Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: Evidence for the involvement of the monoaminergic system

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Abstract

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30–600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT1A receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT3 receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., a D2 receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.

Introduction

Schinus molle L. is a pepper tree belonging to the family Anacardiaceae. It originates from South America, but has been introduced to most of the tropical and subtropical areas of the world (Taylor, 2005).

Pharmacological studies carried out with extracts from S. molle show that this plant exerts several biological effects, such as: hypotensive (Bello et al., 1996), antitumoral (Ruffa et al., 2002), antifungal (Quiroga et al., 2001, Schmourlo et al., 2005), antispasmodic (Bello et al., 1998), anti-inflammatory (Yueqin et al., 2003), and analgesic (Barrachina et al., 1997). Other properties/actions of S. molle suggested by traditional use are: antihemorrhagic, antiseptic, aperient (mild laxative), astringent, cardiotonic, digestive stimulant, diuretic, menstrual stimulant, stimulant, tonic, and antidepressant (Taylor, 2005).

Depression is a common disorder associated with high rates of chronicity, relapse, and recurrence; psychosocial and physical impairment; and a high suicide rate. Currently available therapy for depression treatment is often associated with several undesirable side effects, and it is effective only in a certain portion of the population (Wong and Licinio, 2001, Nestler et al., 2002). Therefore, the identification of alternative therapeutic tools for the treatment of depression is still needed. Herbal therapies may be effective alternatives in the treatment of depression, as in the case of St John's wort (Whiskey et al., 2001, Bilia et al., 2002, Linde and Knüppel, 2005), and the search for novel pharmacotherapy from medicinal plants for psychiatric illnesses, including depression, has progressed significantly in the past decade (Zhang, 2004). It is interesting to note that most of the novel treatments for depression (including St. John's wort) seem to act through a mechanism which does not differ significantly with respect to that of “classical” antidepressants.

In spite of the popular use of S. molle to treat depression (Taylor, 2005) there is no scientific evidence about potential effects of this plant in animal models of depression. Thus, this study aims, firstly, to examine the antidepressant-like action of the hexanic extract from leaves of S. molle in the mouse tail suspension test (TST), a model predictive of antidepressant activity (Steru et al., 1985, Cryan et al., 2005) and, secondly, to investigate by the use of pharmacological procedures the possible participation of the monoaminergic system in its antidepressant-like action.

Section snippets

Plant material and preparation of the hexanic extract

Stems and leaves of Schinus molle L. (Anacardiaceae) were collected in Florianópolis, Santa Catarina, and identified by Dr. Daniel Falkenberg, Department of Botany, Federal University of Santa Catarina. A voucher specimen (FLOR 34411) was deposited in the Herbarium of the Department of Botany, Federal University of Santa Catarina, Santa Catarina, Brazil. Botanical material (390 g) were dried under air circulation and minced. Dried sample was extracted with hexane at room temperature (25 ± 2 °C)

Effect of the extract of S. molle on the immobility time in the TST

The effects of oral administration of the extract of S. molle and fluoxetine on the immobility time in the TST were shown in Fig. 1A and B, respectively. As depicted in Fig 1 A, the extract given by oral route at doses of 30, 100, 300 and 600 mg/kg significantly decreased the immobility time as compared to the control group. The one-way ANOVA revealed a significant effect of treatment [F(4,25) = 11.14, P < 0.01]. As a positive control, we show that the antidepressant fluoxetine (10 mg/kg, p.o.)

Discussion

The TST is a well characterized behavioral model predictive of antidepressant activity that is sensitive to antidepressants from different pharmacological classes (Steru et al., 1985, Cryan et al., 2005). In this study we provide convincing evidence that the extract of S. molle administered by oral route produces a specific antidepressant-like effect in this test, since the reduction of immobility time elicited by its administration cannot be attributable to any psychostimulant effect.

Conclusion

In conclusion, the present study provides the first evidence indicating that the hexanic extract of S. molle produces a specific antidepressant-like effect in an animal model predictive of antidepressant properties, the TST, similar to the result produced by the classical antidepressant fluoxetine. In addition, we have shown that its antidepressant-like effect is dependent on its interaction with the serotonergic (5-HT1A, 5-HT2A and 5-HT3 receptors), noradrenergic (α1 and α2-receptors) and

Acknowledgement

The present study was supported by a grant from FAPESC-SC, CNPq and CAPES (Brazil). We thank Dr. Daniel B. Falkenberg for identifying the specie of S. molle.

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