SlideShare a Scribd company logo
1 of 55
Mr. MALLAPPA. H. SHALAVADI
Neuroprotective activity of
Stereospermum suaveolens DC. against
Parkinson’s disease and global
cerebral ischemia in rat model
Department of Pharmacology
Hangal Shri Kumareshwar College of Pharmacy, Bagalkot-587101,
Karnataka.
INTRODUCTION
Neurodegenerative disorders are characterized by
progressive and irreversible loss of neurons from
specific regions of the brain.
īƒ˜ 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 Dale’s
Pharmacology, 6th
ed.
www.google.com images
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
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
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.
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.
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)
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
īą Changes in facial expression ("mask" appearance, may be unable
to close mouth)
īą Voice/speech changes (slow speech, low-volume voice, difficulty
speaking)
īą Loss of fine motor skills (difficulty writing, eating or any activity that
requires small movements)
īą Memory loss decline in intellectual function
īą gastrointestinal symptoms (mainly constipation)
īą Drooling
īą Loss of smell, vision or color perception.
VIARTIS, AMEZON. COM, PD
HEALTH
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
Genetically Based Parkinson's Disease
AD, autosomal dominant; AR, autosomal recessive,UCH-L1:ubiquitin carboxyl-
terminal hydrolase L1, PINK1: PTEN-induced putative kinase 1,
Harrison's PRINCIPLES OF INTERNAL MEDICINE, 17th
Edition
15
Pre-clinical Parkinson’s 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.
HSK College of Pharmacy & Research
centre, India
16
Surgical Procedure
October 16, 2018
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).
HSK College of Pharmacy & Research centre,
India 21
October 16, 2018
HSK College of Pharmacy & Research
centre, India
22
Biochemical estimations
īƒ˜ 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.
īƒ˜ 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
īƒ˜ The infarction area was measured by 2,3,5-triphenyltetrazolium chloride (TTC)
staining method according to Bederson et al. (1986).
Brain histopathological studies
īƒ˜ 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.
October 16, 2018
10/16/18 23HSK College of Pharmacy & Research
centre,India 23
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kgShamControl
125mg/kg
250mg/kg500mg/kg
0
5
10
15
20
6th
day 12th
day 18th
day 24th
day 30th
day 36th
day 42nd
day
a
a a a
a
a
a
** **
******
*** *** ******
***
******
***
***
***
*** ***
***
*** ***
*** ***
Seconds
Effect of methanol extract of Stereospermum suaveolens DC.
on latency in 6-OHDA induced Parkinson’s 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
Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
Results
Neurobehavioral studies
Results
Neurobehavioral studies
10/16/18 24
10/16/18
HSK College of Pharmacy & Research
centre,India 24
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
0
50
100
150
200
250
0 day 6th
day 12th
day 18th
day 24th
day 30th
day 36th
day 42nd
day
a
b
c
c c c c
*
*
******
***
***
***
*** ***
***
** ***
***
***
***
***
*** ***
***
**
Noofgrooming
Effect of methanol extract of Stereospermum suaveolens DC. on
grooming in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
10/16/18 25
10/16/18
HSK College of Pharmacy & Research
centre,India 25
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
0
2
4
6
8
10
0 day 6th
day 12th
day 18th
day 24th
day 30th
day 36th
day 42nd
day
cc b a a b
b
*
*
***
*** ***
***
**
***
***
Noofrearing
Effect of methanol extract of Stereospermum suaveolens DC. on
rearing in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
10/16/18 26
10/16/18
HSK College of Pharmacy & Research
centre,India 26
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
0
50
100
150
200
250
0 day 6th
day 12th
day 18th
day 24th
day 30th
day 36th
day 42nd
day
***
a a a
a a a a
***
***
***
***
***
***
******
***
***
***
***
***
***
***
***
***
***
***
***
Noofambulatorymovements
Effect of methanol extract of Stereospermum suaveolens DC.
on ambulatory movements in 6-OHDA induced Parkinson’s
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
Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
10/16/18 27HSK College of Pharmacy & Research
centre,India 27
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
0
100
200
300
0 day 6th
day 6th
day 6th
day 6th
day 6th
day 6th
day 6th
day
a a a
a a a
a
******
***
***
***
***
***
***
***
***
***
***
***
*** *** ***
******
*********
Seconds
Effect of methanol extract of Stereospermum suaveolens DC. on
rest in 6-OHDA induced Parkinson’s 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
Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
10/16/18 28
10/16/18
HSK College of Pharmacy & Research
centre,India 28
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
ShamControl
125mg/kg
250mg/kg500mg/kg
0
5
10
15
6th
day 12th
day 18th
day 24th
day 30th
day 36th
day 42nd
day
b
ba
a a a
c
* *
* ** ** ** * * * * * * * * * ***
***
***
Noofrotationclockwise
Effect of methanol extract of Stereospermum suaveolens DC. on
ipsilateral rotation in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
10/16/18 29
10/16/18
HSK College of Pharmacy & Research
centre,India 29
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
0
50
100
150
200
0 day 30th
day12th
day 18th
day 24th
day 36th
day 42nd
day6th
day
a
bb
b
bb
b
*
**
**
*** *
***
*** ***
***
***
***
******
********* ******
***
Falloftime(seconds)
Effect of methanol extract of Stereospermum suaveolens DC. on
muscular coordination in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
10/16/18 30
10/16/18
HSK College of Pharmacy & Research
centre,India 30
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
0
50
100
150
200
0 day 42nd
day12th
day 36th
day30th
day24th
day18th
day6th
day
a
b b b
b
b
b
*
*
***
***
***
***
***
***
***
***
***
*** ***
***
*** ***
***
***
***
******
NoofspontaniuoslocomotionEffect of methanol extract of Stereospermum suaveolens DC. on
spontaneous locomotion in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
10/16/18 31
10/16/18
HSK College of Pharmacy & Research
centre,India 31
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
ShamControl
125mg/kg
250mg/kg
500mg/kg
0
2
4
6
8
10
0 day 6th
day 12th
day 18th
day 24th
day 30th
day 36th
day 42nd
day
aa
aa a
a
a
*
** ** ***
***
***
***
*****
***
*** ***
***
***
***
***
***
***
***
***
Noofforepawadjustingsteps
Effect of methanol extract of Stereospermum suaveolens DC. on
behavioral assessment (contralateral fore paw adjusting steps) in
6-OHDA induced Parkinson’s 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
Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
10/16/18 32HSK College of Pharmacy & Research
centre,India 32
Sham
Control
125
m
g/kg
250
m
g/kg
500
m
g/kg
0
100
200
300
400
500
***
****
a
Lipid peroxidation
nmoles/mgofprotein
Sham
Control
125
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 Parkinson’s disease model.
All the values are expressed as meanÂąSEM, n=9, a
p<0.05 (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 Tukey’s test) as compared to control group. MES= Methanol extract of
Stereospermum suaveolens DC.
Biochemical estimationsBiochemical estimations
10/16/18 33
10/16/18
HSK College of Pharmacy & Research
centre,India 33
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 Parkinson’s
disease model.
All the values are expressed as mean Âą SEM, 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens
DC.
Effect of methanol extract of Stereospermum suaveolens DC. in 6-OHDA induced
Parkinson’s 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.
10/16/18 35
10/16/18
HSK College of Pharmacy & Research
centre,India 35
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)
10/16/18 36
10/16/18
HSK College of Pharmacy & Research
centre,India 36
Discussion
īƒ˜ 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.
īƒ˜ 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.
īƒ˜ 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.
īƒ˜ A significant decrease in infarction area was observed in MES treated groups
as compared with control groups especially in basal ganglia reason of brain.
10/16/18 37
10/16/18
HSK College of Pharmacy & Research
centre,India 37
īƒ˜ 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
īƒ˜ I concluded that, the present study suggest a potential role of methanol extract
of Stereospermum suaveolens DC. against 6-OHDA induced Parkinson’s disease
model.
īƒ˜ Further studies are required for understand basic mechanism and
characterization of active constituents responsible for neuroprotective effect.
īƒŧ Stroke : poor blood flow to the brain results
in cell death.
īƒŧ 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"
īƒŧ Cerebrovascular disease, including stroke, is the
second most frequent cause of death worldwide.
īƒŧ 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.
īƒ˜ 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.
īƒ˜ Oxidative stress, results from imbalance between
generation and removal of ROS.
īƒ˜ During I/R insult, a number of events that predispose
the brain to the formation of ROS may occur.
īƒŧ New damage may be initiated during reoxygenation by
increased generation of ROS from parenchymal and
endothelial cells and from infiltrating leukocytes.
īƒŧ Mitochondrial damage leads to incomplete reduction of
oxygen,
īƒŧ Action of oxidases in leukocytes, endothelial cells, or
parenchymal cells.
īƒŧ Cellular antioxidant defense mechanisms may also be
compromised by ischemia, favoring the accumulation of
free radicals.
īƒŧ Ischemic injury is associated with inflammation, which
may increase with reperfusion because of increased
influx of leukocytes and plasma proteins.
īƒŧ Activation of the complement system may also contribute
to ischemia-reperfusion injury due complement proteins
bind to the deposited antibodies.
Symptoms of stroke
Strokes occur quickly and, as such, symptoms of stroke often
appear suddenly without warning.
The main symptoms of stroke:
īƒŧConfusion, including trouble with speaking and understanding
īƒŧHeadache, possibly with altered consciousness or vomiting
īƒŧNumbness of the face, arm or leg, particularly on one side of the
body
īƒŧTrouble with seeing, in one or both eyes
īƒŧTrouble with walking, including dizziness and lack of co-
ordination.
Strokes can lead to long-term problems.
īƒŧBladder or bowel control problems
īƒŧDepression
īƒŧPain in the hands and feet that gets worse with movement and
temperature changes
īƒŧParalysis or weakness on one or both sides of the body
īƒŧTrouble controlling or expressing emotions.
43
Plant profile
īļ Plant name : Stereospermum suaveolens DC.
īļ Family : Bignoniaceae
īļ Synonyms : Patala, Paral, Padal, Kalagora.
īƒ˜ 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).
īƒ˜ Traditionally, used in brain disorders (Meena, et
al., 2010).
īƒ˜ Scientifically validated this plant for
hepatoprotective, antihyperglycemic,
antioxidant, anti-inflammatory and anticancer
activity.
44
Animals
īƒ˜ 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.
īƒ˜ 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
īƒ˜ The acute toxicity study was performed as per the method described by
Litchfield and Wilcoxon (1949).
īƒ˜ LD50 was calculated accordingly. All tests on rats were performed at
three dose levels 125, 250 and 500 mg/kg of body weight.
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
Induction of ischemia
October 16, 2018
Biochemical estimations
īƒ˜ 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) and⁰
post-mitochondrial supernatant (PMS) will be used for the estimation of
total protein and lipid peroxidation.
īƒ˜ The supernatant will be again centrifuged at 15000 rpm for 1 hr at 4 C. The⁰
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
īƒ˜ The infarction area will be measured by 2,3,5-triphenyltetrazolium chloride
(TTC) staining method according to Bederson et al. (1986).
Brain histopathological studies
īƒ˜ 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.
īƒ˜
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 (Student’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum
suaveolens DC.
49
10/16/18
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 (Student’s 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 Tukey’s test) as compared to control
group. MES= Methanol extract of Stereospermum suaveolens DC.
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.
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.
10/16/18 52HSK College of Pharmacy & Research
centre,India 52
īƒ˜ 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.
īƒ˜ 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.
īƒ˜ 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.
īƒ˜ 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
Instruments used for work:
Lyophylyzer Refrigerated centrifuge
Stereostaxic instrumentsUltra low temperature Freezer UV Spectrophoto
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.
?

More Related Content

What's hot

Biomarkers for Parkinson's Diseases
Biomarkers for Parkinson's DiseasesBiomarkers for Parkinson's Diseases
Biomarkers for Parkinson's DiseasesVivek Misra
 
Pharmacotherapy of Alzheimer's Disease
Pharmacotherapy of Alzheimer's DiseasePharmacotherapy of Alzheimer's Disease
Pharmacotherapy of Alzheimer's DiseaseHarshad Malve
 
Epilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapyEpilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapyDr. Siddhartha Dutta
 
Serotonin and anti serotonin drugs
Serotonin and anti serotonin drugsSerotonin and anti serotonin drugs
Serotonin and anti serotonin drugsNaser Tadvi
 
Cognitive enhancers - Nootropics
Cognitive enhancers - NootropicsCognitive enhancers - Nootropics
Cognitive enhancers - NootropicsChaithanya Malalur
 
Glutamate receptors
Glutamate receptorsGlutamate receptors
Glutamate receptorsVibha Manu
 
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASEANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASEKameshwaran Sugavanam
 
Dopamine receptor agonists
Dopamine receptor agonistsDopamine receptor agonists
Dopamine receptor agonistsDomina Petric
 
Presentation on experimental evaluation of memory enhancers
Presentation on experimental evaluation of memory enhancersPresentation on experimental evaluation of memory enhancers
Presentation on experimental evaluation of memory enhancersAkhil Agarwal
 
parkinsons disease recent updates
parkinsons disease recent updatesparkinsons disease recent updates
parkinsons disease recent updatesNeurologyKota
 
anti-alzheimers drug
anti-alzheimers druganti-alzheimers drug
anti-alzheimers drugVijay Salvekar
 
Old vs New Antiseizure drugs.pptx
Old vs New Antiseizure drugs.pptxOld vs New Antiseizure drugs.pptx
Old vs New Antiseizure drugs.pptxPramod Krishnan
 
RECENT ADVANCES IN ALZHEIMER'S DISEASE
RECENT ADVANCES IN ALZHEIMER'S DISEASERECENT ADVANCES IN ALZHEIMER'S DISEASE
RECENT ADVANCES IN ALZHEIMER'S DISEASEsharad patange
 
Parkinsonism & Alzheimer's disease
Parkinsonism & Alzheimer's diseaseParkinsonism & Alzheimer's disease
Parkinsonism & Alzheimer's diseaseSurendra Chhetri
 
Neuroprotection for stroke
Neuroprotection for strokeNeuroprotection for stroke
Neuroprotection for strokeNeurologyKota
 
Potassium channel openers
Potassium channel openers Potassium channel openers
Potassium channel openers Naser Tadvi
 
screening model for learning and memory
screening model for learning and memoryscreening model for learning and memory
screening model for learning and memoryKundlik Rathod
 
GABA, glutamate receptors and their modulation
GABA, glutamate receptors and their modulationGABA, glutamate receptors and their modulation
GABA, glutamate receptors and their modulationDrSahilKumar
 

What's hot (20)

Biomarkers for Parkinson's Diseases
Biomarkers for Parkinson's DiseasesBiomarkers for Parkinson's Diseases
Biomarkers for Parkinson's Diseases
 
Pharmacotherapy of Alzheimer's Disease
Pharmacotherapy of Alzheimer's DiseasePharmacotherapy of Alzheimer's Disease
Pharmacotherapy of Alzheimer's Disease
 
Epilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapyEpilepsy recent advances and existing pharmacotherapy
Epilepsy recent advances and existing pharmacotherapy
 
Serotonin and anti serotonin drugs
Serotonin and anti serotonin drugsSerotonin and anti serotonin drugs
Serotonin and anti serotonin drugs
 
Cognitive enhancers - Nootropics
Cognitive enhancers - NootropicsCognitive enhancers - Nootropics
Cognitive enhancers - Nootropics
 
Glutamate receptors
Glutamate receptorsGlutamate receptors
Glutamate receptors
 
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASEANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
 
Dopamine receptor agonists
Dopamine receptor agonistsDopamine receptor agonists
Dopamine receptor agonists
 
Presentation on experimental evaluation of memory enhancers
Presentation on experimental evaluation of memory enhancersPresentation on experimental evaluation of memory enhancers
Presentation on experimental evaluation of memory enhancers
 
parkinsons disease recent updates
parkinsons disease recent updatesparkinsons disease recent updates
parkinsons disease recent updates
 
anti-alzheimers drug
anti-alzheimers druganti-alzheimers drug
anti-alzheimers drug
 
Old vs New Antiseizure drugs.pptx
Old vs New Antiseizure drugs.pptxOld vs New Antiseizure drugs.pptx
Old vs New Antiseizure drugs.pptx
 
RECENT ADVANCES IN ALZHEIMER'S DISEASE
RECENT ADVANCES IN ALZHEIMER'S DISEASERECENT ADVANCES IN ALZHEIMER'S DISEASE
RECENT ADVANCES IN ALZHEIMER'S DISEASE
 
Parkinsonism & Alzheimer's disease
Parkinsonism & Alzheimer's diseaseParkinsonism & Alzheimer's disease
Parkinsonism & Alzheimer's disease
 
Memantine
MemantineMemantine
Memantine
 
Neuroprotection for stroke
Neuroprotection for strokeNeuroprotection for stroke
Neuroprotection for stroke
 
Potassium channel openers
Potassium channel openers Potassium channel openers
Potassium channel openers
 
NEURO DEGENERATIVE DISEASES
NEURO DEGENERATIVE DISEASESNEURO DEGENERATIVE DISEASES
NEURO DEGENERATIVE DISEASES
 
screening model for learning and memory
screening model for learning and memoryscreening model for learning and memory
screening model for learning and memory
 
GABA, glutamate receptors and their modulation
GABA, glutamate receptors and their modulationGABA, glutamate receptors and their modulation
GABA, glutamate receptors and their modulation
 

Similar to Neuroprotection

Document (3).docx
Document (3).docxDocument (3).docx
Document (3).docxSatendra35
 
PARKINSON’S DISEASE.pptx
PARKINSON’S DISEASE.pptxPARKINSON’S DISEASE.pptx
PARKINSON’S DISEASE.pptxAmeena Kadar
 
ORGANOPHOSPHOROUS POISONING NEUROVIEW
ORGANOPHOSPHOROUS POISONING NEUROVIEWORGANOPHOSPHOROUS POISONING NEUROVIEW
ORGANOPHOSPHOROUS POISONING NEUROVIEWSrirama Anjaneyulu
 
Parkinson's Disease [Advanced Pharmacology]
Parkinson's Disease [Advanced Pharmacology]Parkinson's Disease [Advanced Pharmacology]
Parkinson's Disease [Advanced Pharmacology]Megh Vithalkar
 
Parkinson's disease
 Parkinson's disease Parkinson's disease
Parkinson's diseaseSunil Pahari
 
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptx
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptxIN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptx
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptxGautamSosa
 
An analysis of Parkinson’s disease (PD) on Physical and Mental Health
An analysis of Parkinson’s disease (PD) on Physical and Mental HealthAn analysis of Parkinson’s disease (PD) on Physical and Mental Health
An analysis of Parkinson’s disease (PD) on Physical and Mental HealthArian Bashtar
 
Anti epileptic screening model
Anti epileptic screening modelAnti epileptic screening model
Anti epileptic screening modelKhushbooThakur15
 
Parkinsons disease V Pharm.D
Parkinsons disease V Pharm.DParkinsons disease V Pharm.D
Parkinsons disease V Pharm.DDr.Sohel Memon
 
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docxSubmission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docxdeanmtaylor1545
 
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docxSubmission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docxdavid4611
 
PARKINSON'S DISEASE PPT PDF.pdf
PARKINSON'S DISEASE PPT PDF.pdfPARKINSON'S DISEASE PPT PDF.pdf
PARKINSON'S DISEASE PPT PDF.pdfDrMalathiVenketesham
 
2.Mysthenia & Parkinson_BDS.ppt
2.Mysthenia & Parkinson_BDS.ppt2.Mysthenia & Parkinson_BDS.ppt
2.Mysthenia & Parkinson_BDS.pptRajendra Dev Bhatt
 
parkinsonism-180214104126.pdf
parkinsonism-180214104126.pdfparkinsonism-180214104126.pdf
parkinsonism-180214104126.pdfJunaid Khan
 
Ameliorative effects of recombinant human erythropoietin ijrpp
Ameliorative effects of recombinant human erythropoietin ijrppAmeliorative effects of recombinant human erythropoietin ijrpp
Ameliorative effects of recombinant human erythropoietin ijrpppharmaindexing
 
PARKINSON’S DISEASE
PARKINSON’S DISEASE PARKINSON’S DISEASE
PARKINSON’S DISEASE ShaistaSumayya
 
parkinson's disease-1.pptx
parkinson's disease-1.pptxparkinson's disease-1.pptx
parkinson's disease-1.pptxfawwazumar3
 

Similar to Neuroprotection (20)

Document (3).docx
Document (3).docxDocument (3).docx
Document (3).docx
 
Parkinsonism.ppt
Parkinsonism.pptParkinsonism.ppt
Parkinsonism.ppt
 
PARKINSON’S DISEASE.pptx
PARKINSON’S DISEASE.pptxPARKINSON’S DISEASE.pptx
PARKINSON’S DISEASE.pptx
 
ORGANOPHOSPHOROUS POISONING NEUROVIEW
ORGANOPHOSPHOROUS POISONING NEUROVIEWORGANOPHOSPHOROUS POISONING NEUROVIEW
ORGANOPHOSPHOROUS POISONING NEUROVIEW
 
Parkinson's Disease [Advanced Pharmacology]
Parkinson's Disease [Advanced Pharmacology]Parkinson's Disease [Advanced Pharmacology]
Parkinson's Disease [Advanced Pharmacology]
 
Parkinson's disease
 Parkinson's disease Parkinson's disease
Parkinson's disease
 
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptx
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptxIN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptx
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptx
 
Parkinson disease
Parkinson diseaseParkinson disease
Parkinson disease
 
An analysis of Parkinson’s disease (PD) on Physical and Mental Health
An analysis of Parkinson’s disease (PD) on Physical and Mental HealthAn analysis of Parkinson’s disease (PD) on Physical and Mental Health
An analysis of Parkinson’s disease (PD) on Physical and Mental Health
 
Anti epileptic screening model
Anti epileptic screening modelAnti epileptic screening model
Anti epileptic screening model
 
Parkinsons disease V Pharm.D
Parkinsons disease V Pharm.DParkinsons disease V Pharm.D
Parkinsons disease V Pharm.D
 
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docxSubmission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
 
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docxSubmission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
Submission Ide 88c19114-7d71-4703-b679-22f6c2ee580479 SI.docx
 
PARKINSON'S DISEASE PPT PDF.pdf
PARKINSON'S DISEASE PPT PDF.pdfPARKINSON'S DISEASE PPT PDF.pdf
PARKINSON'S DISEASE PPT PDF.pdf
 
2.Mysthenia & Parkinson_BDS.ppt
2.Mysthenia & Parkinson_BDS.ppt2.Mysthenia & Parkinson_BDS.ppt
2.Mysthenia & Parkinson_BDS.ppt
 
parkinsonism-180214104126.pdf
parkinsonism-180214104126.pdfparkinsonism-180214104126.pdf
parkinsonism-180214104126.pdf
 
Parkinsonism
ParkinsonismParkinsonism
Parkinsonism
 
Ameliorative effects of recombinant human erythropoietin ijrpp
Ameliorative effects of recombinant human erythropoietin ijrppAmeliorative effects of recombinant human erythropoietin ijrpp
Ameliorative effects of recombinant human erythropoietin ijrpp
 
PARKINSON’S DISEASE
PARKINSON’S DISEASE PARKINSON’S DISEASE
PARKINSON’S DISEASE
 
parkinson's disease-1.pptx
parkinson's disease-1.pptxparkinson's disease-1.pptx
parkinson's disease-1.pptx
 

More from Dr. Mallappa Shalavadi (16)

Drug abuse and Illicit trafficking of drugs
Drug abuse and Illicit trafficking of drugsDrug abuse and Illicit trafficking of drugs
Drug abuse and Illicit trafficking of drugs
 
Drug abuse
Drug abuseDrug abuse
Drug abuse
 
Basics of cellular aging and
Basics of cellular aging andBasics of cellular aging and
Basics of cellular aging and
 
Screening of anti hypertensives2003
Screening of anti hypertensives2003Screening of anti hypertensives2003
Screening of anti hypertensives2003
 
Screening of antiparkinsonian agents
Screening of antiparkinsonian agentsScreening of antiparkinsonian agents
Screening of antiparkinsonian agents
 
Screening of drugs used in MI
Screening of drugs used in MIScreening of drugs used in MI
Screening of drugs used in MI
 
Peptic ulcer disease Mallappa Shalavadi,,
Peptic ulcer disease Mallappa Shalavadi,,Peptic ulcer disease Mallappa Shalavadi,,
Peptic ulcer disease Mallappa Shalavadi,,
 
Peptic ulcer disease Mallappa Shalavadi
Peptic ulcer disease Mallappa ShalavadiPeptic ulcer disease Mallappa Shalavadi
Peptic ulcer disease Mallappa Shalavadi
 
Inflammatory bowel disease
Inflammatory bowel diseaseInflammatory bowel disease
Inflammatory bowel disease
 
2membrane
2membrane2membrane
2membrane
 
Hydrocephalus mallappa hs
Hydrocephalus mallappa hsHydrocephalus mallappa hs
Hydrocephalus mallappa hs
 
Immunology
ImmunologyImmunology
Immunology
 
Multi drug resistance
Multi drug resistanceMulti drug resistance
Multi drug resistance
 
AIDS
AIDSAIDS
AIDS
 
Dna sequencing
Dna sequencingDna sequencing
Dna sequencing
 
Basic uv,visible
Basic uv,visibleBasic uv,visible
Basic uv,visible
 

Recently uploaded

SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptxSOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptxiammrhaywood
 
Science 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its CharacteristicsScience 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its CharacteristicsKarinaGenton
 
Proudly South Africa powerpoint Thorisha.pptx
Proudly South Africa powerpoint Thorisha.pptxProudly South Africa powerpoint Thorisha.pptx
Proudly South Africa powerpoint Thorisha.pptxthorishapillay1
 
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptxPOINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptxSayali Powar
 
Alper Gobel In Media Res Media Component
Alper Gobel In Media Res Media ComponentAlper Gobel In Media Res Media Component
Alper Gobel In Media Res Media ComponentInMediaRes1
 
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdfEnzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdfSumit Tiwari
 
Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111Sapana Sha
 
ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,
ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,
ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,Virag Sontakke
 
CARE OF CHILD IN INCUBATOR..........pptx
CARE OF CHILD IN INCUBATOR..........pptxCARE OF CHILD IN INCUBATOR..........pptx
CARE OF CHILD IN INCUBATOR..........pptxGaneshChakor2
 
Introduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptxIntroduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptxpboyjonauth
 
Painted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of IndiaPainted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of IndiaVirag Sontakke
 
internship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developerinternship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developerunnathinaik
 
EPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptxEPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptxRaymartEstabillo3
 
Final demo Grade 9 for demo Plan dessert.pptx
Final demo Grade 9 for demo Plan dessert.pptxFinal demo Grade 9 for demo Plan dessert.pptx
Final demo Grade 9 for demo Plan dessert.pptxAvyJaneVismanos
 
Mastering the Unannounced Regulatory Inspection
Mastering the Unannounced Regulatory InspectionMastering the Unannounced Regulatory Inspection
Mastering the Unannounced Regulatory InspectionSafetyChain Software
 
“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...
“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...
“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...Marc Dusseiller Dusjagr
 
Paris 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activityParis 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activityGeoBlogs
 
Blooming Together_ Growing a Community Garden Worksheet.docx
Blooming Together_ Growing a Community Garden Worksheet.docxBlooming Together_ Growing a Community Garden Worksheet.docx
Blooming Together_ Growing a Community Garden Worksheet.docxUnboundStockton
 
Science lesson Moon for 4th quarter lesson
Science lesson Moon for 4th quarter lessonScience lesson Moon for 4th quarter lesson
Science lesson Moon for 4th quarter lessonJericReyAuditor
 

Recently uploaded (20)

SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptxSOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
 
Science 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its CharacteristicsScience 7 - LAND and SEA BREEZE and its Characteristics
Science 7 - LAND and SEA BREEZE and its Characteristics
 
Model Call Girl in Bikash Puri Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Bikash Puri  Delhi reach out to us at 🔝9953056974🔝Model Call Girl in Bikash Puri  Delhi reach out to us at 🔝9953056974🔝
Model Call Girl in Bikash Puri Delhi reach out to us at 🔝9953056974🔝
 
Proudly South Africa powerpoint Thorisha.pptx
Proudly South Africa powerpoint Thorisha.pptxProudly South Africa powerpoint Thorisha.pptx
Proudly South Africa powerpoint Thorisha.pptx
 
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptxPOINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
POINT- BIOCHEMISTRY SEM 2 ENZYMES UNIT 5.pptx
 
Alper Gobel In Media Res Media Component
Alper Gobel In Media Res Media ComponentAlper Gobel In Media Res Media Component
Alper Gobel In Media Res Media Component
 
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdfEnzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
Enzyme, Pharmaceutical Aids, Miscellaneous Last Part of Chapter no 5th.pdf
 
Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111Call Girls in Dwarka Mor Delhi Contact Us 9654467111
Call Girls in Dwarka Mor Delhi Contact Us 9654467111
 
ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,
ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,
ā¤­ā¤žā¤°ā¤¤-ā¤°āĨ‹ā¤Ž ā¤ĩāĨā¤¯ā¤žā¤Ēā¤žā¤°.pptx, Indo-Roman Trade,
 
CARE OF CHILD IN INCUBATOR..........pptx
CARE OF CHILD IN INCUBATOR..........pptxCARE OF CHILD IN INCUBATOR..........pptx
CARE OF CHILD IN INCUBATOR..........pptx
 
Introduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptxIntroduction to AI in Higher Education_draft.pptx
Introduction to AI in Higher Education_draft.pptx
 
Painted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of IndiaPainted Grey Ware.pptx, PGW Culture of India
Painted Grey Ware.pptx, PGW Culture of India
 
internship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developerinternship ppt on smartinternz platform as salesforce developer
internship ppt on smartinternz platform as salesforce developer
 
EPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptxEPANDING THE CONTENT OF AN OUTLINE using notes.pptx
EPANDING THE CONTENT OF AN OUTLINE using notes.pptx
 
Final demo Grade 9 for demo Plan dessert.pptx
Final demo Grade 9 for demo Plan dessert.pptxFinal demo Grade 9 for demo Plan dessert.pptx
Final demo Grade 9 for demo Plan dessert.pptx
 
Mastering the Unannounced Regulatory Inspection
Mastering the Unannounced Regulatory InspectionMastering the Unannounced Regulatory Inspection
Mastering the Unannounced Regulatory Inspection
 
“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...
“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...
“Oh GOSH! Reflecting on Hackteria's Collaborative Practices in a Global Do-It...
 
Paris 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activityParis 2024 Olympic Geographies - an activity
Paris 2024 Olympic Geographies - an activity
 
Blooming Together_ Growing a Community Garden Worksheet.docx
Blooming Together_ Growing a Community Garden Worksheet.docxBlooming Together_ Growing a Community Garden Worksheet.docx
Blooming Together_ Growing a Community Garden Worksheet.docx
 
Science lesson Moon for 4th quarter lesson
Science lesson Moon for 4th quarter lessonScience lesson Moon for 4th quarter lesson
Science lesson Moon for 4th quarter lesson
 

Neuroprotection

  • 1. Mr. MALLAPPA. H. SHALAVADI Neuroprotective activity of Stereospermum suaveolens DC. against Parkinson’s 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. īƒ˜ 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 Dale’s 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. īą Changes in facial expression ("mask" appearance, may be unable to close mouth) īą Voice/speech changes (slow speech, low-volume voice, difficulty speaking) īą Loss of fine motor skills (difficulty writing, eating or any activity that requires small movements) īą Memory loss decline in intellectual function īą gastrointestinal symptoms (mainly constipation) īą Drooling īą 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
  • 13. Genetically Based Parkinson's Disease AD, autosomal dominant; AR, autosomal recessive,UCH-L1:ubiquitin carboxyl- terminal hydrolase L1, PINK1: PTEN-induced putative kinase 1, Harrison's PRINCIPLES OF INTERNAL MEDICINE, 17th Edition
  • 14.
  • 15. 15 Pre-clinical Parkinson’s 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.
  • 16. HSK College of Pharmacy & Research centre, India 16 Surgical Procedure October 16, 2018
  • 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).
  • 21. HSK College of Pharmacy & Research centre, India 21 October 16, 2018
  • 22. HSK College of Pharmacy & Research centre, India 22 Biochemical estimations īƒ˜ 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. īƒ˜ 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 īƒ˜ The infarction area was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining method according to Bederson et al. (1986). Brain histopathological studies īƒ˜ 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. October 16, 2018
  • 23. 10/16/18 23HSK College of Pharmacy & Research centre,India 23 ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kgShamControl 125mg/kg 250mg/kg500mg/kg 0 5 10 15 20 6th day 12th day 18th day 24th day 30th day 36th day 42nd day a a a a a a a ** ** ****** *** *** ****** *** ****** *** *** *** *** *** *** *** *** *** *** Seconds Effect of methanol extract of Stereospermum suaveolens DC. on latency in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC. Results Neurobehavioral studies Results Neurobehavioral studies
  • 24. 10/16/18 24 10/16/18 HSK College of Pharmacy & Research centre,India 24 ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg 0 50 100 150 200 250 0 day 6th day 12th day 18th day 24th day 30th day 36th day 42nd day a b c c c c c * * ****** *** *** *** *** *** *** ** *** *** *** *** *** *** *** *** ** Noofgrooming Effect of methanol extract of Stereospermum suaveolens DC. on grooming in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 25. 10/16/18 25 10/16/18 HSK College of Pharmacy & Research centre,India 25 ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg 0 2 4 6 8 10 0 day 6th day 12th day 18th day 24th day 30th day 36th day 42nd day cc b a a b b * * *** *** *** *** ** *** *** Noofrearing Effect of methanol extract of Stereospermum suaveolens DC. on rearing in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 26. 10/16/18 26 10/16/18 HSK College of Pharmacy & Research centre,India 26 ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg 0 50 100 150 200 250 0 day 6th day 12th day 18th day 24th day 30th day 36th day 42nd day *** a a a a a a a *** *** *** *** *** *** ****** *** *** *** *** *** *** *** *** *** *** *** *** Noofambulatorymovements Effect of methanol extract of Stereospermum suaveolens DC. on ambulatory movements in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 27. 10/16/18 27HSK College of Pharmacy & Research centre,India 27 ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg 0 100 200 300 0 day 6th day 6th day 6th day 6th day 6th day 6th day 6th day a a a a a a a ****** *** *** *** *** *** *** *** *** *** *** *** *** *** *** ****** ********* Seconds Effect of methanol extract of Stereospermum suaveolens DC. on rest in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 28. 10/16/18 28 10/16/18 HSK College of Pharmacy & Research centre,India 28 ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg ShamControl 125mg/kg 250mg/kg500mg/kg 0 5 10 15 6th day 12th day 18th day 24th day 30th day 36th day 42nd day b ba a a a c * * * ** ** ** * * * * * * * * * *** *** *** Noofrotationclockwise Effect of methanol extract of Stereospermum suaveolens DC. on ipsilateral rotation in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 29. 10/16/18 29 10/16/18 HSK College of Pharmacy & Research centre,India 29 ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg 0 50 100 150 200 0 day 30th day12th day 18th day 24th day 36th day 42nd day6th day a bb b bb b * ** ** *** * *** *** *** *** *** *** ****** ********* ****** *** Falloftime(seconds) Effect of methanol extract of Stereospermum suaveolens DC. on muscular coordination in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 30. 10/16/18 30 10/16/18 HSK College of Pharmacy & Research centre,India 30 ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg 0 50 100 150 200 0 day 42nd day12th day 36th day30th day24th day18th day6th day a b b b b b b * * *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** ****** NoofspontaniuoslocomotionEffect of methanol extract of Stereospermum suaveolens DC. on spontaneous locomotion in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 31. 10/16/18 31 10/16/18 HSK College of Pharmacy & Research centre,India 31 ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg ShamControl 125mg/kg 250mg/kg 500mg/kg 0 2 4 6 8 10 0 day 6th day 12th day 18th day 24th day 30th day 36th day 42nd day aa aa a a a * ** ** *** *** *** *** ***** *** *** *** *** *** *** *** *** *** *** *** Noofforepawadjustingsteps Effect of methanol extract of Stereospermum suaveolens DC. on behavioral assessment (contralateral fore paw adjusting steps) in 6-OHDA induced Parkinson’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 32. 10/16/18 32HSK College of Pharmacy & Research centre,India 32 Sham Control 125 m g/kg 250 m g/kg 500 m g/kg 0 100 200 300 400 500 *** **** a Lipid peroxidation nmoles/mgofprotein Sham Control 125 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 Parkinson’s disease model. All the values are expressed as meanÂąSEM, n=9, a p<0.05 (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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC. Biochemical estimationsBiochemical estimations
  • 33. 10/16/18 33 10/16/18 HSK College of Pharmacy & Research centre,India 33 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 Parkinson’s disease model. All the values are expressed as mean Âą SEM, 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 Tukey’s 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 Parkinson’s 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.
  • 35. 10/16/18 35 10/16/18 HSK College of Pharmacy & Research centre,India 35 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)
  • 36. 10/16/18 36 10/16/18 HSK College of Pharmacy & Research centre,India 36 Discussion īƒ˜ 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. īƒ˜ 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. īƒ˜ 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. īƒ˜ A significant decrease in infarction area was observed in MES treated groups as compared with control groups especially in basal ganglia reason of brain.
  • 37. 10/16/18 37 10/16/18 HSK College of Pharmacy & Research centre,India 37 īƒ˜ 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 īƒ˜ I concluded that, the present study suggest a potential role of methanol extract of Stereospermum suaveolens DC. against 6-OHDA induced Parkinson’s disease model. īƒ˜ Further studies are required for understand basic mechanism and characterization of active constituents responsible for neuroprotective effect.
  • 38.
  • 39. īƒŧ Stroke : poor blood flow to the brain results in cell death. īƒŧ 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" īƒŧ Cerebrovascular disease, including stroke, is the second most frequent cause of death worldwide. īƒŧ 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. īƒ˜ 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. īƒ˜ Oxidative stress, results from imbalance between generation and removal of ROS. īƒ˜ During I/R insult, a number of events that predispose the brain to the formation of ROS may occur.
  • 41. īƒŧ New damage may be initiated during reoxygenation by increased generation of ROS from parenchymal and endothelial cells and from infiltrating leukocytes. īƒŧ Mitochondrial damage leads to incomplete reduction of oxygen, īƒŧ Action of oxidases in leukocytes, endothelial cells, or parenchymal cells. īƒŧ Cellular antioxidant defense mechanisms may also be compromised by ischemia, favoring the accumulation of free radicals. īƒŧ Ischemic injury is associated with inflammation, which may increase with reperfusion because of increased influx of leukocytes and plasma proteins. īƒŧ 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: īƒŧConfusion, including trouble with speaking and understanding īƒŧHeadache, possibly with altered consciousness or vomiting īƒŧNumbness of the face, arm or leg, particularly on one side of the body īƒŧTrouble with seeing, in one or both eyes īƒŧTrouble with walking, including dizziness and lack of co- ordination. Strokes can lead to long-term problems. īƒŧBladder or bowel control problems īƒŧDepression īƒŧPain in the hands and feet that gets worse with movement and temperature changes īƒŧParalysis or weakness on one or both sides of the body īƒŧTrouble controlling or expressing emotions.
  • 43. 43 Plant profile īļ Plant name : Stereospermum suaveolens DC. īļ Family : Bignoniaceae īļ Synonyms : Patala, Paral, Padal, Kalagora. īƒ˜ 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). īƒ˜ Traditionally, used in brain disorders (Meena, et al., 2010). īƒ˜ Scientifically validated this plant for hepatoprotective, antihyperglycemic, antioxidant, anti-inflammatory and anticancer activity.
  • 44. 44 Animals īƒ˜ 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. īƒ˜ 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 īƒ˜ The acute toxicity study was performed as per the method described by Litchfield and Wilcoxon (1949). īƒ˜ 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 īƒ˜ 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) and⁰ post-mitochondrial supernatant (PMS) will be used for the estimation of total protein and lipid peroxidation. īƒ˜ The supernatant will be again centrifuged at 15000 rpm for 1 hr at 4 C. The⁰ 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 īƒ˜ The infarction area will be measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining method according to Bederson et al. (1986). Brain histopathological studies īƒ˜ 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. īƒ˜
  • 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 (Student’s 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 Tukey’s test) as compared to control group. MES= Methanol extract of Stereospermum suaveolens DC.
  • 49. 49 10/16/18 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 (Student’s 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 Tukey’s 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 īƒ˜ 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. īƒ˜ 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. īƒ˜ 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. īƒ˜ 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.
  • 55. ?

Editor's Notes

  1. 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 effectsâ€Ļ. Studies of adverse effects have been supplemented with studies of adverse events. Pharmacoepidemiology borrows clinical pharmacology’s focus of inquiry (but it often use individual case report), and epidemiology’s 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 1960’s can be thought to have marked the beginning of the field of pharmacoepidemiology. The 1990’s and especially the 2000’s 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
  2. 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.