Antidepressant-Like Effect of Rosmarinus officinalis Extract in Male Mice

Entisar J. Al Mukhtar,Selman M. Selman,Zena Hasan Sahib,Hamid Naji
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Keywords : Rosmarinus officinalis extract; Impramine; Antidepressant effect; Mice.
Medical Journal of Babylon  10:4 , 2014 doi:1812-156X-10-4
Published :03 June 2014

Abstract

Background: Depression is the most common of the mood disorders. There are many types of antidepressant drugs which have various unwanted effects and interactions. Aim of the study: To explore the potential effects of plants in the treatment of depression in comparison to imipramine. Animals, materials and methods: Twenty eight male Swiss albino mice were divided into four groups (A, B, C, D), each group received distilled water 0.3 ml as a control; imipramine 15 mg/kg; R. officinalis 15 mg/kg and R. officinalis 30 mg/kg PO, once daily for 5 successive days respectively. On the fifth day and after thirty minutes of the treatment administration the mice were tested by using the forced swimming test (FST) and the immobility and swimming times were measured. Results: Water extract of R. officinalis extract (15 mg/kg and 30 mg/kg) high significantly reduced the immobility time and increased the swimming time in the FST in comparison to untreated group, but when compared to imipramine (15mg/kg) it produced similar results. Therefore, water extrat of R. officinalis had antidepressant effects which is comparable to that of impramine in mice.

Introduction

Depression is the most common of the mood disorders; it may range from a very mild condition, on bordering on normality, to severe (psychosis) depression accompanied by hallucinations and delusions. The main biochemical theory of depression is the monoamine hypothesis, which states that depression is caused by a functional deficit of monoamine transmitters at certain sites in the brain.[1,2] Initially the hypothesis was formulated in terms of noradrenaline, but subsequent work showed that most of the observations were equally consistent with 5-hydroxytryptamine (5-HT).[3] There are many types of antidepressant drugs which have various unwanted effects and interactions. Therefore, this study was achieved to investigate the potential effects of plants such as Rosmarinus officinalis (R. officinalis) in the treatment of depression in comparison to imipramine. Rosmarinus officinalis, commonly known as Rosemary is a powerful herb belonging to the family Lamiaceae that originates from the Mediterranean region. The name "rosemary" derives from the Latin "dew" (ros) and "sea" (marinus), or "dew of the sea". [4] R officinalis, is a common medicinal and aromatic plant, grown in many parts of the world. Rosemary is indigenous to southern Europe, particularly on the dry rocky hills of the Mediterranean region. Traditionally, rosemary is used as a spice in foods and beverages and as a herbal medicine for various spasmodic conditions such as renal and biliary colic. [5] In folk medicine, rosemary is known for memory improving and treating cognitive decline. It is also used as sedative and relaxant, against headaches, epilepsy, and depression. [6] Additionally, various pharmacological studies have demonstrated the analgesic [7], anti-inflammatory [8], anti-tumor [9], anti-ulcerogenic [10], anti-bacterial [11] and hepatoprotective [12] properties of rosemary.

Materials and methods

1. Preparation of Plant Extract:
Leaves of R. officinalis were purchased from the Hilla local market and identified by a competent botanist at the collage of science for girls, at Babylon university, Iraq. The leaves were washed carefully, then air dried in shade at room temperature, then grinded to fine powder. The plant extract was prepared by mixing 40 gm of leaves powder with 80 ml distilled water by refluxing for 36 hrs at 50-60 ?C. Pellets of the extract were obtained by evaporation of its liquid contents in the incubator. The required dose for treatment was prepared by dissolving the pellets in distilled water and administered by stomach tube at a doses of 15 mg/kg and 30 mg/kg daily for 5 consecutive days. [13]

2. Animals:
Twenty eight male Swiss Albino mice (weighting 25 – 30 g) were used in this study. The mice kept in the animal house in the college of medicine in Babylon university under constant conditions of temperature (22 ± 2 ) ?C and lighting (12:12hr light: dark cycle) for at least two week before and through the experimental work, being maintained on a standard commercial mice chow and water were available ad-libitum with tap water.

3. Drug:
Imipramine hydrochloride ( Tofranil 10 mg, NOVARTIS ) was dissolved in normal saline ( 10 mg in a final volume of 10 ml ).

4. Model for testing antidepressant activities:
Forced swimming test: Forced swimming test was proposed as a model to antidepressant activity by Porsolt et al [14] . Mice were forced to swim individually in glass jar (12 x 30 cm) containing fresh water up to 15 cm height and maintaining at 25 ?C (± 3 ?C). A mouse was considered to be immobile when it remained floating in the water without struggling, making only minimum movements of its limbs, necessary to keep its head above the water. The total duration of immobility was recorded within the total test duration of five minutes. Each mice was used only once.

5. Protocol:
Animals were randomly divided into 4 groups (each group consist of 7 mice):
Group A(control): received 0.3ml distilled water, PO, once daily for 5 days.
Group B: received imipramine 15 mg / kg, PO, once daily for 5 days.
Group C: received R. officinalis 15 mg / kg PO, once daily for 5 days.
Group D: received R. officinalis 30 mg / kg PO, once daily for 5 days.
On the fifth day and after thirty minutes of the dose administration, immobility and swimming times were measured within 5 minutes for each mice by using FST. All behaviors of the mice in the test were recorded by video camera.
6- Video Camera:
Video Camera ( SONY- SD/ DIGITAL VIDEO CAMERA ) was used to record all behaviors of the animals during the test.
7- Statistical analysis:
The data expressed as mean ± SD, SPSS version 17.0 was used for the statistical analysis, ANOVA test was used is this study. P- values less than 0.05, 0.01 and 0.001 were considered as statistically significant, high significant and extremely significant respectively. [15]


Results

Regarding the swimming time the present study showed a high significant increase (p<0.01) in swimming time through FST in both 15 and 30 mg/kg R. officinalis treated groups compared to control group (4.45± 0.19 and 4.46± 0.43 respectively vs.3.74±0.37), while imipramine caused significant increase (p<0.05) in swimming time compared to control group (4.22±0.55 vs. 3.74±0.37). Significant differences were neither found between imipramine and both doses (15 and 30mg/kg) of R. officinalis (4.22±0.55 vs. 4.45± 0.19 and 4.46± 0.43 respectively) nor between 15mg/kg and 30mg/kg of R. officinalis (4.45± 0.19 vs. 4.46± 0.43), as shown in fig. (1) Regarding the immobility time it significantly decreased (p<0.05) in imipramine treated group compared to control group (0.48±0.52 vs. 0.95±0.32), it also decreased high significantly (p<0.01) in 30mg/kg R. officinalis treated group compared to control group (0.19±0.37 vs. 0.95±0.32), while it was extremely significantly decreased in 15mg/kg R. officinalis treated groups compared to control group (0.14±0.19 vs. 0.95±0.32). Significant differences were neither found between imipramine and 15 and 30mg/kg doses of R. officinalis (0.48±0.52 vs. 0.14±0.19 and 0.19±0.37 respectively) nor between 15mg/kg and 30mg/kg of R. officinalis (0.14±0.19 vs. 0.19±0.37), as shown in fig. (2).

Discussions

The antidepressant action of R. officinalis extract found by the present study may be mediated by an interaction with the monoaminergic system as had been found by Machado et al [16], who also found that the pretreatment of mice with p-chlorophenylalanine (5-HT synthesis inhibitor), NAN-190 (5-HT1A receptor antagonist), ketanserin (5-HT2A receptor antagonist), biguanide (mCPBG, 5-HT3 receptor agonist), SCH23390 (dopamine D1 receptor antagonist) or sulpiride (dopamine D2 receptor antagonist) was able to reverse the anti-immobility effect of the extract (10 mg/kg, PO) in the tail suspension test (TST). [16] In this study the antidepressant action of R. officinalis also may be attributed to the presence of the, luteolin, carnosic acid, and rosmarinic acid as these compounds can cause upregulated of the two major genes (tyrosine hydroxylase and pyruvate carboxylase) involved in the regulations of dopaminergic, serotonergic and GABAergic pathway, [17] Regarding the two doses of R. officinalis used in this study, up to knowledge no study were found to which results of the present study can be compared.

Conclusions

The antidepressant like-effect of Rosmarinus officinalis extract is more than that of impramine. Further studies including human s studies are needed.

References

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2. Manji H.K., Drevets W.C., Charny D.S. (2001) The cellular neurobiology of depression. Nat Med 7:541-547.

3. Nutt D.J. (2002) The neuropharmacology of serotonin and noradrenaline in depression. Int Clin Psycopharmacol; 17:S1-12.

4. All about rosemary (Rosmarinus officinalis). 2012. [online], http://www.natuurlijkerwijs.com/english/Rosemary.htm.

5. Al-Sereiti, M.R., Abu-Amer K.M., Sen, P. (1999): Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian J. Exp. Biol. ;37(2):124-130.

6. Heinrich, M., Kufer, J., Leonti, M., Pardo-de-Santayana, M. (2006). Ethnobotany and 17 ethnopharmacology-Interdisciplinary-links with the historical sciences. Journal of 18 Ethnopharmacology 107, 157-160.

7. Takaki, I., L.E. Bersani-Amado, A. Vendroscolo, S.M. Sartoretto, S.P. Diniz and C.A. Bersani-Amado (2008). Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models. J Med Food, 11: 741-746.

8. Juhas, S., A. Bukovska, S. Cikos, S. Czikkova, D. Fabian and J. Koppel (2009). Anti-inflammatory effects of Rosmarinus officinalis essential oil in mice. Acta Vet Brno., 78: 121-127.

9. Cheung, S. and J. Tai (2007). Anti-proliferative and antioxidant properties of Rosmarinus officinalis. Oncol Rep., 17: 1525-1531.

10. Dias, P.C., M.A. Foglio, A. Possenti and J.E. Carvalho (2000). Antiulcerogenic activity of crude hydroalcoholic extract of Rosmarinus officinalis L. J Ethnopharmacol., 69: 57-62.

11. Oluwatuy, M., G.W. Kaatz and S. Gibbons (2004). Antibacterial and resistance modifying activity of Rosmarinus officinalis. Phytochemistry., 65: 3249-3254.

12. Galistco, M., A. Suarez, M. Del Pilar Montilla, M. Del Pilar Utrilla, J. Jimenez, A. Gil and M.J. Faus (2000). Antihepatotoxic activity of Rosmarinus tomentosus in a model of acute hepatic damage induced by thioacetamide. Phytother Res., 14: 522-526.

13. Jindal, A., D. Soyal, I. Sihgh and R. Reszka (2006). Modification of radiation-induced damage in mice by Rosemarinus officinalis extracts (ROE). Pharmacology Line., 2: 63-75.

14. Porsolt R.D., Bertin A.,and Jelfre M. (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther.; 229:327-336.

15. Daniel, W.W. (1999) Probability and distribution. Biostatistics. Afoundation for analysis in the health sciences .7th ed.; 83-123.

16. Machado DG, Bettio LE, Cunha MP, Capra JC, Dalmarco JB, Pizzolatti MG, Rodrigues AL. (2009). Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: involvement of the monoaminergic system. Epub, 15; 33 (4): 642-50.

17. Sasaki, K. , El Omri, A. , Kondo, S. , Han, J. , Isoda, H. (2013) Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation. Behavioural Brain Research, 238: 86–94.


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