Synopsis for m. Pharm dissertation submitted to




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EFFECT OF SESAMUM INDICUM LINN.SEED EXTRACT ON GASTRIC ULCER IN RATS

SYNOPSIS FOR

M. PHARM DISSERTATION
SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE


BY

Mr.MD.MONOWAR HUSSAIN

DEPARTMENT OF PHARMACOLOGY
UNDER THE GUIDANCE OF

Mrs. RUBY. K. KOSHY. M. PHARM (Ph.D)

ASST. PROFESSOR

DEPARTMENT OF PHARMACOLOGY



THE OXFORD COLLEGE OF PHARMACY

HONGASANDRA, BANGALORE

KARNATAKA-68

,

ANNEXURE II



PROFORMA FOR REGISTRATION OF SUBJECTS FOR

DISSERTATION






1.


Name of the Candidate

and Address


MD.MONOWAR HUSSAIN

  1. Permanent Address

S/O.Md.Aynal Haque.

Vill.Kandulimari,

P.O. Kalatoli.

Dist,Kamrup, State.Assam,

Pin.781136

b.Postal Address

The Oxford College of Pharmacy ,

No.6/9, 1st Cross, Begur Road,

Hongasandra,

Bangalore-560068,

Karnataka.









2.

Name of the Institute


The Oxford College of Pharmacy,

No.6/9, 1st Cross, Begur Road,

Hongasandra,

Bangalore-560068,

Karnataka.








3.

Course of Study and Subject


Master in Pharmacy

[Pharmacology]







4.

Date of Admission to Course





03JUNE2011







5.

Title of the Topic:

EFFECT OF SESAMUM INDICUM LINN. SEED EXTRACT ON GASTRIC ULCER IN RATS”.






6.

BRIEF RESUME OF THE INTENDED WORK:

6.1 Need of study:

Gastric ulcer is an illness that affects a considerable number of people worldwide1. The development and progression of gastric ulcer depends to some extent on the type of the food consumed by the patient. It has been shown that spicy food, fatty food or foods containing caffeine stimulates acid secretion in stomach and increase the risk of ulcer formation2. It is among the most serious diseases in the world. The etiology of gastro-duodenal ulcers is influenced by various aggressive and defensive factors such as acid-pepsin secretion, parietal cell, mucosal barrier, mucus secretion, blood flow, cellular regeneration and endogenous protective agents (prostaglandins and epidemic growth factors)3. The gastric mucosa is continuously exposed to potentially injurious agents such as acid, pepsin, bile acids, food ingredients, bacterial products (Helicobacter pylori) and drugs4. On the other hand, food containing flavonoids like apples, celery, cranberries and onion may inhibit the growth of H. pylori and may reduce the development of H. pylori induced gastric ulcers. High fiber diets such as potatoes, banana, peas, and beans etc, also reduce the development of duodenal ulcers and the same is true with fruits rich in vitaminC5. These agents have been implicated in the pathogenesis of gastric ulcer including enhanced gastric acid, pepsin secretion, and inhibition of prostaglandin synthesis, cell proliferation growth, diminished gastric blood flow and gastric motility6. Drug treatment of peptic ulcers is targeted at either counteracting aggressive factors or stimulating the mucosal defences7.

Ulcer therapy has progressed from vagectomy to anti-cholinergic drugs, histamine-H2 receptor antagonists, antacids and more recently to proton pumps inhibitors which revolutionized the treatment of peptic ulcers and other gastro intestinal disorders8. It has been shown that long term use of synthetic drugs leads to various adverse effects.

In recent years, there has been growing interest in alternative therapies and the use of natural products.9,10. Plant extracts are shown to have more attractive sources of new drugs and results for the treatment of gastric ulcer11.



Sesamum Indicum Linn- Family-Pedaliceae. It has reported to possess a wide variety of pharmacological actions, among which, the best known are its effect on the anti inflammatory, anti-fungal and anti-bacterial activity12. Sesame ligans have got antioxidant property also.13Hence, the present study is to evaluate the anti ulcer activity of Sesamum Indicum Linn.seed extract.







6.2 Review of Literature:

SESAMUM INDICUM LINN.-Sesame seed, Family-Pedaliceae.

Synonyms-Sesamum africanum, Sesamum brasiliense, Sesamum luteum, Sesamum malabaricum.14



Common names-Sesame seed, benne seed, til, sim sim, abongra, Hu ma, Zhi ma, Sesamzaa Sesamo, Goma, Shiro goma, Cham kkae, Semilla de ajonjolí, Sesam, Sésamo, Sezam indyjski14.

  • Sesamum Indicum Linn. is an erect tropical annual, original from Africa, but also found abundantly in suriname it is growing up to 6 feet tall. The opposite leaves are oblong or lanceolate and sesame has white to light rose flowers; also the plant is covered with fine hair. The fruit is a grooved capsule often containing more than 100 seeds. It can be off- white brown, grey or black and are used among others for the flavouring of bread14.

  • Sesame seed is a source of edible oil and is also used as a spice. Benne seed contains a high percentage of oil (ca 55 %), which has a very good stability due to the presence of natural anti – oxidents. These seeds contain: manganese, copper and calcium; Vitamin B1 (thiamine) and Vitamin E (tocopherol) they are rich in powerful antioxidants (lignans). The dried seeds taste nutty; the flavor is further increased by toasting14.

  • Chemical constituents of Sesamum Indicum Linn. and its dry flowers have been used to cure alopecia, frostbite and constipation as a Traditional Chinese Medicine. Interestingly, the Flos Sesamum Indicum Linn. was usually used to cure verruca vulgaris and verruca plana in folk of China and showed a pleasant result. Ten compounds were isolated from the 95% ethanol extract of the plant and elucidated as latifonin, momor-cerebroside, soya-cerebroside II, 1-O-beta-D-glucopyranosyl-(2S,3S,4R,5E,9Z)-2-N-(2'-hydroxytetracosanoyl)1,3,4-trihydroxy-5,9octadienine, 1-O-beta-D-glucopyranosyl-(2S,3S,4R, 8Z)-2-N-(2' R) 2'-hydroxytetracosanoyl) 3,4-dihydroxy-8-octadene,(2S,1"S) -aurantiamide acetate, benzyl alcohol-O-(2'-O-beta-D-xylopyranosyl,3'-O-beta-D-glucopyranoside)-beta-D-glucopyranoside,betasitosterol,daucosterol and D-galacititol. Among them, 4 is a new compound, and others were isolated from the flowers of the plant for the first time. Compounds 2 to 4 belong to cerebroside, which is rare to be found in land plants and was proved to possess many bioactivities15.

  • Women of ancient Babylon would eat halva, a mixture of honey and sesame seeds to prolong youth and beauty, while Roman soldiers ate the mixture for strength and energy.16

  • Sesame plant holds its importance from the ancient culture. Beside seeds the other parts of plant are also useful like flowers (cancer, alopecia, and constipation), roots (antifungal activity) and leaves (infant cholera, diarrhoea, dysentery and for urinary infections). Sesamin and sesamolin, two unique phytoconstituents isolated from seeds, possess excellent cholesterol-lowering effect in humans and prevents high blood pressure. They serve as a good source of copper, manganese and calcium which are effective in reducing pain, in osteoporosis and in reduction of swelling in rheumatoid arthritis. Antioxidant action is also observed with seeds.17

  • Wound healing activity has been reported due to its anti oxidant activity.18

  • The seeds of the plant show a antimicrobial activity and anti fungal activity and it is a very old cultivated crop and Chlorosesamone obtained from roots of sesame has antifungal activity.19’20

  • Both sesamin and sesamolin were reported to increase both the hepatic mitochondrial and the peroxisomal fatty acid oxidation rate. Sesame seed consumption appears to increase plasma gamma-tocopherol and enhanced vitamin E activity which is believed to prevent cancer and heart disease.21 Sesame lignans have antioxidant and health promoting activities.13




    1. Objective of study:

The objective of the proposed study is to investigate antiulcer activity of Sesamum Indicum Linn.seed extracts in rats.

Specific objectives:

1. Phytochemical screening Sesamum Indicum Linn.seed extracts.



Experimental animal models

  • Pylorus ligation induced gastric ulcers.

  • Ethanol induced gastric ulcers.

  • Indomethacin induced gastric ulcer.

Biochemical studies

The volume of the gastric juice is measured and used for estimation,

1.Free acidity and total acidity22

2.Pepsin content23

3. Total proteins24

4. Mucous content25

5.Estimation of SOD and Glutathione25



7.


MATERIALS AND METHODS:

7.1 Source of Data:

Data will be obtained from CD-rom, Internet facilities, Literatures and related articles from libraries of The Oxford College of Pharmacy, Indian Institute of Sciences, Government College of Pharmacy etc., and other Research Publications and Journals.







7.2 Method of Collection of Data:

The data collected will be based on animal experimentation as per the parameters studied under each animal model, which are mentioned under the objectives of the study.



EXPERIMENTAL MODELS

Source of animals :

Wistar albino rats of either sex weighing between 150-200 gm will be obtained from animal house of Nimhans, IISC and Veterinary Hospital.



Preparation of Sesamum Indicum Linn. Seed extract:

Procedure:

The Sesamum Indicum Linn. seeds will be collected and dried. The dried powder material (200g) of the Sesamum Indicum Linn. seeds will be extracted with 1000 ml of ethanol in a soxhlet apparatus. The ethanol extract will be distilled, evaporated and dried in vacuum. The concentrated crude Sesamum Indicum Linn.seed extracts will be lyophilized in to powder and used for the study.



Qualitative analysis:

The ethnolic seed extract of Sesamum Indicum Linn. will be tested for different phyto constituents like alkaloids, tannins, steroids, saponins, flavonoids, terpenoids, glycosides, amino acids and carbohydrates26.



Experimental Models

1. Pylorus ligation induced ulcers (Shay rat)27,28

The animals will be fasted for 24 h before pylorus ligation with water ad libitum. Normal saline (1 ml/rat, p.o.) will be administered twice daily to all the animals. Under light ether anesthesia, the abdomen will be opened by midline incision below the xiphoid process. The pyloric portion of the stomach will be slightly lifted out and ligated, avoiding damage to its blood supply. The Sesamum Indicum Linn.seed extract, ranitidine or normal saline will be administered intraduodenally immediately after pylorus ligation. The stomach will be placed back carefully and the abdominal wall will be closed with sutures. Animals will be sacrificed 6 h after pylorus ligation.

The stomach will be isolated and the content of the stomach will be collected and centrifuged. The volume of the gastric juice will be measured and this will be used for estimation of free acidity and total acidity, pepsin content, and total proteins. The ulcer index will be determined as mentioned above and the gastric mucus content will be estimated.

Ethanol induced ulcers29

All the animals will be fasted for 36 h before administration of ethanol. The standard drug (misoprostol 100 µg/kg, p.o.) or Sesamum Indicum Linn.seed extract will be administered 1 h before ethanol administration. Ethanol (90%) will be administered to all the animals at a dose of 1 ml/200 g and after 1 h, the animals will be sacrificed, stomach will be isolated and ulcer index will be determined.



Healing of indomethacin induced gastric ulcers30

The gastric ulcers will be induced by administering indomethacin (5 mg/kg, p.o.) for 5 days, during this period the animals will be fed normally. The animals will be then treated either with misoprostol (100 µg/kg, p.o.), or with different dose of Sesamum Indicum Linn.seed extract (250 mg/kg, p.o. or 500 mg/kg, p.o.) once daily for 5 days after induction of ulcer while the control group received only vehicle. Rats will be sacrificed and the stomach will be removed and they will be cut opened along the greater curvature and ulcer index will be determined.



Statistical Analysis:

All data will be expressed as mean ± SD. Student’s t-test will be performed for each experimental group. Data will be compared by analysis of variance (ANOVA) and only values with P<0.05 will be considered as significant.








7.3 Does the study require any investigation or interventions to be conducted on patients or the human or animals? If so please describe briefly:

YES


Study requires investigation on animals. The effects of the drug Sesamum Indicum Linn. Seed extract will be studied on various parameters using rats as experimental animal model.






7.4 Has ethical clearance been obtained from your institute
Ethical Committee approval letter is enclosed.



8.





List of References:

  1. Alqarousmis, Al- sohaibani M, Al- Howriny T, Al-yahya M, Rafatullah S. Rocket “Eruca sativa” A salad herb with potential gastric anti- ulcer activity. World J Gastro Enterol 2009; 15(16): 1958-1965.

  2. Crawford JM. The Gastrointestinal Tract in Robin’s Pathologic Basis of Disease. Cotran, Kumar and Collin (Eds), Saunders, New Delhi 2003; pp.787-802.

  3. Repetto MG, Llesuy SF. antioxidant, substance that prevents or slows the breakdown of another substance by oxygen. Synthetic and natural antioxidants are used to slow the deterioration of gasoline and rubber, and such antioxidants as vitamin C (ascorbic acid), butylated hydroxytoluene
    ..... Click the link for more information.Antioxidant properties of natural compounds Used in popular medicine for gastriculcers. Braz. J. Med. Biol 2002; Res.35: 523-534.

  4. Peskar BM, Maricic N. Role of prostaglandins in gastroprotection. Dig Dis Sc 1998; 43: 23-9.

  5. http:www.umm.edu\altmed\consconditions\peptic ulcer. html Date of retrieval: 14-10-04, Time; 18:30.IST.

  6. Toma W, Hiruma-Lima CA, Guerrer RO, Souza AR. Preliminary studies Mammea Americana L (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice. Phytomedicine 2005; 12: 345-50.

  7. Borelli F, Izzo AA. The plant kingdom as a source of anti-ulcer remedies. Phytother Res 2000; 14: 581-91.

8) Rotukan K. Molecular stress response in the stomach. Nippon Yakurigaku Zasshi 1999; 114

(Suppl 59): 265-272.

9) Rates SMK. Plants as source of drugs. Toxicon 2001; 39: 603-613.

10) Schmeda-HirschmannG, YesiladaE. Traditional medicine and gastroprotective crude drugs.

J.Ethnopharmacol 2005; 100: 61-66.

11)Shenna Marie Sonio, Pete Wendell Mangmang, Angela Gener, Dhalia Cielo Pau. Health Mad.

Antifungal activity of Sesamum seed( Sesamum Indicum Linn.) in white bread. March 18. 2011

12) Alkofahi A, Atta AH. Pharmacological Pharmacological


Referring to therapy that relies on drugs.

Mentioned in: Pain Management




  1. pharmacological, pharmacologic

    pertaining to pharmacology.
    ..... Click the link for more information. Screening of the anti-ulcerogenic effects of some Jordanian medicinal plants in rats. J. Ethnopharmacology. 1999; 67: 341-345.


13) Kato MJ, Chu A, Davin LB, Lewis NG. Biosynthesis of antioxidant lignans in Sesamum Indicum

Linn. seeds. Phytochemistry.1998; 47: 583-591.

14) http://www.tropilab.com/sesam.html.

15) Hu YM, Ye WC, Yin ZQ, Zhao SX. Chemical constituents from flos Sesamum Indicum Linn

Mar2007;42(3):286-91.

16) http;www.positivehealth.com/articleview.php.articleid.110.

17) Chakraborthy GS, Sharma G,Kaushik KN.Sesamum Indicum:A Review.Journal of Herbal medicine and toxicology.2008;2(2):15-19.

18) Kotade kiran and Mahmad Ashad.Wound healing activity of Sesamum Indicum Linn. Seed and oil in rats.Indian journal of experimental biology.Nov 2008;Vol.46: pp 777-782.

19) Ram R, Catlin D, Romero J, Cowley C. Sesame: New approaches for crop improvement. In: J. Janick and J.E. Simon (eds.), Advances in new crops. Timber Press, Portland, OR.1990; pp. 225- 228.

20) Shittu Laj, Bankole MA, Ahmed T, Bankole MN, Shittu RK, Saalu CL, Ashiru OA. Antibacterial and antifungal activities of essential oils of crude extracts of Sesame Radiatum against some common pathogenic micro-organisms. August 14, 2007.



  1. Cooney RV, Custer LJ, Okinaka L, Franke AA. Effects of dietary sesame seeds on plasma tocopherol levels. Nutr. Cancer. 2001; 39: 66-71.

  2. Hawk PB, Oser BL, Summerson HW. Practical physiological chemistry 12th ed. London: Churchill. 1947;pp347.

  3. Debnath PK, Gore KO, Govinda DD, Sanyal AK. Effect of propranolol on gastric secretion in rats. Br J Pharmacol. 1974; 51:213-16.

  4. Lowry CH, Rose borough NI, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem. 1951; 193:265-75.

  5. Prabha T, Babu MD, Priyambada S, Agrawal VK, Goel RK. Evaluation of Pongamia Pinnata root extract on gastric and mucosal offensive and defensive factors in rats. Indian J Exp Biol 2003; 41(4):304-310.

  6. Dongmei Yang, Qiushuang Wang, Leqin Ke , Jianmei Jiang BE1and Tiejin Ying . Antioxidant activities of various extracts of lotus (Nelumbo nuficera Gaertn) rhizome.Asia Pac J Clin Nutr. 2007;16 (Suppl 1):158-163.

  7. Shay H, Komarov SA, Fele SS, Meranze D, Gruenstein H, Siplet H. A simple method for uniform production of gastric ulceration in rat. Gastroenterology1945; 5:43-61.

  8. Kulkarni SK. Hand book of experimental pharmacology. 3rded. New Delhi: Vallabh prakashan; 1999;pp148-50.

  9. Brzozowski T, Konturek SJ, Kwiecien S, Pajdo R, Brzozowski I, Hahn EG et al. Involvement of endogenous cholecystokinin and somatostatin in gastro protection induced by intra duodenal fat. J Clin Gastroenterol 1998; 27:125-137.

  10. Majumdar B, Chaudhri SGR, Ray A, Bandyopadhyay SK. Effect of ethanol extract of piper betle linn. leaf on healing of NSAID-induced experimental ulcer–A novel role of free radical scavenging action. Indian J Exp Biol 2003; 41(4):311-315.




9.



SIGNATURE OF THE CANDIDATE



Md.Monowar Hussain


10.

REMARKS OF THE GUIDE:

Recommended and Forwarded


11.





    1. Name and Designation of Guide

Mrs. Ruby. K. Koshy

Asst. Professor

Department of Pharmacology.





11.2 Signature








11.3 Head of the Department




Dr. S. Jai Kumar

Professor and HOD

Department of Pharmacology





11.4 Signature





12.


12.1 Remarks of the Principal




Recommended and Forwarded







12.2 Signature


Dr. Padmaa M. Paarakh

Principal

The Oxford College of Pharmacy

Hongasandra, Bangalore-68.







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