Department of Pharmacology, Maratha Mandal College of Pharmacy, Rajiv Gandhi University of Health Sciences, Karnataka, Bengaluru 4th Block, Jayanagar, Bengaluru – 560041
Peptic ulcer disease (PUD) is a gastrointestinal disorder resulting from an imbalance between aggressive factors such as gastric acid and pepsin, and the protective mechanisms of the gastrointestinal mucosa. Common causes include Helicobacter pylori infection, excessive use of non-steroidal anti-inflammatory drugs (NSAIDs), alcohol intake, smoking, and dietary imbalances. Conventional therapeutic approaches, including proton pump inhibitors (PPIs) and histamine-2 receptor antagonists, have proven effective but are often associated with adverse effects, drug interactions, and high recurrence rates, particularly with long-term use. This review provides a comprehensive examination of various experimental models— in vivo —employed in the evaluation of anti-ulcer agents. These models are essential for understanding the mechanisms of ulcer formation and assessing the therapeutic potential of new compounds. Data were gathered through an extensive literature search using databases such as PubMed, Google Scholar, ScienceDirect, and Scopus. In addition to synthetic drug candidates, numerous plant-derived extracts and formulations have shown promising results in ulcer prevention and healing, supported by various pharmacological studies. These agents often exhibit anti-inflammatory, antioxidant, cytoprotective, and mucosal defence-enhancing properties. This review aims to consolidate findings from current literature on experimental ulcer models and bioactive agents, offering insights to support the future development of safer, more effective anti-ulcer therapies.
Peptic ulcer [PU] is a lesion caused due to the imbalance between the aggressive factor hydrochloric acid, pep sin, reactive oxygen species (ROS), bile reflux (1) and defensive factor in stomach and duodenum. this lesion can extend into the submucosa (or) muscularis propria and the lesions which does not reach this deep called erosions the patient with peptic ulcer disease [PUD] report retrosternal pain, nausea, bloating, bleaching, postprandial diarrhoea (2). The risk factor involve in development of PU is most commonly H. pylori infection which is gram -ve bacteria present in gut [3], NSAIDs, smoking [4], alcohol [5], genetics [6], radiation therapy [7], Zollinger – elision syndrome [8]. Cytokines that suppress parietal cell secretion are the primary mediators of H. pylori infection. It can also H+/K+ ATP ase alpha subunit activate calcitonin gene related peptide (CGPR) sensory neurons associated with somatostatin (or) supress gastrin synthesis. [9,10] NSAIDs induced damage to the gastroduodenal mucosa in primarily caused by systemic inhibition of constitutively expressed cyclooxygenase -1 (COX-1) which involved in prostaglandin synthesis and linked to reduce mucosal blood flow, low secretion of mucus and bicarbonates and inhibition of cell proliferation when NSAIDs come in contact with acidic gestic juice (PH 2) they become protonated and penetrated lipid membranes to reach epithelial cells (PH 7.4) where they ionize and release H+ ions [11,12,13] The literature that is available now has extensively documented the link between smoking and PUD nicotine has been demonstrated to lower bicarbonate secretion increase gastric acid secretion and compromised mucosal defence, duodeunogastric reflex and content from stomach to duodenal is monitored by endoscopic pathography it is observed that the cigarette smoking will decrease the gastric mucosal blood flow [14,15,16]. Matrix metalloproteinase (MMPs) is the endopeptidase that are crucial for inflammation, cell division, extracellular matrix (ECM) remodelling. MMPs are produced and released by neutrophils macrophages and gastric and duodenal epithelial cells. MMPs are crucial in this process since ECM degradation is a significant contributing factor to gastric and duodenal mucosal injury and subsequent PUD there is proof that one of the element causing gastric ulcer is MMPs cleavage and modification of the ECM it has been demonstrated that MMP9 is crucial in the early stages of chronic GU in causes of chronic H.pylori infection polymorphism in the MMPs gene ( MMP9,MMP7,MMP3) may add to a gastric risk profile for duodenal and stomach ulcer increasing expression of MMP 9 in the stomach mucosa at the ulcer’s boarder the MMP 9 gene’s polymorphism maybe a factor in complicated genetic risk profile of PUD in chronic H. pylori infection [17,18,19] It has been reported that 1-16% of patents after gastric bypass surgery developed ulcer disease mainly the marginal ulceration and the symptoms reported are severe abdominal pain, constipation, nausea, obstipation [20,21,22]
Different in vivo screening methods to induce ulcer in experimental animals
Pylorus ligation induced gastric mucosal ulcers [23,24]:
Healthy rats of weight (150-200 g) either sex was taken, they are fasted for 24 hrs in individual cage after 1hr of drug treatment, they are anesthetized with anaesthetic agents like diethyl ether and the small midline incision of 1cm made at peritoneal region and stomach was taken out. pass a thread around the pylorus sphincter and apply a tight knot without damaging the other side blood vessels. the stomach was replaced carefully and the abdominal wall was closed by interrupted sutures, after 4 hrs animal are sacrificed by decapitation or cervical dislocation or administrant of high dose of anaesthetic agents. the proper care should be taken while collecting the stomach contents it should not flow out from the cardiac end of stomach, so the stomach was opened from the greater curvature with the help of scissors and gastric juice was collected into a proper measuring vessel for further studied
Ethanol induced ulcer method [25,26]:
Animals were starved for 24 hrs but were allowed free access to drinking water. the test sample were administered for selected days 1 hr after the last treatment acidified ethanol (95%) is administered after 1 hr of induction animals were sacrificed by giving euthanizing agent and different parameters were measured
Acetic acid induced ulcer modal [27,28]:
Healthy animals of either sex is taken fasted for 24hrs and they are immobilized by using ketamine (75mg/kg) and by midline incision the stomach are access , next using a small syringe (0.05ml) acetic acid (20%,30mueL) was injected into the subserosa layer to avoid adhesion to the anterior part of the ulcered region , the stomach was carefully cleaned with saline after the inducer was administered for 45sec each group received treatment for 2 weeks starting the day after inducer was administered. Rats were killed on the 15th day and their stomach were removed dissected along the major curvature and examined using 10X magnifying hand Lense.
Water immersed stress induced modal [29,30,31]:
The animals were fasted for 24-36hrs before the experiment ulcers are then induced by placing individual animal in a plastic (or) glass cylindrical or cage and immersed up to xiphoid level in controlled temperature water(230C) for 10hrs. 1hr after the last treatment animals are kept for fasting for 24hrs and allow to swim in water for 17hrs , the animal are sacrificed under euthanizing agent and stomach opened from greater curvature washed carefully with 5.0ml of 0.9% Nacl further different parameters were performed.
Diethyldithiocarbamate-Induced Gastric Ulcer
The animals are given unlimited access to water and are fasted for 24 hours before to the experiment. Two hours before to the start of the experiment, the water is removed. One millilitre of diethyldithiocarbamate in saline (800 mg/kg body weight) administered subcutaneously, followed by a one millilitre oral dose of 0.1N HCl, causes acute glandular lesions. Rats are killed one, three, and seven hours after DDC is administered. The stomachs are taken out right after and put in ice-cold buffer (0.1 M Tris-HC1 at pH 7.4). In order to examine the ulceration site, the stomach is cut open. Because of DDC, a sizable ulcer that penetrates the muscular layer may be seen in the antrum along the lesser curvature.
Indomethacin induced ulcer modal [34,35]:
Animals are starved for 24 hrs and 50mg/kg of indomethacin is administered after last dose the animals are fasted on the last day overnight then next day morning blood is collected and serum separation for biochemical, lastly rats were sacrificed by decapitation under anaesthesia.
Aspirin induced ulcer modal [36,37]:
Rats housed in metabolic cage with broad mesh raised flooring to prevent coprophagy which has an impact on gastric ulcer induction the animals fasted for 24 hrs so in order to clear their stomach of food and raise their stomach acid level which made aspirin to cause gastric damage water was also restricted for an hour before to the testing. on oral dosage of acetyl salicylic acid (500mg/kg) caused damage to the stomach mucosa.
Histamine-Induced Gastric Ulcer [38,39]:
The animals are given unlimited water and starved for 36 hours before the trial. Histamine phosphate administered subcutaneously or intraperitoneally (40–100 mg/kg body weight) causes ulcers. A medication called promethazine hydrochloride (5 mg) is administered intraperitoneally (15 min before and 15 min after the histamine injection) to shield the animals from systemic histamine toxicity. The test treatments are given intravenously (s.c.) or orally 30 to 45 minutes prior to histamine injection. The animals are given histamine for four hours before being killed. The animal's stomach is removed from its body. The stomach is exposed, and the contents are examined for both free and total acidity.
Cysteamine induced duodenal ulcer [40,41,42]:
Healthy animals of 7-8 weeks and weight of 250-300 g were housed in specific pathogen free cage cysteamine is prepared by dissolving 50mg/ml in distilled water for oral administration and it can also be given through subcutaneous rout. the dose for oral administration can be 230 to 465 mg/kg were as for subcutaneous rout it can be 400-900mg/kg. cysteamine is administered after the last dose of test treatment then the animals are sacrificed by giving anastatic agents and stomach contents were collected carefully by opening greater curvature and further analysis were done.
Methylee Blue-Induced Ulcer [43]:
Animals are fasted for 24 hours prior to the experiment and given unlimited water in order to induce ulcers with MB. MB is given orally at a dose of 125 mg/kg body weight, and then the drug or drugs under test are administered. Following four hours of MB administration, the animals are sacrificed. The ulcer index is calculated by dissecting the experimental animals' stomachs and cutting them open by the greater curvature.
Reserpine-Induced Peptic Ulcer [44,45]:
Before the experiment, the animals are taken and fasted for 48 hours. One hour before to the experiment, they are given free access to a liquid diet consisting of 0.8% sucrose in 0.2% NaCl w/v while they are fasting. Typically, test animals receive medications or plant extracts for evaluation at least half an hour before to reserpine delivery. Reserpine 5 mg/kg diluted in 10% Tween 80 is delivered intraperitoneally one to two hours later. Hyper motility appears to be more crucial for the production of gastric mucosal lesion than hypersecretion, despite the fact that the model is acid dependent. Twenty-four hours later, test animals are killed, and their stomachs are taken out. Mucosal lesions are inspected when the stomach is sliced through its larger curvature.
Serotonin-Induced Gastric Ulcer [46,47]:
Animals in this model are weighed and given water for 24 to 36 hours before the experiment. Two hours before to the start of the studies, the fasting animals are not given any water. After receiving a single dosage of serotonin creatinine sulfate (0.5 mL of 50 mg/kg subcutaneous injection), glandular lesions are formed. Using an oro-gastric cannula, intra-gastric intubation is used to deliver serotonin. Six hours later, the animals are sacrificed via cervical dislocation. For more ulcer index research, the stomach is dissected.
Different parameters for ulcer:
Ulcer index [48]:
The following arbitrary scoring system was used to grade the incidence and severity of lesion. 0 = Normal, 1 = Red coloration, 2 = Spot ulcers, 3 = Haemorrhagic streaks, 4 = Ulcers ? 3 but ? 5 and 5 = Ulcers ? 5. Mean ulcer score for each animal is expressed as Ulcer Index
An ulcer index UI is calculated:
UI = UN + US+ UP × 10–1
• UN= average of number of ulcers per animal
• US = average of severity score
• UP = percentage of animals with ulcers
PH measurement [49]:
1ml of distilled water id added to the 1ml of gastric juice then the PH is determined by using PH meter
Determination of myeloperoxidase activity [50]:
In the stomach mucosa, myeloperoxidase (MPO) activity measured by The tissue was weighed and then homogenized (1: 10 w/v) in 50 mM potassium phosphate buffer (pH 6.0) with 0.5% hexadecyl trimethyl ammonium bromide before being sonicated for 20 seconds in an ice bath. Three cycles of freezing and thawing were followed by sonication (20 seconds in an ice bath). The samples were centrifuged at 17000g for 5 minutes at 4°C. The supernatant's myeloperoxidase content was measured by combining 0.1 ml of the supernatant with 2.9 ml of 50 mM potassium phosphate buffer (pH 6.0) that contained 0.0005% hydrogen peroxide (H2O2) and 0.167 g/L o-dianisidine dihydrochloride. For four minutes, an ultraviolet visible spectrophotometer was used to quantify the change in absorbance at 460 nm.
Determination of non-protein sulfhydryl groups [51]:
After being removed and cleaned, the stomach's glandular section was weighed and mixed with five millilitres of 0.02 M cold ethylenediaminetetraacetic acid (EDTA). Four millilitres of homogenate, 3.2 millilitres of distilled water, and 0.8 millilitres of 50% trichloroacetic acid were combined, and the mixture was centrifuged at 3000 g for 15 minutes. 0.1 mL of 5-dithiobis (2-nitrobenzoic acid) (DNTB, 0.01 M) and 4 mL of TRIS buffer (0.4 M, pH 8.9) were combined with 2 mL of supernatants. At 412 nm, absorbance was measured, and each value was extrapolated onto a glutathione (GSH) standard curve (1000–0.488 lg). mg/g of tissue was used to express the results.
Catalase activity [52]:
Using this method, 100 ml of tissue supernatant was mixed with 3 ml of an H202-phosphate buffer mixture. The catalase activity was measured by the change in optical density (OD) at 240 nm. Standardization of the H202-buffer concentration resulted in an OD against buffer at 240 nm of 0.500 _+ 0.01 (d=lcm).
Superoxide dismutase assay [53]:
To evaluate the enzyme's activity the test measures how well it inhibits the reduction of nitro blue tetrazolium (NBT) by superoxide radicals (O??) Tissue samples are mixed with phosphate buffer and centrifuged at (10 minutes, 3,600rpm, 4?C) and the supernatant was removed and centrifuged for second time (20 minutes, 12,000rpm, 4?C). In a dark room, mix 1 mL of a reaction solution (50mM phosphate buffer, 100nMEDTA, and13mMl-methionine, pH7.8) with 30 µL of the sample, 150 µL of NBT, and 300 µL of riboflavin Expose the tubes to fluorescent light for 15 minutes After exposure, measure the absorbance at 560 nm using a spectrophotometer.
Malondialdehyde Measurement [54]:
After thawing, the sample was weighed. The 0.15 M KCl solution was used to homogenize them. A set of malondialdehyde standards was also freshly made after one milliliter of homogenate, 1.5 milliliters of thiobarbituric acid, 1.5 milliliters of acetic acid (pH 3.5), and 0.2 milliliters of sodium dodecyl sulphate were combined. Following mixing, all standards and samples were heated for an hour at 100°C. After cooling on ice, 5 ml of 1-butanol was added to each sample and standard to extract MDA. For 10 minutes, each tube was centrifuged at 2000 rpm in order to separate the organic and aqueous phases. After that, the 1-butanol phase absorbance was measured at 532 nm and contrasted with measurements made using malondialdehyde standards.
Histopathological examination of the stomach [55]:
A section of each rat's stomach was preserved in 13% formalin. After being encased in paraffin wax, the specimens were divided into 5 mm thick slices. For the histological analysis, haematoxylin and eosin (H and E) dye was used to stain the sections. An experienced pathologist who was blind to the treatment evaluated the histological sections for the following conditions: grade and type of inflammation (score: 0-4), presence of epithelial erosions (score: 0-2), presence of epithelial ulcers (score: 0-1), edema in the lamina propria (score: 0-1), congestion of blood vessels (score: 0-5), epithelial atrophy (score: 0-1), and epithelial hyperplasia (score: 0-1). The ultimate score was 15.
Gastric wall mucosa [56]:
Rats' gastric wall mucus was measured by removing, weighing, and evaluating the glandular segments of the stomach. The surplus dye was eliminated by rinsing with sucrose solution after each segment was promptly shifted to a 1% Alcian blue solution (in sucrose solution, buffered with sodium acetate at pH 5). Magnesium chloride solution was used to remove the dye complexes with the stomach wall mucus. Next, an equivalent volume of diethyl ether was mixed with a 4 mL aliquot of blue extract. After centrifuging the resultant emulsion, the aqueous layer's absorbance at 580 nm was measured. Next, it was determined how much Alcian blue was removed per gram of glandular tissue (net).
Glutathione [GSH] assay [57]:
The procedure for figuring out how much GSH was in the stomach mucosa was explained. The stomach's glandular region was weighed and homogenized in a 1:10 (w/v) ratio using 0.02 M ice and ethylene ethylenediaminetetraacetic acid (EDTA). 800 μL of distilled water and 200 μL of 50% aqueous trichloroacetic acid (TCA) were added to 1 mL of this homogenate. After one minute of shaking, the samples were centrifuged for ten minutes at 952 x g. 50 μL of 5.5-dithiobis acid ((2-nitrobenzoic (DTNB) 0.01 M)) and 2 mL of 0.4 M TRIS buffer, pH 8.9, were added to 0.5 mL of the resulting supernatant. μg GSH/g tissue was used to express the results.
Determination of NO in gastric mucosa [58]:
Using the Griess reagent, the amount of nitric oxide in the stomach tissue was assessed as total nitrate/nitrite, and the operational procedures were measured in compliance with the specifications provided by the NO kit. In short, 50 µl of tissue supernatant was combined with 50 µl of Griess reagent (i.e., 0.1% N-(1 naphthyl) ethylenediamine dihydrochloride, 1% sulphanilamide, and 2.5% H3PO4) and stirred. Following a 10-minute incubation period at room temperature, the absorbance at 540 nm was measured. The findings were presented as µmol/g protein.
Protein assay [59]:
By combining 90% alcohol with gastric juice in a 9:1 ratio, an alcoholic precipitate was produced, which was used to measure the amount of dissolved protein in the gastric juice. Next, 0.1 mL of the gastric juice's alcoholic precipitate was dissolved in 1 mL of 0.1 N NaOH. From this 0.05 mL, 4 mL of the alkaline mixture was added, and the mixture was left for 10 minutes. After that, 0.4 mL of phenol reagent was added, and further 10 minutes were given for colour development. Readings were made using a Hitachi 15-20 spectrophotometer at 610 nm against a blank made with distilled water. Using a standard curve made using bovine albumin, the protein content was computed and expressed as mcg/mL of gastric juice.
Drugs used in the treatment of ulcer:
Proton Pump Inhibitors (PPIs):
Examples: Omeprazole, Lansoprazole, Rabeprazole, Esomeprazole, Pantoprazole
MOA: Protein pump inhibitors (PPIs) act by irreversibly binding to and inhibiting the hydrogen/potassium ATPase enzyme system (also known as the proton pump) located on the parietal cells of the stomach. This enzyme is responsible for the final step in the secretion of gastric acid into the stomach lumen. By blocking this pump, PPIs effectively suppress both basal and stimulated gastric acid secretion. The inhibition is long-lasting because new enzyme molecules must be synthesized by the cell before acid secretion can resume.
Adverse effects: Headache, Abdominal pain, Diarrhoea, Nausea, Vomiting, Constipation, Flatulence, Vitamin B12 deficiency, Osteoporosis.
H2 Receptor Blockers:
Examples: Ranitidine, Famotidine, Cimetidine, Nizatidine.
MOA: H2 receptor antagonists (H2RAs) are drugs that reduce stomach acid by reversibly blocking H2-receptors on parietal cells. These receptors are found on the basolateral membrane of the cells that produce stomach acid. H2RAs decrease acid secretion by about 60–70% and are especially effective at reducing basal (resting) acid levels, particularly at night. They are best taken after dinner or at bedtime for optimal control of nighttime acid. However, they are less effective at blocking acid triggered by meals or gastrin.
Adverse effects: Headache, Anxiety Depression, Dizziness, Cardiovascular.
Antacids:
Examples: Calcium carbonate, Magnesium hydroxide, Aluminium hydroxide, Sodium bicarbonate, Combination antacids.
MOA: Antacids act by directly neutralizing gastric hydrochloric acid in the stomach lumen through a simple acid-base reaction, thereby increasing the gastric pH from highly acidic levels (pH 1-2) to a less acidic environment (pH 4-5), which provides rapid relief from symptoms like heartburn and indigestion This neutralization not only reduces gastric acidity but also inhibits the activity of pepsin, a proteolytic enzyme that can damage the mucosa at low pH, and may provide additional mucosal protection by binding bile salts and phosphates.
Adverse effects: Constipation, Diarrhoea, Hypophosphatemia, Hypermagnesemia, Hypercalcemia, Gastric distension.
Cytoprotective Drugs:
Examples: Sucralfate, Bismuth subsalicylate, Misoprostol
MOA: Cytoprotective drugs enhance the natural defences of the gastric mucosa rather than directly reducing acid production. Sucralfate, for instance, forms a protective gel in the acidic environment of the stomach, adhering to ulcer sites and shielding them from acid, pepsin, and bile while also stimulating local prostaglandin and bicarbonate secretion. Bismuth compounds similarly coat ulcers, promoting mucus and bicarbonate production, and possess antibacterial properties against Helicobacter pylori. Misoprostol, a prostaglandin E1 analog, bolsters mucosal defence by increasing mucus and bicarbonate secretion and enhancing blood flow and reduces acid secretion, especially in the context of NSAID-induced ulcers. These drugs collectively support mucosal integrity and promote healing through various mechanisms that reinforce the stomach's inherent protective capabilities.
Adverse effects: Abdominal pain Headache Constipation.
Antibiotics (for H. pylori eradication):
Examples: Amoxicillin, Clarithromycin, Metronidazole, Tetracycline, nitazoxanide, doxycycline, Levofloxacin, Furazolidone
MOA: Treatment for Helicobacter pylori infections often involves several antibiotics that target the bacteria in different ways. while clarithromycin, tetracycline, and doxycycline stop the bacteria from making proteins, Levofloxacin interferes with the bacteria's ability to make DNA, and metronidazole and nitazoxanide interfere with energy processes which can damage DNA, Furazolidone also damages bacterial DNA, and rifabutin stops the bacteria from making RNA.
Adverse effects: nausea, abdominal pain, diarrhoea, vomiting, and dizziness.
Prostaglandin Analogues:
Examples: Misoprostol.
MOA: Prostaglandin (PG) analogues like misoprostol help heal ulcers mainly by reducing stomach acid. They may also help the body make more protective enzymes (COX-1 and COX-2) at the ulcer site, which support healing. Natural prostaglandins made by COX-2 help ulcers heal by promoting new cell growth, improving blood flow, and repairing the stomach lining. COX-1 prostaglandins help protect the stomach by increasing mucus and bicarbonate and keeping good blood flow.
Adverse effects: Uterine contractions, Abdominal cramps, Skin rashes, Abortifacient effect.
Different medicinal plants used in the treatment of gastric ulcer:
|
Sl.no |
Plant |
family |
Part |
Constituents |
Method |
ref |
|
1 |
Bidens pilosa L. |
Asteraceae |
radiata Schult |
flavonoids |
indomethacin-induced gastric lesions |
73 |
|
2 |
Maytenus robusta |
Celastraceae |
aerial parts |
Flavonoids, pentacyclic triterpenes. friedelane, oleanane, sesquiterpenes, alkaloids, tannins |
(NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer |
74 |
|
3 |
Albizzia lebbeck |
Mimosaceae |
Leaves (ethanolic extract) |
Flavonoids Tannins |
Ethanol induced method |
75, |
|
|
|
|
Bark (Petroleum ether extract, Ethyl acetate extract, Methanol extract) |
Petroleum ether extract: Steroids, terpenes Ethyl acetate extract: Flavonoids, terpenoids, tannins, phenolics2 Methanol extract: Saponins, flavonoids, phenolics, glycosides |
Ethanol induced method, pylorus ligation method, Aspirin induced method, cold stress induced method. |
76 |
|
4 |
Bauhinia purpurea |
Fabaceae |
Leaves (chloroform extract) |
Flavonoids, steroids tannins |
ethanol-induced model |
77 |
|
5 |
Cassia sieberiana |
Caesalpiniaceae |
Rootbark (aqueous extract) |
Flavonoids Tannins, terpenoid, glycoside, anthraquinones |
Ethanol induced method |
78 |
|
6 |
Momordica charantia L. |
Cucurbitaceae |
Fruits (methanolic extract) |
Flavonoids Alkaloids Steroids Carotenoids
|
acetic acid induced chronic gastric ulcer, pylorus ligation induced gastric ulcer, ethanol induced gastric ulcer, stress induced gastric ulcer, indomethacin induced gastric ulcer, cysteamine induced |
79 |
|
7 |
Morinda lucida |
Rubiaceae |
Leaves (boiled aqueous extract) |
alkaloids, anthraquinones, flavonoids, saponins, tannins, cardiac glycosides, and phlobatannins |
Ethanol induced method |
80 |
|
8 |
Psidium guajava |
myrtaceae |
Leaves (methanol extract) |
Quercetin, Guaijaverin, Flavonoids, Galactose, polyphenolic compounds |
Ethanol induced gastric ulcer |
81 |
|
9 |
Aloe vera |
Asphodelaceae |
mucilaginous gel |
Tannins, saponins, and flavonoids |
indomethacin induced gastric ulcer |
82 |
|
10 |
Mangifera indica |
Anacardiaceae |
Seed (ethanolic extract) |
flavonoids, phenolic compounds, tannins, and alkaloids |
Acid Ethanol Induced Ulcer Model |
83 |
|
11 |
Zingiber officinale |
Zingiberaceae |
rhizome (root) (aqueous extract) |
zingiberene, bisabolene, gingerols, and shogaols 6-gingesulphonic acid |
indomethacin induced model |
84 |
|
12 |
Ocimum sanctum |
Lamiaceae |
Dried powder (aqueous extract) |
- |
Ethanol induces ulcers |
85 |
|
13 |
Musa paradisiaca |
Musaceae |
tepal and skin(methanol) |
Flavonoids Phenols Glycosides Saponins |
indomethacin-induced ulcer model, pylorus ligation |
86 |
|
14 |
Mimosa pudica |
Fabaceae |
Leaves (aqueous and ethanol) |
Glycosides Saponins Alkaloids Steroids Flavonoids Tannins Quercetin Naringin |
Ethanol-induced method, Pylorus ligated ulcer model |
87 |
|
15 |
Alpinia galangal |
Zingiberaceae |
Rhizomes (aqueous extract) |
alkaloids, glycosides, steroids, flavonoids, tannins, and polyphenols |
Indomethacin induced ulcer modal |
88 |
|
16 |
Daucuscarota sativus Linn. |
Apiaceae |
Root (aqueous extract)
|
flavonoids, tannins. |
Pylorus ligated ulcer model, Ethanol-induced method, Aspirin induced method |
89 |
|
17 |
Lantana camara |
Verbenaceae |
leaves (methanolic extract) |
Saponins Glycosides Carbohydrates Tannins Flavonoids Steroids Triterpenoids |
Aspirin-induced gastric ulcer Ethanol-induced gastric ulcer model, Cysteamine-induced duodenal ulcer model |
90 |
|
18 |
Panax ginseng |
Araliaceae |
Leaves (Polysaccharide Fraction)
|
ginsenosides, amino acids, alkaloids, phenols, proteins, polypeptides |
water immersion stress model, indomethacin induced modal, pylorus ligation model. |
91 |
|
19 |
Terminalia chebula |
Combretaceae |
Fruit (hydroalcoholic extract) |
carbohydrates, glycosides, triterpenoids, saponins, tannins, polyphenols, proteins, amino acids, and flavonoids |
Aspirin-induced ulcer, Ethanol-induced ulcer, Cold restraint stress-induced ulcer. |
92 |
|
20 |
Carica papaya |
Caricaceae |
unripe fruit (hydroalcoholic extract) |
Alkaloids Saponins Phenols Tannins Flavonoids |
Pyloric Ligation Induced Ulcers, Swimming Induced Ulcer Model |
93 |
|
21 |
Azadirachta indica |
Meliaceae |
Leaves (Aqueous and ethanolic extracts) |
flavonoids, tannins, carbohydrates, and proteins |
Pylorus ligation-induced gastric ulcer model, Cold restraint stress model Forced swimming endurance test |
94 |
|
22 |
Salvadora indica |
Salvadoraceae |
Leaves (Ethanolic Extract) |
flavonoids, alkaloids, phenolics, terpenoids, tannins, saponins, carbohydrates, and amino acids |
Pylorus Ligation Induced Ulceration, Ethanol Induced Mucosal Damage, Cysteamine Induced Duodenal Ulceration |
95 |
|
23 |
Centella Asiatica
|
Apiaceae |
Leaves(ethanol) |
Flavonoids Triterpenoid Saponins Phytosterols Tannins Alkaloids |
indomethacin induced modal
|
96 |
|
24 |
Cordia africana Lam |
Boraginaceae |
Seed (hydro methanolic extract) |
Tannins Flavonoids Saponins Phenols
|
Pylorus Ligation Method |
97 |
|
25 |
Phyllanthus niruri |
Euphorbiaceae |
leaves (methanolic extract) |
Carbohydrates Saponins Alkaloids Terpenoids Steroids Flavonoids Phenolics and Tannins |
ethanol-acid induced model |
98 |
DISCUSSION:
This review highlights the importance of using various models to test drugs for anti-ulcer activity, which can help identify effective treatments for peptic ulcers. Peptic ulcers are a common issue caused mainly by H. pylori infection and excessive use of NSAIDs, and they impact people of all ages, especially older adults. As the global population ages, the burden of this disease on healthcare systems is expected to grow. The review emphasizes that both natural and synthetic drugs can be tested through specific in-vivo models, which can also check for any harmful side effects. There is a need for more research on herbal medicines to improve treatment outcomes. Early diagnosis and treatment are crucial to prevent complications. Additionally, preventing ulcers in high-risk individuals, such as those using NSAIDs or infected with H. pylori, is important for reducing illness and death. More clinical trials are needed to validate the effectiveness of natural compounds. Finally, the findings suggest that further exploration of natural sources could lead to better, safer anti-ulcer drugs.
REFERENCES
Sruthi Y.*, Dr. Vishnu Kangralkar, A Comprehensive Review of Experimental Models, Evaluation Parameters, And Natural-Synthetic Therapeutics for Peptic Ulcer Treatment, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 929-946. https://doi.org/10.5281/zenodo.15350568
10.5281/zenodo.15350568
