1

EVALUATION OF Citrus medica Linn.

FOR ANTIULCER ACTIVITY

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE.

BY

BEERENAGARAJU

DEPARTMENT OF PHARMACOLOGY,

NARGUNDCOLLEGE OF PHARMACY,

BANGLORE-560085.

(2009-2011)

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR P.G DISSERTATION

1. / Name of the candidate and address(in block letters) /

BEERE NAGARAJU, M.PHARM PHARMACOLOGY,

NARGUND COLLEGE OF PHARMACY,
DATTATREYA NAGAR, BSK THIRD STAGE,BANGALORE 560085.
2. /

Name of the institution

/

NARGUNDCOLLEGE OF PHARMACY

NARGUND COLLEGE OF PHARMACY

M.PHARM (2009-11)PHARMACOLOGY
DATTATREYA NAGAR,II MAIN,
100 FT RING ROAD,BSK III STAGE,
BANGLORE-85
3. /

Course of study and subject

/

MASTER OF PHARMACY IN

PHARMACOLOGY

4. /

Date of the admission

/ 20.06.2009
5. / Title Of The Topic
EVALUATION OFCitrus medica Linn.
FOR ANTIULCER ACTIVITY
6.
7.
8. / BRIEF RESUME OF THE INTENDED WORK
6.1: NEED FOR THE STUDY:
Ulcer is an acute inflammatory lesion of which generally heals quickly. Such a healing ulcer is called a healthy ulcer. Some times an ulcer may fail to heal and be unhealthy because of continued infection or erosion in the part. Ulcer may be defined as the gradual destruction of the stomach; duodenumor both bathed by acid gastric juice and is caused by disruptions of the gastric mucosal surface and repair system1.
Ulcer in the mucosal layer of the stomach which tends to recur with stress and is characterized by episodes of burning epigastric pain, belching and nausea, especially where the stomach is empty or after eating certain foods of which is called gastric ulcer or also known as stress ulcer and in the duodenum is called duodenal ulcer together called as peptic ulcer.
Peptic ulcer may be acute or chronic. Acute lesions are almost always multiple and superficial. They may be totally asymptomatic and usually heal. Chronic ulcers are true ulcers. They are deep, single, persistent and symptomatic. Peptic ulcers are caused by a combination of poorly understood factors including an excessive secretions of gastric acid, inadequate protection of mucous membrane, stress, heredity and taking of some drugs (Aspirin,Steroids,NSAIDS, Caffeine) and other ulcerogenic agents like alcohol, smoking, coffee etc..,
Clinically, peptic ulcer is one of the most prevalent gastrointestinal disorders commonly occurs in developed countries. Treatments are available for ulcer is generally non-specific and is usually aimed at reducing the production of gastric acid and re-enforcing gastric mucosal protection such as regular food, adequate rest and avoidance of exogenous agents. The drugs used in the treatment of ulcer include receptor blockers, proton pump inhibitors, drugs affecting the mucosal barrier and act on CNS. Even though a range of drugs are available for the treatment of ulcer, many of those do not fulfill all the requirements and have side effects2.
Treatment should aim at relieving the symptoms with healing and preventing from further recurrences. Usually, an ulcer will take 3-6weeks to heal and it would not produce any scar. Mostly, many people do not care about their stomach disorders. They temporarily manage their complaints such as gas trouble, poor appetite and pain with antacid by purchasing in local medical shops. There is a study which shows antacids will produce more sodium in blood which in turn gives risk to heart attack or heart disorders. When suffering is constant, some people give no importance to chest pain or heart burn. Also,everyone should be aware that the same set of symptoms may occur in the case of ischaemic heart disease-heart attack. So regular checkup of B.P and E.C.G is a must. Peptic ulcers will get worse if they are not cared for by taking the right food and sticking to the timings and treated well. In allopathic system of medicine, they depend mainly on antacids which give very fast relief. Treating peptic ulcer is tough, since the digested treat can not take rest for healing and is also exposed to irritants which hinder the healing process. By using herbal plants, besides treating the disease, it helps in improving body’s defense mechanism fight against various disease conditions, general resistance, also to avoid recurrences
Prevention is first care better than cure to reduce gastric irritation and acid secretion with growing interest in herbal therapy. We have to find the new herbal drug which can be used for ulcer with more efficacy and least side effects3.
6.2: REVIEW OF LITERATURE:
* Citrus medica linn.(citron) belongs to family, Rutaceae is a large shrub attaining a height of about 6meters with pale yellowish greenish, thorny bark and fruit is ovate in shape and has a sharp apex widely distributed in Himalayas and hill areas in India and also this herb found in many parts of the tropical world, Mediterranean, south and central America.
* Citrus medica contains citroflavonoids have been found to possessarange of anti-inflammatory, antihistamine and diuretic action and cause the dilation of the coronaries.
* In ayurvedic practice, the dried rind or citrus juice is used in kapha and vata diseases, as a vermifuge, for asthma and digestive disorders, as antiscorbutic and also used to counteract nausea and to increase appetite.
* According to analysis made in central America, the food value per 100gmof edible portion contains Moisture-87.1gm, Protein-0.081gm,Fat-0.04gm,Fibre-0.04gm,Ash-0.41gm,Calcium-36.5mg,Phosphorous-16mg,Iron-0.55mg,Carotene-0.009mg,Thiamine-0.052mg,Riboflavine-0.029mg,Niacin-0.125mg,and Ascorbic acid-368mg. Hence, it has antioxidant activity and can be used as comprehensive tonic4.
* The essential oils of four varieties of Citrus medica ( C..medica var.sarcodactylis ,C..medica var.ethrog ,C..medica var .1 and C.medica var .2 were obtained by hydro distillation and analyzed by GC, GC/MS and linear retention indices. All of the citrus oils were found to be rich in monoterpene hydrocarbonswith leminone being the principle component. The essential oil of the whole fruit of C.medica var.sarcodactyliscontained limonene (48%), y-terpinene (26.3%), and (Z)-citral (5.7%) and (E) citral (6.3%).Limonene and y-terpinene were also the major components found in the peel oils of C.medica var.1however, was made up entirely of limonene (84.5%) and a-terpineol (4.2%)5.
Estrogenic activity of petroleum ether extract of seeds of Citrus medica has been studied on immature albino rats6.
Genotoxicity assessment of water extracts of Citrus medica has been studied by using Allium cepa assay7.
Growth inhibition of struvite crystals has been studied in the presence of juice of Citrus medica Linn8.
6.3 OBJECTIVE OF THE STUDY
Main objective of the proposed work is to evaluate the beneficial effects of Citrus medica extract for its anti ulcer effect using stress ulcer through immobilization stress and ethanol induced mucosal damage in rats.
MATERIAL AND METHODS
7.1. Source Of The Data :
Whole work is planned to generate data from laboratory studies i.e. experiments are performed as described in references. Experimental studies in journals and in text books available with college and various institutions.
7.2 METHOD OF COLLECTION OF THE DATA:
Data collected from the different models of antiulcer activity done in the laboratories and from journals.
METHODOLOGY :
1.STRESS ULCER THROUGH IMMOBILISATION STRESS9.
Animals: FemaleWisterratweight b/w 150-170 gm will be procured and maintained under standard conditions with access to food and water ad libitum.
Six Female Wister rats /group are used
Following groups will be made:
Group1:Normal Control
Group2: Stress immobilization ulcer
Group3: Stress immobilization ulcer + Standard drug
Group4: Stress immobilization ulcer + Test dose 1
Group 5: Stress immobilization ulcer + Test dose 2
PARAMETERS TO BE EVALUATED:
1. Ulcer index is calculated versus controls.
2. ETHANOL-INDUCED MUCOSAL DAMAGE10:
Animals: MaleWister Rat weight b/w 150-170gm will be procured and maintained under standard conditions with access to food and water ad libitum.
Six Male Wister rats /group are used
Following groups will be made :
Group1:Normal Control
Group 2:Ethanol treated
Group3: Ethanol + Standard drug
Group 4: Ethanol + test dose 1
Group 5: Ethanol + test dose 2
PARAMETERS TO BE EVALUATED:
1.Ulcer index
2. Optical density of photographic negative of gastric mucosa.
STASTICAL ANALYSIS
The data will be analyzed using single tail students t-test.
7.3 Does the study require any investigation to be conducted on patients
Or other humans or animals? If so please describe briefly
Yes. The above study requires investigation on animals. The effect of drug will be studied on Various parameters usingRats as animal model.
7.4 Has ethical clearance been obtained from your Institution?
Applied for IAEC and Certificate will be produced as soon as the committee clears
REFERENCES:
  1. Tortora Grabowski, Principles of Anatomy and Physiology Wiley International, 10th Edition 2003; Chapter 24, p851-905.
  2. Rang HP, Dale MM, Ritter JM, Flower RJ,Rang and Dale’s Pharmacology, Churchill Livingstone, 6th Edition 2008; Section 3 (25) p385-396.
3 . Willemijntje A,Hoogerwerf,Pasricha PJ,Goodman and Gillman’s . The Pharmacological
Basis of Therapeutics. McGraw-Hill International 11th Edition 2006; p967-980
4. Julia F, Morton, Miami FL. Fruits of Warm climates 1987;p179-82.
5. Mohd.Ali NA. et al.Essential Oil Constituents of Four Varieties of Citrus medica
(Rutaceae). Malaysian J of Science.2005;24(1):85-8 .
6. Sharangouda, Patil SB. The Estrogenic activity of petroleum ether extract of seeds of
Citrus medica on immature albino rats. International J of green pharmacy. 2008 April-.
june; 2(2):91-4 .
7. Oyedare B, Bakari A, Akinboro A. Genotoxicity assessment of water extracts of
Ocimum gratissimum, Morinda lucida and Citrus medica using the Allium cepa assay.
Bol Latinoam Caribe Plant Med Aromat 2009; 8(2):97-103.
8. Chauhan CK, Joshi MJ. Growth inhibition of Struvite crystals in the Presence of juice
of Citrus medica Linn.Urol Res. 2008 Oct; 36(5):265-73
9. Vogel H. Drug Discovery and Evaluation Pharmacological Assays.2nd Edition 2002.
New York: Springer-VerlagBerlinHeidelberg, chapter J, p 870.
10. Gupta SK, Text book of Drug Screening Methods ,Jaypee Brother’s Medical
publication, 2nd Edition 2009;chapter 35, p 515
9. / SIGNATURE OF THE CANDIDATE
10. / REMARKS OF THE GUIDE / RECOMMENDED
11. / NAME AND DESIGNATION
11.1 NAME OF THE GUIDE / PROF.D.S.PURANIK
PROFESSOR
DEPARTMENT OF PHARMACOLOGY,
NARGUNDCOLLEGE OF
PHARMACY.
11.2 SIGNATURE
11.3 CO-GUIDE (IF ANY) / ------
11.4 SIGNATURE / .
1111.5 HEAD OF THE
DEPARTMENT / Dr. H.J.HRISHIKESHAVAN
PROFESSOR
DEPARTMENT OF PHARMACOLOGY
NARGUNDCOLLEGE OF
PHARMACY.
11.6 SIGNATURE
12. / 12.1 REMARKS OF THE
CHAIRMAN & PRINCIPAL
12.2 SIGNATURE