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www.wjpps.com Vol 9, Issue 2, 2020. 1146 Kavitha et al. World Journal of Pharmacy and Pharmaceutical Sciences EVALUATION OF ANTIDEPRESSANT ACTIVITY OF ALBIZZIA LEBBECK (L) BENTH. IN BEHAVIORAL DESPAIR MODEL Kavitha S. K.* 1 , Syed Nizamuddin 2 and Nagaraj N. 3 1 Department of Pharmacology, R.R. College of Pharmacy, Bangalore, India. 2,3 Department of Pharmaceutical Chemistry, R.R. College of Pharmacy, Bangalore, India. ABSTRACT Depression being a state of sadness may be defined as a psychoneurotic disorder characterized by mental and functional activity, sadness, reduction in activity, difficulty in thinking, loss of concentration, perturbations in appetite, sleeping, and feelings of dejection, hopelessness and generation of suicidal tendencies. It is a common and recurrent disorder causing significant morbidity and mortality worldwide. The antidepressant compounds used against depression are reported to be used also for treating pain, anxiety syndromes etc. They have been grouped in five different categories such as Tricyclic antidepressants (TCAs), Selective serotonin-reuptake inhibitors (SSRIs), Monoamine oxidase inhibitors (MAOIs), Serotonin-nor epinephrine reuptake inhibitor (SNRI) and Non-TCA antidepressants based on their mode of action. Most of the antidepressants have been reported to possess adverse effects on the health of users. The present review article focuses on an updated current of antidepressants, their mechanism of actions, path physiology of these compounds, their side effects and the strategies to combat the drug induced toxicity. KEYWORDS: Antidepressant drugs, Depression, Neurotransmitters, MAOIS , psychoneurotic disorder. INTRODUCTION The human nervous system (CNS) is an extremely complex structure, having more than 12 billion nerve cells. Together with the endocrine system, it coordinates and regulates the flunctioning of all body organ. [1] Major depression and mania are two extremes of affective disorder which refer to pathological change in mood state. Major depression is characterized WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES SJIF Impact Factor 7.632 Volume 9, Issue 2, 1146-1163 Research Article ISSN 2278 – 4357 *Corresponding Author Prof. Kavitha S. K. Department of Pharmacology, R.R. College of Pharmacy, Bangalore, India. Article Received on 15 Dec. 2019, Revised on 05 Jan. 2020, Accepted on 26 Jan. 2020 DOI: 10.20959/wjpps20202-15509

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Kavitha et al. World Journal of Pharmacy and Pharmaceutical Sciences

EVALUATION OF ANTIDEPRESSANT ACTIVITY OF ALBIZZIA

LEBBECK (L) BENTH. IN BEHAVIORAL DESPAIR MODEL

Kavitha S. K.*1, Syed Nizamuddin

2 and Nagaraj N.

3

1Department of Pharmacology, R.R. College of Pharmacy, Bangalore, India.

2,3Department of Pharmaceutical Chemistry, R.R. College of Pharmacy, Bangalore, India.

ABSTRACT

Depression being a state of sadness may be defined as a

psychoneurotic disorder characterized by mental and functional

activity, sadness, reduction in activity, difficulty in thinking, loss of

concentration, perturbations in appetite, sleeping, and feelings of

dejection, hopelessness and generation of suicidal tendencies. It is a

common and recurrent disorder causing significant morbidity and

mortality worldwide. The antidepressant compounds used against

depression are reported to be used also for treating pain, anxiety

syndromes etc. They have been grouped in five different categories

such as Tricyclic antidepressants (TCAs), Selective serotonin-reuptake

inhibitors (SSRIs), Monoamine oxidase inhibitors (MAOIs), Serotonin-nor epinephrine

reuptake inhibitor (SNRI) and Non-TCA antidepressants based on their mode of action. Most

of the antidepressants have been reported to possess adverse effects on the health of users.

The present review article focuses on an updated current of antidepressants, their mechanism

of actions, path physiology of these compounds, their side effects and the strategies to combat

the drug induced toxicity.

KEYWORDS: Antidepressant drugs, Depression, Neurotransmitters, MAOIS,

psychoneurotic disorder.

INTRODUCTION

The human nervous system (CNS) is an extremely complex structure, having more than 12

billion nerve cells. Together with the endocrine system, it coordinates and regulates the

flunctioning of all body organ.[1]

Major depression and mania are two extremes of affective

disorder which refer to pathological change in mood state. Major depression is characterized

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 2, 1146-1163 Research Article ISSN 2278 – 4357

*Corresponding Author

Prof. Kavitha S. K.

Department of

Pharmacology, R.R. College

of Pharmacy, Bangalore,

India.

Article Received on

15 Dec. 2019,

Revised on 05 Jan. 2020,

Accepted on 26 Jan. 2020

DOI: 10.20959/wjpps20202-15509

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Kavitha et al. World Journal of Pharmacy and Pharmaceutical Sciences

by symptoms like sad mood loss of interest and pleasure. low energy, Pscychomotor

retardation or agitation, change in appetite or sleep, suicidal thoughts etc.[2]

Depression is

highly prevalent condition, affecting approximately 121 million people worldwide according

to WHO 2008,[3]

it is clinically and biologically heterogeneous disease. It is one of the most

prevalent and costly psychiatric disorders worldwide, with 10-30 percentage of woman

and 7-15p of men likely to suffer from depression in their life time.[4]

Furthermore, the

WORLD HEALTH ORGANIZATION revealed that depression is the fourth leading cause of

disability world wide exceeded by lower respiratory infections, prenatal condition and

HIV\AIDS.[5]

It is common in the elderly and increasingly recognized in young adults,

adolescents, and children. Proactive and sustained antidepressant treatment is essential to

achieve optimal remission and to avoid the considerable danger of relapse, despite their

improved safety profiles compared to first generation drugs. Such as Imipramine, even agents

such as the selective (5-HT) serotonin reuptake inhibitors (SSRI S) Fluoxetine offer little

advantages in terms of efficacy. There remains, thus, a passing need for more effective

antidepressants that do not require several weeks of administration prior to full expression of

clinical efficacy. Furthermore, there is a need to reduce undesirable side effects such as

sexual dysfunction, insomnia, and weight gain Which compromise patient compliance and

curtail drug efficacy.[6]

Interestingly, similar opinion that ideally, a new antidepressant should

not only have greater efficacy and be cast effective and to have a rapid onset of action.[7]

The

plant kingdom may be a part of this search for the ‘Holy Grail‘ of antidepressant

psychopharmacology, as evidenced by the emergence of Hypericumperforatum (St, John‘s

Work) as an effective clinical antidepressant. Herbal drugs play important role in healtheare

programs in treatment of various diseases including depression disorders. In india ayurveda is

traditional medicinal system, assigns much importance to the pharmacological aspects of

many plants. The term ayurveda in Sanskrit consists of two words ‘AYUR‘ meaning life and

‘Veda‘ meaning knowledge or science thus. Ayurveda is science of life. Ayurveda is

considered as the up veda of atharveda which deals with different type of herb, plant, the

anatomy and physiology of different organ of body and principles of treatment of diseases.

Plant kingdom is rich of various medicinal species having their effect on nervous system.

They are used or abused for medicinal or narcotic purpose, some of them like opium.

pilocarpus and brahmi have potential therapeutic uses also. Now a day‘s pharmacological

spectrum and biological efficiency of such herbal drugs can be suitably established due to

development of various neuropharmacological testing of herbal drugs with effect on CNS &

ANS.[10]

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HERB USED FOR DEPRESSION

Healing with herbs has a story as long as the human history itself, Neanderthal to tombs

shows the presence of aromatic herbs-ones that are currently documented as medicinal herbs.

Using herbs or their parts: leaves, roots, rhizomes, flowers, seeds, as well as their extracts or

natural material isolated metabolites can act both as a prophylaxis or a cure diseases and

enhance general organs functioning especially immunologic system. Many herbs have a role

in curing mood disorders. Natural cures (drugs) have different active compounds that may

help to treat the condition holistically acting on the body of the patient, the more that

depression affects the whole body, causing multi-organ dysfunction. The need for effective

and well tolerated remedies for depression has influenced investigators to analysis of herb

drugs and natural products which are traditionally used for depression treatment. The use of

herbs or their parts: leaves, roots, rhizomes, flowers, seeds, natural strains as well as extracts

or isolated metabolites is becoming more and more popular. Natural origin plays a role in

treatment of health problems, and also in case of serious diseases such as depression.

Natural raw materials such as, Bacopa monnieri, Crocus sativus Eleutherococcus2

senticosus, Griffonia simplicifolia, Hypericum perforatum, sceletium tortuosum piper

methysticum, Rhodiola rosea, Aspalathus linearis camellia sinensis ficus carica. Lycium

chinense, Cuminum cyminum, Panax ginseng can effectively assist the prevention and

treatment of depression.[11]

The current investigation envisages evaluating the leaves

of Albizia lebbeck (L) Benth. for antidepressant activity using predictive animals models of

depression in view of reported neuropharmacological profile.[12]

Including anxiolytic

activities, besides wide range of pharmacological activities in animal and in vitro models.

The results of this study helps to establish and extend the reported neuropharmacological

profile of leaves, as well help a potential source of herb for further investigations.

MATERIALS AND METHODS

4.1 Leaves of Albizia lebbeck: Fresh leaves of Albizia lebbeck was collected from the been

on irritation and dried, the sample was anthenticated by seminar faenlty member of Dept of

pharmacognosy, Kle univerity‘s college of pharmacy, Bengalare the dried leaves were

powered and fine powder was used for the study. Experimental animals Naïve, healthy,

Albino Wistar rats, of either sex weighing b/w Albino Wistar rats of were randomly assinged

to five groups of 6 animals each(n=6) for forced swim test. Naïve, healthy, Albino Swiss

mice, either sex weighing b/w Albino Swiss mices were randomly assigned to four groups of

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6 animals each (n=6) for tail suspension test. Experimental animals were procured form

commercial breader v/s venkateshwar traders, Bengalore, quartined for a week to on animal

house and subsequenty assigned to experiment. Experimental animals were housed in animal

house facilityof the institution and maintained as per CPCSEA guidelunce (Ref)ie room

temp 19-250 c, RH 30-70%, light dark cycle (12:12hrs) with adequate ventilation& hygiene

conditions. Every day, animal cages were cleaned and were feed with commercial pelleted

animal food &water q s. All experiments were performed b/w 9am to 1 pm to avoid

circurdium rhythm the result. IAEC clearance: IAEC of the institution cleared the

experimental protocol (IAEC|01|GSP/2016).

4.2: Pharmacological investigation

1. Rat forced swim test: The rat swim consist of 2 parts namely

a. Acute test- where the behavioral parameters are recorded after single oral dose of extract

under study and 20 b.Subchronic study- where the behavioral parameters are recorded after

fifteen days oral dose of extract under study treatment for fifteen days[15]

Forty[40]

naïve,

healthy, albino Wistar rats (of either sex ) weighing between 160-180 grams will be randomly

assigned to five (5) groups of eight (8) animals each (n=8) .Group 1 will be vehicle control

group and 2, 3, 4 and 5 will receive extract-2 increasing doses and imipramine (20mg/kg) and

fluxotiene (20mg/kg) respectively. The acute study consists of two parts namely 1. Pretest

and 2. Main test. The details are as follows

Pre test: One hour prior to the performance of pretest, experimental animals of above

mentioned groups will receive respective treatment and will be subject to forced swim test of

15 minutes session and behavioral parameters like duration of immobility, swimming and

climbing will be recorded by a person/s blind to the treatment protocol, according to

porsolt et.al[26]

with slight modification. Experimental animals will receive another dose of

drug oral route after an hour completing the test. Twenty four hours.[24]

after the pretest, main

test will be performed in the same set of animals after an hour oral treatment specific to the

group. At the end of fifteen days.[15]

days of oral treatment, twenty four hours after the last

dose, animals are again subjected to forced swim test and same parameters are recorded as

described above.

2. Mouse forced swim test: The mouse swim test consist of 2 parts namely

a. Acute test- where the behavioral parameters are recorded after single oral dose of extract

under study and b. Subchronic study- where the behavioral parameters are recorded after

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once a day oral dose of extract under study treatment for fifteen days[15]

21 Thirty two[32]

naïve, healthy, albino swiss mice (either sex) weighing between 18-22 grams will be

randomly assigned to four[4]

groups of eight[8]

animals each [n=8]. Group 1 will be vehicle

control and group 2, 3, and will be treated with two doses of extract and amitryptilin

[10mg/kg]. After one hour of respective administration specific to the group, animals will be

subjected to forced swim test according to method suggested by porsolt et al 61 With slight

modification to suit our laboratory conditions. In a session extending to 15 minutes, duration

of immobility, climbing and swimming (all in seconds) will be recorded by a person blind to

the treatment protocol.

5. RESULTS

Results of assessment of behavioral change – Duration of immobility, swimming and

climbing and ambulatory activity in animals exposed forced swimming during FST and TST

is as follows.

1. WEIGHT OF EXPERIMENTAL ANIMALS

Change in weight of experimental animals of FST and feed intake is as shown in table 1 and

graphically represented as Fig 1. Statistically significant increase in bodyweight of all

experimental animals of all groups was recorded at the end of the study.

Table1: Change in bodyweight of experimental animals undergoing FST.

Group Treatment Weight of animals ( Gms) Mean ± SEM ( n=6)

Day 0 Day 8 Day 15

1. Control 160 ± 2.1 162±3.67 170 ±1.8a,b

2. Low dose (500mg) 165 ±2.599 169.± 2.50 173±1.6

3. High dose (1000mg) 164 ±4.3 169 ± 2.70 176±4.1c

4. Imipramine 158 ±5.2 162.± 2.00 178±2.1c

5. Fluoxetine 161±2.8 170±3.45 179±1.8

All Values are expressed as Mean ± SEM (n=6) One way ANOVA, followed by NewMann

Keuls Test a p<0.01 Vs on day 0 of the same group b p<0.05 Vs on day 8 of the same

group c p<0.001 Vs on day 15 of the same group 23 one way ANOVA, followed by

NewMann Keuls Test

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2: Changes in Duration of Immobility in Experimental Animals Undergoing Forced Swim

Test.

Change in the DOI of experimental animals belonging to various group during Day 0, 8th and

on day 15th is recorded and is tabulated as shown in the table 2 and represented by Fig 2.

Statistically significant reduction in duration of immobility was recorded (p<0.05) in vehicle

control, LD and HD treated animals, when compared to Day 0 score. Further, significant

(p<0.05) (p<0.01) and (p<0.001) reduction in duration of immobility was recorded by HD

treated animals compared to LD treated animals.

Table 2: Change in duration of Immobility in experimental animals undergoing forced

swim test.

Group Treatment Duration of Immobility (Seconds) (Mean ± SEM)

Day 0 Day 8 Day 15

1 Control 526±63.00 548±48.32 487±15.20

2 Low Dose 508±23.12 465±43.10 546 ±56.00

3 High Dose 443±34.08 431±21.43 389±12.05

4 Imipramine 410±32.05 510±22.00* 423±12.21*

5 Fluoxetine 368±18.05*,β 324±23.02 * 356±12.15*

One way ANOVA, followed by NewMann Keuls Test * p<0.05 Vs Day 0 Score, β p< 0.001

Vs Day 15 of low dose treated group 25

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3. Changes in Duration of climbing in experimental animals undergoing Forced Swim Test

Change in the DOC of experimental animals belonging to various group during Day 0,

8th and on day 15th is recorded and is tabulated as shown in the table 3 and represented by

Fig 3, Marginal, but significant increase the duration of swimming was recorded the animals

of all groups.

Table 3: Change in duration of Climbing in experimental animals undergoing forced

swim test. One way ANOVA, followed by NewMann Keuls

Group Treatment

Duration of Climbing

( Seconds) (Mean ± SEM )

Day 0 Day 8 Day 15

1 Control 225±33 376±45 428.±43

2 Low Dose 381±36 329±32 421.±32

3 High Dose 375±27 394±12 398.±21

4 Imipramine 307±32 387±21 312.±12

5 Fluoxetine 276±21 298±21 301.±23

Test * p<0.05 Vs Day 0 Score, β p< 0.001 Vs Day 15 of low dose treated group

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4: Changes in Duration of swimming in experimental animals undergoing Forced Swim

Test Change in the DOS of experimental animals belonging to various group during Day 0,

8th and on day 15th is recorded and is tabulated as shown in the table 4 and represented by

Fig 4.Statistically significant increase in duration of swimming (p<0.01) compound to then

Day 0 duration was recorded by LD and HD treated animals.

Table 4: Change in duration of Swimming in experimental animals undergoing forced

swim test.

Group Treatment Duration of swimming (Seconds) (Mean ± SEM)

Day 0 Day 8 Day 15

1 Control 155±21.35 169.±27.21 221.±32

2 Low Dose 134.±18.87 172.±27.67 211.±32.23

3 High Dose 321.±27.23 321.±24 a 276.±18a

4 Imipramine 158.±21.59 168.±12.21 154.±12

5 Fluoxetine 165.±19.21 105.±23.01 141.±14

One way ANOVA, followed by NewMann Keuls Test * p<0.05 Vs Day 0 Score, β p< 0.001

Vs Day 15 of low dose treated group[29]

5. Locomotor activity of experimental animals: Changes in locomotor activity in

experimental animals undergoing Forced Swim Test. Change in locomotor activity of

experimental animals belonging to various group during Day 0, 8th and on day 15th is

recorded and is tabulated as shown in the table 5 and represented by Fig 5.1: Marginal, but

insignificante change in locomotor activity was recorded by experimental animals of various

groups.

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Table 5: Change in duration of Locomotor activity in experimental animals undergoing

forced swim test.

Group Treatment

Duration of swimming (Seconds) (Mean ±

SEM)

Day 0 Day 8 Day 15

1 Control 167.0 ±21.0 187.00 ±21..9 195.0±13.7

2 Low Dose 176.8±23.4 210.09±12.8 187.0±18.9

3 High Dose 182.3±19.8 168.00±15.5 211.0±11.7

4 Imipramine 172.6±10.9 98.70±13.5 201.0±21.8

5 Fluoxetine 189.8±21.0 88.75±11.0 126.9±12.0

One way ANOVA, followed by NewMann Keuls Test * p<0.05 Vs Day 0 Score, β p< 0.001

Vs Day 15 of low dose treated group.[31]

Day 0 Day 8 Day 15 Fig 3: Effect of extract treatment on locomotor activity score All

values are Mean +/- SEM. One way ANOVA followed by NK Multiple comparison Test.

Fig 5: Effect of extract treatment on locomotor activity score. All values are Mean +/-

SEM. One way ANOVA followed by NK Multiple comparison Test.[32]

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6. Weight of experimental animals undergoing TST. Change in weight of experimental

animals of TST and feed intake is as shown in table 6 and graphically represented as Fig

6.1:No significant change in body weight of experimental animals was. Recorded in groups

of animals undergoing tail suspension test.

Table 6: Change in bodyweight of experimental animals undergoing TST. All values are

expressed as Mean ± SEM (n=6) One way ANOVA, followed by NewMann Keuls

Test[33]

Group Treatment Weight of animals ( Gms) (Mean ± SEM)

Day 0 Day 8 Day 15

1 Control 21.70±1.5 23.70±7.8 26.8±8.9141

2 Low Dose 22.10±1.8 23.00±1.5 24.8±1.5

3 High Dose 22.00±0.9 24.00±1.9 25.8±1.9

4 Imipramine 21.70±1.5 25.10±1.8 29.0±1.8

Fig 6: Change in bodyweight of experimental animals undergoing TST. All values are

expressed as Mean ± SEM ( n=6) One way ANOVA, followed by NewMann Keuls

Test[34]

7 Changes in Duration of immobility in experimental animals undergoing TST.

Change in the DOI of experimental animals belonging to various group during Day 0, 8th and

on day 15th is recorded and is tabulated as shown in the table 7 and represented by Fig 7.1.

Recorded in LD and HD treated statistically significant reduction (p<0.01) in DOI was

animals

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Table 7: Change in duration of Immobility in experimental animals undergoing forced

swim test. One way ANOVA, followed by NewMann Keuls Test * p<0.05 Vs Day 0

Score, β p< 0.001 Vs Day 15 of low dose treated group 35

Group Treatment Duration of Immobility ( Seconds) (Mean ±

SEM ) Day 15

1 Control 188.45±35.1 175.00±32.9 168.76±21.0

2 Low Dose 170.23±20.3 128.37±14.5 108.27±13.5

3 High Dose 160.35±13.5 154.70±8.6 117.90±12.6

4 Imipramine 156.56±19.5 108.50±3.9 98.76±3.90

Fig 7: Change in duration of Immobility in experimental animals undergoing forced

swim test. One way ANOVA, followed by NewMann Keuls Test * p<0.05 Vs Day 0 score,

β< 0.001 Vs Day 15 of low dose treated group[36]

DISCUSSION

The current investigation was based on

1.Growing demand for herbal drugs for several disorders including that of CNS related neuro

psychiatric conditions like depression. 2.Paucity of studies about the antidepressant activity

of the Albizia lebbeck, although being evaluated for anxiolytic activity and learning.

3.Synthetic antidepressants have undesirable adverse effect in long term use The

antidepressant activity of leaf powder of Albizia lebbeck was established in conventional

most acceptable model of depression- porsolt‘s behavioral despair model two doses

(increasing) were selected for the study and was given orally to fasted animals. Duration of

immobility, swimming and climbing was recorded in a 15 min session to record the

antidepressant activity another two groups of animals were treated with standard

antidepressant drugs namely Imipramine a tricyclic antidepressant and Fluoxetine, a SSR

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inhibitory, to understand the likely mechanism of action. Ambulatory activity in the form of

locomotor activity score was also recorded by placing the experimental animal in the central

arena of photoactometer to exclude false positive result, sinces psycho stimulants exerts

indiscriminate motor stimulating activity in the dose employed for establishing antidepressant

activity. The results of antidepressant study recorded a statistically significant, dose

dependent reduction in duration of immobility, on day 8th and 15th, compound to then day

zero result and the effect of Albizzia lebbeck treatmenton motor stimulating activity was ruled

out, as indicated by insignificant change in locomotor activity score. The study was in 2

folds. One was the acute study and subchronic study, when the experimental animals are

exposed to herb for relatively longer periods time, since is proposed that a treatment period of

14 days is a valid interval for demonstrating antidepressants were augmented following

chronic treatment.[37]

The increase in food intake and weight of experimental animals of all

groups, some being statistically significant suggest a positive influence on the depression.

Tail suspension test, reffered to as ‘dry test‘ was also employed the results was encouraging

the duration of immobility displayed by test animals when subjected to unavoidable stress

such as forced swimming and suspened from its tail reflects a state of despair or lowered

mood, which one believed to the like the depressive disorder in human beings. Acute and sub

chronic treatment on the leaf powder significantly altered the duration of immobility,

suggesting the potential of herb to severse depressive states. Further, this investigation

employed recording of duration of swimming and climbing when animals were subjected to

forced swimming to give additional information on the possible mechanism mediating the

antidepressant activity swimming is mediated by serotomingeric neurotransmission, while

climbing is mediating by norepinephrinergic neurotransmission. However, due to

insignificant change, it was difficult to understand the possible mechanism of action. Using

leaf powder is also proved to the disadvantages, as the powder is a compound mixture of

several phytochemicals and duration of study is insufficient to arrive at a conclusive result.

Despite this limitation Albizia lebbeck holds potential to be a useful antidepressant herb.

CONCLUSION

Leaf powder in selected dose demonstrates dose dependent antidepressant activity. In the

models employed for this study.

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ACKNOWLEDGEMENT

The present study would not have been possible without the assistance, help &

encouragement of many people. This one is certainly no exception.” This work is not the

result of an individual effort, which is the product of collective wisdom and experience of all

those who have shared their views for beyond those with in the covers of this book. During

the completion of this dissertation work I was accompanied and supported by many people. I

am glad that I now have an opportunity to express my gratitude for all of them. My sincere

thanks to principal Dr. Hippargi SM Kle university’s college of pharmacy. Bangalore. I am

very grateful to my research guide Dr, Prasanna GS for all his valuable advice and support

throughout the M, pharmacy course and his constructive comments during the writing of this

thesis. With love and honour, my sincere thanks to my mom, Mrs Kenchamma and Dad Mr,

Kempanna SK for being on my side and helping me in every way. I pay my gratitude for my

entire life to my parents, Mrs Kenchamma, Mr. Kempanna S K who have taken lots of pain

for my post- graduation and also for their moral support throughout my life I am thankful to

everyone who have either directly & indirectly helped me to successfully complete this

project.

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