22 days. From the 16th day on, mice were grouped to receive either corticosterone or L. sidoides essential oil (100 and 200 mg/kg), or thymol (25 and 50 mg/kg) or fluoxetine (35 mg/kg) by gavage. The forced swimming test, tail suspension, open field, elevated plus maze and sucrose preference tests were performed from the 19th to 22nd day. Data were analyzed by ANOVA followed by the Student-Newman-Keuls as a post hoc test and the results were considered significant when p < 0.05. It was shown that L. sidoides essential oil, thymol and fluoxetine decreased the immobility time in the tail suspension and forced swimming tests and none of these altered locomotor activity in the open field test. However, the drugs increased the amount of grooming. In the elevated plus maze, all drugs increased the number of entries and the time of permanence in the open arms. In the sucrose preference test, the L. sidoides essential oil, thymol and fluoxetine reversed anhedonia. These results suggest that the thymol and L. sidoides essential oil have an antidepressant-like effect, similar to fluoxetine. However, future studies should be encouraged to enhance understanding of the effects of essential oil and thymol for the treatment of depression.

Involvement of monoaminergic system in the antidepressant-like effect of riparin I from Aniba riparia (Nees) Mez (Lauraceae) in mice.

In past studies conducted by our group, riparin I (rip I) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice, while its analogs rip II and III showed anxiolytic and antidepressant-like actions. This time around, we investigated a possible antidepressant activity of rip I using the forced swimming test (FST) and tail suspension test (TST) as predictive tests for antidepressant activity in rodents. In addition, the involvement of the monoaminergic system in this effect was also assessed. rip I was acutely administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that rip I at both tested doses and administration routes produced a significant decrease in immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1 -adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2 -adrenoceptor antagonist), SCH23390 (15 µg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p-chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis) or ritanserin (4 mg/kg, a serotonin 5-HT2(A)/2(C) receptor antagonist) blocked the anti-immobility effects elicited by rip I (50 mg/kg, p.o.) in the FST. Taken together, results indicate that rip I produces significant antidepressant-like activity in the FST and TST, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic and serotonergic systems.

Evidence for the involvement of the serotonergic, noradrenergic, and dopaminergic systems in the antidepressant-like action of riparin III obtained from Aniba riparia (Nees) Mez (Lauraceae) in mice.

Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant-like action of ripIII. Following intraperitoneal administration of ripIII at doses of 25 and 50 mg/kg, there were decreases in the immobility time in the FST and tail suspension test without accompanying changes in ambulation (data not shown). The pretreatment of mice with sulpiride (50 mg/kg, i.p.), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and p-chlorophenylalanine (PCPA, 100 mg/kg, i.p. for, four consecutive days) significantly prevented the anti-immobility effect of ripIII in the FST. On the other hand, the anti-immobility effect of ripIII (50 mg/kg, v.o.) was not altered by pretreatment of mice with SCH23390 (15 µg/kg, i.p.) Furthermore, ripIII potentiated the sleeping latency and sleeping time of the pentobarbital-induced sleeping time test and also potentiated apomorphine (16 mg/kg, i.p.)-induced hypothermia in mice. In conclusion, the present study provides evidence that the antidepressant-like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1- and α2- receptors), and dopaminergic (dopamine D2 receptors) systems.

Antidepressant-like effect of riparin II from Aniba riparia in mice: evidence for the involvement of the monoaminergic system.

In a previous study conducted by our group, riparin II (ripII) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice. This study investigates a possible antidepressant activity of rip II using two predictive tests for antidepressant activity in rodents: the forced swimming test (FST) and tail suspension test (TST). Additionally, the mechanisms involved in the antidepressant-like effect in mice were also assessed. Rip II was acute administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that ripII at both tested doses and administration routes produced a significant decrease of immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), SCH23390 (15 µg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p-chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis), or NAN-190 (0.5 mg/kg, a serotonin 5-HT1A receptor antagonist) completely blocked the anti-immobility effects elicited by riparin II (50 mg/kg, p.o.) in the FST. This study indicates that riparin II produces significant antidepressant-like activity in the forced swimming and TSTs, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic, and serotonergic systems.

Evaluation of effects of N-(2-hydroxybenzoyl) tyramine (riparin II) from Aniba riparia (NEES) MEZ (Lauracea) in anxiety models in mice.

In order to evaluate the effects produced by N-(2-hydroxybenzoyl) tyramine (riparin II) isolated from the unripe fruit of Aniba riparia (NEES) MEZ (Lauraceae) on the central nervous system, different behavioral tests were performed. Riparin II (rip II) was administered orally (p.o.) and intraperitoneally (i.p.) in male mice, at doses of 25, 50 and 75 mg/kg, and tested on elevated plus maze (EPM), open field, rota rod and hole board tests. The results revealed that rip II caused considered increase of the number of head dips in hole board test and increased the number of entries and the time of permanence in the open arms in plus maze test in both routes. No significant effect was evidenced on rota rod and open field test, except an increase observed in the number of rearing. These results showed that riparin II presents anxiolytic-like effects in the plus maze and hole board tests which are not influenced by the locomotor activity as detected in the open field test.

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.

Anxiolytic-like effects of (O-methyl)-N-2,6-dihydroxybenzoyl-tyramine (riparin III) from Aniba riparia (Nees) Mez (Lauraceae) in mice.

This work presents behavioral effects of (O-methyl)-N-2,6-dihydroxybenzoyl-tyramine (riparin III) isolated from the unripe fruit of Aniba riparia (Nees) Mez (Lauraceae) in animal models of open field, rota rod, elevated plus maze and hole board tests in mice. Riparin III (ripIII) was administered orally, in male mice, at single doses of 25 and 50 mg/kg. The results showed that ripIII, at both doses, had no effects on the spontaneous motor activity in the rota rod test nor in the number of squares crossed in the open field test. However, riparin III decreased the number of grooming and rearing. In the plus maze test, ripIII, at both doses increased the following parameters: percentage of entries in the open arms (PEOA), time of permanence in the open arms (TPOA) and percentage of time of permanence in the open arms (PTOA) and at the dose of 50 mg/kg, increased the number of entries in the open arms (NEOA). Similarly, ripIII, at both doses, showed an increase in the number of head dips into the holes of the hole board test. These results show that riparin III presents anxiolytic effects in the plus maze and hole board tests which are not influenced by the locomotor activity in the open field test.

Antianxiety effects of riparin I from Aniba riparia (Nees) Mez (Lauraceae) in mice.

This work presents the behavioral effects of riparin I (methyl ether of N-benzoyl tyramine) from unripe fruit of Aniba riparia (Lauraceae) on the elevated plus maze, open field, rota rod and hole board tests in mice. Riparin I was administered acutely by intraperitoneal (i.p.) and oral routes to male mice at doses of 25 and 50 mg/kg. The results showed that riparin I (25 and 50 mg/kg, i.p. and per os) increased the number of entries and the time of permanence in the open arms in the plus maze test. Similarly, in the hole board test, riparin I in both routes increased the number of head dips. Riparin I with both doses and routes had no effects on spontaneous motor activity in mice or in the rota rod test, but decreased the number of groomings. These results showed that riparin I by both administration routes has effects on the central nervous system with antianxiety effects on the plus maze and hole board tests. The substance is devoid of myorelaxant effects.