Natural antiulcer agents: A Pharmacological Review - International ...

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701__________________________________________ReviewArticleNatural antiulcer agents: A Pharmacological ReviewAteeq Ahmad * , Vinay Kumarand Santosh Kumar MauryaFaculty of Ayurveda, I.M.S.Banaras Hindu University, Varanasi, India.__________________________________________________________________________________________ABSTRACTHerbal drugs are traditional method of treating the disease in the worldwide, the plant having ability to treatthe disease is known as medicinal plants. Several type of medicinal plants are existing in the nature andeffective in different type of disease. Peptic ulcers are a broad term that includes ulcers of digestive tract in thestomach or the duodenum. The formation of peptic ulcers depends on the presence of acid and peptic activityin gastric juice plus a breakdown in mucosal defenses. There are two major factors that can disrupt themucosal resistance to injury: non-steroidal antiinflammatory drugs (NSAIDs) example, aspirin and Helicobacterpylori infection. Numerous natural products have been evaluated as therapeutics for the treatment of avariety of diseases, including peptic ulcer. This article reviews the antiacid/anti-peptic, gastroprotective and/orantiulcer properties of the most commonly employed herbal medicines. This article will be concerned only thepharmacology of that plant which shows the antiulcer and gastro-protective effects.Keywords: Antiulcer, Pharmacology, Natural products.INTRODUCTIONPlants have been a valuable source of newmolecules and considered as analternative strategyin search for new drugs. There is a rich abundanceof plantsused in traditional medicine known topossess antiulcer properties that may, after possiblechemical manipulation, provide new and improvedantiulcer drugs (Zakaria et al., 2011).Peptic ulcerdisease (PUD), which includes gastric andduodenal ulcers, is the most prevalentgastrointestinal disorder and requires a welltargetedtherapeutic strategy. The pathophysiologyof PUD involves an imbalance between offensive(acid,pepsin, and Helcobacter pylori) and defensivefactors (mucin), prostaglandin,bicarbonate, nitricoxide, and growth factors). The most common sitesfor ulcers are the stomach and the first fewcentimeters of the duodenum. Acute peptic ulcersinvolvetissues down to the depth of the submucosa,and the lesions may be single or multiple. Reasonsfor the development of ulcers include severeillness, shock, burns, severe emotional disturbance,and postsurgical complications. Chronic pepticulcers penetrate through the epithelial and musclelayers of the stomach wall.Complications of pepticulcers include hemorrhage, perforation, pyloricstenosis, and the development of malignant tumors.Poor digestion and elimination, impropermetabolism, mental and physical stress, anddifficult to digest food enhance the development ofulcers. A number of drugs are available for thetreatment of peptic ulcers, but clinical evaluation ofthese drugs indicates high incidences of relapse,side effects, and drug interactions. These negativeeffects are the rationale for the development of newantiulcer drugs and the search for novel moleculesin natural products (plants), such asOcimumsanctum,Azadirachtaindica, Asparagusracemosus,Musa sapientum, Centellaasiatica,Bacopamonnieri, andBidenspilosa, that offer couldbetter protection and decreased relapse( Vasudevaet al., 2012). In Ayurveda ancient system of Indianmedicine, gastric disorder are classified as sula,parinamsula and amlapitta which corresponds toclinical condition of peptic ulcers and functionaldyspepsia (P.V. Sharma 1994). In currentmedicine, ulcer therapy mainly includes H 2 recepterantagonist, proton pump inhibitors orcytoprotective agents such as sucralfate. Oxygenderived free radical have been implicated in thepathogenesis of a wide variety of clinical disordersand gastric damage(Saha and Goswami, 2010).Thefirst drug effective against gastric ulcer wascarbenoxolone, discoveredas a result of research ona commonly used indigenous plant,Glycyrrhizaglabra(Leguminosceae) (Brown et al.,1959). The plant drugs which posses the activeprinciples such as flavonoid, tannins, terpenoids,shows the antiulcer activity (Gadekar et al.,2010).Different classes of drugs are used in thetreatment of peptic ulcer but most of these drugsexhibits serious side effects like arrhythmias,gynaecomastia, impotence, arthralgia,hypergastrinemia and haemopoeitic changes.Alternative approach in recent days is the researchof medicaments from ayurvedic or traditionalmedicinal system. The use of phytoconstituents asdrug therapy to treat major ailments has proved tobe clinically effective and less relatively toxic thanthe existing drugs and also reduces the offensivefactors serving as atool in the prevention of pepticVol. 4 (2) Apr– Jun 2013 www.ijrpbsonline.com 535

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701serotonin and stress-induced ulceration. Fixed oilreduces the ulcer index in a dose dependentmanner, both in aspirin-induced (500 mg/kg, p.o.)and in indomethacin- induced (20 mg/kg, p.o.)gastric lesions in rats. The fixed oil offeredsignificant dose dependent protection against 50%ethanol-induced (5 ml/kg, p.o.) gastric ulceration inrats (at 1.0, 2.0 and 3.0 ml/kg, i.p.) as well as inhistamine-induced (50 mg base, i.p.) gastric ulcerin guinea pigs at (3.0 ml/kg, p.o). (Majumdar et al.,1999).Microgrammasquamulosa(Polypodiaceae)Crude extract of M. squamulosaandits ethanol andethanol water (1:1) fractions,wasadministered atthe doses level of 400 mg/kg, 29.9 mg/kg, 32.0mg/kg (oral) respectively, in the rats in whichulcers is induced by 30% acetic acid. Itssignificantly reduces the ulcer index in dosedependent manner, which showed the antiulceractivity of the plant.(Suffredini et al., 1999).FicusreligiosaL. (Moraceae)The hydroalcoholic extract leaves of Ficusreligiosawere studied at two dose levels (250 mg/kg and500 mg/ kg, oral) in rats against absolute ethanol(0.2 ml, oral), aspirin (200 mg/kg) and pyloricligation induced gastric ulcer. Ranitidine (50mg/kg, oral), was used as standard drug.Administration ofFicusreligiosa extracts to ratssignificantly decreases the ulcer index value whencompared with controlled treated group.(Saha etal., 2010).Aervapersica Merrill (Amaranthaceae)The ethanol extract of root of A. persica wasadministered at the dose of 200 mg/kg orally, p.ofor 15 consecutive days. Ulcer was induced byethanol and pylorus ligation. The ulcer index of theethanol extract was found to be significantlyreduced compared with control animals. The effectwas also assessed by determining the free acidity,pepsin activity, total carbohydrate (TC), andprotein content (PK) in control, standard, and testgroup animals.(Vasudeva et al., 2012).ToonaciliataRoemer (Meliaceae)The ethanol extract of ToonaciliataRoemer (heartwood) was evaluated for its anti-ulcer activityagainst aspirin plus pylorous ligation inducedgastric ulcer (antisecretory), HCl–ethanol inducedulcer (cytoprotective) and water immersion stressinduced ulcer in rats. We found thatToonaciliataextract at a dose of 300 mg/kg p.o.markedly decrease the incidence of ulcers in all thethree models. Ethanol extract ofToonaciliatashowed significant reduction in gastricvolume, free acidity, total acidity and ulcer index.The plant extract also showed gastro protectiveactivity (52.94%), whereas standard drug sucralfateshowed 94.85%.(Malairajan et al., 2007).Excoecariaagallocha(Euophorbiaceae)The lyophilized extract was given by oral gavages(125 and 62.5mg/kg) three times at 12 h intervalsbefore administering dicolofenac 100mg/kg in amodel of NSAIDS induced rats. Pretreatment withthe extract resulted in a significant decreased of theulcerated area. The volume and acidity of thegastric juice decreased in the pretreated rats, whichsignified the antiulcer potential of plant.(Thirunavukkarasu et al., 2009).Abutilon indicumLinn. (Malvaceae)Methanolic extracts of Abutilon indicum is to beadministered at the dose of 250 and 500 mg/kg inthe pylorus ligated and ethanol induced ulceratedrats. Pretreatment of methanol extract of A.indicumleaves showed significant (P

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701BuchananialanzanSpreng.(Anacardiaceae)The effect of ethanolic extracts (Dose 200, 400mg/kg) of Buchananialanzanwas investigated inrats to evaluate the anti-ulcer activity by using twomodels, ethanol induced ulcer in mice and pylorusligation induced ulcer in rats. Ethanolic extractsshowed a dose-dependent protection against grossdamaging action of ethanol and Pylorus ligation ongastric mucosa of animals. The treatment withEthanol extracts shown significant protection ofulcer index in both the models as well as alsoinhibited the pylorus ligation-accumulated gastricsecretion. (Pareta et al ., 2010).Aeglemarmelos Linn. (Rutaceae)Ulcers is induced by aspirin plus pylorus ligatedgastric ulceration in rats andaqueous extract ofleaves is to be administered orally for 21 days,daily dose of 1 gm/kg body weight. The resultindicated a significant reduction in the ulcer lesioncount, volume of gastric juice and acidity andincrease in pH and hexosamine after treatment withextract. However the pepsin and hexose content notsignificantly altered.(Ilavarasan. R et al., 2002)Tephrosiapurpurea(Fabaceae)Ulcer was induced by oral administration ofethanol or 0.6 M HCL or indomethacine or bypyloric ligation . Aqueous extract ofTephrosiapurpurea was administered in the dose of1 to 20 mg/kg orally 30 minute prior to ulcerinduction. Omeprazole was used as reference drug.Its results ulcer index in the treated animal was findto be significantly less in all models compared tovehicle control models, which signified theantiulcer activity of the plant.(Deshpande et al.,2003).Terminaliachebula(Combretaceae)Methanolic extract of Terminaliachebula wasadministered in the dose of 250 and 500 mg/kgorally. Gastric lession was induced by pylorusligation induced ulcer and ethanol induced gastriculcer. Omeprazole was taken as reference drug.The extract showed significant reduction in gastricvolume, free acidity, and ulcer index as compare tocontrol. (Raju. D et al., 2009)Rhizophora mangle L. (Rhizophoraceae)Freeze- dried aqueous extract of Rhizophoramangle Lin. was administered in the dose of 500mg/kg body weight orally. Gastric ulceration wasinduced by ethanol hydrochloric acid andcimetidine was taken as reference drug. It givessignificant result on dose dependentmanner.(Perera et al., 2001).SolanumpaniculatumL.(Solanaceae)The aqueous extract of Solanumpaniculatum whichis obtained from root, stem and flower inhibited thegastric acid secretion in pylorus ligated mice withED 50 values of 418, 777, and 820 mg/kg bodyweight respectively. The extract of leaves did notaffect gastric secretion whereas fruit extractstimulated gastric acid secretion, which signifiedthe antiulcer activity of plant.(Mesia- Vela etal.,2002).Sapindussaponaria L.(Sapindaceae)Extracts of leaves and fruits of SapindussaponariaL. was orally administered to rats for 30 days andthe parameters of gastric secretion(volume, pH andacidity) were evaluated after pylorus ligature.Lesions induced by stress and standard drug wasgiven as cimetidine. It showed the significantreduction of the lesions index. These resultssuggest that S. saponaria fruits have an antigastriculcer potential.(Albiero et al., 2002).Piper aleyreanum(Piperaceae)Essential oils from the aerial parts of the Piperaleyreanum was given in the dose of 1-30 mg/kgp.o. to thr rat in which ulcer induced by ethanolinduced gastric lesions. Essential oils protected therats against ethanol induced gastric lesions andincreased the mucus level in gastric mucosa, whichshowed plant have the antiulcer potentials.(Santoset al., 2012).Scopariadulcis(Scrophulariaceae)Oral treatment with the water extracts ofScopariadulcis whole aerial parts, at doses of 50,100 and 200 mg/kg, dose dependently inhibited theindomethacin-induced gastric damages in rats,which signified the antiulcer activity of plant.(Babincova et al.,2008).Qualeagrandiflora(Vochysiaceae)The hydroalcoholic extract of bark ofQualeagrandiflorawas investigated for their abilityto prevent and heal lesions in the gastricmucosa.Theoral administration of hydroalcoholicextract (at the doses of 250, 500, 1000 mg/kg bodyweight)exhibited antiulcer activity decreasing theulcerative index induced by HCl/ethanol solution,indomethacin/bethanecholand stress.(Hiruma-Lima et al., 2006).Mangiferaindica(Anacardiaceae)Mangiferaindicaflowersdecoctionwasadministeredat the doses of 250, 500, 1000 mg/kgorally, in rats with gastric lesions induced byethanol, decrease the gastric lesions in dosedependent manner. Pretreatment with aqueousdecoction at the doses of (250, 500 and 1000mg/kg) to mice with HCl/ethanol- or stress inducedgastric lesions resulted in a dose-dependentVol. 4 (2) Apr– Jun 2013 www.ijrpbsonline.com 538

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701significant decrease of lesion index. (Hiruma- Limaet al., 2006).Pithecellobiumdulce(Fabaceae)Gastric ulcer was induced by administering alcohol(or) acetylsalicylic acid (or) hypothermic restraintstress to rats pretreated with hydroacoholic fruitextract of Pithecellobiumdulce at the dose of 200mg/kg body wt for 30 day. Ulcer score wassignificantly minimized in hydroacoholic fruitextract administered animals. pH and acidity ofgastric fluid were significantly minimized and themucin, PGE 2 levels were significantly maintained indrug pre administered animals.(Megala and Geethaet al., 2012).Lafoensiapacari(Lytraceae)Methanol extract of stem bark of Lafoensiapacariwas administered in different doses in rats in whichulcer s were induced by ethanol, indomethacin,cold-restraint stress-induced (acute) and acetic acid(chronic) models. The results of thepharmacological studies on methanol extract ofstem bark of Lafoensiapacari demonstrated potentand effective gastroprotection against ethanol,indomethacin and cold stress-induced acute ulcersand ulcer healing in acetic acid induced chroniculcer.(Martins et al., 2012).Teucriumbuxifolium(Lamiaceae)The Teucriumbuxifolium extracts wereadministered at the dose of 12.5 gm/kg bodyweight in the rats in which ulcers were induced byindomethacin. It shows that the organic extract andinfusion of Teucriumbuxifolium preventedulcerogenesis induced by indomethacin. Thehexane extract exerted a potent inhibitory effect onthe formation of gastric lesions.( Fresno et al.,1997).Bidenspilosa(Compositeae)Ethanolicextract of B. pilosa were administered atthe doses of 0.5 and 2 g/kg in the rats in whichulcers were induced by indomethacine. It showsthat B. pilosa extract significantly protect thegastric mucosa. Ranitidine were taken as standarddrug.(Montero et al., 1999).Albizzialebbeck(Mimoceae)Ethanolic extract of Albizzialebbeckwasadministered at the different doses in the rats inwhich ulcers induced by pylorus ligation, ethanolandindomethacine. Extract shows the significantreduction in ulcer in dose dependent manners. Itsignify the antiulcer activity of plant.(Lawande etal., 2012).Andrographispaniculata(Acanthacea)Hydroalcoholic extract of theAndrographispaniculata was administered in thedifferent doses in the rats and ulcer was induced bycysteamine (CYSinduced duodenal ulcer ). Extractshows the significant reduction in ulcer in dosedependent manners. (( Lawande et al., 2012),(Gupta et al., 2011).AllophylusserratusKurz (Sapindaceae)Ethanolic extract of the plant was administered inthe different doses in the rats in which ulcer wasinduced by pylorus ligation it results the reductionin the ulcer by decreasing acid secretion and pepticactivity and increasingthe mucussecretion.(Dharmani et al., 2006).Picralimanitida (Apocyanaceae)Oral administration of methanol extract,chloroform fraction and methanol fraction at 100mg/kg reduced the gasric ulcer by 56.4%, 40%, and56.3 %, respectively; and the fraction of extractsignificantlyreduced gastric emptying time whencompared to the control. Ulcer was inducedaspirin- pylorus ligation method and cimetidinewas taken as standard drug (Ogochukwu et al.,2011).Kielmeyeracoriacea (Guttiferae)Hydromethanolic extract of the plant wasadministered at the doses of 30, 60, and 102 mg/kgin the rat in which ulcer was induced by ethanolacidinduced ulcer, acute stress- induced ulcer andindomethacine- induced ulcer. It showed thereduction in ulcer index in dose dependent manners(Audi et al., 2005).DISCUSSIONOldest medicinal systems in the world providesleads to find therapeutically useful compoundsfrom plants. Therefore, ethno medicinal knowledgesupported by modern science is necessary toisolate, characterise, and standardize the activeconstituents from herbal source. This combinationof traditional and modern knowledge can producebetter antiulcer drugs with fewer side effects. Herbsare widely available in different countries. Thepresent folklore review has to focus on the certainherbs, which are traditionally mentioned as aantiulcer in a folk literature ofMateriaMedica and are to be investigated for theirantiulcer activity.Research on natural productsoften is guided by ethnomedicinal knowledge, andhas brought substantial contributions to druginnovation by providing novel chemical structuresand/or mechanisms of action . Large number ofherbal extracts are used in folk medicine to treatvarious types of disorders.This review has widescope for researcher to compile literature data ofantiulcer drug and intense study on evaluated useof certain herbs for their better acceptability intherapeutics. Hence the review study is concludedthat the herbal drug possesses antiulcer activity andVol. 4 (2) Apr– Jun 2013 www.ijrpbsonline.com 539

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701it has been proved by different animal models givemany links to develop the future trials.REFERENCES1. AL-Bayaty FHM, Abdulla A, Younis LT,Hassan MIA Anti-ulcer activity ofCentellaasiaticaleaf extract against ethanolinducedgastric mucosal injury in rats.J MedPlants Res. 2010; 4(13): 1253-1259.2. Albiero ALM, Sertie J A A, Bacchi E M.Antiulcer activity of Sapindussaponaria L. inthe rat.,J Ethnopharmacol2002;82: 41-/44.3. AudiEA, Goulart Y CF, Sela VR, Obici S,Martins JVC, Otobone F, Cortez DAEvaluation of Gastric Anti-ulcer Activity in aHydroethanolic Extract fromKielmeyeracoriacea.BrazArchBiolTechnol2005;48(1): 211-216.4. Babincová M, Schronerová K, Sourivong P.Antiulcer activity of water extract ofScopariadulcis., Fitoterapia2008;79: 587–588.5. Brown HM, Christie AB, Colin Jones E, etal.,Glycyrrhetinic acid hydrogen succinate(disodium) salt, a new anti-inflammatorycompound. Lancet 1959; 2: 492–496.6. Dashputre N L, Naikwade N S. Evaluation ofAnti-Ulcer Activity of Methanolic Extract ofAbutilon indicumLinn Leaves inExperimental Rats., Int J PharmaSci DrugRes 2011; 3(2): 97-100.7. Deshpande, S.S., Shah, G.B., Parmar, N.S.Antiulcer Activity Of TephrosiaPurpurea InRats., Indian J Pharmacology 2003; 35: 168-172.8. Dharmani P, Mishra PK, Maurya R,Chauhan VS, Palit G, Allophylusserratus: aplant with potential anti-ulcerogenic activity.J Ethnopharmacol 2005;99:3616.9. Dharmani, P., Palit, G. Exploring Indianmedicinal plants for antiulcer activityactivity., Indian J Pharmacol2006;38(2):95-9.10. Error! Hyperlink reference not valid., Error!Hyperlink reference notvalid.,Antiulceractivityofandrographispaniculata (burm.f.) Wall.Against cysteamine-induced duodenal ulcerin rats. Indian JExpBiol 2011;49: 525-533.11. Fresno VD, Puntero BF, Peinado II, AngelM. Anti- inflammatory and Antiulcer activityof Teucriumbuxifolium. JEthnopharmacol1997; 55: 93-98.12. Gadekar R, Singaur PK, Chaurasia PK,Pawar RS, PatilUK. A potential of somemedicinal plants as an antiulceragents.Pharmacogn Rev 2010; 4(8): 136–146.13. Geetha A, Megala J. Antiulcerogenic activityof hydroalcoholic fruit extract ofPithecellobiumdulce in different experimentalulcer models in rats. JEthnopharmacol2012;142: 415–421.14. Goel RK, Sairam K, Rao CV, Babu MD,Kumar KV, Agrawal VK. Antiulcerogeniceffect of methanolic extract ofEmblicaofficinalis: an experimental study. JEthnopharmacol2002;82:1- 9.15. Goel RK, Sairam K, Priyambada S, AryyaNC. Gastroduodenal ulcer protective activityof Asparagus racemosus: an experimental,biochemical and histological study. JEthnopharmacol2003;86:1–10.16. Gupta SK, Singhvi IJ. Herbal andhepatoprotective drugs acting on peptic ulcerand liver disease: a review. IntJ PharmTechnol2011; 3(1): 824-853.17. Hiruma-Lima CA, Lima ZP,SeveriJA,Pellizzon CH, Brito ARMS, SolisPN, Caceres A, Giron LM, VilegasW.Canthe aqueous decoction of mango flowers beused as an antiulcer agent?., JEthnopharmacol2006;106: 29–37.18. Hiruma-Lima CA, Santos LC, Kushima H,Pellizzon CH, Silveira GG, VasconcelosPCP, Vilegas W, Souza Brito ARM.Qualeagrandiflora, a Brazilian “Cerrado”medicinal plant presents an importantantiulcer activity. JEthnopharmacol2006;104: 207–214.19. Hossain CF, Al-Amin M, SultanaGNN.Antiulcer principle fromZingibermontanum.JEthnopharmacol2012;14: 57– 60.20. Ilavarasan JR, Monideen S, VijayalakshmiM. Antiulcer Activity Of AegleMarmelosLinn.,AncientSci Life 2002; 21(4).y plant/kgbody weight21. Jafri MA, Jamal A, Javed K, Aslam M.Gastroprotective effect of cardamom,ElettariacardamomumMaton. fruits in rats. JEthnopharmacol2006;103:149–153.22. Küfrevioglu ÖI, Gülçin I, Oktay M,BüyükokurogluME.Antioxidant,antimicrobial, antiulcer and analgesicactivities of nettle (UrticadioicaL.). JEthnopharmacol2004;90:205–215.23. Lawande YS, Hase RS, Jadhav DP, HyalijTA. Recent Advances In Research OfAntiulcer DrugOf Natural Origin : A Review.IntJPharmRes Dev2012; 3(11): 160 - 170.24. Majumdar DK, Singh S. Evaluation of thegastric antiulcer activity of fixed oil ofOcimum sanctum (Holy Basil). JEthnopharmacol1999;65:13–19.25. Malairajan P, Gopalakrishnan G,Narasimhan S, Jessi Kala Veni K, KavimaniS. Anti-ulcer activity of crude alcoholicextract of ToonaciliataRoemer (heart wood). JEthnopharmacol2007;110: 348–351.26. Martins DTO, Filho PT, Olaitan BS,Almeida DAT, Lima JCS, Marson-Ascˆencio PG, Ascˆencio SD, Rios-SantosVol. 4 (2) Apr– Jun 2013 www.ijrpbsonline.com 540

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