Review Article R.Ramasubramaniaraja et al. / Journal of Pharmacy Research 2011,4(1),156-160 ISSN: 0974-6943 Available online through http://jprsolutions.info Peptic Ulcer and Phytochemistry : An Overview *R.Ramasubramaniaraja1 and M Niranjan Babu2 1Lecturer, Department of Pharmacognosy, Seven Hills College of Pharmacy, Tirupathi 2Principal, Seven Hills College of Pharmacy, Tirupathi Received on: 15-09-2010; Revised on: 18-10-2010; Accepted on:13-12-2010

ABSTRACT Peptic ulcer disease is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. As many as 70-90% of ulcers are associated with H.pylori a spiral shaped bacterium that lives in the acidic environment of the stomach. Ulcers can also be caused by drugs such as aspirin and other NSAIDS. Naturally occurring the Pytoconstituents like flavanoids, Saponin, tannins gums and mucilage are functioned to cure the peptic ulcer. Phytoconstitents is very cheap with economic and with out side effect produce when compare to allopathic drugs. Phytochemicals produced medicinal herbs also screened.

Key words: Peptic ulcer, Flavanoids, phytochemicals, Azadirachtra indica, Tannins.

INTRODUCTION3 Ulcer is an open discontinuation on the skin or on mucous membrane it may · Melena (tarry, foul –smelling feces due to oxidized iron from hemo- be shallow or deep. Ulceration occurs when there is a disturbance of the globin) normal equilibrium caused by either enhanced aggression or diminished mu- · Rarely an ulcer can bead to a gastric or duodenal perforation which cosal resistance. (or) It is a excavation of the surface, of an organ or tissue, leads to acute peritonitis. This is extremely painful and requires produced by sloughing of necrotic inflammatory tissue. A peptic ulcer, also immediate surgery. called as ulcerpepticum, PUD or peptic ulcer disease is an ulcer (defined as mucosal erosions equal to or greater than 0.5cm) of an area of the gastrointes- A history of heartburn, gastroesophageal refulx disease (GERD) and use of tinal tract that is usually acidic and thus extremely painful. As many as 70- certain forms of medication can raise the suspicion for peptic ulcer. Medicines 90% of ulcers are associated with H.pylori a spiral shaped bacterium that lives associated with peptic ulcer include NSAID that inhibit cyclooxy genase & in the acidic environment of the stomach, however only 40% of those cases most glucocorticoids. go to a doctor. Ulcers can also be caused or worsened by drugs such as aspirin and other NSAIDS5. (Non Steroidal anti-inflammatory drugs). Contrary to Ex: dexamethasone and prenisolone. In Patients over 45with more that two general belief more peptic ulcers arise in the duodenum (Ist part of the small weeks of the above symptoms that odds for ulceration are high enough to intestine just after the stomach) rather than in the stomach about 4% of warrant rapid investigation by Esophagoggastroduodenoscopy. The timing of stomach ulcers are caused by malignant tumor, so multiple biopsies are needed symptoms in relation to the meal my differentiate between gastric and duode- to exclude cancer. Duodenal ulcers are generally benign. nal ulcers. A gastric ulcer would give epigastria pain during the meal as gastric acid is secreted or after the meal as the alkaline duodenal contents reflux in to Classification3 the stomach. Symptoms of duodenal ulcers would manifest mostly before the · Stomach is called as Gastric ulcer / peptic ulcer meal when acid is passed into the duodenum. However, this is not a reliable · Duodenum is called duodenal ulcer sign in clinical practice. · Oesophagus is called oesophageal ulcer · Meckel’s Diverticulum is called meckel’s Diverticulum ulcer. The symptoms of peptic ulcers may vary with the location of the ulcer and the patients age usually children and the elderly do not develop any symptoms Types of Peptic ulcer3 unless complications have arisen. · TypeI : Ulcer along the lesser curve of stomach · TypeII : Two ulcers present - one gastric, one duodenal Burning or growing feeling in the stomach area lasting between 30minutes and · TypeIII : Prepyloric ulcer 3 hours commonly accompanies ulcers. This pain can be misinterpreted as · TypeIV : Proximal gastro esophageal ulcer hunger, indigestion or hear burn pain is usually caused by the ulcer but it may · TypeV : Anywhere be aggravated by the stomach acid when it comes into contact with the ulcer- ated area. The pain caused by peptic ulcers can be felt anywhere from the Signs and symptoms3,5 navel upto the breast bone it may last from few minutes to several hours and · Symptoms of a peptic ulcer can be it may be worse when the stomach is empty. Also times the pain may flare at Abdominal pain-Classically epigastria with severity relating to meal- nigh and it can commonly be temporatily relived by eating foods that buffer times after around 3 hours of taking a meal stomach acid or by taking anti-acid medication. · Bloating and abdominal fullness · Water brash Cause5 · Nausea, and copious vomiting A major causative factor (60% of gastric and upto 90% od duodenal ulcers) is · Loss of appetite and weight loss chronic inflammation due to H.pylori that colonizes the antral mucosa. The · Hematemesis (Vomiting of blood): This can occur due to bleeding immune system is unable to clear the infection despite the appearance of directly from a gastric ulcer or from damage to the esophagus from antibodies. Thus the bacterium can cause a chronic active gastric resulting in severe / continuing vomiting. a defect in the regulation of gastrin production by that part of the stomach and gtastrin secretion can either be decreased resulting in hypo- or achlorhydria or *Corresponding author. increased Gastrin stimulates the productio9n of gastric acid by parietal cells and in H.pylori cononization responses that increase gastrin, the increases in R.Ramasubramaniaraja acid can contribute to the erosion of the mucosa and therefore ulcerformatrion. M.Pharm., Another major causes is the use of NSAIDS. The gastric mucosa protects itself Lecturer Department of Pharmacognosy, from gastric acid with a layer of mucus, the secretion of which is stimulated by Seven Hills College of Pharmacy certain prostaglandins. NSAIDS block the function of clyclooxygenase1 (cox- Tirupathi,Andhra Pradesh, India 1). This is essential for the production of these prostoglandins Cox-2 selec- Tel.: + 91-9494516207 E-mail:[email protected] Journal of Pharmacy Research Vol.4.Issue 1. January 2011 156-160 R.Ramasubramaniaraja et al. / Journal of Pharmacy Research 2011,4(1),156-160 tive anti-inflammatoryes (such as celecoxib or the since with drawn rofecoxib) 1. Flavonoids preferentially inhibit COX-2 which is less essential in the gastric mucosa and 2. Saponins roughly halve the risk of NSAID-related gastric ulceration. 3. Tannins 4. Gums and mucillages Stress5 Flavonoids Researchers also continue to look at stress as a possible cause, or at least Flavanoids are a group of about 4000 naturally ocurring compounds with wide complication in the development of ulcers. There is debate as to whether range of biological effects, including anti-ulcer activity. They are important psychological stress can influence the development of peptic ulcers. Burns constituents of the human diet and are also found inseveral medicinal plants and head trauma, however can lead physiological stress ulcers which are re- used in folk medicine around the world. Mechanism have been proposed to ported in many partients who are on mechanical ventilation. explain the gastro protective effect of flavonoids these include increase of mucosal prostaglandin content. Decrease of histamine secretion from mast cells by inhibition of histidine decarboxylase and inhibition of H.pylori growth. Been found to be free radical scavenges free radical play an important role in ulcerative and erosive lesions of the gastrointestinal tract. Flavonoids could have a therapeutic potential ideal for treatment of gastrointestinal disease associated with H.pylori infection.

Saponins Saponins are widely distributed in plants and are a particular form of glyco- sides. They are so –called because of their soap –like effect. This is due to their surfactant properties. According to the structure of the aglycone or sapogenins two kinds of saponin are recornized the steroidal and triterpenoid type with regard to plants with anti ulcer activity liquorice root contains about 2% - 12% of glycyrrhizic acid and the seeds of the horse chest nut up to 13% 4 Diagnosis -Endoscope image of gastric ulcer of aescin. Some oleanolic acid oligoglycosides extracted from p.japonicus and - Biopsy proven to be gastric cancer K.scoparia showed protective effects on ethanol and indomethacin induced gastric damage. The protective activities of all these active spaonins are not The diagnosis is mainly established based on the characteristic symptoms. due to inhibition of gastric acid secrtion but probably due to activation of The stomach pain is usually the first to signal a peptic ulcer. In some causes mucous membrane protective facors. doctors may treat ulcers without diagnosing them with specific tests and observe if the symptoms resolve, meaning their primary diagnosis was accu- Botanical name Part plant rate. Calendula officinalis Rhizome Calliandra portoticensis Leaves Confirming the diagnosis is made with the help of test such as 1. Endoscopies Glycyrrhiza glabra Root 2. Barium contrast x-rays. The tests are typically ordered if the symptoms do Kochia scoparia Fruit not resolve after a few weeks of treatment or when they first appear ion a person who is over age 45 or who has other symptoms such as weight loss Tannins: because stomach cancer can cause similar symptoms also, when severe ulcer Tannins are used in medicine primarily because of their astringent properties resist treatment particularly if a person has several ulcers or the ulcers are in which are due to the fact that they react with the proteins of the layers of unusual place a doctor may suspect an underlying condition that causes the tissue with which they come into contact. Tannins are called to “tan” the stomach to over produce acid. outer most layer of the mucosa and to render it less permeable and more resistant to chemical and mechanical injury or irritation.; low concentration An esophagastroduodenoscopy a form of endo scopy also called as a gastro of tannins is applied to the mucosa, only the outermost layer is tanned, scopy is carried out on patients in whom a peptic ulcer is suspected by direct becoming less permeable and affording an increased protection to the subja- visual identification the location and severity of an ulcer can be described cent layers against the action of bacteria, chemical irritation, and, to a certain moreover if not ulcer is present; EGD can often provide an alternative diagno- extent, against mechanical irritation. High concentrations of tannins cause sis. One of the reasons why blood tests are not reliable o establishing an coagulation of the proteins of the deeper layer of the mucosa, resulting in accurate ulcer diagnosis on their own is their differentiate between past expo- inflammation, diarrhoea and vomiting. A crude extract of Linderae umbellatae sure to the bacteria and current infection additionally a false-negative is pos- exhibited anti-peptic and antiulcerogenic activity, and these effects were con- sible with a blood test it the patient has recently been taking certain drugs, sidered ascribable to the presence of tannins or related compounds . Nine such as antibiotics or proton pump inhibitors. condensed tannins (monomers, dimers, trimers and tetramers) have been iso- lated and their anti-peptic and anti-ulcer activity confirmed experimentally The diagnosis of H.pylori can be made by (pylorus-ligated in rats and stress-induced gastric lesions in mice). Marked · Urea breath test differences were observed among monomers, dimers, trimers and tetramers. · Direct culture from an EGD biopsy specimen, this is difficult to do, Monomers and dimers, did not inhibit peptic activity in vitro, while trimers and can be expensive most labs are not set up to perform H.pylori displayed higher inhibition of peptic activity than tetramers (though tetram- cultures. ers showed higher astringency than trimers). · Direct detection of unease activity in a biopsy specimen by rapid unease test. Plants containing tannins with anti-ulcer · Measurement of antibody levels in blood , it is still some what Botanical name Part plant controversial whether a positive antibody with out EGD is enough Calliandra portoticensis Leaves to warrant eradication therapy. Entandrophragma utile Bark · Stool antigen test Linderae umbellatae Stem · Histological examination and staining of an EGD biopsy. Mallotus japonicus Bark The breath test uses radioactive carbon atom to detect H.pylori to perform this exam the patient will be asked to drink a tasteless Gums and mucilages liquid which contains the carbon as part of the substance that the The colloidal character of gums, mucilages and other mucoids accounts largely bacteria beaks down After an hour the patient will be asked to blow for their use as therapeutic agents. Mucilaginous drugs have the property of in to a bag that is sealed if the patient is infected with H.pylori, the covering and protecting the mucosa of the stomach and are used in the treat- breath sample will contain carbon dioxide. This test provides the ment of gastric ulcer. Plants containing mucilages traditionally used in several advantage of being able to monitor the response to treatment used countries in the treatment of gastric ulcer include Althaea officinalis, Cetraria to kill the bacteria. islandica, Malva sylvestris, Matricaria chamomilla and Aloe species.

Phytoconstituents in Peptic ulcers6, 7, 8,9,10 Guar gum is obtained from the endosperm of the seed of Cyamopsis Naturally occurring compounds in plants Journal of Pharmacy Research Vol.4.Issue 1. January 2011 156-160 R.Ramasubramaniaraja et al. / Journal of Pharmacy Research 2011,4(1),156-160 tetragonolobus, a plant long cultivated in India and Pakistan and nowadays Description: also grown in the United States . The main constituent is a galactomannan, a Allium sativum is a perennial that can grow 2 feet high or more. The Garlic b-1,4-linked D-mannose linear polysaccharide with an a-1,6-linked D-galac- plant have 6-12 long, narrow and flat like grass leaves. The most important tose residue attached to every other D-mannose unit. Gum guar increased the part of this plant for medicinal purposes is the bulb. The bulb consists of healing rate of stress-induced gastric ulcers in the rat. Proposed mechanisms numerous bulblets, known as ‘cloves’ held between the papery membrane and are reduced acidity, increased local mucosal supply of energy and mechanical enclosed within a whitish skin as a sac. Each bulb is made up of 4 to 20 cloves, protection . Moreover, guar gum, in duodenal ulcer patients, decreases gastric and each clove weighs about 1 gram. The flowers rise direct from the bulb and acidity and the rate of emptying of gastric contents, probably because of its are white in color. Allium sativum has an annual life cycle. effects on viscosity and neutralization of gastric acidity . Cucurbita moschata2 Myrrh, an oleo-gum-resin obtained from Commiphora molmol, contains up to 60% gum and up to 40% resin Myrrh pre-treatment produced a dose- dependent protection against the ulcerogenic effects of different necrotizing agents such as ethanol, indomethacin, sodium hydroxide or hypertonic sodium chloride. The protective effect of myrrh is attributed to its effect on mucus production or increase in nucleic acid and non-protein sulphydryl concentra- tion, which appears to be mediated through its free-radical scavenging, thy- roid-stimulating and prostaglandin- inducing peroperties. Description of Antiulcer Herbs:1 Azadirachta indica2

Common name Pumpkin, winter squash, calabaza, West Indian pumpkin, zapallo,labu manis, butternut squash, Cuban pumpkin, seiyou, auyama, ayote, kalamasa. Scientific Classification: Kingdom Plantae Division Magnoliophyta Class Magnoliopsida Order Cucurbitales Family Cucubitaceae English: Indian lilac, margosa, neem, nim Genus Curcurbita Species C.moschata French: azadirac d’Inde, margosier, margousier Description: Scientific Classification Cucurbita moschata is a species native to the Eastern United States as well as Kingdom Plantae Puerto Rico. It includes varieties of squash and pumpkin. C. moschata variet- Devision Magnoliophyta ies are generally more tolerant of hot, humid weather than C. maxima or Order Spindales C. pepo. They also generally display a greater resistance to disease and in- Family Meliaceae sects, especially to the squash vine borer. Genus Azadirachta Datura herb2 Species A.indica

Description: Neem is a fast-growing tree that can reach a height of 15–20 m (about 50–65 feet), rarely to 35–40 m (115–131 feet). It is evergreen, but in severe drought it may shed most or nearly all of its leaves. The branches are wide spread. The fairly dense crown is roundish or oval and may reach the diameter of 15–20 m in old, free-standing specimens. Allium sativum2

Common name: Thorn Apple, Apple of Peru Scientific Classification: Kingdom:Plantae Order: Solanales Family: Solanaceae Subfamily:Solanoideae Tribe: Datureae Common Name: Organic Garlic, Poor Man’s Treacle, Ail, Lasan, Rosina Genus: Datura.L Scientific classification: Kingdom Plantae Description: Order Asparagales Datura are herbaceous, leafy annuals and short-lived perennials which can Familly Alliaceae reach up to 2 meters in height. The leaves are alternate, 10–20 cm long and Subfamily Allioideae 5–18 cm broad, with a lobed or toothed margin. The flowers are erect or Tribe Allieae spreading (not pendulous like those of the closely allied Brugmansia), trum- Genus Allium pet-shaped, 5–20 cm long and 4–12 cm broad at the mouth; colors vary from Species A.sativum Journal of Pharmacy Research Vol.4.Issue 1. January 2011 156-160 R.Ramasubramaniaraja et al. / Journal of Pharmacy Research 2011,4(1),156-160 white to yellow, pink, and pale purple. The fruit is a spiny capsule 4–10 cm Liquorice Root2 long and 2–6 cm broad, splitting open when ripe to release the numerous seeds. The seeds disperse freely over pastures, fields and even wasteland loca- tions.

Isapgol 2

Common Names: Desert Indianwheat, Desert Plantain, Blonde Psyllium, Common name: Licorice root, licorice, liquorice, sweet root, gan zao (Chi- Indian Plantago, Isabgol nese licorice)

Scientific Classification: Scientific Classification: Kingdom:Plantae Kingdom: Plantae Order: Lamiales Division: Magnoliophyta Family: Plantaginaceae Class: Magnoliopsida Genus: Plantago Order: Fables Species: P.ovata Subfamily:Faboideae Tribe: Galegeae Description: Genus: Glycyrhiza The flowers are on short, rounded, terminal flower spikes. The individual flowers have 4 round-ovate lobes and 4 stamens. The leaves are green, basal, Species: G. glabra and narrowly linear in shape. The plants are covered in fuzzy, white hair at right angles to the stems and leaves. Description: The roots are unearthed in the autumn of the fourth season. It is grown in India, Myrobalan 2 Spain, Iran, Russia, China & Italy.

Table No: 1 List of Anti ulcer activity Medicinal herbs2

Botanical name Family Part used

Azadirachta indica Meliaceae Leaf, Albizia amara Anacardiaceae flower Ammanmia baccifera Anacardiaceae Whole plants Allium sativum Alliaceae bulb Bauhinia varegata Basellaceae Stem bark Bindens pilosa Moraceae leaf Canavalia gladiata fabaceae pod Clitoria ternatea fabaceae root Cassia abus Caryophyllaceae leaf Carallia brachiata Capparaceae Fruits Calycopteris floribunda Caesalpiniaceae Leaf Combretum albidum compretaceae Leaf Cucurbita moschata Cucurbitacea Seed, Fruit Celosia argentea Celastraceae Whole plant Cucuma longa curcumaceae Rhizome Canna indica cannaceae Rhizomes and seeds Dalbergia latifolia Cyperaceae Root Dioscoria pentaphylla Dioscoreaceae Tuber Ficus benjamina Fabaceae Leaf Fiscus virens Fabaceae Stem, bark Common name: Vayastha, Amla, Vrushyaa, Jatiphalarasa, Shiv Dhatriphala, Glinus oppositifolius Gesneriaceae Whole plant Gardenia gummifera Flindersiaceae Gum Hedera helic Haloragaceae leaf Scientific Classification: Homonoia riparia Lythraceae Root Kingdom:Plantae Jatropha gossypifolia Lythraceae Latex Kalanchoe laciniata Iridaceae Leaf Division: Magnoliophyto Lablab purpureus Iridaceae Fruit Class: Magnoliopsida Lowsonia inermis Lauraceae Flower and seed Order: Myrtales Lactura sativa Lauraceae Latex and Stem Mangifera indica Fabaceae Root bark, stem bark Family: Combretaceae Myrtus communis Myrtaceae fruit Genus: Terminalia Momordica charantia Molluginaceae Fruit Morinda pubescens Moraceae Root and Fruit Species: T.chebula Macaranga pellata Lythraceae Leaf Pongamia pinnata Polygonaceae Root Description: Pimpinella tirupatiensis Periplocaceae Tuberous root Phyla nodiflora Periplocaceae Whole plant Amalaki is available in small or moderate sized deciduous trees. The leaves are Persea macrantha Periplocaceae Leaf small, simple, subsessile, many in each branchlet, linear-oblong and entire. Rosa centifolia Rhododendraceae Flower Flowers are small, greenish yellow, unisexual in dense axillary fascicles along Sesbania sesban Scrophulariaceae Flower Syzygium alternifolium Symphoremataceae Fruit the branchlets. There are 6 tepals. The fruits are globose, fleshy, spherical, Solanum melongea Solanaceae Root light greenish yellow, quite smooth and hard on appearance, with 6 vertical Solanum giganteum Solanaceae Leaf stripes or furrows. The fruiting Period is Autumn. Yucca gloriosa Agavaceae Whole plant

Journal of Pharmacy Research Vol.4.Issue 1. January 2011 156-160 R.Ramasubramaniaraja et al. / Journal of Pharmacy Research 2011,4(1),156-160 CONCLUSION: REFERENCES: Ulcer is an open discontinuation on the skin or on mucous membrane it may be 1. C.K. Kokate (2008) Text book of Pharmacognosy Page No: 41.7 2. Dr.K. Madhava chetty (2008) Book of flowering plats of chittoor district P.No: 61-107 shallow or deep. Ulceration occurs when there is a disturbance of the normal 3. K.K. Sharma (2007) Text book of pharmacology P.no: 387 - 390 equilibrium caused by either enhanced aggression or diminished mucosal resis- 4. Peptic ulcer – peptic disorders (2007) Merck manual home edition:P.No:10-10 tance. Peptic ulcer disease is an ulcer of an area of the gastrointestinal tract that 5. Martin U.S.A.F.M.C, Deavid F, Captain Elizabeth Montage mery, U.S.A , M.C., Atrthus s, Dobek, Ph.D, Geoffery A. Patrissi. M.A. colonel David A, Peura, U.S.M.C, F.A.C.G. (2008) is usually acidic and thus extremely painful. As many as 70-90% of ulcers are Compylobacter phlori, NSAIDS, and smoking :Risk factors for peptic ulcer disease- American associated with H.pylori a spiral shaped bacterium that lives in the acidic envi- journal of Gastroenterology. 1268-1272. 6. Aguwa CN. (1986) Pharmacologic effects of an aqueous extract of Rhigiocarya racemifera. J ronment of the stomach. Ulcers can also be caused by drugs such as aspirin and Ethnopharmacol / 15:145-151. other NSAIDS. Naturally presenting the Pytoconstituents like flavanoids, Sa- 7. Gala EE, Kandil A, Hegazy R. (1975) Aloe vera and gastrogenic ulceration. J Drug Res 7:73. ponin, tannins gums and mucilage are functioned to cure the peptic ulcer. 8. Garg GP, Nigam SK, Ogle CW (1993) The gastric antiulcer effects of the leaves of the Neem tree. Planta Med 59:215-217 Pytoconstituents is very cheap with economic and with out side effect produce 9. Yesilada E, Takaishi Y. (1999) A saponin with anti- ulerogenic effect from the flowers of Spartium when compare to allopathic drugs. Anti ulcer Phytochemicals produced medici- junceum. Phytochemistry 51:903-908. nal herbs also screened. 10. Lambrecht N, Burchert M, Respondek M, Muller KM, Paskar BM. (1993) Role of calcitonin gene-related peptide and nitric oxide in the gastroprotective effect of capsaicin in the rat. Gas- troenterology 104:1371-1380. Source of support: Nil, Conflict of interest: None Declared

Journal of Pharmacy Research Vol.4.Issue 1. January 2011 156-160