INTRODUCTION:

Depression is a state of low mood activity that can affect a person's thoughts, behavior, feelings and sense of well-being¹. It can be long lasting or recurrent, substantially impairing a person’s ability to function at work or school, or cope with daily life. At its most severe, depression can lead to suicide. When mild, depression can be treated without medicines but, when moderate or severe, people may need medication and professional talking treatments.

People with depressed mood can feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable and restless. They may lose interest in activities that were once pleasurable, experience loss of appetite or overeating, have problems concentrating, remembering details or making decisions, and may contemplate, attempt or commit suicide. Insomnia, excessive sleeping, fatigue, aches, pains, digestive problems or reduced energy may also be present².

Depression is often referred to as the common cold of psychiatry. But this analogy’s wrong: although common, most depressive disorders are not mild and self limiting. It is time that we treated depression as the chronic disease that it is. The World Bank ranks unipolar depression as the number one contributor to the global burden of disease in adults aged 19-45 in the developed world³. Up to 15% of adults may experience clinical depression, 20% will not recover fully from the in dexepisode, and 70-80% of those achieving remission succumb to at least one recurrence. Eighty per cent of individuals with milder persistent symptoms or dysthymia will develop a major depressive episode, and 15% of all patients with depression will eventually commit suicide.

There are important differences between unipolar depression and bipolar depression – differences in how the illness makes people feel and behave, and differences in how they are supported through treatment. In addition to going through low moods or depression, individuals with bipolar disorder also have high moods known as mania during which they may experience increased energy, feelings of euphoria, insomnia(inability to sleep) or impulsive behaviours like shopping sprees or promiscuous sex. Someone with unipolar depression doesn’t go through the highs of bipolar depression. Below is a closer look at the symptoms of both depression and mania.

Depression is a major cause of morbidity worldwide. Lifetime prevalence varies widely, from 3% in Japan to 17% in the US. In most countries the number of people who would suffer from depression during their lives falls within an 8–12% range^4,5. Depression often starts at a young age. Depression is the leading cause of disability for both males and females, It affects women more often than men, the burden of depression is 50% higher for females than males (WHO, 2008), and unemployed people are also at high risk. Today, depression is estimated to affect 350 million people. The World Mental Health Survey conducted in 17 countries found that on average about1 in 20 people reported having an episode of depression in the previous year. Depressive disorders often start at a young age; they reduce people’s functioning and often are recurring. For these reasons, depression is the leading cause of disability worldwide in terms of total years lost due to disability⁶. PERMENT is a poly herbal formulation manufactured by AVN Ayurveda Formulation Pvt. Ltd. Each PERMENT capsule contains aqueous extracts of Bacopa monnieri (Brahmi), Withania somnifera (Aswagandha), Asparagus racemosa (Satavari) and Clitoria ternatea (Shankapushpi)⁷.

These plants due to the presence of Triterpenes, Glycosides, alkaloids as a chief chemical constituents have individually shown potential CNS activities. Apart from that this particular formulation has already been marketed with the claim of antidepressant activity. But till now there is no study has been carried out which indicates the effect of PERMENT on antidepressant activity. So the present study has been designed to evaluate the antidepressant activity of PERMENT using different experimental models^8,9The various herbs present in the formulation are described below:

1.Aswagandha (Withania somnifera):

Biological source:

The drug contains dried leaves of Withania somnifera belongs to the family Solanaceae.

Chemical constituents:

The main constituents of Aswagandha are Alkaloids, Steroidal lactones, Within alkaloids , Withanine is the main alkaloid. Other constituents are amino acids, choline, beta-sitosterol, chlorogenic acid, scopoletin, with a ferin etc. Steroidal lactones include tropine and cuscohygrine¹⁰.

Uses:

It restores the neuro transmitters and hence useful in various mental disorders like depression, anxiety, insomnia, etc. Aswagandha is a revitalizing herb that maintains proper nourishment of tissues particularly Muscles and bones¹¹.

2. Shankupushphi (Clitoria ternatea):

Biological source:

Shankupushpi is the dried flowers of the plant Clitoria ternatea belongs to the family Solanaceae.

Chemical constituents:

It contains glycosides, coumarins, flavonoids, alkaloids (shankhu pushpine is believed to be the Principle active ingredient¹²).

Actions: Rasa:Tikta (Bitter) Guna: Pichchilla (Slimmy), Snigdha (Unctous) Virya: Shita (Cold)¹³.

Vipaka; Madhura (Sweet¹⁴).

Uses:

The whole herb is used medicinally in the form of decoction with cumin and milk in fever, nervous debility, loss of memory, also in syphilis, and scrofula¹⁵.

3. Satavari ( Asparagus racemosa).

Biologicalsource:

The drug contains tuberous roots of the plant Asparagus racemosa belongs to the family Aspargaceae.

Chemical constituents:

Asparagamine A, a polycyclic alkaloid was isolated from the dried roots[5][6] and subsequently synthesized to allow for the construction of analogs¹⁶. Two new steroidal saponins, shatavaroside A and shatavaroside B together with a known saponin, filiasparoside C, were isolated from the roots of Asparagus racemosus^17,18. Five steroidal saponins, shatavarins VI-X, together with five known saponins, shatavarin I (or asparoside B), shatavarin IV (or asparinin B), shatavarin V, immunoside and schidiger asaponin¹⁹. D5 (or asparanin A), have been isolated from the roots of Asparagus racemosus.[9]Also known is the isoflavone 8-methoxy-5,6,4'-trihydroxyisoflavone 7-O-beta-D-glucopyranoside²⁰.

Uses:

Shatavari is used in Ayurveda to balance pitta and vata, but can increase kapha due to its heavy nature.Its bitter and sweet taste has a cooling effect on the system, and its unctuous (oily),²¹ building nature makes it a great support for anyone looking for a nourishing, grounding effect²². These combined qualities make it a rasayana (rejuvenative) for the reproductive system (particularly female),the digestive system (particularly when pitta is involved), and for the blood^23,24.

4. Brahmi (Bacopa monniera)

Biological source:

The leaves of the plant Bacopa monniera belongs to the family scrophulariaceae.

Chemical constituents:

Bacopa monniera contains alkaloid brahmine, nicotinine and herpestine²⁵. Bacosides A, Triterpenoid saponins, saponins A, B and C were also isolated from Bacopa monniera. Bacopasides I, II , III, IV and V were also isolated^26,27.It also contains betulinic acid , D-mannitol , stigmastanol , β-sitosterol and stigmasterol6²⁸.

Uses:

Bacopa administration shows improved acquisition and retention of memory²⁹.The extract of Bacopa monniera exhibited antidepressant activity³⁰.The crude plant extract or bacosides have also shown anxiolytic effects³¹.

The Methanol extract and aqueous fractions showed a significant anti inflammatory action³². Fresh Bacopa monniera juice exerted significant anti ulcerogenic activity³³.

MATERIALS AND METHOD:

Material selection:

Animal selection:

Swiss albino mice weighing 18-30 gm, Albino Rats weighing 200-250 gm were used for the study. The mice were in bred in the central animal house of the Department of Pharmacology, Karavali College of Pharmacy, Mangalore, under suitable conditions of housing, temperature, ventilation and nutrition were used for anti depressant activity. They were kept in clean dry cages week before the beginning of the experiment to acclimatize with the experimental conditions. The animals were fed with standard pelleted diet (Lipton India Ltd., Mumbai) and distilled water ad libitum was maintained at 210C-230C under a constant 12hrs light and dark cycle. The animal care and experimental protocols were in accordance with CPCSEA /IAEC .

Housing :

Mice and rats were housed in groups of six in each clean cage. The bedding material of the cages was removed and replaced thrice a week with fresh materials as often as necessary to keep the animals clean and dry. Bedding materials used in sufficient amount to keep animals dry between cage changes without coming into contact with watering tubes. Drinking tubes were examined routinely to ensure their proper function^34,35.

Chemicals used:

· Ethanol

· Chloroform

· 5 % Tween

· Imipramine ( 15 mg/kg )

· Diazepam ( 1 mg/kg )

Test drug:

PERMENT tablet is a polyherbal formulation manufactured by AVN Ayurveda formulation Pvt Ltd 75-A and is purchased from Ernakulam district, Kerala. It is preserved in the department library for future reference.

Preparation of test solution:

The tablets are crushed in to powder, a small quantity of water is added to make a smooth suspension, triturated with mortar and pestle, a pinch of Tween 80 is added to make a uniform suspension. Required quantity of water is added.

Antidepressant Activity:

Preparation of animals:

The animals were selected in such a way that they were free from illness, injury, disease and keep in their cages for at least 5prior to dosing to allow for acclimatization to the laboratory conditions. Only those animals which are healthy having weights 18-30 g were selected and maintained at standard laboratory conditions.

Dose Selection:

The doses which were administered to rats were calculated accordingly from human dose. The human dose was converted to rat dose by using Human equivalent dose method (HED)³⁶. The low, moderate and high doses of PERMENT were selected as53.85mg/kg, 102.77mg/kg and 154.16mg/kg respectively.

Observations:

Animals were observed initially after dosing at least once during the first 30 min, periodically during the first 24 h. additional observations like changes in skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous systems and somato motor activity and behavioral pattern were also done. Attention was also given to observations of tremors and convulsions³⁷.

ANTIDEPRESSANT MODELS:

Forced Swim Test:

The forced swimming model to test antidepressant activity was developed by Porsolt et al. the model used in the present study was similar to the original method described^36,38.

MATERIALS:

· Clean glass cylinder (25 x 15 x 25 cm)

· Water maintained at 23-25oC.

· Towels to dry animals after swimming.

· Stop watch to calculate the duration of immobility.

Procedure :

Mice were individually placed into a glass cylinder filled with 15 cm of water for6 min. As a measure of depression-like behavior, the total duration of immobility and the number of immobility episodes were recorded. Immobility is defined as the absence of movement, unless they are necessary for the animal to stay afloat (head above water).Maintained the temperature of water at 26 ± 10c. At this height of water, animals were not able to support themselves by touching the bottom or the side walls of the chamber with their hind-paws or tail. Water in the chamber was changed after subjecting each animal to FST because“ used water” has been shown to alter the behavior. Each animal showed vigorous movement during initial 2 min period of the test. The duration of immobility was manually recorded during the next 4 min of total 6 min testing period.

Mice were 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 sessions, the mice were dried with towel and placed in a cylinder heated under 60 W bulb. The animals were dried under heated cylinder for 15 minutes before returning to the home cages. Groups of Animals:

The animals were divided as follows.

· Group I – Received 0.05ml/10g of Normal saline intra peritoneally.

· Group II – Received 15 mg/kg Imipramine intra peritoneally.

· Group III –Received 53.85 mg/kg PERMENT orally.

· Group IV – Received 102.77 mg/kg PERMENT orally.

· Group V– Received 154.16 mg/kg PERMENT orally.

Tail Suspension Test:

Mice tail suspension test (TST) is one of the most frequently employed test for screening of antidepressant activity. In the tail suspension test, mice initially engaged invigorous escape behaviors but eventually succumb to immobility. Like the FST, longer duration of TST immobility in for a height ened degree of behavioral despair. As such, TST is a commonly used screening method for antidepressant properties of drug and highly sensitivity to pharmacological manipulations. Antidepressant drug generally decrease the duration of TST immobility in mice¹².

Materials:

· A shelf or tail suspension apparatus to suspend mice. The apparatuses may be wooden or plastic boxes (e.g. 680 x 365 x 280 mm), painted to contrast with mice.

· Tape measure to determine the height of suspension.

· Adhesive tape to secure mice to suspension apparatus.

Procedure:

Animals were moved from their housing colony to laboratory in their own cages and allowed to adopt to the laboratory conditions for 1-2 hr. Each mice was individually suspended to the edge of a table, 50cm above the floor by adhesive tape placed approximately 1 cm from the tip of the tail. Each animal under test was both acoustically and visually isolated from other animals during the test. Total period of immobility was recorded manually for 6 min. Animal was considered to be immobile when it didn’t show any body movement, hung passively and completely motionless. The test was conducted in a dim lighted room and each mice was used only once in the test. The observer, recording the immobility of animals was blind to the drug treatment given to the animals under study^37,38.

Groups of Animals:

The animals were divided as follows.

· Group I – Received 0.05ml/10g of Normal saline intra peritoneally.

· Group II – Received 15 mg/kg Imipramine intra peritoneally.

· Group III – Received 53.85 mg/kg PERMENT orally.

· Group IV – Received 102.77 mg/kg PERMENT orally.

· Group V – Received 154.16 mg/kg PERMENT orally.

Learned Helplessness Test:

Animals exposed to in escapable and unavoidable electric shocks in one situation later fail to escape shock in a different situation when escape is possible. (Overmier and Seligman 1967; Maier and Seligman 1976). This phenomenon was evaluated as a potential animal model of depression³⁶.

Procedure:

Learned helplessness was produced in rats by exposure to electric shock (rat-0.7mA, mice-0.2 mA) for 1 hr on a schedule of 10 s of shock/min. The apparatus was a 30 x 45 x 30 cm box with a grid floor. At a height of 20 cm above the floor, a platform (7.5 x 7.5) can be inserted through one side wall to allow a jump-up escape response. The platform was not available during training. After the appropriate treatment, the animals were tested for acquisition of jump-up escape in the same apparatus. At the beginning of a trial, the platform was pushed into the box and 0.2 mA shock initiated. Shock was terminated in 10 s if the animal has not escaped onto the platform by this time. If an escape response occurred, the animal was allowed to remain on the plat form for the duration of 10 s, and then returned to the grid floor. Ten such trails with an inter-trial interval of 20 s were given. In control group of rats, this training resulted in 80% acquiring learned helplessness behavior. Drugs were given before the training and test period. A drug was considered to be effective, if the learned helplessness was reduced and number of failure to escape was decreased and avoidance response was increased³⁹.

Groups of Animals:

The animals were divided as follows.

· Group I – Received 0.05ml/10g of Normal saline intra peritoneally.

· Group II –Received 15 mg/kg Imipramine intra peritoneally.

· Group III – Received 53.85 mg/kg PERMENT orally.

· Group IV – Received 102.77 mg/kg PERMENT orally.

· Group V –Received 154.16 mg/kg PERMENT orally.

Reserpine induced Test:

Materials:

· Electronic thermometer

· Stopwatch

Procedure:

Groups of 5 male rats are used. On the day of test they are dosed with drug after 18 hrs of administration they are placed separately. The initial rectal temperature is determined by insertion of an electronic thermometer. After administration of test drug temperature is tested for 60 mint for 7 hrs.

Groups of Animals:

The animals were divided as follows.

· Group I –Received 0.05ml/10g of Normal saline intra peritoneally.

· Group II – Received 1 mg/kg Diazepam intra peritoneally.

· Group III – Received 53.85 mg/kg PERMENT orally.

· Group IV – Received 102.77 mg/kg PERMENT orally.

· Group V – Received 154.16 mg/kg PERMENT orally.

Hole Cross Test:

Materials:

· Wooden box ( 100 x 100 x 30 cm)

· Stopwatch

Procedure:

This test utilizes the rodents are placed at the intersection of the four arms of the maze facing an open arm. The number of entries and time spent in each arm is recorded and valid results are obtained in a single 5-minute testing session. An increase in the open-arm time is an index of anti-anxiety behavior of rodents. The test comprises of configuration of a + and comprises two open arms (25 x 5 x 0.5 cm) across from each other and perpendicular to two closed arms (25 x 5 x 16 cm) with a center platform (5 x 5 x 0.5 cm). Rats are housed with a 12-h light/dark cycle. Behavioral testing is performed between 9:00 AM and 6:00 PM. All the experimental mice are transferred to the behavior testing room30 min. The very first mouse in the entire session would experience somewhat different condition with others. A mouse is placed in the center area of the maze with its head directed toward a closed arm. The number of entries an entry is defined as the center of mass of the mouse enters the arm into each arm and the time spent in the open arms are recorded and these measurements serve as an index of anxiety-like behavior. Rats are allowed to move freely about the maze for 10 min. Each mouse receives one trial in our test. The distance traveled, the number of entries into each arm, the time spent in each arm, and the percent of entries into the open arms are calculated. Thus the number of entries and time spent in each arm is recorded and valid results are obtained in a single 5-minute testing session. An increase in the open-arm time is an index of anti-anxiety and anti depressant activity behavior of rodents^40,41.

Groups of Animals:

The animals were divided as follows.

· Group I –Received 0.05ml/10g of Normal saline intra peritoneally.

· Group II – Received 1 mg/kg Diazepam intra peritoneally.

· Group III – Received 53.85 mg/kg PERMENT orally.

· Group IV – Received 102.77 mg/kg PERMENT orally.

Statistical Analysis:

ANOVA (Analysis of variance):

Results are prepared as Mean ± SEM. One way ANOVA was used for multiple comparison followed by Dunnett’s multiple comparison tests. For all tests a “P” value of0.05 or less was considered for statistical significance. In statistics, analysis of variance is a collection of statistical models and their associated procedures, in which the observed variance is partitioned into components due to different explanatory variables. In its simplest form ANOVA gives a statistical test of whether the means of several groups are all equal and therefore generalize Dunnett’ s multiple comparison tests to more than two groups.

RESULTS:

I) Antidepressant activity of perment:

Antidepressant models namely Forced Swim Test (FST), Tail Suspension Test (TST), Learned Helplessness Test (LHT) and Open field test were carried out.

Forced Swim Test:

In FST, Table No.1 shows that animals treated with three doses of PERMENT (53.85, 102.77 and 154.16 mg/kg) showed decrease in their immobility times, which was significant (136.50±0.65; p<0.01 and 131.42±0.56, 123.26±0.72; p<0.001)when compared with control (139.41±0.68). Similarly, animals treated with imipramine (15 mg/kg), as expected, showed a significant decrease in the immobility time (61.36±0.88; p<0.001). Animals treated with high dose (154.16 mg/kg) and moderate dose (102.77 mg/kg) shows more significant decrease in immobility time when compared with low dose (53.85 mg/kg).

Tail Suspension Test:

Animals treated with three doses of PERMENT showed decrease in their immobility times, which was significant (159.14±0.78; p<0.05, 157.88±1.14; p<0.01 and 138.24±1.08; p<0.001) when compared with control (162.35±0.85). Similarly, animals treated with imipramine (15 mg/kg) as expected, showed a significant decrease in the immobility time (72.22±068; p<0.001). Animals treated with high dose (154.16 mg/kg) showed more significant decrease in immobility time (Table No 2).

Learned Helplessness Test:

Animals treated with three doses of PERMENT day 1, day 2 and day 3 showed the significant increase in avoidance response and decrease in escape failure (Table No.3).

Reserpine Induced test:

Reaserpine induced test the rectal temperature is recorded for every hour. Difference in temperature from vehicle control is calculated for each time and the maximal difference is scored. The differences are then statistically compared using test.

4. Hole cross test:

In the Hole Cross test the rodents are placed at the intersection of the four arms of the maze (two open, two closed), facing an open arm. The number of entries and time spent in a charm is recorded and valid results are obtained in a single 5-minute testing session. An increase in the open-arm time is an index of anti-anxiety behavior of rodents. In PERMENT treated groups but it was not statistically significant compared to control. There was a significant increase in no. Of crossings in diazepam group as compared to control group. There was significant increase in the rearing of animals with diazepam in comparison to the control group. There was no increased number of rearing in test drug treated groups (Table No.4)

Table No 1 Effect of PERMENT on Immobility time in FST.

Group No.	Drug Treatment	Dose (mg/kg)	Immobility period, mean ± S.E.M [n=6]
I	Control	0.05 ml/10 g	139.41±0.68
II	Imipramine	15	61.36±0.88***
III	PHFP LD	53.85	136.50±0.65**
IV	PHFP MD	102.77	131.42±0.56***
V	PHFP HD	154.16	123.26±0.72***

Values were mean ± S.E.M. for (n=6) expressed as the time (in sec) of 6animals each group. Data analysis was performed using Dunnett’s test.

Effects of PERMENT on Immobility time in FST

Fig 1:Effect of PERMENT on Immobility time in FST

FST Values were mean ± S.E.M. for (n=6) expressed as the time (in sec) of 6 animals each group. Data analysis was performed using Dunnett’s test. *P < 0.05, **P < 0.01, ***P < 0.00

Table No 2: Effect of PERMENT on Immobility time in TST

Group No.	Drug Treatment	Dose (mg/kg)	Immobility period, mean ± S.E.M [n=6]
I	Control	0.05 ml/10 g	162.35±0.85
II	Imipramine	15	72.22±0.68***
III	PERMENT (Low dose-LD)	53.85	159.14±0.78*
IV	PERMENT (Moderate dose-MD)	102.77	157.88±1.14**
V	PERMENT (High dose-HD)	154.16	138.24±1.08***

Values were mean ± S.E.M. for (n=6) expressed as the time (in sec) of 6animals each group. Data analysis was performed using Dunnett’s test.

*P < 0.05, **P < 0.01, ***P < 0.001.

Effect of PERMENT on immobility time in TST

Fig 2 : Effect of PERMENT on Immobility time in TST

Values were mean ± S.E.M. for (n=6) expressed as the time (in sec) of 6 animals in each group. Data analysis was performed using Dunnett’s test. *P < 0.05, **P < 0.01, ***P <0.001 vs. Control

Groups

Table No 3: Effect of PERMENT on Learned helplessness test in albino rats.

Group

No.

Drug

Treatment

Dose

mg/kg

Day I

Day II

Day III

Control

0.05ml/10g

20.41±

0.854

.26±

0.66

19.56±

0.64

4.17±

0.48

19.86±

0.58

5.08±

0.36

Imipramine

11.48±

0.72***

19.34±

0.86***

7.36±

0.86****

20.48±

0.96**

3.48±

0.64***

21.58±

0.76***

III

MLD

53.85

19.22±

0.62*

7.26±

0.72**

16.42±

0.62**

6.82±

0.64**

17.12±

0.96**

7.68±

0.48**

MGMD

102.77 **

17.64±

0.829.

48±

0.76**

14.68±

0.72**

7.28±

0.48***

14.36±

0.86***

11.24±

0.52***

PHFPHD

154.16***

16.24±

0.88***

11.64±

0.86**

11.68±

0.88**

10.72±

0.86**

10.68±

0.76***

14.18±

0.62***

Values were mean ± S.E.M. for (n=6) expressed as the time (in sec) of 6animals each group. Data analysis was performed using Dunnett’s test

*P < 0.05, **P < 0.01, ***P <0.001.

Table No 4: Effect of PERMENT on Reserpine induced test in rats.

Group No.	Drug Treatment	Dose (mg/kg)	No. of squares crossed (Mean) ± SEM )		No Of Rearings Mean± SEM)
Group No.	Drug Treatment	Dose (mg/kg)	Centre	Periphery	No Of Rearings Mean± SEM)
I	Control	0.05ml/10g	10.20±0.68	76.12±0.38	3.64±0.58
II	Diazepam	1	28.42±0.56***	114.36±0.42***	8.64±0.68***
III	PL	53.85	10.48±0.54	76.28±0.36	3.18±0.36
IV	PMD	102.77	10.64±0.74	76.46±0.54	3.26±0.32
V	PHD	154.16	10.26±0.64	76.14±0.64	3.28±0.42

Values were mean ± S.E.M. for (n=6) expressed as the time (in sec) of 6 animals in each group. Data analys test.

*P < 0.05, **P < 0.01, ***P < 0.001 vs. control.

DAY I

Effect of PERMENT on escape failure in learned helplessness test

Effect of PERMENT on Avoidance response in learned helplessness test

Figure 3: Comparative profile of escape failure (I) and avoidance response (II) in LHT after administration of 53.87,102.77and 154.16 mg/kg of PERMENT at day 1.

Day II

Effect of PERMENT on escape failure in learned helplessness test

Effect of PERMENT on Avoidance response in learned helplessness test

Figure 4: Comparative profile of escape failure (I) and avoidance response (II) in LHT after oral administration of 53.87,102.77and 154.16 mg/kg of PERMENT at day 2.

Day III

Effect of PERMENT on escape failure in learned helplessness test

Effect of PERMENT on Avoidance response in learned helplessness test

Figure 5: Comparative profile of escape failure (I) and avoidance response (II) in LHT after oral administration of 53.87,102.77and 154.16 mg/kg of PERMENT at day 3.

CONCLUSION:

The present study was aimed to expose the antidepressant activity of PERMENT in Swiss albino mice and albino rats using five animal models of depression namely, Forced swim test, Tail suspension test, Learned helplessness test, Hole Cross Test and Reserpine induced test. The Data obtained was satisfactory and conclusive and so as to accomplish our objectives. In conclusion the present data indicate that the administration of Perment to mice has shown significant dose dependant antidepressant activity supporting folk information regarding antidepressant activity of the formulation, relatively sub-chronic study may be necessary to arrive at a better picture.

The exact mechanism underlying antidepressant effect is not clear but it may be apparently related to active components present in them. Hence further studies would be necessary to evaluate the contribution of active chemical constituents for the observed antidepressant activity, as it still remains to be determined which components were responsible for these effects. In our study we have made an attempt to prove its efficacy in experimental animals. Further study can be done in human subjects.

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Received on 17.03.2016 Modified on 08.04.2016

Research J. Pharmacology & Pharmacodynamics.2016; 8(2): 45-54

DOI: 10.5958/2321-5836.2016.00009.4