Download EVALUATION OF ANTIEPILEPTIC AND NOOTROPIC EFFECTS OF

EVALUATION OF ANTIEPILEPTIC AND NOOTROPIC EFFECTS OF
GALLIC ACID IN RATS.
M. Pharm Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore – 560 041
By
Mr. SHAIK IMRAN B.Pharm
Under the Guidance of
Dr. Kalyani Divakar M.Pharm, Ph.D.
Professor and Head,
Department of Pharmacology
Acharya & B.M.Reddy College of Pharmacy,
Soldevanahalli, Chikkabanavara (Post),
Hesaraghatta Main Road, Bangalore – 560 090.
2012-2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1.
Name of the candidate &
Address
Shaik Imran
8-6-74
Thummala Gadda
Khammam(507001)
Andhra Pradesh
2.
Name of the Institution
Acharya & B.M. Reddy College Of Pharmacy
Soldevanahalli, Hesaraghatta main Road,
Chikkabanavara Post,
Bangalore-560090.
Phone No: 080 65650815
Fax No: 080 28393541
3.
Course of the study & subject
M.Pharm (Pharmacology)
4.
Date of admission
16/08/2011
5.
Title of the Topic
Evaluation of antiepileptic and nootropic effects
of gallic acid in rats
6.
Brief resume of intended work
6.1 Introduction and need of the work
6.2 Review of Literature
6.3 Aim of the study
Enclosure I
Enclosure II
Enclosure III
7.
Materials & Methods
7.1 Source of data
7.2 Methods of collection of data
7.3 Does the study require investigation
on animals?
a. If yes give details
7.4 Has ethical clearance been obtained
from your institution in case of 7.3
Enclosure IV
Enclosure V
Yes. The above study requires investigation on
Albino Wistar Rats (either sex) for anti-epileptic
and nootropic activities.
Enclosed
8.
List of references
Enclosure VI
9.
Signature of the candidate
10.
Remarks of the guide
RECOMMENDED
11.
11.1. Name & Designation of Guide
Dr. Kalyani Divakar, M.Pharm., Ph.D.
Professor & Head, Dept. of Pharmacology,
Acharya & B.M. Reddy College of Pharmacy.
11.2. Signature of Guide
11.3. Name & Designation of Co-guide
Mr. Uday Raj Sharma. M.Pharm
Assistant professor
Acharya & B.M. Reddy College of Pharmacy.
11.4. Signature of Co-guide
11.5. Name & Signature of HOD
Dr. Kalyani Divakar, M.Pharm., Ph.D.
Professor & Head, Dept. of Pharmacology,
Acharya & B.M. Reddy College of Pharmacy.
12
12.1. Remarks of the Principal
12.2. Name & Signature of Principal
Dr.Divakar Goli M.Pharm., Ph.D.
Professor & Head, Dept. of Pharmacology,
Acharya & B.M. Reddy College of Pharmacy.
Chikkabanavara (Post),
Bangalore-560090
ENCLOSURE - I
6. BRIEF RESUME OF INTENDED WORK
6.1 NEED OF THE WORK:
Epilepsy is a common and diverse set of chronic neurological disorders characterised
by seizures1. Epilepsy results from abnormal, excessive (or) hyper synchronous neuronal
activity in brain2. Epilepsy is usually controlled but cannot be cured with medication.
However over 30% of people with epilepsy do not have seizures controlled even with best
available medicines3, 4, 5.
About 50 million people worldwide have epilepsy, with almost 90% of these people
being in developing countries. Epilepsy is more likely to occur in young children (or) people
over the age of 65 years. It can occur at any time6, 7.
According to WHO, about 450 million people in the entire world have suffered from
mental, neurological, (or) behavioural problems at some time in their life6, 8.
This chronic disorder involves alteration in the voltage – dependent ion channels
reduction in inhibitory i.e. GABA mediated decrease (or) increase in excitatory i.e. glutamate
mediated inputs9.
Nootropic:Nootropic also referred as smart drugs. These are mainly used in the treatment of
memory and intelligence enhancement10, 11.
Memory is the ability of an individual to record sensory stimuli, events, information,
etc. to retain them at over a short or long period of time to recall at latter when it needed12.
Poor memory, lower retention and slow recall are common problems in today’s stress full and
competitive world. Age, stress, emotion may lead to memory loss13, 14, 15, 16.
Cognitive disorders are common in patients who are under the treatment of epilepsy.
Nootropic agents are used to correct observed cognitive defects17.
Nootropics are thought to work by altering the availability of the brain’s supply of
neurochemicals (neurotransmitters, enzymes, & hormones), by improving brain’s oxygen
supply, or stimulating nerve growth12, 18, 19.
The most common cause of dementia is a progressive neurodegenerative disorder
associated with loss of neurons in distinct brain areas. The central cholinergic pathway plays
a prominent role in learning and memory processes20. Central acting anti muscaranic drugs
impair learning and memory in both animals and human beings21 22.
The nootropic drugs belong to the class of psychotropic agents with selective
facilitator effect on intellectual performance, learning memory23.
Gallic acid is also known as gallate. Its IUPAC name is 3, 4, 5 – trihydroxybenzoic
acid. Gallic acid is used as starting material in synthesis of psychotic alkaloid mescaline24, 25.
Gallic acid has anti fungal and anti viral property26. It has an antioxidant property which
helps to protect human cells against oxidative damage. Gallic acid was found to be cytotoxic
against cancer cells without harming healthy cells. Also used to treat albuminuria and
diabetes25, 26, 27.
Based on the literature survey we found that Amla, Tulasi, Ocimum sanctum, Galla
rhois are using in treatment of epilepsy however gallic acid is the one of the chemical
constituent in treatment of epilepsy. However gallic acid alone having anti epileptic property,
and till now no one scientifically evaluated, Hence the parent study is planned to find out
antiepileptic and nootropic activities of synthetic gallic acid.
ENCLOSURE – II
6.2 REVIEW OF LITERATURE:
Gallic acid is a trihydroxybenzoic acid, a type of phenolic acid, a type of organic acid,
also known as 3, 4, 5-trihydroxybenzoic acid. The chemical formula is C6H2(OH)3COOH,
[C7H6O5]. Gallic acid is found both free and as part of tannins.
Therapeutic uses25, 26, 27, 28
1. Anti-fungal
2. Anti-viral
3. Strong antioxidant
4. Cytotoxic agent for cancer cells
5. Astringent in cases of internal haemorrhage
6. Used to treat albuminuria and diabetes.
7. As ointment to treat psoriasis and external haemorrhoids contain gallic acid
8. Also used as a standard for determining the phenol content of various analytes by
the Folin-Ciocalteau assay; results are reported in gallic acid equivalents
Reported Pharmacological actions.
1. S. Tavassoli and Z. Emam Djomeh shows Antimicrobial Activity of Methanol Extract
of Rosemary (Rosmarinus officinalis L.) and they concluded that rosemary extract
were a stronger inhibitory effect on the bacteria. Minimum inhibitory concentration
values for both bacteria Leuconostoc mesenteroides and Lactobacillus
delbruekiiranged between 1. 5 mg/ml and 1.75 mg/ml29.
2. Hari Om Saxena, Uzma Faridi, Suchita Srivastava, Kumar J. K, Darokar M. P, Suaib
et.al. Proved that Gallic acid-based indanone derivatives as anticancer agents. In
conclusion, gallic acid-based indanone derivatives showed potent anticancer activity
against hormone-dependent breast cancer, oral and liver cancer cell lines. As one of
the potent molecules was found non-toxic to human erythrocytes, this compound may
further be optimised to better anticancer leads with no or low toxicities to normal
cells30.
ENCLOSURE – III
6.3 AIM OF THE STUDY
AIM:
To evaluate antiepileptic and nootropic effects of Gallic acid in rats.
ENCLOSURE – IV
7. MATERIALS AND METHODS
MATERIALS:
Chemical: Gallic acid, PTZ, Diazepam, Lithium carbonate, Scopolamine (SigmaAldrich, Bangalore), all other chemicals to be used in this project are of highly
analytical grade.
Dose: Gallic acid (dose-I)-15mg/kg, Gallic acid (dose-II)-30mg/kg, PTZ-40mg/kg
Diazepam-2.0mg/kg, Lithium carbonate-190mg/kg, Scopolamine-1.4mg/kg.
Animals: All experiments and protocols proposed in present study will be carried out
according to the guidelines of CPCSEA, New Delhi and approved by the Institutional
Animal Ethical Committee (IAEC) of Acharya & B. M. Reddy college of Pharmacy,
Bangalore. Albino Wistar rats of either sex (150-200gm) will be housed in group of 6
animals per cage and maintained under standard laboratory conditions ( 12-h
light/dark cycle, 24hrs) and provided free access to palleted PRANAV AGRO Pvt.
Ltd. diet and purified drinking water ad libitium.
7.1 SOURCE OF DATA:
The source of data will be obtained from,
 Laboratory based studies.
 Literature survey, CD ROM.
 National & International Journals.
 Text books.
 Internet.
The sources of data are from experiments on animals which involves the following:
To evaluate the antiepileptic and nootropic effects of Gallic acid in animals (Albino Wistar
rats).
ENCLOSURE – V
7.2 METHOD OF COLLECTION OF DATA
1. Pharmacological studies:
To evaluate the antiepileptic and nootropic effects of Gallic acid in animals (albino
Wistar rats).
I. Healthy Albino Wistar rats (Either sex), weighing between 150-200g will be
selected.
II. Rats will be randomly divided for two models for epilepsy, one for nootropic
with four groups each consisting of Six animals
Antiepileptic activity
 Method (a):- MES model

Group 1: vehicle control

Group 2: Standard (diazepam)

Group 3: Gallic acid (dose I)

Group 4: Gallic acid (dose II)
All rats will be stimulated with MES simultaneously to produce convulsions. Group-I
will be treated with vehicle, group-II with standard drug (diazepam) and group-III & IV
with gallic acid of different doses. Each group undergoes pre-treatment for 7 days.
Report will be noted by the observation of behavioural studies.
 Method (b):- PTZ model

Group 1: vehicle control

Group 2: Standard (diazepam)

Group 3: Gallic acid (dose I)

Group 4: Gallic acid (dose II)
All rats will be treated with PTZ simultaneously to produce convulsions. Group-I will
be treated with vehicle, group-II with standard drug (diazepam) and group-III & IV with
gallic acid of different doses. Each group undergoes pre-treatment for 7 days. Report
will be noted by the observation of behavioural studies.
Nootropic Activity
 Method: - Scopolamine model
 Group 1: vehicle control
 Group 2: Standard (lithium carbonate)
 Group 3: Gallic acid (dose I)
 Group 4: Gallic acid (dose II)
All rats will be treated with scopolamine simultaneously to produce amnesia. Group-I
will be treated with vehicle, group-II with standard drug (lithium carbonate) and
group-III & IV with gallic acid of different doses. Each group undergoes four trails
per day for 7 days. Report will be noted by the observation of behavioural studies.
2. Behavioural studies:
A. Antiepilepsy31
a. The number of animals protected from hind limb tonic extension
seizure (HLTE).
B. Nootropic
a. Memory deficit activity32.
b. Elevated plus maze model32.
c. Passive avoidance activity33.
3. Statistical analysis
The data will be expressed as mean ± S.D and will be analyzed using one way
ANOVA and Student t-test. The Value of p<0.05 will be considered significant.
ENCLOSURE – VI
8. LIST OF REFERENCES:
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for ictal semiology: report of the ILAE task force on classification and terminology.
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(cited2009nov 22).
Available from URL: http://www.who.int/mediacenter/factsheets/fs165/en/.
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Available from: URL: http://content.nejm.org/cgi/content/extract/334/10/647
8. Dorland’s Medical Dictionary. Archived from the original on 2008-01-30
9. Lanni C, Lenzken SC, Pascale A, Del Vecchio I, Racchi M, Pistoia F et al., Cognition
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performance in mice. Indian drugs 1993; 16A; 30:97-107.
11. Chang BS, Lowenstein DH Epilepsy N. Engl. J. Med Abstract for Reference 3 of
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