A study on evaluation of antidepressant
effect of Imipramine adjunct with Ashwagandha
and Bramhi
Research
article
Tamoghna Maiti1*, Anjan Adhikari2, Amrita Panda3
1. Assistant Professor, Dept. of
Pharmacology, BankuraSammilani Medical College, Bankura
2. Assistant Professor & Assistant
Director of Medical education, Dept. of H&FW, Kolkata
3. Junior Research Fellow, Anthropological
Survey of India, Nagpur
*Corresponding Author: Tamoghna Maiti, Assistant
Professor, Dept. of Pharmacology, Bankura Sammilani Medical College, Bankura-722102.
e-mail:- dr.tamoghna.maiti@gmail.com, Mob: 9903425385
Abstract
Introduction: Depressive
disorders increase the risks of self-harm or even suicide in patients. Indigenous
drugs are being tried to treat such patient along with conventional
antidepressant drugs.
Objective: To
investigate the antidepressant action of Ashwagandha and Bramhi and also to
confirm its efficacy in the behavioral despair animal model of depression.
Material
and methods: Normal saline as control (5ml/kg), imipramine as standard
(16,32,64 mg/kg) and ashwagandha (50,100,150 mg/kg), bramhi (20,40,80 mg/kg) as
test drugs were introduced to the albino rats weighing between 200-250gm for 2
weeks, 1 hr before electric shock in Learned helplessness test (LHT) and
swimming in Forced swimming test (FST). Effects of individual drugs as well as
their combination were evaluated.
Result: Avoidance
response, escape failure and immobility period in case of imipramine and
ashwagandha showed highly significant (p<0.01) result on individual use. There was no significant result in case of
Bramhi used alone except in escape failure and immobility period (FST), where at
higher doses it showed significant (p<0.01) result . But combination of Bramhi
and ashwagandha in low doses with low dose of imipramine gave a highly
significant result (p<0.01) in all the parameters.
Conclusion:
Ashwagandha
had significant antidepressant action, but bramhi had not when used alone. Combination
of these two indigenous drugs with imipramine showed high efficacy in animal model.
Key
Words:
Ashwagandha, Bramhi, Forced swimming test, Indigenous drug, learned
helplessness test.
Key
massages:
Ashwagandha and bramhi showed high efficacy in depression model when combine with
low dose imipramine. So these drugs may be tried in the treatment of depression
and further scientific research should be under taken for cost effectiveness
and reduce the adverse effect of modern therapy.
Introduction:
Depression is a heterogeneous
disorder that affects a person’s mood, physical health and behaviour.
Incidence of depressive mood disorders is rising in the modern stressful
society leading to increased risks of self-harm or suicide as well as increased
mortality from related general medical conditions.(1) As many as 10-15% of
individuals with this disorder exhibit suicidal tendency during their life
time. These groups of patients respond well to anti depressant drugs and in
severe cases to ECT (Electro Convulsive Therapy).
Treatments of major mood
disorders have improved in recent years with the advent of newer antidepressant
drugs like TCAs (Imipramine), SSRIs (Fluoxetine), MAO-Is and atypical
antidepressants, which are more selective with insignificant side effects.
Generally the antidepressant agents are reserved for severe & otherwise
incapacitating depressive disorders.(2) Though they
are effective they are not totally devoid of side effects & relatively
expensive for long-term use. Therefore evaluation of natural products for the management
of major mood disorders was justified. Research trials are continuing to
introduce numerous herbal formulation approved by food and drug administration for
the treatment of several psychological conditions.(3) Ashwagandha
(Withania somnifera), bramhi
(Bacopa monniera)
have memory enhancing and anxiolytic effect along with improvement of cognitive
function(4) But data relating to their antidepressant action is yet to be
established. Therefore it was justified to investigate the antidepressant action
of ashwagandha and bramhi in this present study.
Study aim was to investigate the
antidepressant actions of ashwagandha and bramhi in behavioural
despair animal model of depression for confirmation of the already reported
efficacy.
Material
& Methods
Learned helplessness test (LHT)(5) and Forced swimming test (FST)(6) models
were used for preparation of behavioral despair animal model. Albino rats
weighing between 200-250gm were allowed free access to food and water adlibitum
and were maintained under standard laboratory conditions with a natural light
and dark cycle following CPCSEA (Committee For The Purpose Of Control and
Supervision on Experiments on Animals) guidelines. The animals were
acclimatized for 5 days before behavioral experiments which were carried out
between 09.00 A.M and 1.00 P.M.
Apparatus
1. Gemini
Avoidance System: This apparatus is divided into two equal compartments by a
retractable door. Floors of the chambers in the shuttle box consisted of
stainless steel rods. This apparatus was for LHT.
2. Polypropylene
vessel (45x40x30cm) for FST, 3.Stop watch, 4. Pediatric nasogastric tube.
Drugs: Pure
powder form of the following drugs were obtained from different sources
Study
Design:
Experimental protocol was approved by Institutional Animal Ethics Committee
before starting the study. Design of this study was comparative and parallel
groups. Animals were divided into 24
groups (12 groups for LHT & FST each) containing six rats in each group.
Study
Groups with drug administered and doses -
|
Group |
Drugs & Doses (mg/kg) |
Group |
Drugs & Doses (mg/kg) |
Group |
Drugs
& Doses (mg/kg) |
|
Group
I |
Normal saline (5ml/kg) |
Group
V |
Bramhi
(20) |
Group
IX |
Ashwagandha
(100) |
|
Group
II |
Imipramine (16) |
Group
VI |
Bramhi
(40) |
Group
X |
Ashwagandha
(150) |
|
Group
III |
Imipramine (32) |
Group
VII |
Bramhi
(80) |
Group
XI |
Imipramine
(16)+Bramhi (20) |
|
Group
IV |
Imipramine (64) |
Group
VIII |
Ashwagandha
(50) |
Group
XII |
Imipramine (16) +Ashwagandha (50) |
|
Following
is the schedule for each group (n=6) receiving drug orally through pediatric
nasogastric tube with mentioned dose in parenthesis for each test (LHT &
FST). |
|||||
Normal saline as control, imipramine
as standard, Ashwagandha & bramhi as test drugs were administered orally as
per the study protocol. The doses of control, standard and the test drugs were
selected after observing the response of pilot doses of each, calculated by
considering their recommended dose for clinical use and on the basis of earlier
studies available in literature respectively.(7) Freshly
prepared suspension of the drugs with vehicle normal saline, was administered
orally through a pediatric nasogastric tube followed by 5ml of distilled water.
Each dose of individual and combinations drugs were
given for 14 days, 1 hr before the experiment. Earlier studies (8-10) stated
that repeated oral administration did not causes signs
of intoxication.
Learned
Helplessness Test (5):
In this test, an animal is
initially exposed to uncontrollable stress (unavoidable response). When the
animal is later placed in a situation in which shock is controllable
(escapable), the animal not only fails to acquire the escape responses but also
often makes no efforts to escape the shock at all. This escape deficit is
reversed by chronic antidepressant treatment.(11)(12)
Learned helplessness behavioral tests were performed with the Gemini Avoidance
System. This apparatus is divided into two equal compartments by a retractable
door. Floors of the chambers in the shuttle box consisted of stainless steel
rods. Scrambled shocks were delivered through a shock generator.
The drugs were used at three dose
levels. Low dose combination of imipramine, bramhi and ashwagandha was
administered orally for 2wks, starting on day 1 ,
60min before the inescapable shocks, and on day 12, the rats were individually
placed in the chamber and given 90 inescapable shocks (0.8 mA) of 15 s duration
at 45sec intervals. Control rats were not given shocks. On day 14, the rats
were subjected to the 30-trial escape test. The animals were individually
placed in the shuttle box and given a 5-min adaptation period; a tone signal
was given during the first 5sec of each trial (conditioned response). If there
was no avoidance response within this period, the tone signal remained on and a
0.8mA shock (15sec duration) was delivered through the
grid floor. If no escape response was made within this period, both the tone
signal and the shock were automatically terminated. The intertrial
interval was 5 s. The number of escape failures and avoidance response which
refers to a noncrossing-crossing response during the
shock delivery was recorded.
Forced
swimming Test (6):
The test was based on the method
described by Porsolt. Rats were made to swim
individually in a polypropylene vessel (45x40x30cm) with a water level of 20 cm
height and maintain at a temperature 22± 1˚C, this ensued that the rats’
feet didn’t touch the floor of the vessel and that it could not climb out of
it. The entire study was divided in to two sessions.
A. Pretest session: Animals
(rats) were forced to swim individually for 15 minutes in the polypropylene
container for 14 days.
B. Test session: 24 hours latter i.e. on 15th
day each animal was again forced to swim for a period of 6 minutes in a test
session. Each animal made vigorous attempt to get out of the polypropylene
container during the first couple of minutes and there after surrendered to experimental
conditions and became immobile with occasional escape attempts (characterized
by complete cessation of swimming with the head lifting just above the water
level as noted). This immobility period,
after frenzied attempts to escape is postulated to represent the “Behavioural despair” in an animal experimental model. The
total duration of immobility during last 4 minutes of a 6 minutes test was
recorded as period of despair.
Statistical
Analysis
Data were statistically analyzed
by one way ANOVA followed by Dunnet’s t-test. Results
were expressed as mean number of each group + standard error of mean(SEM)[mean ± SEM]. ‘P’ value <0.05 was considered significant.
Observation
and results
The results (Table 1& 2) showed
significant increase in the number of rats showing avoidance response also
reduction in the number of rats showing escape failure and immobility period.
Avoidance response and escape failure in case of imipramine and ashwagandha showed
highly significant result on individual use. But there was no significant
result in case of all doses of bramhi except in case of escape failure and
immobility period, bramhi in higher doses showed just significant result. In
combination doses there was highly significant increase in the number of
avoidance response also reduction in escape failure and in immobility period when
compared to low doses of all drugs given alone.
Discussion
Ashwagandha an
indigenous herbal product of Indian origin at the given dose levels produces
significant reduction in both the parameters. The potency of Ashwagandha
against depression in animal models was demonstrated earlier by Griebel et al(13) who compared the
above indigenous herbal products with that of the standard SSRI. Bhattacharya
SK & Goel RK also reported similar reduction in
all the parameters which comparable to the present.
Bramhi is famous
for its memory enhancing tranquilizing and antioxidant properties.(14) Bramhi in low dose level, no
significant reduction in any of the parameter were detected. This is comparable
to that of Achiliya GS.(15)
The positive effect of imipramine
in the learned helplessness test and Forced swimming test model seems to be due
to increased availability of these neurotransmitters norepinephrine (NE) and
serotonin (5HT) at the post synaptic site following their reuptake inhibition.
But uptake blocked is not directly responsible for antidepressant action. Thus
it is attributed to these coronary events that followed the primary drugs on
presynaptic α2, 5HT1a, 5HT1d auto receptors and amines turn over in
brain. However, the antidepressant action of a drug is due to the respective
synaptic sites in the brain region, net effect is enhancement of noradrenergic
and serotonergic transmission.(16)
Ashwagandha is
an essential popular Indian medical plant with marked antiaging,
immunomodulatory, anti anxiety and stress relieving
property, acts by normalizing the augmented Lipoxygenese
(LPO) activities and enhancing the activities Glutathione peroxidase
(GPX).(17) From our study, we have seen that it has
marked antidepressant effect and it also causes the enhancement of effect when
combined with low dose of imipramine. This result corroborates with
Bhattacharya SK.(18) Although it has marked memory
enhancing activity and antioxidant property but have very little antidepressant
effect and our study also shows similar antidepressant effect when used alone.
But potentiate the effect of imipramine when combine in low doses.
Conclusion:
The present study evaluated that Ashwagandha
had significant antidepressant action but Bramhi had not when used alone. These
two drug showed high efficacy in depression model when combine with low dose
imipramine. So these drugs may be tried in the treatment of depression and
further scientific research should be under taken towards this dimension.
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