Alamgeer, Taseer Ahmad, Iradat Hussain, Muhammad Naveed Mushtaq...
1. Faculty of Pharmacy University of Sargodha, Sargodha, Pakistan 2. Shifa Institute of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 3. Riphah Institute of pharmaceutical sciences, Riphah International University, Islamabad 4. Margalla College of pharmacy, Margalla Institute of Health and Sciences, Rawalpendi
Keywords: Plant extract, depression, animal model, herbal medicine.

Depression is a mood disorder which is among the most dominant forms of psychiatric disorders and a major cause for morbidity and mortality. Since, many synthetic drugs are being used as anti-depressant, but due to adverse effects it leads to patient non-compliance. Thus, there is a need to search for plants oriented anti-depressant drugs and also develop a suitable animal model to clearly elucidate its effects. A number of medicinal plants have shown anti-depressant activities. This review attention is towards plant extract and its use in best animal model which will certainly highlights their influence on the development of novel therapeutic drugs.

Article Information

Identifiers and Pagination:
First Page:159
Last Page:163
Publisher Id:JAppPharm (2013 ). 5. 159-163
Article History:
Received:July 17, 2013
Accepted:September 11, 2013
Collection year:2013
First Published:October 1, 2013


Depression is the most common disorders of mood rather than disturbances of thought or cognition; it may range from a very slight condition, bordering on normality, to severe depression accompanied by hallucinations and delusions. Worldwide, depression is a major cause of disability and premature death. In addition to the noteworthy suicide risk, depressed individuals are more likely to die from other causes, such as heart disease or cancer. There are two distinct types of depressive syndrome, namely unipolar depression, in which the mood swings are constantly in the same direction, and bipolar affective disorder, in which depression alternates with mania. The monoamine theory in 1965, recommends that depression results from functionally deficient monoaminergic (noradrenalin and/or 5hydroxytryptamine) transmission in the central nervous system[1]

According to the WHO report, approximately 450 million people suffer from a mental or behavioral disorder and only a small minority of the patient receives the basic treatment [2]. This mounts to 12.3% of the global burden of disease, and will rise to 15% by 2020[3]. Presently, out of a population of some 152 million the estimated number of mentally disturbed people in Pakistan is more than 14 million. According to World Health Organization statistics, about 46% to 66% of women and 15% to 25% of men in Pakistan, suffer from depression and anxiety (WHO, 2005).

Ambiguity about the biochemical pathogenesis of depression raises the opportunity of finding new antidepressants acting on other (non-amine-related) targets. Many different approaches have been taken, and several compounds are in development [4].



Figure: 1 Mechanisms supposed to be involved in the pathophysiology of depression [1]

They include antagonists of neuropeptides- including CRH and substance P-as well as compounds active on NMDA, acetylcholine and histamine receptors, and compounds that act on the signal transduction pathways responsible for neurogenesis, neural plasticity and apoptosis [1]. Antidepressant drugs such as,  selective serotonin reuptake inhibitors (SSRI) are used to treat depression showing various side effect i-e nausea, anxiety, drowsiness, insomnia, sexual dysfunction, serotonin syndrome and thus, the search for a new antidepressant herb with less side effects is deemed important[5][6].In the search for new therapeutic products for the treatment of neurological disorders, medicinal plant research, worldwide, has progressed constantly, demonstrating the pharmacological effectiveness of different plant species in a variety of animal models[7].

Although synthetic drugs have been commonly used for the treatment of various psychological disorders in developed countries, herbal medicines still remain the widespread choice in the developing countries due to their ease of availability, lesser side effects and lower cost. According to world health organization (WHO), it has been estimated that about 75% of the world’s population depend entirely on traditional medicines for the treatment of various diseases. Moreover, it has been estimated that approximately 70,000 plant species are used in traditional herbal medicines worldwide [8]. The plants reported for anti-depressant activity include Ginko biloba Linn, Magnola officinlis Rehdher & E.H.Wilson, Mimosa pudica Linn, Curcuma long Linn, Mimosa pudica Linn, Ociumum sanctum Linn, Withania somnifera Dunual, Hypericum perforatum Linn, Piper methyticum Forst, Siphocampylus verticillatus (Cham.) G.Don, Perilla frustescens (Linn.) Britton, Rhizoma acori tatarinowii, Areca catechu Linn, Bacopa monnieri (Linn.) Penn, Centella asiatica (Linn.) Urbab, Clitoria ternatea Linn, Cimicifuga racemosa (Linn.), Circuma longa Linn, Evening primrose (Oenothera spp.) oil [9].

Mouse as a model for depression

 Major advantages of using mouse as a model, is their remarkable similarity to human in genetics, anatomy and physiology. More than 95% of the mouse genome is similar to human beings, making mouse genetic research specifically appropriate to human disease. Other advantages of selecting mice as a model are, cost-effectiveness, small dose in relation to body weight, easy to handle and an accelerated breeding time, these points will definitely make the research easily manageable for the researcher. In addition, animal models of depression are crucial for identifying novel therapies for depression [10].

Behavioral tests for depression in mice

Tail suspension test (TST)

The Tail suspension test commonly used as behavioral model for screening antidepressant activity in mice [11]. The animals will be hung by the tail on a plastic string 75 cm above the surface with the help of an adhesive tape. The duration of immobility was observed for a period of 8 minutes. Mice will be considered to be immobile when they ceased struggling and remained floating motionless in water, making only those movements necessary to keep their head above water. After the swimming session, mice will be dried by a towel and returned to their housing conditions [9][12].

Forced swim test (TST)

The most frequently used behavioral model for screening antidepressant effect in rodents [13]. All mice were individually forced to swim in open glass chamber (25 ×15 × 25cm) containing fresh water to a height of 15 cm maintained at 26°±1°C. Each animal will show enthusiastic movement during initial 2 min period of the test. The duration of immobility will be manually recorded during the next 4 min of the total 6 min testing period. Mice will mbe considered to be immobile when they ceased struggling and remained floating motionless in water, making only those movements necessary to keep their head above water. Following swimming session, mice will be towel dried and returned to their housing conditions [9][12].

Light-dark test (LDT)

The apparatus consisted of a Plexiglas box with two compartments (20 cm×20 cm each), one of which will be illuminated with a white light while the other remained dark. Each animal will be placed at the center of the illuminated compartment, facing one of the dark areas. The time spent in illuminated and dark places, as well as the number of entries in each space, will be recorded for 5 minutes [14].

Open field test (OFD)

This test utilizes behavioral changes in rodents exposed to novel environments and is used to confirm that the observed antidepressant effect is not due to stimulation of general motor activity.                                              

The following parameters will be observed for 5 min10: activity in the center (number of central squares crossed), spontaneous ambulation (number of squares crossed at periphery) and rearing (No. of times the animal stands on the rear paws) [15].




Medicinal plants have played a significant role in human health care since the prehistoric times. Herbal medicines are getting more popularity because allopathic medicines have a lot of side effects. South Asian population is using traditional system of medicines to treat a number of diseases.

The available drugs for the treatment of depression, has shown numbers of relapses, side effects, and drug interactions. Like, Tricyclic antidepressants causes dry mouth, sour or metallic taste, epigastric distress, constipation, dizziness, tachycardia, palpitations, blurred vision and urinary retention. Cardiovascular effects include orthostatic hypotension, sinus tachycardia, and variable prolongation of cardiac conduction times with the potential for arrhythmias, particularly with overdoses [16][17]. Due to mention drawbacks of the available antidepressant drugs, attempts are proceeding to explore plants with antidepressant activity. Some important medicinal plants extracts reported as anti-depressant are: Agapanthus campanulatus, Akebiae fructus, Albizzia julibrissin, Ginko biloba Linn. Allium cepa, Asparagus and Artemisia absinthium [18]. Appropriate animal model is crucial for an activity to be fruitful. Most of the studies reported for evaluation of plants antidepressant activities confirm that mouse is the best animal model. However, more clinical studies are required for the plants showing anti-depressant activities in animal studies, so that depression can be treated effectively by using plants-based formulation. Medicinal plants are widely available in Pakistan and other countries. The widespread variety makes them attractive candidates for further research.



Thus, there is a need to conduct more research to explore the full potential of the alternative herbal medicine by using mouse as animal model to confirm its activity.



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Prof. Dr. Cornelia M. Keck (Philipps-Universität Marburg)
Marburg, Germany


Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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