Nitu V. Madan*, Mahesh S. Sahu, Yogeshwari T. Jambhulkar, Atreyee S. Mamidwar,
Nilesh T. Hingawe, Amit N. Maliye.
Sonekar College of Pharmacy, Devi Road, Mahadula, Koradi, Nagpur, Maharashtra, India. 441111.
Peptic ulcer is one of the most common gastrointestinal disorders. The occurrence of peptic ulcer disease is attributed to the imbalance between aggressive factors like acid, pepsin and Helicobacter infection on one hand, and the local mucosa defense like bicarbonate, mucus secretion and prostaglandin synthesis on the other hand. A number of drugs including proton pump inhibitors and H2 receptor antagonists are available for the treatment of peptic ulcer, but these drugs has shown incidence of relapses, side effects, and drug interactions. Thus the development of new antiulcer drugs and the search for novel molecules has been extended to, herbal drugs that offer better protection and decreased relapse. Medicinal plants provide an effective and safer way in disease management. This review aims to compile data on plants from Euphorbiaceae family reported for their antiulcer properties.
Peptic ulcer is characterized by an excoriated segment of the GI mucosa, typically in thestomach or first few centimeters of duodenumwhich penetrates through the muscularis mucosa. Ulcer may range in size from millimeters to centimeters1. It is chronic and recurrent disease, and is most predominant of the gastrointestinal disease.It is generally recognized that peptic ulcer is caused by a lack of equilibrium between the gastric aggressive factors and mucosal defensive factors2,3.Pepsin is a proteolytic enzyme which works with gastric hydrochloricacid to digest food. Normally these secreted acid and pepsin do not produce any ulceration as protective and aggressive factors work within their range. In case of overactivity of aggressive factors and: or damage to protective factors may results in peptic ulceration. Peptic ulcers are classifiedas acute (stress) ulcers and chronic4, 5.
Types of Ulcers:
Acute (stress) Peptic Ulcers
These are small, multiple mucosal ulcers usually seen in stomach and occasionally in duodenum.In majority of cases stress is the most important etiological factor for this type of ulcers. other factors are prolong administration of NSAIDS, myocardial infarction, hemorrhage, local irritants, sepsis, upper G.I. bleedings are also responsible.
Chronic ulcers are classified into two major forms, gastric ulcers and duodenal ulcers, these forms of, peptic ulcer disease of the upper G.I tract in which the acid pepsin secretions are implicated in their pathogenesis.The features of gastric and duodenal ulcers are described below.
a) Duodenal Ulcer:It occurs in duodenum, the first few inches of small intestine, just below the stomach. The peak incidence for this ulcer is between 40 to 50 years of age and more common in males. The factors responsible for duodenal ulcers are acid hyper secretion, helicobacter pylori infections, decreased bicarbonate production, Poor secretion of mucus, poor blood supply cigarette smoking, liver disorders, emotional factors, diet, increased gastric stimulation and gastric emptying time.
b) Gastric Ulcer:It is less common, usually occurring along the lesser curvature of stomach. Majority of patients have low to normal gastric acid level, hyperacidity occur rarely due to increased gastrin level. These are commonly seen in persons above 50 years of age and almost equally occurring in both the sexes. The factors responsible for gastric ulcers are diminished mucosal resistance, helicobacter pylori infections, pyloroduodenal reflux, mucosal trauma, local ischemia and prolong NSAIDs therapy 4,5,6.
Regulation of Acid Secretion by Parietal Cells
The regulation of acid secretion by parietal cells is especially important in the pathogenesis of peptic ulcer, and constitutes target for drug action. The secretion of the parietal cells is an isotonic solution of HCl (150 m mol/l) with a pH less than 1, the concentration of hydrogen ions being more than a million times higher than that of the plasma.The principal stimuli acting on the parietal cells are gastrin, acetylcholine, histamine and prostaglandins7.
Signs and symptoms of Peptic ulcer
Abdominal pain, classically epigastric strongly correlated to mealtimes. In case of duodenal ulcers the pain appears about three hours after taking a meal; bloating and abdominal fullness; water bash (rush of saliva after an episode of regurgitation to dilute the acid in esophagus - although this is more associated with gastro esophageal reflux disease); nausea, and copious vomiting; loss of appetite and weight loss; hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or from damage to the esophagus from severe continuing vomiting. Melena (tarry, foul-smelling feces due to presence of oxidized iron from hemoglobin); rarely, an ulcer can lead to a gastric or duodenalperforation, which leads to acute peritonitis, extreme and stabbing pain 8,9.
Thefollowing tests could be done to diagnose peptic ulcer:
Esophagogastroduodenoscopy (EGD): in which a thin tube with a camera on the end is inserted through the mouth into the GI tract to see the stomach and small intestine. During an EGD, a biopsy may be taken from the wall of the stomach to test for H. pylori. X-ray for the upper gastrointestinal tract (GIT) whichtaken after drink a thick substance called barium.Hemoglobin blood test to check if there is anemia. Stool guaiac to test if there is blood in the stool 10.
Management of Peptic Ulcer
Peptic ulcer is a gastrointestinal disorder that requires a well targeted therapeutic strategy11.The current therapeutic approach for gastric ulceration is to achieve inhibition of gastric secretion, promotion of gastric protection, blockage of apoptosis, and epithelial cell proliferation for effective healing12. The goals of treating peptic ulcer disease are to relieve pain, heal the ulcer and prevent ulcer recurrence13. Even though a range of drugs are available for the treatment of ulcer, but they produce side effects such as arrhythmias, impotence, gynaecomastia, arthralgia, hypergastrinemia and hematopoietic changes14,15. Plant extracts have been used for centuries, as popular remedies against several health disorders16. Medicinal plants comprise a large number of plant species, which provide raw material for pharmaceuticals, nutraceuticals and cosmetic industries17. The use of phytoconstituents as drug therapy to treat major ailments has proved to be clinically effective and relatively less toxic than existing drugs and also reduces the offensive factors serving as a tool in the prevention of peptic ulcer18. The present review deals with some of the reported antiulcer plants of Euphorbiaceae family.
Reported Plants from Euphorbiaceae family with Ulcer Healing Property
Berezi et.al (2017) investigated the gastro protective potential of aqueous leaves extracts of Phyllanthus amarus against ibuprofen; a non-steroidal anti-inflammatory drug (NSAID) induced gastric mucosal injury in wistar rats. The ulcer surface area and ulcer index of experimental rats were also seen. It was observed that the ulcer surface area and ulcer index were significantly decreased in rats administered with P. amarus. There was a significant increase in the mucus weight. The values of the enzymatic antioxidant and oxidative stress marker, superoxide dismutase (SOD) were significantly increased while the lipid peroxidation (MDA) was decreased. Histopathological assessment of the stomach of experimental rats showed restoration of the mucosal fold suggesting the cytoprotective effect of P. amarus as an anti-ulcer agent19.
Rathnakumar.K et.al (2013) evaluated the ethanolic extract of aerial parts of Euphorbia hirta family Euphorbiaceae for its anti-ulcer activity by various gastric ulcer models. Oral administration of the Euphorbia hirta at 200 and 400 mg/kg significantly inhibited ulcer formation induced by various ulcer models like pylorus ligation, indomethacin, HCl / Et OH and restraint-stress in rats The findings indicate that the ethanolic extract of Euphorbia hirta possesses gastro protective potential which is related partly to preservation of gastric mucus secretion and anti-secretary action 20.
Racchhadiyaet.al (2011) evaluated the antiulcer potential of Ricinus communis seeds using aspirin, ethanol and pyloric ligation induced ulcer models. The results suggested that Castor oil possess significant antiulcer properties which could be either due to cytoprotective action of the drug or by strengthening of gastric mucosa and thus enhancing mucosal defence21.
Jaikumaret.al (2010) investigated the effect of methanolic extract of leaves of Jatrophacurcas Linn. (JC) on pylorus ligation and Aspirin-induced gastric ulcers in Wistar rat. The findings indicate that a significant dose depend antreduction in the acid parameters like gastric volume pH, total acidity, total acid output, total proteins and ulcer index were observed after treatment with 100 mg, 200 mg JC extracts14 .
Okoliet.al (2009) assessed antiulcer activity of extract of the aerial parts of Phyllanthus niruri using indomethacin, ethanol acid and cold-restraint stress-induced ulcer models. In antiulcer studies, extract significantly inhibited the development of ulcers induced by indomethacin and moderately inhibited ethanol acid-induced ulcer. It was, however, devoid of any such effect in cold-restraint stress induced lesions at the doses used22.
Somasundaram et.al (2008) investigated the antiulcer potential and its correlation with antioxidant activity of Acalypha indica. The animal models used for antiulcer activity was pyloric ligation in rats. The results revealed that Acalypha indica administered animals produced significant antiulcer effects in pylorus ligated model with good antioxidant activity. The antioxidant and antiulcer activity was correlated for the reduction in ulcer level 23.
Ukwe et.al (2008) reported the antiulcer activity of an aqueous extract of Hymenocardia acida was studied in rats. Ulcers were induced by cold restraint stress, indomethacin and serotonin. The extract was found to exhibit significant antiulcer activity in all the models studied. Phytochemical studies revealed the presence of glycosides, saponins and tannins 24.
Lima et al., () assessed antibacterial and gastroprotective effect of methanol extract of Alchornea triplinervia methanol extract using ethanol induced ulcer in rats.It was seen that gastric injuries were reduced in the rats treated with methanol extract of A. triplinervia and also it possessed antibacterial property25.
Calvoet. Al (2007) evaluated the antiulcer potential of Alchornea glandulosa (Euphorbiaceae) using absolute ethanol. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (85%) in relation to the control group 26.
Hiruma-Lima et.al (2006) evaluated the hydroethanolic extract of the leaves (HEL) and bark (HEB) obtained from Alchornea castaneaefolia (Euphorbiaceae) for their ability to prevent ulceration of the gastric mucosa in animal models. The results revealed that HEL (500 and 1000 mg/kg) and HEB (1000 mg/kg) significantly reduced the gastric injuries induced by the combination of HCl/ethanol and lowered the severity of gastric damage formation induced by indomethacin/bethanechol in mice and also inhibited formation of ulcers in mice submitted to stress and pylorus ligature. HEL was also effective in promoting the healing process in chronic gastric ulcer induced by acetic acid in rats27.
Rafatullah et. al (2002) evaluated ethanolic extract of ‘Amla’ Emblica officinalis Gaertn. for its antisecretory and antiulcer activities employing different experimental models in rats including, pylorus ligation Shay rats, indomethacin, hypothermic restraint stress-induced gastric ulcer andnecrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl). The results indicate that Amla extract possesses antisecretory, antiulcer, and cytoprotective properties 28.
C.A. Hiruma-Lima et. al (2001) isolated a furan diterpenoid with a clerodane skeleton, called aparisthman from bark of Aparisthmium cordatum(Juss.) Bail. (Euphorbiaceae).Aparisthman was assessed for antiulcerogenic activity. The results suggest that aparisthman significantly reduced gastric injury induced by the indomethacin/bethanechol, ethanol, pylorus ligature, and hypothermic restraint-stress models, in mice and rats29.
Phytoconstituents derived from plants have been used to treat human diseases since the dawn of medicine. The herbal products are continuously gaining recognition as safe remedy for treatment of various disorders including peptic ulcers. Many medicinal plants have shown antiulcer activity. These plants provide lead to find therapeutically useful compounds, thus more efforts should be made towards isolation and characterization of active principles and their structure activity relationship. The combination of traditional and modern knowledge can produce better drugs for treatment of peptic ulcer with fewer side effects. From this study we can conclude thatstudies with plant sources belonging to euphorbiaceae family can result in novel and effective pattern of treatment for peptic ulcer.
1. Goyal RK, Bhatt PA, Burande MD. Elements of clinical pharmacy B.S. Shah Prakashan, 2012, pp – 285-288.
2. Rupesh MK, Mohamed NK, Tamizh MT, Fasalu Rahiman OM, Satyakumar B A review on medicinal plants for peptic ulcer scholars research library ,2011, 3(2): 180 – 186.
3. Harsh Mohan. Textbook of Pathology, 7th edition, Jaypee Brothers Medical Publishers (P) Ltd., New Delhi 2015 p.p 533 – 537.
4. Borkar V S, Senthil Kumaran K, Senthil Kumar KL. Medicinal Plants with Potential Wound Healing Activity.Res. J. Pharmacognosy & Phytochem. 2015; 7(2): 116-123.
5. Bodhankar SL, Vyawhare NS, Pathophysiology 6th edition Nirali Publication Pune 2008 p.p 6.1 - 6.6.
6. D. Benito Johnson, C. Senthil Kumar, C. Glince Raphael, R. Venkatnarayanan and Siraj Kattuppar-uthi Gastroprotective Activity of Avipathi Choornam.Research Journal of Pharmacognosy and Phytochemistry. 5(1): January–February 2013, 37-41
7. S. Prakash Rao, Indu Amrit, Vijay Singh, Parag JainAntiulcer activity of natural compounds: A reviewResearch Journal of Pharmacognosy and Phytochemistry.7(2): April–June 2015, 124– 130
8. Bashir AA, Mahadeva UR, Abdurrazaq M, Thant Z, Nur HM, Nasir M, Khamsah SM: Reviews of herbal and their secondary metabolites in the treatment of ulcerative colitis and peptic ulcer. Journal of Applied Pharmaceutical Science 4 (08); 2014: 080-090.
9. Mahurkar N, Sayeed UlHasan S.M, Malpani A.A. Gastroprotective Influence of Vitamin C and its Combination with Rabeprazole in Pylorus Ligation Induced Ulcers. Asian J. Res. Pharm. Sci. 4(2): April-June 2014; Page 71-76.
10. Amani S, Reham M, El-Meligy, Gamal A and Soliman.Natural products in treatment of ulcerative colitis and peptic ulcer. Journal of Saudi Chemical Society.2013; 17: 101–124.
11. Karwani G, Singhvi I, Gupta S. Antisecretory and Antiulcer Activity of Cartaevanurvala against Indomethacin plus Pyloric Ligation Induced Gastric Ulcers in Rats. Research J. Pharmacology and Pharmacodynamics. 2011; 3(5): 256-259.
12. B Bavaji Naidu, MN Palaksha, K Ravishankar, M Naveen , N Basha. Evaluation of Antidiarrhoeal and Antiulcer Activities of Hydroalcoholic Extract of Luffaaegyptiaca Fruits.Research Journal of Pharmacology and Pharmacodynamics. 2014; 6(4):184-189.
13. Gadekar R, Singour P. K, Chaurasiya P.K , Pawar, R. S, Patil U.K A potential of some medicinal plants as anantiulcer agents Pharmacogn Rev. 2010 Jul-Dec;4(8): 136–146
14. Jaikumar S, Ramaswamy S, Asokan BR, Mohan T, Gnanavel M Anti ulcer activity of methanolic extract of Jatropha curcas (Linn.) on Aspirin-induced gastric lesions in Wistar strain rats Research Journal of Pharmaceutical, Biological and Chemical Sciences October – December 2010 :1(4) 887 – 891.
15. Lalita P, Gajendra S.K , Nagori B. P. Anti-ulcer activity of Cleome viscose Linn.against gastric ulcer in rats. Research J. Pharmacognosy and Phytochemistry 2013; 5(3): 115-118.
16. Himgauri V. Naik, Navanath Chavan, Himanshu A. Deshmukh, Pratip K. Chaskar, Nikhil S. More. Study of Antiulcer Activity of Leaves of Sesbania grandiflora Linn.(Fabaceae).Research Journal of Pharmacognosy and Phytochemistry. 2012; 4(6): 322-325.
17. Prashar D, Saklani S. Pharmaceutical and Economical Aspects of Medicinal Herbs: An Overview. Research J. Pharmacognosy and Phytochemistry 2011; 3(5):187-190.
18. M. Rupesh Kumar, Mohmad Niyas K, T Tamizh Mani, OM. Faisalu Rahiman, Satyua Kumar. B: A review on medicinal Plants for peptic Ulcer. Der Pharmacia Lettre, 2011, 3(2): 180 - 186.
19. Berezi, EP. Uwakwe, AA., Monago-Ighorodje, C.C, Nwauche, KT. Gastroprotective potentials of aqueous leaf extracts of Phyllanthus amarus on ibuprofen-induced ulcer in Wistar rats. Int. J. Adv. Res. Biol. Sci. (2017). 4(10): 138-146.
20. Rathnakumar K, Jaikumar S, Sengottuvelu S. Antiulcer Activity of Euphorbia hirta against Experimentally Induced Ulcer in Rats. Asian J. Pharm. Res. 3(3): July-Sept. 2013; Page 122-124.
21. Rachhadiya RM, Kabra MP, Shete RV Evaluation of antiulcer activity of Castor oil in rats International Journal of Reasearch in Ayurveda and Pharmacy 2011 2(4) 1349-1353.
22. Okoli, CO., Ezike, AC., Akah, PA., Udegbunam, SO., Okoye, TC., Mbanu, TP., Ugwu, E. Studies on wound healing and antiulcer activities of extract of aerial parts of Phyllanthus niruri L. (Euphorbiaceae). American Journal of Pharmacology and Toxicology 2009 Vol.4 No.4 pp.118-126.
23. Somasundaram. R, J. Usha Prathima, S.M. Shaheedha, S. Nandha Kumar, M.D. Dhanaraju Antioxidant activity of leaf extracts of Acalypha indica in animal models of gastric ulcer NPAIJ, 4(3), 2008 [230-232].
24. C. V. Ukwe Antiulcer activity of aqueous stembark extract of Hymenocardia acida Tul. (euphorbiaceae). International Journal of Pharmacognosy, 2008, 35:5, 354-357.
25. Lima ZP, Calvo TR, Silva EF, et al. (2008). Brazilian medicinal plant acts on prostaglandin level and Helicobacter pylori. J Med Food 11:701–8.
26. Calvo TR, Lima ZP, Silva JS, Ballesteros KV, Pellizzon CH, Hiruma-Lima CA, Tamashiro J, Brito AR, Takahira RK, Vilegas W. Constituents and antiulcer effect of Alchornea glandulosa: activation of cell proliferation in gastric mucosa during the healing process. Biol Pharm Bull. 2007 Mar;30(3):451-9.
27. Antiulcerogenic activity of Alchornea castaneaefolia: effects on somatostatin, gastrin and prostaglandin. J Ethnopharmacol. 2006 Mar 8;104(1-2):215-24. Epub 2005 Oct 25.
28. A.J. Al-Rehaily S. Rafatullah Gastroprotective effects of ‘Amla’ Emblica officinalis on in vivo test models in rats. Phytomedicine Volume 9, Issue 6, 2002, Pages 515-522.
29. Hiruma CA, Lima A.R, Souza M B Gastroprotective effect of aparisthman, a diterpene isolated from Aparisthmium cordatum, on experimental gastric ulcer models in rats and mice Phytomedicine Volume 8, Issue 2, 2001, Pages 94-100.
Received on 06.03.2018 Modified on 25.05.2018
Accepted on 19.06.2018 ©A&V Publications All right reserved