COMPARATIVE STUDY ON ANTIULCER ACTIVITY

BETWEEN Curcuma longa AND Mentha piperita

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA

BY

DIVYA EDISON

I M.PHARM

DEPARTMENT OF PHARMACOLOGY

VISVESWARAPURA INSTITUTE OF

PHARMACEUTICAL SCIENCES

BANGALORE-560070

(2011-2012)

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1.0 / NAME OF THE CANDIDATE AND ADDRESS(IN BLOCK LETTERS) / DIVYA EDISON
D/O EDISON PARACKAL
GBJ-432,13TH CROSS
HAL TOWNSHIP
MARATHAHALLI
BANGALORE-560037
.
2.0 /

NAME OF THE INSTITUTION

/

VISVESWARAPURA INSTITUTE OF PHARMACEUTICAL SCIENCES BANGALORE-560070

3.0 /

COURSE OF STUDY AND SUBJECT

/

MASTER OF PHARMACY IN

PHARMACOLOGY

4.0 /

DATE OF THE ADMISSION

/ 06th JULY 2010
5.0 /

TITLE OF THE TOPIC:

COMPARATIVE STUDY ON ANTIULCER ACTIVITY
BETWEEN Curcuma longa AND Mentha piperita
6.0
/ BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY
Ulcer is defined as the erosion in the lining of the stomach or duodenum and is caused by the disruptions of the gastric mucosal defense and repair systems. Ulcer in the stomach is called gastric ulcer and in the duodenum is called duodenal ulcer, together peptic ulcer.
In clinical practice, peptic ulcer is one of the most prevalent gastrointestinal disorder, commonly
occurs in developed countries1.
Pathophysiology: Ulcer is due to an imbalance between aggressive factors (acid, pepsin,H.pylori and NSAID’S) and local mucosal defensive factors (mucus bicarbonate, blood flow and prostaglandins).2
A lot of studies with functional foods have been done for evaluation of their anti-ulcer potential. Turmeric (Curcuma longa) and Mint (Mentha piperita) have proved to have anti-ulcer activity. As these are the components in our regular diet, an attempt is being made to compare the anti-ulcer potential of Turmeric and Mint. This will enable us to suggest to increase the frequency of the more potent of the two in diet for prophylactic /curative purpose.
6.2 REVIEW OF LITERATURE:
Turmeric(Curcuma longa L. ), which belongs to the Zingiberaceae family, is a perennial herb that measures up to 1m height with a short stem, distributed throughout tropical and subtropical regions of the world, being widely cultivated in Asiatic countries, mainly in India and China. In India it is popularly known as “Haldi’’. Its rhizomes are oblong, ovate and pyriform and often short- branched3.
.Turmeric contains proteins (6.3%),fat(1.5%),minerals(3.5%),carbohydrates(69.4%) and moisture (13.1%).The essential oil(5.8%) obtained by stem distillation of rhizomes α-phellendrene (1%), sabinene(0.6%), cineole(1%), bomeol(0.5%), zingiberene (25%) and sesquiterpines (53%). Curcumin (diferuloylmethane) (3-4%) is responsible for the yellow colour, and comprise curcumin I (94%), curcumin II (6%) and curcumin III (0.3%). Demethoxy and bisdemothoxy derivatives of curcumin have also been isolated4.
It is extensively used as a spice, food preservative and colouring material in India, China and South East Asia. It has been used in traditional medicine as a household remedy for various diseases, including biliary disorders, anorexia, cough, diabetic, wounds, hepatic disorders ,
rheumatism and sinusitis. Curcumins has been shown to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities4.
Mint(Mentha piperita L.), an aromatic herb of the Lamiaceae family known by the common names of mint, pepper mint, spear mint, American mint, brandy mint, lamb mint, or lam mint may present branches of different colour varying from dark- green to purple-violet5. The plant is a strongly scented, perennial, glabrous, herb, 30-90 cm in height6.
The major constituent reported is volatile oil, of which the principle component is (-) menthol, together with menthol stereo isomers such as (+) neomenthol and (+) isomenthol. Other monoterpenes include menthone (10-40%), menthyl acetate (1-10%), menthofuran (1-10%), cineole (eucalyptol, 2-13%) and limonene (0.2-6%),monoterpenes like pinene, terpinene, myrcene, β-caryophyllene, piperitone, piperitenone, piperitone oxide, pulegone, eugenol, menthone, isomenthone, carvone, cadinene, dipentene, linalool, α-phellandrene, ocimene, sabinene, erpinolene, γ-terpinene, fenchrome, p-menthane, and β-thujone are also present in small quantities.
Flavanoids like luteolin and its 7-glucoside (cynaroside), menthoside, isorhoifolin and others including a number of oxygenated flavones have been reported. Phenolic acids including caffeic, chlorogenic and rosmarinic acid and “pseudotannins’’ derived from them are reported to be present.Triterpenes in small amount including squalene, α-amyrin, urosolic acid and sitosterol and other constituents, azulene and minerals are also reported6.
Peppermint oil vapour is used as an inhalant for respiratory congestion. Peppermint tea is used to treat coughs, bronchitis and inflammation of the oral mucosa and throat. It has traditionally been used to treat a variety of digestive complaints such as colic in infants, flatulence, diarrhoea, indigestion, nausea and vomiting, morning sickness and anorexia, and as a spasmolytic to reduce gas and cramping. The oil is also used in toothache, rheumatism, muscular pains and to relieve menstrual cramps. Mentha piperita is currently used to treat irritable bowel syndrome, Crohn’s disease, ulcerative colitis, gallbladder and biliary tract disorders and liver complaints6.
7.0
8.0 / 6.3 OBJECTIVE OF THE STUDY
The comparative study of anti-ulcer activity of TURMERIC and MINT will be carried out using
1.  Water immersion stress induced ulcer in rats7.
2.  Aspirin plus Pylorus ligation induced gastric ulcer in rats7.
3.  Ethanol induced ulcer11.
.MATERIAL AND METHODS
7.1 Source Of Data :
Data will be generated by performing experiments on animals. The standard information will be collected from various journals, standard Text books available in library of Visveswarapura Institute of Pharmaceutical Sciences, Indian Institute of Science, RGUHS digital library and from various standard websites.
Web sites: www.sciencedirect.com
www.pubmed.com
www.google.com
www.rguhs.ac.in/j-gate@helinet
www.greenchem.biz
METHOD OF COLLECTION OF DATA:
The data will be generated by performing the experiments using animal models as rats.
EXTRACTION OF PLANT MATERIAL
Aqueous extract of Turmeric and mint will be procured from Green Chem, Herbal Extracts and Formulations, Bangalore.
7.2  METHODOLOGY :
The comparative study of anti-ulcer activity of TURMERIC and MINT will be done by following method ;
7.2.1 WATER IMMERSSION STRESS INDUCED ULCER IN RATS7
Stress ulcers will be induced by forced swimming in the glass cylinder (height 45 cm, diameter 25 cm) containing water to the height of 35 cm maintained at 25°C for 3 hours. Wistar albino rats weighing 150 ±5 gm will be fasted for 24 hours prior to the experiments and divided in 4 groups with 6 animals each7.
Group 1: ulcer control
Group 2: 20 mg/kg, p.o. omeprazole as standard control7
Group 3: 500mg/kg, p.o aqueous extract of Curcuma longa8 x 5 days10.
Group 4: 500mg/kg, p.o aqueous extract of Mentha piperita9x 5 days10.
Selection of dose of omeprazole, Curcuma longa, Mentha piperita will be given according to the literature.
After the drug treatment the animals will be allowed to swim in water for three hours7, sacrificed by cervical dislocation and stomach will be dissected out and contents will be collected into tubes for estimation of free acidity, total acidity. The stomach will be cut open along the greater curvature, wash with saline and examined for ulcer score and ulcer index. The stomach tissue homogenate will be prepared using 0.15M KCl12 and glutathione level13, catalase13, and super oxide dismutase13 will be estimated using standard procedure.
7.2.2 ASPIRIN PLUS PYLORUS LIGATION INDUCED GASTRIC ULCER IN RATS7
NSAIDs like indomethacin and aspirin induces gastric lesions by inhibiting cyclo-oxygenase (COX) resulting in less formation of prostacyclin, the predominant prostanoid produced in the gastric mucosa.
Wistar albino rats weighing 150±5 gm of either sex are divided into 4 groups, each group consists of 6 animals and will be fasted for 24 hours with water ad libitum prior to experiment7.
The animals will be divided in the following groups,
Group 1: ulcer control.
Group 2: 50 mg/kg, p.o. ranitidine as standard7.
Group 3: 500mg/kg, p.o aqueous extract of Curcuma longa8 x 5 days10.
Group 4: 500mg/kg, p.o aqueous extract of Mentha piperita9 x 5 days10.
Selection of dose of ranitidine, Curcuma longa, Mentha piperita will be given according to the literature.
Aspirin 200mg/kg once daily for three days will be administered to all the animals. On the fourth day pylorus part will be ligated following 36h fasting. Four hours after the pyloric ligation the animal will be sacrificed by cervical dislocation 7 and stomach will be dissected out and contents will be collected into tubes for estimation of free acidity, total acidity. The stomach will be cut open along the greater curvature, wash with saline and examined for ulcer score and ulcer index. The stomach tissue homogenate will be prepared using 0.15M KCl12 and glutathione level13, catalase13, and super oxide dismutase13 will be estimated using standard procedure.
7.2.3 ETHANOL INDUCED ULCER11
Intragastric application of absolute ethanol is a reproducible method to produce gastric lesions in experimental animals.
The Wistar albino rats weighing 150±5 gm of either sex are divided into 4 groups, each consists of 6 animals.
Grouping and treatment:
Group-1: ulcer control.
Group-2: 50 mg/kg, p.o. ranitidine as standard11.
Group-3: 500mg/kg, p.o aqueous extract of Curcuma longa8 x 5 days10.
Group-4: 500mg/kg,p.o aqueous extract of Mentha piperita9 x 5 days10.
Selection of dose of ranitidine, Curcuma longa, Mentha piperita will be given according to the literature.
After 1h all the animals are treated with 1 ml of 99.5% of ethanol to induce gastric ulcer11. Animals are sacrificed by cervical dislocation one hour after administration of ethanol and stomach will be dissected out and contents will be collected into tubes for estimation of free acidity, total acidity. The stomach will be cut open along the greater curvature, wash with saline and examined for ulcer score and ulcer index. The stomach tissue homogenate will be prepared using 0.15M KCl12 and glutathione level13, catalase13, and super oxide dismutase13 will be estimated using standard procedure.
STATISTICAL ANALYSIS
Values will be expressed as a mean ± SEM. Data will be statistically evaluated using one way ANOVA, followed by Dunnets multiple comparisons using graph pad INSTAT 37 and all the results obtained in the study are compared with the ulcer control group.
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 rats.
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
Yes, ethical clearance certificate will be attached with the hard copy.
REFFERENCES:
1.  Gregory M, Vithalrao KP, Franklin G, Kalaichelavan V. Anti-ulcer Activity of Ficus arnottiana Miq.Leaf Methanolic Extract. Ame. J. Pharmacol. Toxicol. 2009;4(3):89-93.
2.  Dharmani P, Kumar KV, Srivastava S, Palit G. Ulcer Healing Effect of Anti-ulcer Agents: A Comparative Study. Int. J. Acad. Phys. Ass. 2003;3(2):53-6.
3.  Araujo CAC, Leon LL. Biological Activities of Curcuma longa L. Mem Inst Oswaldo Cruz, Rio de Janeiro. 2001;96(5):723-8.
4.  Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee KR. Turmeric and Curcumin:Biological actions and medicinal applications. Curr. Sci. 2004;87(1):44-53.
5.  Valmorbida J, Boaro Fernandes SC. Growth and Development of Mentha piperita L. in Nutrient Solution as affected by rates of potassium. Braz. Arch. Biol. Technol. 2007;50(3):379-84.
6.  Shah PP, Mello PMD. A review of medicinal uses and pharmacological effects of Mentha piperita. Nat. Prod. Rad. 2004;3(4):214-21.
7.  Malairajan P, Gopalkrishnan G, Narsimhan S, Veni JK. Evaluation of anti-ulcer activity of Polyalthia longifolia (sonn) thwaites. Ind. J. Pharmacol. 2008;40(3):126-8.
8.  Piper TJ, Singhal SS, Salameh SM, Torman TR, Awasthi S. Mechanism of anticarcinogenic properties of Curcumin:the effect of Curcumin on glutathione linked detoxification enzymes in rat liver. Int. J. Biochem. Cell. Biol. 1998;30:445-6.
9.  Al-Mofleh I, Alhaider A, Mossa J, Al-Sohaibani M, Qureshi S, Rafatullah S. Antisecretagogue, Antiulcer and Cytoprotective Effects of ‘Peppermint’ Mentha piperita L. J.Med.Sci. 2006;6(6):930-36.
10.  Khandare AR, Gulecha VS, Mahajan MS, Mundada AS, Gangurde HH. Evaluation of antiulcer activity of Polyherbal Formulation. Int. J. Pharm. Rsch. Dev. 2006;1(10):1-6.
11.  Londonkar LR, Poddar VP. Studies on activity of various extracts of Mentha arvensis Linn against drug induced gastric ulcer in mammals. World. J. Gastrointest. Oncol. 2009;1(1):82-88.
12.  Meera S, Rana AC. In vivo antioxidant activity of hydroalcoholic extract of Taraxacum officinale roots in rats. Indian. J. Pharmacol. 2006;38(1):54-5.
13.  Muthusamy P, Suresh JA, Balamurugan G. Antiulcer activity of Azima Tetracantha. Research. J. Pharm. Tech. 2009;2(2):344-8.
9.0 / Reg. No.
SIGNATURE OF THE CANDIDATE
10. / REMARKS OF THE GUIDE / FORWARDED FOR APPROVAL
11. / NAME AND DESIGNATION
11.1 GUIDE / Dr. MEERA SUMANTH
PROFESSOR
DEPT. OF PHARMACOLOGY
V.I.P.S, BANGALORE-560070.
11.2 SIGNATURE
11.3 CO-GUIDE (IF ANY)
11.4  SIGNATURE
11.5  HEAD OF THE DEPARTMENT / Dr. MEERA SUMANTH
PROFESSOR
H.O.D;
DEPT. OF PHARMACOLOGY,
VIPS, BANGALORE-560070.
11.6 SIGNATURE
12. / 12.1 REMARKS OF THE
PRINCIPAL
12.2 SIGNATURE / Prof.Dr. D. H. HARISH KUMAR
PRINCIPAL
VIPS, BANGALORE-560070.

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