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www.wjpps.com Vol 9, Issue 2, 2020.
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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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Kavitha et al. World Journal of Pharmacy and Pharmaceutical Sciences
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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