1. Mr. MALLAPPA. H. SHALAVADI
Neuroprotective activity of
Stereospermum suaveolens DC. against
Parkinsonâs disease and global
cerebral ischemia in rat model
Department of Pharmacology
Hangal Shri Kumareshwar College of Pharmacy, Bagalkot-587101,
Karnataka.
2. INTRODUCTION
Neurodegenerative disorders are characterized by
progressive and irreversible loss of neurons from
specific regions of the brain.
ī Prototypical neurodegenerative disorders.
1. Parkinson's disease (PD)
2. Huntington's disease (HD)
-In both there is loss of neurons from
structures of the basal ganglia results in abnormalities in
the control of movement.
3. Alzheimer's disease (AD)
-Where the loss of hippocampal and
cortical neurons leads to impairment of memory and
cognitive ability.
4. Amyotrophic lateral sclerosis (ALS)
-Where muscular weakness results from
the degeneration of spinal, bulbar, and cortical motor
neurons. Rang and Daleâs
Pharmacology, 6th
ed.
4. HISTORY
JAMES PARKINSON
ī Parkinson's disease was first
formally described in modern times
in "An Essay on the Shaking
Palsy," published in 1817 by a
London physician named James
Parkinson (1755-1824).
ī James Parkinson systematically
described the medical history of six
individuals who had symptoms of
the disease that eventually bore
his name.
ī Unusually for such a description,
he did not actually examine all
these patients himself but
observed them on daily walks.
VIARTIS, AMEZON. COM, PD
HEALTH
5. ī The purpose of his essay was to document the
symptoms of the disorder, which he described as
"Involuntary tremulous motion, with lessened muscular
power, in parts not in action and even when supported;
with a propensity to bend the trunk forwards, and to pass
from a walking to a running pace ; the senses and
intellect being uninjured."
ī It was not until 1861 and 1862 that Jean-Martin Charcot
(1825-1893) with Alfred Vulpian (1826-1887) added
more symptoms to James Parkinson's clinical
description (Charcot and Vulpian, 1861, 1862) and then
subsequently confirmed James Parkinson's place in
medical history by attaching the name Parkinson's
Disease to the syndrome.
VIARTIS, AMEZON. COM, PD
HEALTH
6. Etiology
CAUSES OF IDIOPATHIC PARKINSON'S DISEASE
ī There are a variety of causes of Parkinson's Disease
including toxic, genetic, head trauma, drug induced, plus
a number of medical disorders that can cause the same
symptoms.
ī However, these causes of Parkinson's Disease
represent only a minority of cases.
ī The majority of people with Parkinson's Disease suffer
from idiopathic Parkinson's Disease, which is effectively
no obvious initiating cause.
7. TOXIC CAUSES
ī There are a number of toxins that may cause Parkinson's disease or
cause symptoms mimicking Parkinson's disease. These include :
Paraquat (herbicide), Rotenone (pesticide), Maneb (fungicide),
Manganese, MPTP (drug by product), Toluene (solvent), N-hexane
(solvent), Carbon disulfide (usually in solvents or pesticides), Carbon
monoxide, Mercury, Cyanide, and Copper.
GENETIC CAUSES
ī There are also genetic causes of Parkinson's Disease, that can be
inherited or acquired. These include genetic mutations named PARK1,
PARK2, PARK3, PARK5, PARK6, PARK7, PARK8, and PARK12.
Rather than inevitably cause Parkinson's Disease, these genetic
mutations normally make somebody more prone to developing
Parkinson's Disease.
8. DRUG INDUCED
ī Some of the Anti-psychotics - drugs that are used to
treat schizophrenia and psychosis - can induce the
symptoms of Parkinson's disease by lowering
dopaminergic activity, phenothiazines (perphenazine
and chlorpromazine), thioxanthenes (flupenthixol and
zuclopenthixol)
and butyrophenones (haloperidol), piperazines (ziprasid
one)
9.
10. Tremor : Tremor can occur in the fingers, hands,
arms, legs, chin, tongue, lips, eyelids, and the head.
It is most commonly in the hand and fingers
because of the large size of the colony of pyramidal
tract cells concerned with hand and finger
movement. It often ceases during sleep only to
return again on waking.
Rigidity : Rigidity and stiffness occurs in the
muscles as a primary symptom, because of their
constant muscle contraction. This can lead to pain in
rigid areas.
Hypokinesia: Hypokinesia, which is a poverty of
movement of muscles goes through three stages.
Firstly, there is hypokinesia, which is impaired
movement without any obvious disturbance of power
or of coordination. Movement tends to be interrupted
by pauses. There can also be difficulty with small
movements. Secondly, there is bradykinesia, which
is when voluntary movements can be performed, but
slowly. Thirdly, there is akinesia, which is a loss of
physical movement, which can begin with brief
periods of complete immobility called akinetic
attacks.
VIARTIS, AMEZON. COM, PD
11. īą Changes in facial expression ("mask" appearance, may be unable
to close mouth)
īą Voice/speech changes (slow speech, low-volume voice, difficulty
speaking)
īą Loss of fine motor skills (difficulty writing, eating or any activity that
requires small movements)
īą Memory loss decline in intellectual function
īą gastrointestinal symptoms (mainly constipation)
īą Drooling
īą Loss of smell, vision or color perception.
VIARTIS, AMEZON. COM, PD
HEALTH
12. Pathogenesis of dopamine cell death in Parkinson's disease (PD) and
possible sites for therapeutic intervention in PD
Harrison's PRINCIPLES OF INTERNAL MEDICINE, 17th
Edition
15. 15
Pre-clinical Parkinsonâs disease model:
Sprague-Dawley rats of either sex
(200-250g) were divided into five
groups of 9 rats each and fed with
drug or vehicle for 42 days and
treated as follows.
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Surgical Procedure
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17.
18.
19.
20. 6-OHDA: It was originally isolated by Senoh in 195960
. 6-OHDA is unable
to cross the blood brain barrier, production of central neuronal lesions can be
achieved only after direct intracerebral administration (intracisternally,
intraventricularly or directly into the brain parenchyma).
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Biochemical estimations
ī The 10% homogenated brain tissue in cold phosphate buffer (pH 7.4) was
centrifuged at 10000 rpm for 10 min at 4o
C (MPW-350R, Korea) and post-
mitochondrial supernatant (PMS) was used for the estimation of total protein and
lipid peroxidation.
ī The supernatant was again centrifuged at 15000 rpm for 1 hr at 4o
C. The
supernatant obtained was used for further estimation of superoxide dismutase
(SOD), catalase (CAT), glutathione (GSH), and total thiols (Chandrashekhar et al.,
2010).
Measurement of infarction area
ī The infarction area was measured by 2,3,5-triphenyltetrazolium chloride (TTC)
staining method according to Bederson et al. (1986).
Brain histopathological studies
ī The brains from control and experimental groups was fixed with 10% formalin
and embedded in paraffin wax and cut into longitudinal section of 5 Âĩm
thickness. The sections were stained with H&E dye for histopathological
observation.
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ShamControl
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Seconds
Effect of methanol extract of Stereospermum suaveolens DC.
on latency in 6-OHDA induced Parkinsonâs disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.001 (Studentâs t-test) as compared to sham group and
*p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple comparison
Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
Results
Neurobehavioral studies
Results
Neurobehavioral studies
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ShamControl
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Noofgrooming
Effect of methanol extract of Stereospermum suaveolens DC. on
grooming in 6-OHDA induced Parkinsonâs disease model.
All the values are expressed as mean Âą SEM, n=9, a
p<0.05, b
p<0.01 and c
p<0.001 (Student,s t-test) as compared to
sham group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
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ShamControl
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cc b a a b
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Noofrearing
Effect of methanol extract of Stereospermum suaveolens DC. on
rearing in 6-OHDA induced Parkinsonâs disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.05, b
p<0.01 and c
p<0.001 (Student,s t-test) as compared to
sham group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
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ShamControl
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Noofambulatorymovements
Effect of methanol extract of Stereospermum suaveolens DC.
on ambulatory movements in 6-OHDA induced Parkinsonâs
disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.001 (Studentâs t-test) as compared to sham group and
*p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple comparison
Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
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Seconds
Effect of methanol extract of Stereospermum suaveolens DC. on
rest in 6-OHDA induced Parkinsonâs disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.001 (Studentâs t-test) as compared to sham group and
*p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple comparison
Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
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* ** ** ** * * * * * * * * * ***
***
***
Noofrotationclockwise
Effect of methanol extract of Stereospermum suaveolens DC. on
ipsilateral rotation in 6-OHDA induced Parkinsonâs disease
model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.05, b
p<0.01 and c
p<0.001 (Studentâs t-test) as compared to
sham group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
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ShamControl
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Falloftime(seconds)
Effect of methanol extract of Stereospermum suaveolens DC. on
muscular coordination in 6-OHDA induced Parkinsonâs disease
model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.01 and b
p<0.001 (Studentâs t-test) as compared to sham
group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
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ShamControl
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NoofspontaniuoslocomotionEffect of methanol extract of Stereospermum suaveolens DC. on
spontaneous locomotion in 6-OHDA induced Parkinsonâs disease
model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.01 and b
p<0.001 (Student,s t-test) as compared to sham
group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
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ShamControl
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Noofforepawadjustingsteps
Effect of methanol extract of Stereospermum suaveolens DC. on
behavioral assessment (contralateral fore paw adjusting steps) in
6-OHDA induced Parkinsonâs disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.001 (Student,s t-test) as compared to sham group and
*p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple comparison
Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
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Sham
Control
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m
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g/kg
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m
g/kg
0
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****
a
Lipid peroxidation
nmoles/mgofprotein
Sham
Control
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m
g/kg
250
m
g/kg
500
m
g/kg
0
200
400
600
800
*
**
a
Superoxide dismutase
U/mgofprotein
Effect of methanol extract of Stereospermum suaveolens
DC. in 6-OHDA induced Parkinsonâs disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.05 (Studentâs t-test) as compared to sham
group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by
multiple comparison Tukeyâs test) as compared to control group. MES= Methanol extract of
Stereospermum suaveolens DC.
Biochemical estimationsBiochemical estimations
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S
h
a
m
C
o
n
tro
l
1
2
5
m
g
/kg
2
5
0
m
g
/kg
5
0
0
m
g
/kg
0.00
0.05
0.10
0.15
0.20
0.25 ****
b
Catalase
U/mgofprotein
S
h
a
m
C
o
n
tro
l
12
5
m
g
/kg
2
5
0
m
g
/kg
5
0
0
m
g
/kg
0
20
40
60
80
b
* *
***
Glutathion
nmoles/mgofprotein
S
ham
C
ontrol
125
m
g/kg
250
m
g
/kg
500
m
g/kg
0
10
20
30
40
50
** **
***
a
Total thiols
Âĩmoles/mgofprotein
Effect of methanol extract of Stereospermum
suaveolens DC. in 6-OHDA induced Parkinsonâs
disease model.
All the values are expressed as mean Âą SEM, n=9, a
p<0.01 and b
p<0.001 (Studentâs t-test) as compared to sham
group and *p<0.05, **p<0.01 and ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
34. Effect of methanol extract of Stereospermum suaveolens DC. in 6-OHDA induced
Parkinsonâs disease can be evaluated by 2,3,5- triphenyltetrazolium chloride (TTC)
staining. Brain coronal sections were prepared (2 mm thickness) and then each section
was stained with TTC. A: Sham group, B: Control, C: MES 125 mg/kg, D: MES 250
mg/kg, E: MES 500 mg/kg. In plate B a large infarction area was observed in basal
ganglia reason, whereas the infarction area was markedly reduced in rats brains treated
with MES, this reduction in infarction in treated rats were mostly comparable with sham
group (A). MES= methanol extract of Stereospermum suaveolens DC.
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A1 A2 B1 B2 C1
C2 D1 D2 E1 E2
40X
40X
40X
40X40X
10X
10X 10X
10X10X
Neurohistopathological studiesNeurohistopathological studies
Effect of methanol extract of Stereospermum suaveolens DC. in 6-OHDA induced oxidative stress in rat. Plates;
A1 and A2: Sham group, B1 and B2: Control group, C1 and C2: MES 125 mg/kg,
D1 and D2: MES 250 mg/kg, E1 and E2: MES 500 mg/kg;
In B1 and B2 there was marked infiltration of neutrophils, intracellular space increased and more vacuoles
seen, density of cells decreased, architecture completely altered, also haemorrhage and neuronal cell death
was observed in striatum. There is significant reversal of damage observed in MES treated groups (C1-E2),
reversal observed in treated groups were mostly comparable with sham group (A1 and A2). MES= methanol
extract of Stereospermum suaveolens DC. (H&E)
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Discussion
ī Oxidative stress to dopamergic neurons of SNpc is believed to be one of the
leading causes of neurodegeneration in PD. The antioxidants may play an
important role in the prevention of PD and combat against oxidative stress
induced progressive neurodegeneration by ROS.
ī In present study, the extract treated groups shows significant improvement in
spontaneous locomotor activity, behavioral assessment, muscular coordination
and locomotor activities as compared with control animals.
ī Antioxidant activity of extract was showed by reducing the elevated Lipid
peroxidation (LPO) and severity of oxidative damage in brain tissue was
significantly reduced by increasing the levels of antioxidant enzymes SOD, CAT
and non enzymatic markers like GSH and total thiols.
ī A significant decrease in infarction area was observed in MES treated groups
as compared with control groups especially in basal ganglia reason of brain.
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ī In histopathology, the extract treated groups shows significant decrease in
infiltration of neutrophils, intracellular space and regained normal architecture,
also very less neuronal cell death was observed in striatum
ī I concluded that, the present study suggest a potential role of methanol extract
of Stereospermum suaveolens DC. against 6-OHDA induced Parkinsonâs disease
model.
ī Further studies are required for understand basic mechanism and
characterization of active constituents responsible for neuroprotective effect.
38.
39. īŧ Stroke : poor blood flow to the brain results
in cell death.
īŧ In the 1970s the World Health
Organization defined stroke as a "neurological
deficit of cerebrovascular cause that persists
beyond 24 hours or is interrupted by death within
24 hours"
īŧ Cerebrovascular disease, including stroke, is the
second most frequent cause of death worldwide.
īŧ Stroke imposes a tremendous socioeconomic
burden because the large majority of patients that
survive the acute course of the disease remain
physically or mentally disabled.
40. ī Brain is the most susceptible organ to the damage due
to oxidative stress, because neurons are rich in
polyunsaturated fatty acids and levels of endogenous
antioxidant enzymes [superoxide dismutase (SOD),
catalase, glutathione peroxidases] and non enzymes
(vitamins C and E) in neuronal tissue are low.
ī Oxidative stress, results from imbalance between
generation and removal of ROS.
ī During I/R insult, a number of events that predispose
the brain to the formation of ROS may occur.
41. īŧ New damage may be initiated during reoxygenation by
increased generation of ROS from parenchymal and
endothelial cells and from infiltrating leukocytes.
īŧ Mitochondrial damage leads to incomplete reduction of
oxygen,
īŧ Action of oxidases in leukocytes, endothelial cells, or
parenchymal cells.
īŧ Cellular antioxidant defense mechanisms may also be
compromised by ischemia, favoring the accumulation of
free radicals.
īŧ Ischemic injury is associated with inflammation, which
may increase with reperfusion because of increased
influx of leukocytes and plasma proteins.
īŧ Activation of the complement system may also contribute
to ischemia-reperfusion injury due complement proteins
bind to the deposited antibodies.
42. Symptoms of stroke
Strokes occur quickly and, as such, symptoms of stroke often
appear suddenly without warning.
The main symptoms of stroke:
īŧConfusion, including trouble with speaking and understanding
īŧHeadache, possibly with altered consciousness or vomiting
īŧNumbness of the face, arm or leg, particularly on one side of the
body
īŧTrouble with seeing, in one or both eyes
īŧTrouble with walking, including dizziness and lack of co-
ordination.
Strokes can lead to long-term problems.
īŧBladder or bowel control problems
īŧDepression
īŧPain in the hands and feet that gets worse with movement and
temperature changes
īŧParalysis or weakness on one or both sides of the body
īŧTrouble controlling or expressing emotions.
43. 43
Plant profile
īļ Plant name : Stereospermum suaveolens DC.
īļ Family : Bignoniaceae
īļ Synonyms : Patala, Paral, Padal, Kalagora.
ī It is widely used by traditional practitioners as
an analgesic, antidyspeptic, astringent, liver
stimulant and has wound healing property.
Flowers are used in semen debility (Chattarjee
and Chandra, 1997).
ī Traditionally, used in brain disorders (Meena, et
al., 2010).
ī Scientifically validated this plant for
hepatoprotective, antihyperglycemic,
antioxidant, anti-inflammatory and anticancer
activity.
44. 44
Animals
ī The Sprague-Dawley rats of either sex (200-250g) were obtained from the
central animal house of H. S. K. College of Pharmacy and Research Centre,
Bagalkot, Karnataka, India.
ī The study was approved and conducted as per the norms of the
Institutional Animal Ethics Committee (HSKCP/IAEC, Clear/2009-10/1-8,
Dated 28/11/ 2010).
Acute toxicity study
ī The acute toxicity study was performed as per the method described by
Litchfield and Wilcoxon (1949).
ī LD50 was calculated accordingly. All tests on rats were performed at
three dose levels 125, 250 and 500 mg/kg of body weight.
45. 45
Pre-clinical model for global ischemia
Sprague-Dawley rats of either sex (200-250g) were divided into five groups of 8 rats each
and fed with drug or vehicle for 10 days prior to the experiment and treated as follows
MES=Methanol extract of Stereospermum suaveolens
47. Biochemical estimations
ī The 10% homogenated brain tissue in cold phosphate buffer (pH 7.4) will
be centrifuged at 10000 rpm for 10 min at 4 C (MPW-350R, Korea) andâ°
post-mitochondrial supernatant (PMS) will be used for the estimation of
total protein and lipid peroxidation.
ī The supernatant will be again centrifuged at 15000 rpm for 1 hr at 4 C. Theâ°
supernatant obtained will be used for further estimation of superoxide
dismutase (SOD), catalase (CAT), glutathione (GSH) and total thiols
(Chandrashekhar et al., 2010).
Measurement of infarction area
ī The infarction area will be measured by 2,3,5-triphenyltetrazolium chloride
(TTC) staining method according to Bederson et al. (1986).
Brain histopathological studies
ī The brains from control and experimental groups will be fixed with 10%
formalin and embedded in paraffin wax and cut into longitudinal section of
5 Âĩm thickness. The sections will be stained with H&E dye for
histopathological observation.
ī
48. 10/16/18
HSK College of Pharmacy & Research
centre,India
Results
Biochemical estimation
Results
Biochemical estimationSham
C
ontrol
125
m
g/kg
250
m
g/kg
500m
g/kg
0
200
400
600
800
******
***
a
Lipid peroxidation
nmoles/mgofprotein
S
ham
C
ontrol
125
m
g/kg
250
m
g/kg
500m
g/kg
0
500
1000
1500
*
Superoxide dismutase
U/mgofprotein
Fig.1. Effect of methanol extract of Stereospermum suaveolens DC. in global cerebral ischemia/
reperfusion induced oxidative stress.
All the values are expressed as mean Âą SEM, n=9, a
p<0.001 (Studentâs t-test) as compared to sham group
and *p<0.05, **p<0.01, ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple
comparison Tukeyâs test) as compared to control group. MES= Methanol extract of Stereospermum
suaveolens DC.
49. 49
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HSK College of Pharmacy & Research
centre,India
S
h
a
m
C
o
n
tro
l
1
2
5
m
g
/kg
2
5
0
m
g
/kg
5
0
0
m
g
/kg
0.0
0.1
0.2
0.3
0.4
b
***
***
***
Catalase
U/mgofprotein
S
h
a
m
C
o
n
tro
l
1
2
5
m
g
/kg
2
5
0
m
g
/kg
5
0
0
m
g
/kg
0
20
40
60
80
100
a
*
**
***
Glutathion
nmoles/mgofprotein
S
h
a
m
C
o
n
tro
l
1
2
5
m
g
/k
g
2
5
0
m
g
/k
g
5
0
0
m
g
/k
g
0
10
20
30
40
50
b
*
***
Total thiols
Âĩmoles/mgofprotein
Fig.2. Effect of methanol extract of Stereospermum suaveolens DC. in global cerebral ischemia/
reperfusion induced oxidative stress.
All the values are expressed as meanÂąSEM, n=9, a
p<0.01 and b
p<0.001 (Studentâs t-test) as compared to sham group and *p<0.05,
**p<0.01, ***p<0.001 (One way Analysis of Variance [ANOVA] followed by multiple comparison Tukeyâs test) as compared to control
group. MES= Methanol extract of Stereospermum suaveolens DC.
50. 10/16/18 HSK College of Pharmacy & Research
centre,India
Measurement of infarction areaMeasurement of infarction area
A B C
D E
Brain coronal sections (2,3,5- triphenyltetrazolium chloride (TTC) staining) were prepared (2 mm thickness) and then each section
was stained with TTC. A: Sham group (normal saline 10ml/kg), B: Control (normal saline 10 ml/kg+ischemia 30min followed by 4h
reperfusion), C: MES 125 mg/kg+ischemia 30min followed by 4h reperfusion, D: MES 250 mg/kg+ischemia 30min followed by 4h
reperfusion, E: MES 500 mg/kg+ischemia 30min followed by 4h reperfusion. In plate B a large infarction area was observed in gray
matter and less in brain stem, whereas the infarction area was markedly reduced in rats brains treated with MES, this reduction in
infarction in treated rats were mostly comparable with sham group (A). MES= methanol extract of Stereospermum suaveolens DC.
51. 10/16/18
HSK College of Pharmacy & Research
centre,India
Neurohistopathological studiesNeurohistopathological studies
A1 A2 B1 B2 C1
C2 D1 D2 E1 E2
10X 10X 10X
10X 10X
40X 40X
40X 40X 40X
Plates; A1 and A2: Sham group (normal saline 10ml/kg), B1 and B2: Control (normal saline 10 ml/kg+ischemia 30min followed by 4h
reperfusion), C1 and C2: MES 125 mg/kg+ischemia 30min followed by 4h reperfusion, D1 and D2: MES 250 mg/kg+ischemia 30min
followed by 4h reperfusion, E1 and E2: MES 500 mg/kg+ischemia 30min followed by 4h reperfusion. In B1 and B2 there was marked
infiltration of neutrophils, intracellular space increased and density of cells decreased, architecture completely altered, also
haemorrhage and neuronal cell death was observed. There is significant reversal of damage observed in MES treated groups (C1-E2),
reversal observed in treated groups were mostly comparable with sham group (A1 and A2). In B1 and B2 there was marked
infiltration of neutrophils, intracellular space increased and architecture completely altered. There is significant reversal of damage
observed in MES treated groups (C1-E2), reversal observed in treated groups were mostly comparable with sham group (A1 and A2).
MES= methanol extract of Stereospermum suaveolens DC.
52. 10/16/18 52HSK College of Pharmacy & Research
centre,India 52
ī Oxygen is essential for aerobic life, but also precursor to formation of harmful ROS
(Halliwell, 1991). Oxygen free radicals are known to contribute ischemic brain damage.
ī In present study, potential neuroprotective activity of methanol extract of
Stereospermum suaveolens DC. were showed by reducing the elevated LPO and
severity of oxidative damage in brain tissue was significantly reduced by increasing
the levels of antioxidant enzymes SOD, CAT and non enzymatic markers like GSH and
total thiols during I/R induced oxidative stress.
ī The histopathological studies revealed that extract treated groups showed significant
decrease in infiltration of neutrophils, intracellular space and density of cells
increased, regained normal architecture and moderate necrosis was observed as
compared to control group. Cerebral infarction area was vary less in extract treated
groups.
ī I Conclude that, these findings suggest a potential protective role of Stereospermum
suaveolens DC. against cerebral I/R induced brain injury. Further studies are progress
to characterised the lead emerging from the present results to exploit the full
therapeutic potential of Stereospermum suaveolens DC. as neuroprotective.
DiscussionDiscussion
53. Instruments used for work:
Lyophylyzer Refrigerated centrifuge
Stereostaxic instrumentsUltra low temperature Freezer UV Spectrophoto
54. 10/16/18 54HSK College of Pharmacy & Research
centre,India
ContRibutoRsContRibutoRs
Mallappa H. Shalavadi
Kallappa S. Halagali0Ramesh B. Nidavani
Source of support:
Financial support by
Rajiv Gandhi University of
Health Sciences, Bangalore,
Karnataka, India.
(RGUHS/Research activity/ P12/
2010-11)
Research team
Dr. Chanadrashekhar V. M.
Safe and effective
The harm that drugs can cause has also led to the development of the field of pharmacoepidemiology.
Drug regulation has led to the development of pharmacoepidemiology.
The field of pharmacoepidemiology has primarily concerned itself with the study of adverse drugs effectsâĻ. Studies of adverse effects have been supplemented with studies of adverse events.
Pharmacoepidemiology borrows clinical pharmacologyâs focus of inquiry (but it often use individual case report), and epidemiologyâs methods (chronic disease epi., e.g. controlled studiese) of inquiry.
Serious but uncommon drug effects have led to an accelerated search for new methods to study drug effects in large number of patients. This led to a shift from adverse effect studies to adverse event studies.
The 1960âs can be thought to have marked the beginning of the field of pharmacoepidemiology.
The 1990âs and especially the 2000âs have seen another shift in the field, away from its exclusive emphasis on drug utilization and adverse reactions, to the inclusion of other interests as well, such as the use of pharmacoepidemiology to study beneficial drug effects, the application of health economics to the study of drug effects, quality-of-life studies, meta-analysis, etc.
How to prevent adverse effects/drug safety crises: improper use of drugs; patients safety movement
Risk assessment
Trimetazidine inhibits beta-oxidation of fatty acids by blocking long-chain 3-ketoacyl-CoA thiolase, which enhances glucose oxidation.[7] In an ischaemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in the beta-oxidation process. Potentiation of glucose oxidation optimizes cellular energy processes, thereby maintaining proper energy metabolism during ischaemia. By preserving energy metabolism in cells exposed to hypoxia or ischaemia, trimetazidine prevents a decrease in intracellular ATP levels, thereby ensuring the proper functioning of ionic pumps and transmembrane sodium-potassium flow whilst maintaining cellular homeostasis.