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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

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Open Access  Full Text Article                                                                                                                                                              Review Article

A Review of Antiulcer Activity of Some Medicinal Plants

Mangirish Deshpande ¹*, Pearl Dighe ², Sujit Nagare ³

¹ Department of Pharmacology, PES’s Rajaram & Tarabai Bandekar College of Pharmacy, Ponda- Goa

² Department of Pharmaceutics, PES’s Rajaram & Tarabai Bandekar College of Pharmacy, Ponda- Goa                                            

³ Dnyandeep College of Pharmacy, Boraj, Maharashtra 415709

 

 

Introduction:

Peptic ulcer also called as ulcus pepticum has become a common disorder in the world affective major population of different countries. Ayurveda describes peptic ulcer as Amlapitta¹ . Peptic ulceration is common, chronic, recurrent and occasionally life-threatening disease of poorly defined pathogenesis in humans. Peptic ulcer is break in the continuous mucosal barrier in stomach, duodenum or the digestive tract exposing the underlying tissue to the corrosive action of pepsin and hydrochloric acid. Ulcer also can be described as defect in the mucosa of the stomach or duodenum that has a depth which may protrude in to submucosa or deeper². Peptic ulcer occurs due to disturbance of balance between aggressive or damaging factors such as high acid -pepsin secretion and protective or defensive factors such as gastromucosal integrity, bicarbonate and prostaglandin secretion ³. Ulceration may result due to frequent damage to the endothelial layer or failure of restoration or healing of mucosal layer thus compromising the integrity of the mucosa ⁴.

Symptoms: 

Minor ulcer may not show any signs and symptoms but big ulcers may cause serious bleeding. Common signs and symptoms of peptic ulcers are loss of appetite, feeling of fullness, mild nausea, pain and discomfort in the upper abdomen, insomnia due to pain in upper abdomen, bloody or dark stools, chest pain, fatigue and weight loss ⁵.

Adverse effects of the synthetic drugs:

Any obnoxious, unintended and undesirable effect of the drugs on the body other than its anticipated effect is termed as adverse effect. Synthetic drugs which are used for the treatment of peptic ulcer have been reported many adverse effects which limits its use over a long period of time⁶. Proton pump inhibitors (PPIs) have been reported to cause minor side effects like nausea, abdominal pain, constipation, flatulence and diarrhoea. PPIs cause major side effects such as sub-acute myopathy, arthralgia, arrhythmias and intestinal nephritis. Recent studies have proven that prolong use of PPIs increases the risk of chronic kidney disease and dementia ⁷. H₂ receptor antagonists are known to cause drowsiness, muscular pain, confusion, hallucinations, slurred speech and headache. Cimetidine causes impairment in sexual drive, impotence and can lead to gynacomastia. Use of Misoprostol is limited as it causes clinical exacerbations of inflammatory bowel disease and is contraindicated in pregnancy as it increases uterine contractility during pregnancy⁸. Antacids may worsen the condition for the patient suffering from renal insufficiency by interfering with electrolyte balance. Al⁺³ containing antacids may contribute to encephalopathy, proximal myopathy and osteoporosis leading to risk of bone fracture in elderly patients. Cytoprotectant drugs like Pirenzepine a M₁ muscarinic receptor antagonist is rarely used today because of it causes blood disorders and hemopoeitic changes with risk of anticholinergic side effects⁴

Search for the drugs from herbal origin can be boost to mankind as drugs from natural sources have been found to possess less side effects as compared to synthetic drugs⁹. Thus current review aims at compiling data of reported antiulcer activity from medicinal plants. 

Reported Antiulcer activity of Medicinal plants:

Cenostigma macrophyllum Tul. Var. acuminata Teles Freire (Cm-FHA) is herbal plant of medicinal importance, native from Brazil. Traditionally it has been used as remedy for gastrointestinal illness, studies have revealed antinociceptive and analgesic properties specially useful in neuropathic pain in experimental diabetes. ¹⁰

A.F.S.C Viana et al. (2013) studied gastro-protective activity of ethanolic extract of leaves of Cm-FHA on rats. Various ulcer inducing models such as Absolute ethanol induced gastric ulcer, HCl/ethanol-induced gastric ulcers, ischemia reperfusion-induce gastric ulcers, cold restrain stress-induced gastric ulcers, indomethacin induced ulcer gastric ulcers were used to induce ulcers in rats. Extract was prepared using 4kg of dried leaves of Cm-FHA and subjected to extraction using 95% of ethanol. Concentrated ethanol extract was further subjected to methanol/water (1:2) and successively extracted with ethyl acetate, concentrated extract of which was further suspended with methanol/water (1:2) and was extracted with hexane. Cm-FHA when compared with standard drug cimetidine significantly exhibited gastroprotective effect in ethanol induced ulcer model at dose of 100 and 200mg/kg by showing lesion inhibition by 40%. In HCl /ethanol induced model lesion inhibition by 50 and 48% at a dose of 100 and 200mg/kg respectively. In ischemia reperfusion model lesion inhibition was 49% at 100mg/kg and 90% at 200mg/kg and in cold restrain stress induced model lesion inhibition was 63% at 100mg/kg and 76% at 200mg/kg. Study was concluded that results satisfactorily proved gastroprotective activity of Cenostigma macrophyllum which reinforces its traditional use in treatment of peptic ulcer as described in folk medicine¹¹.

Maytenus robusta Reissek is traditionally used as decoction in curing gastrointestinal illness in South America continent, mainly popular in countries such as Brazil. ¹²

L. Mota da Silva et al. (2015) carried in vivo and in vitro studies to determine ulcer healing activity of hydro alcoholic extract of aerial plants of Maytenus robusta Reissek (HEMR) using acetic acid induced chronic ulcer model. Pylorus ligation induced ulcer induced model was used to study antisecretory property. In vitro antiulcer activity was determined by carrying out radical scavenging activity, cytoprotective effect and cell proliferation activity in fibroblast (L929 cells), with the assessment of anti-helicobacter pylori activity. HEMR at oral dose of 10mg/kg caused reduction in gastric ulcer area by 53% in acetic acid induced chronic ulcer model. However in pylorus ligated ulcer induced model, HEMR 10mg/kg when administered by intraduodenal route did not show significant changes in volume, pH, total acidity and pepsin activity. In vitro studies of HEMR at the concentration of 1-1000µg/ml significantly scavenge free radical DPPH and also have shown cytoprotection in fibroblasts against hydrogen peroxide at concentration of 0.1-100 µg/ml¹³

3. Rhizophora mangles L.

Rhizophora mangles L is plant rich in tannins, is native to Caribbean countries. ¹⁴ Research studies has discovered antioxidant, anti-inflammatory & wound healing potential¹⁵ of the drug 

F. M.de-Faria et al. (2012) studied mechanism of action of antiulcer activity of Rhizophora mangle L. The bark of Rhizophora mangles L. was powdered and was extracted by maceration using acetone: water (7:3) to obtain crude extract (CE) which was later subjected to fractionation using different solvent to obtain aqueous fraction (Aq), ethyl acetate fraction (EtoAc) and butanolic fraction (BuOH). Gastic ulcer was induced in rats using ethanol induced and pylorus ligation induced ulcer model. Results showed that all the fractions of Rhizophora mangle L. showed a gastroprotective activity at all the tested doses. BuOH extract exhibited significant antiulcer activity so was further examined to determine the possible underlying mechanism of action. Involvement of Nitric oxide(NO), Sulfydril compounds(SH), mucus adhering to gastric wall and levels of PGE2 were determined along with the expression of COX-1,COX-2 and EGF. It was concluded that gastroprotective, ulcer healing and antisecretory effect of BuOH may be contributed by enhancement of PGE2 levels and upregulation of COX-2 and EGF¹⁶.

4. Malvastrum tricuspidatum

Malvastrum tricuspidatum is a plant native to India, is used traditionally as anti-inflammatory, analgesic, and as antiulcer agent.¹⁷

Balekar N et al. (2012) evaluated antiulcer activity of ethanolic extract of Malvastrum tricuspidatum using different ulcer inducing models such as ethanol induced, aspirin induced, cold restrain stress and pylorus ligation induced ulcer induced models. Whole plant of Malvastrum tricuspidatum was dried, powdered and defatted with petroleum ether and was extracted with ethanol. Ethanolic extract was evaluated for antiulcer activity using omeprazole as standard. Ethanolic extract of Malvastrum tricuspidatum at a dose of 500mg/kg showed a significant antiulcer activity in all the models¹

5. Hyptis martiusii Benth

Hyptis martiusii Benth is shrub species found in some parts of Northen Brazil. It has been investigated for its antimicrobial,¹⁸ analgesic¹⁹ and its hypnotic sedative activity. ²⁰

G. F. R. Caldas et al. (2011) studied antiulcerogenic activity of the essential oil Hyptis martiusii Benth.(EOMH). Leaves of Hyptis martiusii Benth were dried and subjected to hydrodistillation to obtain essential oil. Antiulceruogenic activity of EOMH was evaluated using ethanol induced, HCl/ethanol induced, Indomethacin induced and pyloric ligation induced ulcer models. Results revealed that EOMH at 100, 200, 400mg/kg inhibited gastric ulcers and increased gastric pH²¹

6. Pluchea sagittalis (Lam) Cabrera

Pluchea sagittalis (Lam) Cabrera is the plant with great potential which has been used as traditional medicine in several diseases such as inflammation, diarrhoea, & gastrointestinal disorder  

S. M. Figueredo et al. (2011) evaluated Pluchea sagittalis (Lam) Cabrera for its antinociceptive and gastroprotective actions. Aerial plants of Pluchea sagittalis were dried, powdered and extracted with ethanol. Extract was studied for antinociceptive property in mice using different models such as abdominal constriction induced by acetic acid, nociception induced by glutamate, nociception induced by formalin and gastroprotective actions were investigated using ethanol induced ulcer model. Results showed that ethanolic extract of Pluchea sagittalis inhibition of acetic acid induced abdominal constriction with ID50 value of 624mg /kg and decrease in glutamate induced pain in mice with ID50 value of 368mg/kg. Extract also showed promising results by decreasing inflammatory phase induced by formalin at ID50 value of 411mg/kg. Ethanolic extract of Pluchea sagittalis also reduced gastric lesions produced by ethanol with ID₅₀ value of 55 mg/kg²².

7. Byrsonima intermdia A. Juss.

Byrsonima intermdia A.Juss is a plant belonging to family Malpighiaceae commonly found in south American continent and traditionally used for stomach ache, fever, skin infection ²³

R. C. Santos et al. (2011) studied gastric and duodenal anti-ulcer activity of methanolic extract of leaves of Byrsonima intermdia A.Juss.(MBI). Antiulcer activity was determined by ethanol induced ulcer model in rats, NSAID induced gastric ulcer, HCl/ethanol induced ulcer and pylorus ligation induced ulcer in mice. Ulcer protective effect of MBI was determined by evaluating following parameters such as gastric juice volume, pH, total acidity, mucus, NO, sulfhydryl compound, vanilloid receptor, glutathione level and myeloperoxide activity in gastric and duodenal mucosa. MBI was administered orally at the dose of 250, 500 and 1000mg/kg of body weight. Research work clearly demonstrates antiulcer activity of MBI by inhibiting gastric and duodenal ulcer by 69%. It is subsequently proved that gastroprotective action of MBI is mainly by participation of endogenous sulfhydryl compounds and increase in GSH level to provide gastric and duodenal protection²⁴.

8. Allium hookerii

Allium hookerii is the plant of medicinal importance mainly distributed in Indian subcontinent. Plant is of ethnobotanical importance which was traditionally used for ailments such as ulcers, fever, stomach ache.  ²⁵

Singh et al. (2015) studied antiulcer and in vitro antioxidant activity of Allium hookerii-an ethnomedicinal plant of Manipur. Leaves of Allium hookerii were collected, shade dried and powdered in mechanical grinder. Powder was defatted using petroleum ether and extracted with methanol. Methanolic extract of Allium hookerii was subjected to phytochemical evaluation to identify the presence of different phyto-constituents. MEAH was administered orally at the dose 200 and 400 mg/kg for seven days for acute ulcer protective study. Antiulcer activity was studied by pylorus ligation induced, ethanol induced and indomethacin induced gastric ulcer models. In vitro antioxidant activity was evaluated by DPPH assay, reducing power assay, superoxide radical scavenging activity and hydrogen peroxide radical scavenging activity. Phytochemical studies revealed presence of flavonoids, carbohydrates, glycosides, steroids, saponins and phenolic compounds. Results showed that in pylorus ligated induced ulcer rats there was significant decrease total and free acidity 50% and 30.42% at dose of 200mg/kg and 55% and 41% at a dose of 400mg/kg respectively, with increase in pH i.e. 3.1 at 200mg/kg and 4.1 at 400mg/kg as compared to control 2.8, ulcer index showing 31.0% protection at 200mg/kg and 40.5% protection at 400mg/kg,total hexoses 20.4 and 28.6 at 200mg/kg and 400mg/kg respectively as compared to control 12.6, hexosamine 19.1 and 22.8 at 200mg/kg and 400mg/kg respectively as compared to control 11.6 which satisfactorily proved antisecretory activity of MEAH with in vitro antioxidant potential²⁶²⁷.

9. Muktashukti Bhasma

Muktashukti Bhasma is an Ayurvedic preparation consisting of Aloe vera, vinegar and pearl. Outer covering of oyster shell is triturated with Aloe vera and vinegar. It is used for asthma, heart disease, vomiting, dyspepsia.   

Chouhan Omi et al. (2010) studied Muktashukti Bhasma for antipeptic ulcer activity. Ash or paste of pearl oyster called as Muktashukti Bhasma (MSB) is used to treat various gastric disorders in ayurvedic system of medicine. In this study rats of either sex was divided into seven containing eight animals each. Group I was treated with distilled water and was kept as control, Group II, III and IV were treated with MSB with dose of 100mg/kg, 300mg/kg and 1000 mg/kg. Group V, VI and VII were treated subcutaneously with standard drug ranitidine with dose range of 0.5, 2 and 5 mg/kg of body weight. Assessment of peptic ulcer activity was carried out using pylorus ligated induced ulcer model. It was observed that MSB showed promising antiulcer activity with decrease in ulcer score and ulcer index in all administered doses. Ulcer score exhibited by MSB at dose of 100, 300, and 1000mg/kg of body weight was 1.66 ± 0.20, 0.66 ± 0.20 and 0.50 ± 0.22 as compared to control 2.00 ± 0.47. Ulcer index was 166, 44 and 25 as compared to control 200.0. At the same dose levels pH raised by MSB was 2.66, 3.66 and 6.0 as compared to control 2.0. It was concluded that MSB showed significant reduction in acid output and has anti-ulcer activity²⁷.

10. Vitis vinifera

Vitis vinifera popularly known as grape seeds belonging to family vitaceae is native plant of Mediterranean region and European countries. Studies have revealed that is possesses antioxidant activity as it is rich source of antioxidants.²⁸ It has been found to possess anti-inflammatory and antibacterial actions.²⁹

Ingale A. M et al. (2016) evaluated anti-ulcer activity of grape (Vitis vinifera) seed extract using hydrochloric acid- ethanol induced ulcer model using wistar albino rats. Grape seed extract (GSE) was prepared by removing the seeds from grapes and were air dried. Seeds were then extracted with 95% ethanol. Rats of either sex were divided 4 groups containing 6 animals each. Group I served as control and were treated with 1ml distilled water, group II was treated with standard drug 100mg/kg of sucralfate, Group III and IV were treated with GSE at 100mg/kg and 200mg/kg respectively. All the treatment was administered orally. Ulcer was introduced 30 minutes after the treatment by administering 1ml of 0.3M HCl and 60% ethanol. It was observed that though there was no significant change in the gastric volume, pH, total acidity and bound acidity, GSE significantly reduced ulcer number 30 + 3.23 and 27+ 2.97 as compared to control 41.66. Ulcer inhibition was 27.98% and 34.67% respectively³⁰

11. Albizzia lebbeck linn

Albizzia lebbeck linn is the plant commonly found in Indian subcontinent and have been investigated for its efficacy in several infectious diseases and proved to be antimicrobial and antifungal agent ³¹

Neelam Balekar et al. (2013) evaluated antiulcer activity of bark extract of Albizzia lebbeck Linn. Ulcers were induced using models such as ethanol induced ulcer, aspirin induced ulcer, cold stress restraint and pylorus ligation induced ulcer. Ethanolic extract of Albizzia lebbeck Linn. at the dose of 500mg/kg showed substantial decrease in ulcer index number, gastric volume, free acidity and total acidity and substantial increase in mucous content as compared to control. This study reveals that Albizzia lebbeck Linn. has good antiulcer potential due to its antisecretory activity³².

12. Baccharis trimera

Baccharis trimera is one of the integral components of Brazilian folk medicine widely used for diarrohea, fever and renal disorder.³³ 

T. M. A Biondo et al. (2011) studied the antisecretory potential of aqueous extract of Baccharis trimera (Less.) DC and isolated active constituent to determine mechanism of action involved. In vivo antiulcer test were performed using cold restraint stress induced ulcer and pylorus ligated induced ulcer. Fractions were isolated using HPLC . 14C- aminopyrine [14C]-AP was used as measurement of gastric acid secretion. Fractions were also subjected to enzymatic assay of H⁺ K⁺ ATPase. It was observed that aqueous extract Baccharis trimera (Aq) at dose of 25mg/kg reduced ulcer lesions. Fraction of aqueous extract (FrAq) signified that increase in mucus production, nitric oxide pathway and endogenous prostagalndins may be responsible for antiulcer efficacy of Baccharis trimera. Extract also showed considerable activity against Helicobacter pylori³⁴.

13. Calophyllum brasiliesnse Camb

Calophyllum brasiliense Camb. (Clusiaceae) is the medicinal plant found in Latin America, possessing antimicrobial with gastroprotective activity. ³⁵

L. M. S Lemos et al. (2012) evaluated antiulcer activity of chromanone isolated from Calophyllum brasiliesnse Camb. Antiulcer activity of hexane extract Calophyllum brasiliense (HECb) and extract chromanone(BI) was evaluated by ethanol induced gastric ulcer pre-treated with L- NAME and indomethacin induced gastric ulcer. Both the test compounds BI and HECb at a dose of 20 and 100mg/kg, p.o. were subjected to measurement of malondealdehyde, reduced glutathione and catalase activity and determination of anti-Helicobacter pylori activity. It was concluded that BI significantly reduced gastric ulceration and its mechanism was partly due to reduction of malondealdehyde and catalase activity. BI exhibited anti Helicobacter pylori activity ³⁶.

14. Terminalia chebula

Terminalia Chebula holds important place in Ayurvedic system of medicine. It has exemplary power of healing and is considered as king of medicine. ³⁷

Raju D et al. (2009) evaluated anti-ulcer potential of Terminalia chebula fruit by extracting it with methanol (METC). Ulcers were induced in rats with pylorus ligation and ethanol induced ulcer model. METC at a dose of 250 and 500mg/kg produced significant reduction in gastric ulcer by reducing number of gastric lesion, gastric volume, free acidity and ulcer index as compared to control. It was concluded that METC possesses anti-ulcerogenic and ulcer healing properties may be due to its anti-secretory actions³⁸.

15. Bauhinia variegata Linn

Bauhinia variegata Linn is medicinal plant traditionally used for Bronchitis and Hansens disease. It is commonly found in Indian Subcontinents mainly in Srilanka, India and Bangladesh.

Yamini R. K. et al. (2011) evaluated and revealed root of Bauhinia variegata Linn possesses antiulcer activity. Ethanolic (BVE) and alcoholic (BVA) extract of Bauhinia variegata Linn showed antiulcer activity as compared to control group by reducing ulcer index in rats when ulcers were induced with ethanol, aspirin and pylorus ligation induced ulcer. BVE and BVA proved to be having anti-secretory property as it reduced gastric volume, free acidity, total acidity and raised the pH³⁹.

16. Boswellia serrata

Boswellia serrata is used in Ayurveda since ancient time for treatment of osteoarthritis and also as analgesic and anti-inflammatory. It is 30ft long tree native to Deccan peninsula of India and also found in some parts of Africa.⁴⁰

Zeeyauddin K. et al. (2011) evaluated petroleum ether and aqueous extract of bark Boswellia serrata for its antiulcer activity. Ulcers were induced in rats using aspirin induced ulcer model. At the oral dose of 250mg/kg petroleum ether extract and aqueous extract of the bark showed ulcer healing at 71.4% and 60% respectively. Study reinforced traditional claim of Boswellia serrata for its antiulcer efficacy⁴¹.

17. Gardenia gummifera L.

Gardenia gummifera L. is the plant belonging to southern region of Indian subcontinent and research studies has established anthelmintic, antispasmodic, antiepileptic potential of the drug. ⁴²

Pradeep Kumar et al. (2015) studied and proved that methanolic extract of whole plant of Gardenia gummifera L. (MEGG) possesses antiulcer activity in rats. Groups of animals after being treated with MEGG at the oral dose of 150mg/kg and 300 mg/kg for six days found to decrease ulcer index in aspirin plus pylorus ligation induced ulcer model with percentage protection of 44.61 and 70.66 respectively ⁴³

18. Orthosiphon stamineus (Benth.)

Orthosiphon stamineus (Benth.) is the plant of medicinal importance found in parts of southeast Asia and Australia. Plant has shown its efficacy in screening of hyperglycaemia, hypertension and pyrexia.⁴⁴ 

Yuniarto et al. (2017) studied that leaves extract of Orthosiphon stamineus (Benth.) significantly showed gastric ulcer healing activity. Test was carried out at dose level of 250 and 500mg/kg orally and showed ulcer healing percentage of 31.47 and 35.74 respectively as compared to control group in aspirin induced ulcer model. Orthosiphon stamineus leaves extract also showed a slight increase in gastric pH. Results reveal that Orthosiphon stamineus has ulcer healing potential⁴⁵.

19. Salvadora indica (W.)

Salvadora indica (W.) is the plant found in African and Asian continents and is well known for its astringent antiseptic property and also proved to be antihyperlipidemic.⁴⁶

Saroj Kumar Sahoo et al. (2016) studied Salvadora indica (W.) for its antiulcer efficacy. Fresh leaves of S.indica were collected from Srikakulam area of Andhra Pradesh, were washed thoroughly and shade dried. The dried leaves were powdered, defatted with petroleum ether and extracted with 95% ethanol. Extract was administered orally at the dose range of 150,300 and 600mg/kg for 7 days. Ulcers were induced in rats using different ulcer inducing models like pylorus ligation ulcer induced model, ethanol induced mucosal damage and cysteamine induced duodenal ulceration. It was observed that there was significant decrease in volume of gastric content, free acidity, total acidity and pepsin activity. Extract at different dose levels showed dose dependent rise in pH. There was decrease in number of ulcer index as compared to control. It was concluded that ethanolic extract of Salvadora indica showed significant antiulcer activity⁴⁷.

20. Azadirachta indica

Azadirachata indica is one of the popular plant in India and widely used in Ayurvedic system of medicine. Traditionally it has been used for treatment of ailments like asthma, diabetes, urinary tract infections. ⁴⁸

Bhajoni et al. (2016) evaluated Azadirachta indica leaves for its ulcer protective activity. Aqueous extract of leaves of Azadirachta indica was studied on rats at oral dose of 150, 300 and 600mg/kg, pylorus ligation, aspirin induced and cold restraint stress induced ulcer model. There was significant decrease in ulcer index in all the ulcer inducing models. There was rise in gastric pH signifying leaves of Azadirachta indica have promising antiulcer activity⁴⁹.

21. Osyris quadripartita Decne

Osyris quadripartita Decne is a shrub of around 7m height mostly grown in America Asia and some parts of Europe. ⁵⁰

Abebaw et al. (2017) validated Ethiopian folk medicine claim of Osyris quadripartita Decne for its antiulcer activity. Methanolic extract of leaf of Osyris quadriparita (OQ) when tested in albino rats inducing ulcer with pylorus ligation and ethanol induced ulcer model showed antiulcer activity with decrease in ulcer index and by increasing gastric pH⁵¹.

22. Anvillea garcinii

Anvillea garcinia is the plant with medicinal properties traditionally used to treat gastrointestinal disorder including peptic ulcer. ⁵²

Shagufta Perveen et al. (2018) collected shrub Anvillea garcinii and evaluated antiulcer activity of ethanol, chloroform and n butanol extract. Gastric lesions was induced with various ulcerogens such as Indomethacin and hypothermic restrain stress. Ethanol extract showed better ulcer protective activity then n-butanol extract. Chloroform extract showed weakest activity. Further research was carried out to isolated two compounds spinacetin 3-O-[α-L-rhamnopyranosyl-(1-6)-β-D-glucopyranoside]-7-O[α-L-rhamnopyranoside] and kaempferol 3-O- rutinoside from the Anvillea garcinii. It was concluded that isolated compounds are of flavonoid group which are having documented antioxidant and ulcer healing activity⁵³ .

23. Phyllanthus urinaria

Phyllanthus urinaria L. is annual perennial plant which is found at altitude from sea level to 1800m and is widely used traditionally for cough, dysentery, haemorrhoids, enteritis. Research have revealed that Phyllanthus urianaria possesses hepatoprotective activity, anticancer activity, antidiabetic activity and anticonvulsant activity. ⁵⁴

Deshpande et.al evaluated antiulcer activity of the Phyllanthus urinaria using ethanolic extract of the plant in albino rats and was proved that at dose level of 500mg/kg reduced the ulcer which were induced by pylorus ligated model, ethanol induced model, cold stress restrain induced model and aspirin induced ulcer model.⁵⁵

24. Adiantum lunulatum

Adiantum lunulatum is fern found in Indian subcontinent constituting phytoconstituents terpenoids, flavonoids and steroids. ⁵⁶It grows in monsoon season and is used as component of folk medicines in the form of decoction for antidiarrheal and antidysentric activity. Leaf juice was used for the relief from ulcers. Deshpande and Balekar evaluated gastroprotective activity of ethanolic extract of Adiantum lunulatum in albino rats using different ulcer inducing models such as Pylorus ligated induced ulcer, ethanol induced ulcer, Aspirin induced ulcer and cold restrain stress induced ulcer model. Ethanolic extract of Adiantum lunulatum showed significant reduction in ulcer and histopathological studies revealed ulcer healing potential of the drug. ⁵⁷ 

25. Morinda lucida (L.) Benth

Morinda lucida commonly known in Africa as Brimstone tree was evaluated by Christophe et al for antipeptic ulcer activity. Aqueous extract of the Morinda lucida was screened a dose level of 100, 200 and 400mg/kg of body weight for its antiulcer efficacy on rats by inducing ulcers using models such as indomethacin and acetic acid induced ulcer. The results showed significant reduction in ulcer formation and ulcer recovery may be dure to increase in level of prostaglandin which is proved cytoprotective.⁵⁸

 

26. Cnestis ferruginea Vahl ex D.C.

Cnestis ferruginea is an African plant which is traditionally used for treatment of fever, wounds, gum pain etc was evaluated for antiulcer properties at dose level of 300-500mg/kg of body weight using immobilisation induced gastric ulcer stress model in mice and rats and shown marked decrease in gastric ulcer.⁵⁹

27. Momordica charantia Linn.

Momordica charantia commonly known as bitter ground constituting phytoconstituents such as flavonoids, saponins and sterols exhibited antiulcer activity of its methanolic extract in stress induced ulcer model. Fruits of the plants also have shown to prevent the growth of bacteria H. pylori. Ethanolic and aqueous extract of the fruits of Momordica charantia L. also have shown excellent anti-ulcer activity in aspirin, pylorus ligation induced ulcer models. ⁶⁰

28. Vernonia amygdalina Del.

Vernonia amygdalina is a tropical shrub commonly known as bitter leaf, and was traditionally used for treatment of microbial infection and gastrointestinal disturbance. Scientifically it has been proved to possess antimicrobial, anti-inflammatory, analgesic, antipyretic activity. Adefisayo et.al showed that Methanolic leaf extract has shown significant reduction inn gastric ulcer in rats. ⁶¹

29. Lantana camara Linn.

Lanata camara is the plant from American continent and traditionally used as component of antimalarial therapy, management of influenza, fevers, ulcer and chicken pox. Satish et.al and Kazmi et al observed reduction in ulcer index of the methanolic extract of the plant when screened at dose level of 250 and 500mg/kg. ⁶²

30. Psidium guajava Linn.

Livingston et al demonstrated that extract of Psidium guajava leaves reduced the ulcer index by 70.5%, 70.4% and 65.07% in aspirin induced ulcer, ethanol induced ulcer and pylorus ligated induced ulcer model respectively. This observation were comparable with standard drug Omeprazole, which reduced ulcer index by 74.1%. It was concluded that Psidium guajava has marked antiulcer potential. ⁶³

31. Trema orientalis Linn.

Trema orientalis Linn was investigated for its antiulcer activity by Uddin et al and was found that ethanolic leaf extract of the plant at dose level of 100mg/kg, 150mg/kg and 200mg/kg reduced the ulcer index and was in corelation with the standard drug Pantoprazole. ⁶⁴

32. Persea americana Mill.

Pesea americana is cultivated mostly in America and Mexico, all over the world it is commonly known as Avacado. In folk medicine it was used for treatment of anemia, stomachache, bronchitis and diarrhoea. Reported pharmacological activities of these plant include anticancer, antioxidant, cardiovascular and antiobesity activity. ⁶⁵

33. Spondia mombin Linn.

Spondia mombin is an tree of medicinal importance found mostly in American and African continents. Traditionally it is known as yellow mombin. In folk medicine it finds its important place in treating stomach ache, diarrhoea, dysentery and inflammation. Oluwatoyin et. al evaluated antiulcer activity of the aqueous leaf extract of the plant using ibuprofen induced ulcer, alcohol induced ulcer and pylorus ligated induced ulcer. Extract was screened at the dose level of 50, 100 & 200mg/kg. it was revealed that at dose level of 200mg/kg 90.60%of ulcer protection was shown.^{66 67}

34. Citrus aurantifolia Linn.

Citrus aurantifolia is the herb found in East Asia and traditionally used for Urinary tract infection, Stomach upsets, diarrhoea. It has been evaluated for anticancer activity, antioxidant activity, cardiovascular activity and antiobesity activity. Citrus aurantifolia was investigated for antiulcer activity using aspirin induced ulcer model. Ethyl acetate extract of citrus aurantifolia showed significant ulcer protective action at dose level of 400mg/kg po. ⁶⁸

35.Bidens pilosa L.

Bidens Pilosa natively African plant now distributed worldwide and found in all parts of the word. Traditionally  Bidens Pilosa was used for management of gastrointestinal disorder, treatment of ulcers, hypertension etc. Ethanolic leaves extract of the plant was screened for peptic ulcer which was introduced by indomethacin and pylorus ligated ulcer induced model and showed significant reduction in ulcer, and exhibited ulcer protective action. Gastric volume was reduced.  ⁶⁹

36. Maytenus senegalensis (Lam.)

Maytenus senegalensis is a 9-12m tall shrub found in Africa. In folk medicine this plant was used for treatment of helminths infection, cough, asthma, diarrohea etc. Haule et al developed polyherbal extract and screened it for its antiulcer effect using ethanol induced ulcer model. It was observed that gastric ulcers were significantly reduced which was comparable with standard Pantoprazole. ⁷⁰

37. Trichilia monadelpha (Thonn.) JJ De Wilde

Trichilia Monadelpha was investigated for antiulcer activity by Avande et al, by using ethanolic extract of the drug in indomethacin induced ulcer model. It was found that epithelium layer of gastric mucosa was restored when treated with 100mg/kg and 300mg/kg. ⁷¹

38. Cassia siebieriana D. C.

Cassia siebieriana is a shrub found in south and west Africa. Ethanolic extract of Cassia siebieriana showed significant ulcer reduction in ethanol induced ulcer model, further extract was fractionated with ethyl acetate and butanol fraction which showed promising results as compared to standard drug cimetidine.⁷²

39. Plumbago zeylanica 

Plumbago zeylanica is the plant of ethnomedicinal importance. In India it is commonly known as Chitrak.⁷³ Phytochemical investigation has revealed presence of phytoconstituents such as flavonoids, terpenoids, alkaloids, tannins and glycosides. It has been reported to possess antibacterial, memory enhancing activity, hepatoprotective and antidiabetic activity⁷⁴. Kakjing Dadul Falang et al evaluated antiulcer activity of the aqueous extract of the plant at 25,50 and 100mg/kg of dose and found that plant exhibit significant antiulcer activity comparable to Omeprazole 20mg/kg showing reduction in gastric lesion. ⁷⁵

40. Solanum nigrum 

Solanum nigrum is the plant of medicinal importance have been used to treat various disorders. Solanum nigrum fruit extract have been found having antiulcer and gastroprotective activity when screened using ulcer inducing models such as Cold restrain stress, Indomethacin induced ulcer, Pyloric ligation induced ulcer and ethanol induced ulcer gastric models. Solanum nigrum fruit extract treatment when given at dose level of 400 mg/kg showed more then 75% reduction in gastric ulcer in all the ulcer inducing models. Results were comparable with the standard drug Omeprazole. ⁷⁶

 

 

 

Table 1: Pharmacognostic profile of anti-ulcer

Sr. no	Botonical name	Family	Classification		Phytoconstituents	Uses
			Order	Genus
1.	Cenostigma macrophyllum	Fabaceae	Fabales	Cenostigma  Tul. (1843)	Flavonoids Vitexin, Isovitexin, (2''-O-galloyl) Isovitexin and nicotiflorin. gallic acid	Gastroprotective,Anti-inflammatory Hypoglycemic77
2.	Maytenus robusta Reissek	Celastraceae	Celastrales	Monteverdia A.Rich	β-sitosterol, triacontanol fatty alcohol, β-sitosterol-3-O-β-glucoside, rosmarinic acid, 6-O-p-coumaroyl-β-D-fructofuranosyl α-D-glucopyranoside	Antiulcer, Hepatoprotective70
3.	Rhizophora mangles L	Rhizophoraceae	Malpighiales	Rhizophora	Quercetin and proanthocynidins	antiseptic, astringent, haemostatic and antifungal properties.16
4.	Malvastrum tricuspidatum	Malvaceae	Malvales	Malvastrum A.Gray	Stigmasterol, ß-sitosterol, phenylethylamine, lutein, indole alkaloids, fatty acids (palmitic, oleic, malvalic acid, sterulic, linoleic, and) alkaloids, tannins, with fair content of phenolic and flavonoid contents.	Immunomodulaotry, Inflammation, antiulcer1
5.	Hyptis martiusii Benth	Lamiaceae	Lamiales	Medusantha	1,8-cineole (32.80%), δ-3-carene (17.43%), camphor (6.70%), α-pinene (3.52%), and caryophyllene oxide (3.50%).	Anti-inflammatory, Antinociceptive 21
6.	Allium hookerii	Amaryllidaceae	Asparagales	Allium	Sulfur-containing compounds [14], flavonoids [15], fatty acids, phenolic, and polyphenols [5,6,15,16], and essential oils	anti-obesity, anti-inflammatory, and immunomodulating effects78
7.	Vitis vinifera	Vitaceae	Vitales	Vitis	Phenolic compounds, aromatic acids, flavonoids, proanthocyanidins, and stilbenoids.	antioxidative, anti-inflammatory, and antimicrobial activities32
8.	Albizzia lebbeck linn	Mimosaceae	Fabales	Albizia	Alkaloids, flavonoids, saponins, and terpenoids	antiseptic, anti-dysenteric, anti-tubercular, helminth infection 32
9.	Baccharis trimera	Asteraceae	Asterales	Baccharis	Saponins, mainly echinocystic acid, and the flavonoids rutin apigenin, quercetin, luteolin, eupafolin, and hispidulin	Anti-inflammatory, analgesic34
10.	Calophyllum brasiliesnse Camb	Clusiaceae	Malpighiales	Calophyllum	Flavonoids, triterpenes, coumarins, chromones, and xanthones	Diabetes, analgesic ulcer, antileishmanial 36
11.	Terminalia chebula	Combretaceae	Myrtales	Terminalia	Flavonoids and falvins, terpenoids to steroids, alkaloids, tannins and their derivatives and glycosides.	Antioxidant, anti-diabetic, anti-atherosclerotic, anti-bacterial, anti-viral, anti-inflammatory, and analgesic properties79
12.	Bauhinia variegata Linn	Fabaceae	Fabales	Bauhinia	Quercetin, rutin, apigenin and apigenin 7-O-glucoside	Anticancer, antioxidant, hypolipidemic, antimicrobial, anti-inflammatory, nephroprotective, hepatoprotective, antiulcer, immunomodulatory80
13.	Boswellia serrata	Frankincense	Sapindales	Boswellia	Monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids i.e. β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid	Sedative and analgesic activity 41
14.	Gardenia gummifera L.	Rubiaceae	Gentianales	Gardenia	Glycosides, phytosterols, fats and oils, phenols, resins, tannins, flavonoids, tannins, and terpenoids	Indigestion, constipation, menstrual cycle problem, muscle pain, dental problems, parasitic worms42
15.	Orthosiphon stamineus (Benth.)	Lamiaceae	Lamiales	Orthosiphon	Diterpenoids, flavonoids, triterpenoids, phenolic acids,	diuretic, hypouricemic, renal protective, antioxidant, anti-inflammatory, hepatoprotective, gastroprotective, antihypertensive, antidiabetic, antihyperlipidemic, antimicrobial, and anorexic activities.
16	Salvadora indica(W.)	Salvadoracea	Brassicales	Salvadora	Alkaloids, glycosides, tannins, Flavonoids, proteins, terpenoids and sterols.	Antiulcer, antidiabetic, antioxidant.
17	Azadirachta indica	Meliaceae	Sapindales	Azadirachta	Azadirachtin, limonoids, quercetin, catechins, carotenes, and vitamin C.	Used for treating skin troubles and rheumatism,
18	Osyris quadripartita Decne	Santalaceae	Santalales	Osyris	Flavonoids, anthracene derivatives, and sesquiterpene lactones	Antimicrobial, antioxidant, enzyme inhibitory activity, antiulcer, anticonvulsant, sedative, analgesic, anti-inflammatory, hypoglycemic, hypolipidemic, antiosteoporosis, and antitumor activities.
19	Anvillea garcinii	Asteraceae	Asterales	Anvillea	Sesquiterpenoids belonging to the guaiane (4α,9α,10α-trihydroxyguaia-11(13)en-12,6α-olide, (1)) and germacranolide (9β-hydroxyparthenolide-9-O-β-D-glucopyranoside, (2)	Intestinal diseases, lung and liver diseases, digestive problems, and as an antidiabetic agent.
20	Phyllanthus urinaria	Phyllanthaceae	Malpighiales	Phyllanthus	Tannins, Flavonoids, Naringin, Phyllanthin	Antiulcer, antioxidant, antidiabetic, hepatoprotective
21	Adiantum lunulatum	Pteridaceae	Polypodiales	Adiantum	Alkaloids, phenols, triterpenoids, glycosides, steroids and carbohydrate	Antioxidant, antibacterial, antiulcer, hypoglycemic, antifungal.
22	Morinda lucida (L.) Benth	Rubiaceae	Gentianales	Morinda	Anthraquinones, alkaloids, tannins, flavonoids, saponins and triterpenoids	Malaria, diabetes, hypertension, inflammation, typhoid fever, cancer, cognitive disorders, sickle cell disease, trypanosomiasis, onchocerciasis58
23	Cnestis ferruginea Vahl ex D.C.	Connaraceae	Oxalidales	Cnestis	Alkaloids, flavonoids, saponin, tannins, phenol and cardinolides	Anti-inflammatory and anti-nociceptive properties, antioxidant , hypoglycaemic, aphrodisiac, antimicrobial and laxative activities 59.
24	Momordica charantia Linn.	Cucurbitaceae	Cucurbitales	Momordica	Charantin, vicine, and polypeptide	Antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles81
25	Vernonia amygdalina Del.	Asteraceae	Asterales	Vernonia	Saponins, alkaloids, flavonoids, terpenoids, tannins, steroids, and phenols	Treatment of diabetes, yellow fever, dysentry, constipation, malaria and stomach ache61
26	Lantana camara Linn	Verbenaceae	Lamiales	Lantana	Alkaloids, glycosides, saponins, steroids, terpenoids, carbohydrates, flavonoids, and coumarins	Colds, coughs, pox, bronchitis, and hypertension.62
27	Psidium guajava Linn	Myrtaceae	Myrtales	Psidium	α-terpineol, β-caryophyllene (trans-caryophyllene), rutin, α-humulene, oleanolic acid, flavonoids, and quercetin	Gastrointestinal diseases such as vomiting and simple diarrhea to the treatment of wounds63
28	Trema orientalis Linn.	Cannabaceae	Rosales	Trema	Tannins, flavonoids, saponins, cardiac glycoside, phytosterols, fatty acids, carbohydrates, iridoids, xanthones and phenolic compounds	treatment of diabetes mellitus, respiratory diseases, oliguria, and malaria64
29	Persea americana Mill.	Lauraceae	Laurales	Persea	Alkaloids, flavonoids, saponin, tannins, phenol and cardinolides	Diarrhea, dysentery caused by helminths and amoebas, toothache, intestinal worms, diabetes, skin rashes65
30	Spondia mombin Linn.	Anacardiaceae	Sapindales	Spondias	Flavonoids (3.00%), tannins (3.82%), cardiac glycosides, saponins	Anti-inflammatory, nociceptive67,68
31	Citrus aurantifolia Linn	Rutaceae	Sapindales	Citrus	lavonoids including apigenin, hesperetin, kaempferol, nobiletin, quercetin, and rutin, flavones,     flavanones and naringenin, triterpenoid, and limonoids.	Arthritis, asthma, headaches, abdominal pain, intestinal parasites and psychological problems68
32	Bidens pilosa L.	Asteraceae	Asterales	Bidens	Porphyrins, tannins, aliphatics, terpenoids, alkaloids, phenylpropanoids, cardiac glycosides, flavonoids, and aromatics	Glandular sclerosis, wounds, colds and flu, acute or chronic hepatitis, and urinary tract infections69
33	Maytenus senegalensis (Lam.)	Celastraceae	Celastrales	Maytenus	Flavonoids, pentacyclic triterpenes, sesquiterpenes, alkaloids, and tannins as well as maytansinoids	Respiratory diseases, inflammation, microbial affections and topical application for healing wounds.70
34	Trichilia monadelpha (Thonn.) JJ De Wilde	Meliaceae	Sapindales	Trichilia	Limonoids (1 and 2): 24-acetoxy-21,25-dihydroxy-21,23-epoxytirucall-7-en-3-one (1) and (6R)-1-O-deacetylkhayanolide E (2), together with eleven known compounds (3-13), including additional limonoids, flavonoids, triterpenoids, steroids, and fatty acid	Anti-inflammatory antipyretic82
35	Cassia siebieriana D. C.	Fabaceae	Fabales	Cassia	Polyphenols, flavonoids, tannins, alkaloids, saponins, steroids and triterpenes	Purgative, diuretic, analgesic, antibiotic, anti-inflammatory agent72
36	Plumbago Zeylanica	Plumbaginaceae	Caryophyllales Juss. ex Bercht. & J. Presl	Plumbago	Naphthoquinones, flavonoids, alkaloids, glycosides, steroids, tri-terpenoids, tannins, fixed oils, fats, proteins, etc.	Antidiabetic, antiulcer, antimicrobial, hepatoprotective, wound healing and nephroprotective. 74
37	Solanum nigrum	Solanaceae	Solanales	Solanum	Steroidal saponins, steroidal alkaloids, flavonoids, coumarin, lignin, organic acids, volatile oils, polysaccharides	Anti-inflammatory, antioxidant76

 

 

 

 
 

Conclusion: 

This review reinforces that medicinal plants can be potential source for search of new drugs and can play crucial role in development of new drugs of herbal origin. Various plant extracts and isolated compounds from them have significant antiulcer and gastroprotective activity. Flavonoids and tannins isolated from plant extract can play important role in ulcer healing. There is scope for designing and developing polyherbal preparation from extracts of  these medicinal plants. 

Acknowledgment:

Authors are grateful to the Management of Ponda Education Society’s Rajaram and Tarabai Bandekar college of Pharmacy for providing necessary facilities to carry out review work.

Authors Contribution:

All authors contributed equally to carry out the review work 

Funding Source:

This work did not receive any specific grant to carry out the work. 

Conflicts of interest:

Authors declare no conflict of interest 

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