A comprehensive review of peptic ulcer disease: epidemiology, experimental models, and mechanistic insights

Authors

  • Laliteswar Pratap Singh Gopal Narayan Singh University, Sasaram, Bihar, India 821305
  • Sandip Chatterjee Gopal Narayan Singh University, Sasaram, Bihar, India 821305
  • Sanjeeb Kumar Kar Florence College of Pharmacy, Irba, India 835219

DOI:

https://doi.org/10.69857/joapr.v13i2.953

Keywords:

Animal Models, Helicobacter pylori, Pathophysiology, Preclinical Models

Abstract

Background: Peptic ulcer disease (PUD) is one of the most common gastrointestinal disorders, resulting from an imbalance between aggressive and protective factors, leading to mucosal erosion. Various factors influence its pathogenesis, including Helicobacter pylori infection, NSAID use, and oxidative stress. Objective: We review PUD epidemiology, varying experimental models, and mechanistic insights into PUD and promising therapeutics. Methodology: We systematically reviewed previous literature on PUD, including epidemiological trends, commonly used in vivo, and molecular mechanisms. Results and discussion: The global prevalence of peptic ulcer disease (PUD) follows an epidemiological pattern influenced by geography, lifestyle, and genetic factors. Experimental models using ethanol, NSAIDs, or Helicobacter pylori induction provide valuable insights into disease progression and pathophysiology. Emerging trends:  Recent research in peptic ulcer disease focuses on molecular mechanisms, gut microbiome interactions, personalized therapies, and novel pharmacological agents. Molecular studies explore genetic and epigenetic factors influencing ulcer formation, while microbiome research examines the role of gut bacteria beyond H. pylori. Personalized treatment approaches use genetic profiling and biomarkers to enhance efficacy and reduce toxicity. Additionally, emerging pharmacological agents aim to improve acid suppression, promote mucosal healing, and develop more effective H. pylori eradication strategies. Conclusion: A deeper understanding of PUD pathophysiology through epidemiological studies and experimental models can aid in developing novel, targeted therapies. Future research should focus on alternative treatments, including phytochemicals and probiotics, to enhance ulcer prevention and management.

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References

Okabe S, Amagase K. An overview of acetic acid ulcer models--the history and state of the art of peptic ulcer research. Biol Pharm Bul.l, 28 (8), 1321-41 (2005) https://doi.org/10.1248/bpb.28.1321

Xie X, Ren K, Zhou Z, Dang C, Zhang H. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol, 22 (1), 58 (2022) https://doi.org/10.1186/s12876-022-02130-2

Zhang Q, Huang N, Wang J, Luo H, He H, Ding M, Deng WQ, Zou K. The H+/K+-ATPase inhibitory activities of Trametenolic acid B from Trametes lactinea (Berk.) Pat, and its effects on gastric cancer cells. Fitoterapia, 89, 210-7 (2013) https://doi.org/10.1016/j.fitote.2013.05.021

Wang S, Zhang T, Li D, Cao X. The global, regional and national burden of peptic ulcer disease attributable to smoking from 1990 to 2021: A population-based study. Preventive Medicine Reports, 51, 103019 (2025) https://doi.org/10.1016/j.pmedr.2025.103019

Ameen AA, El-Masry HG, Bashatly MYMHE. The effect of licorice (Glycyrrhiza glabra) on peptic ulcer in rats. International Journal of Health Sciences, 6 (S4), 12173-83 (2022) https://doi.org/10.53730/ijhs.v6nS4.11829International

Shell EJ. Pathophysiology of peptic ulcer disease. Physician Assistant Clinics, 6 (4), 603-11 (2006) https://doi.org/10.1016/j.cpha.2021.05.005

Kang, D.W, Lee, JW., Park, M.Y. et al. Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study. GeroScience , 47, 1161–1174 (2025). https://doi.org/10.1007/s11357-024-01284-z

Nejati S, Karkhah A, Darvish H, Validi M, Ebrahimpour S, Nouri HR. Influence of Helicobacter pylori virulence factors CagA and VacA on pathogenesis of gastrointestinal disorders. Microbial pathogenesis, 117, 43-8 (2018) https://doi.org/10.1016/j.micpath.2018.02.016

Fang B, Yang S, Liu H, Zhang Y, Xu R, Chen G. Association between depression and subsequent peptic ulcer occurrence among older people living alone: A prospective study investigating the role of change in social engagement. Journal of Psychosomatic Research, 122, 94-103 (2019) https://doi.org/10.1016/j.jpsychores.2019.04.002

Satapathy T, Sen K, Sahu S, et al. Experimental animal models for gastric ulcer/peptic ulcer: an overview. J Drug Deliv Ther, 14 (1), 204-212 (2022) http://dx.doi.org/10.22270/jddt.v14i1.6258

Silen W. Experimental models of gastric ulceration and injury. Am J Physiol Gastrointest Liver Physiol, 255 (4), G395-G401 (1988) https://doi.org/10.1152/ajpgi.1988.255.4.G395

Suleyman H, Küçükler S, Kandemir FM, Yıldırım S. Protective effect of chrysin on indomethacin induced gastric ulcer in rats: Role of multi-pathway regulation. Biotechnic & Histochemistry, 97 (7), 490-503 (2022) https://doi.org/10.1080/10520295.2021.2014569

Salari, N., Darvishi, N., Shohaimi, S. et al. The Global Prevalence of Peptic Ulcer in the World: a Systematic Review and Meta-analysis. Indian J Surg, 84, 913–921 (2022) https://doi.org/10.1007/s12262-021-03189-z

Bardhan KD, Royston C. Time, change and peptic ulcer disease in Rotherham, UK. Digestive and Liver Disease, 40 (7), 540-6 (2008) https://doi.org/10.s1016/j.dld.2008.02.024

Dugani, A.M, and Glavin, G.B. Capsaicin effects on stress pathology and gastric acid secretion in rats. Life Sci, 39, 1531–1538 (1986) https://doi.org/10.1016/0024-3205(86)90383-8

Sonnenberg A. Pathogenesis of peptic ulcer disease. Clin Gastroenterol Hepatol, 11 (8), 936–42 (2013) https://doi.org/10.1016/B978-0-12-821232-5.00021-5

Soll AH. Jaiswal F, Rai AK, Wal P, Wal A, Singh SP. Peptic ulcer: a review on etiology, pathogenesis and treatment. Asian Journal of Pharmaceutical Education and Research, 10 (4), 1 (2021) https://dx.doi.org/10.38164/AJPER/9.4.2021.01-17

Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology, 134 (7), 1842–60 (2008) https://doi.org/10.1053/j.gastro.2008.05.021

Megraud, F.; Brouter, N. Review article: Have we found the source of Helicobacter pylori? Aliment. Pharmacol Ther, 14 (Suppl. 3), 7–12 (2000) https://doi.org/10.1046/j.1365-2036.2000.00095.x

Stolte M, Meining A. The updated Sydney system classification and grading of gastritis as the basis diagnosis and treatment. Can. J. Gastroenterol, 12, 591–598 (2001) https://doi.org/10.1155/2001/367832

Salleh KL, Iversen E, Ibsen B, Fehsenfeld M. Exploring the impact of stressful life events on quality of life: meaning making and narrative reconstruction. International journal of qualitative studies on health and well-being, 19 (1), 2330117 (2024) https://doi.org/10.1080/17482631.2024.2330117

Glavin GB, Szabo S. Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies. The FASEB journal, 6 (3), 825-31 (1992) https://doi.org/10.1096/fasebj.6.3.1740232

Musumba C, Pritchard DM, Pirmohamed M. cellular and molecular mechanisms of NSAID‐induced peptic ulcers. Alimentary pharmacology & therapeutics, 30 (6), 517-31, (2009) https://doi.org/10.1111/j.1365-2036.2009.04086.x

Miller, A.K., Williams, S.M. Helicobacter pylori infection causes both protective and deleterious effects in human health and disease. Genes Immun, 22, 218–226 (2021). https://doi.org/10.1038/s41435-021-00146-4

Nrayanan M, Reddy KM, Marsicano E. Peptic Ulcer Disease and Helicobacter pylori infection. MoMed, 115 (3), 219-224 (2018) https://pmc.ncbi.nlm.nih.gov/articles/PMC6140150/

Adinortey MB, Ansah C, Galyuon I, Nyarko A. In vivo models used for evaluation of potential antigastroduodenal ulcer agents. Ulcers, 2013 (1), 796405 (2013) https://doi.org/10.1155/2013/796405

Bertleff MJ, Lange JF. Perforated peptic ulcer disease: a review of history and treatment. Digestive surgery, 27 (3), 161-9 (2010) https://doi.org/10.1159/000264653

Beiranvand M. A review of the most common in vivo models of stomach ulcers and natural and synthetic anti-ulcer compounds: a comparative systematic study. Phytomedicine Plus, 2 (2), 100264 (2022) https://doi.org/10.1016/j.phyplu.2022.100264

Cherqui S. Cysteamine therapy: a treatment for cystinosis, not a cure. Kidney international, 81 (2), 127-9 (2012) https://doi.org/10.1038/ki.2011.301

Robert A, Nezamis JE, Lancaster C, Badalamenti JN. Cysteamine-induced duodenal ulcers: a new model to test antiulcer agents. Digestion, 11 (3-4), 199-214 (1974) https://doi.org/10.1159/000197584

Minaiyan M, Ghannadi A, Salehi E. Antiulcerogenic effect of Zataria multiflora Boiss. on cysteamine induced duodenal ulcer in rats. Iranian journal of pharmaceutical sciences, 1 (4), 223-9 (2005) https://doi.org/10.22037/ijps.v1.39542

Choi KS, Kim EH, Hong H, Ock CY, Lee JS, Kim JH, Hahm KB. Attenuation of cysteamine‐induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5‐lipoxygenase and activating γ‐glutamylcysteine synthetase. Journal of Gastroenterology and Hepatology, 27, 13-22 (2012) https://doi.org/10.1111/j.1440-1746.2012.07065.x

Fukuhara S, Suzuki H, Masaoka T, Arakawa M, Hosoda H, Minegishi Y, Kangawa K, Ishii H, Kitajima M, Hibi T. Enhanced ghrelin secretion in rats with cysteamine-induced duodenal ulcers. American Journal of Physiology-Gastrointestinal and Liver Physiology, 289 (1), G138-45 (2005) https://doi.org/10.1152/ajpgi.00298.2004

Khomenko T, Szabo S, Deng X, Ishikawa H, Anderson GJ, McLaren GD. Role of iron in the pathogenesis of cysteamine-induced duodenal ulceration in rats. American Journal of Physiology-Gastrointestinal and Liver Physiology, 296 (6), G1277-86 (2009) https://doi.org/10.1152/ajpgi.90257.2008

Sikiric P, Boban BA, Krezic I, Zizek H, Kalogjera L, Smoday IM, Vukovic V, Oroz K, Chiddenton HM, Buric S, Antunovic M. From Selye’s and Szabo’s Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities. Pharmaceuticals, 16 (12), 1699 (2023) https://doi.org/10.3390/ph16121699

Martins Prizão V, de Moura de Souza M, de Athayde De Hollanda Morais BA, Ximenes Mendes B, Cosendey Martins O, Defante ML, Queiroz Vasconcelos Muniz J, Francisco Buzetti Spinelli B. Impact of low-dose aspirin on the prevalence of anemia in elderly patients: a systematic review and meta-analysis. Postgraduate medicine; 137(2), 148-54 (2025) https://doi.org/10.1080/00325481.2024.2446010

Wang X, Kong Y, Li Z. Advantages of Chinese herbal medicine in treating rheumatoid arthritis: a focus on its anti-inflammatory and anti-oxidative effects. Frontiers in Medicine, 11, 1371461 (2024) https://doi.org/10.3389/fmed.2024.1371461

Mahmoud YI, Abd El-Ghffar EA. Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation. Biomedicine & Pharmacotherapy, 109, 314-21 (2019) https://doi.org/10.1016/j.biopha.2018.10.118

Odashima Nehlig A. Effects of coffee on the gastro-intestinal tract: a narrative review and literature update. Nutrients,14(2), 399 (2022) https://doi.org/10.3390/nu14020399

Bora M, Mandal S, Singh PK, Das H, Bora GK, Bora D, Baruah D, Gautam MK. Phytochemical and pharmacological profile of Desmodium gangeticum (L.) DC.: a comprehensive review. Current Traditional Medicine, 10 (4), 52-9 (2024) https://doi.org/10.2174/2215083810666230523145738

Arefpour H, Sadeghi A, Zayeri F, Hekmatdoost A. The application of ginger supplementation on peptic ulcer disease management: A randomized, double blind, placebo-controlled clinical trial. Clinical Nutrition Open Science, 57, 231-40 (2024) https://doi.org/10.1016/j.nutos.2024.08.008

Badapanda SS, Kaur A, Jain D, Bhatia D. Epidemiology, Pathogenesis, and Induction of Peptic Ulcer: A Comprehensive Review. New Emirates Medical Journal, 5 (1), e02506882348139 (2024) https://doi.org/10.2174/0102506882348139241210080210

Altyar AE, Munir A, Ishtiaq S, Rizwan M, Abbas K, Kensara O, Elhady SS, Rizg WY, Youssef FS, Ashour ML. Malva parviflora leaves and fruits mucilage as natural sources of anti-inflammatory, antitussive and gastro-protective agents: A comparative study using rat models and Gas chromatography. Pharmaceuticals, 15 (4), 427 (2022) https://doi.org/10.3390/ph15040427

Cherrada N, Chemsa AE, Gheraissa N, Laib I, Gueboudji Z, EL‐Shazly M, Zaater A, Abid A, Sweilam SH, Emran TB, Nani S. Gastroprotective Efficacy of North African Medicinal Plants: A Review on Their Therapeutic Potential for Peptic Ulcers. Food Science & Nutrition, 12 (11), 8793-824 (2024) https://doi.org/10.1002/fsn3.4536

Kamar SA, Bayoumi AH, Rady HY. Spirulina supplements: An approach moderating aspirin persuaded histological and ultra-structural alterations in albino rats gastric mucosa. Ultrastructural Pathology, 46(2), 204-16 (2022) https://doi.org/10.1080/01913123.2022.2052779

Marhuenda E, Martin MJ, Alarcon Lastra CD. Antiulcerogenic activity of aescine in different experimental models. Phytotherapy Research, 7 (1), 13-6 (1993) https://doi.org/10.1002/ptr.2650070105

Akhtar MS, Malik A, Arshad H, Batool S, Raza AR, Tabassum T, Murtaza MA, Riaz M, Noreen M, Rasool G. Protective effect of newly synthesized indole imines against ethanol-induced gastric ulcer in rats. Biotechnology & Biotechnological Equipment, 35(1), 231-7 (2021) https://doi.org/10.1080/13102818.2020.1868330

Wylie MR, Merrell DS. The antimicrobial potential of the neem tree Azadirachta indica. Frontiers in pharmacology, 13, 891535 (2022) https://doi.org/10.3389/fphar.2022.891535

Glavin GB, Mikhail AA. Stress and ulcer etiology in the rat. Physiology & behavior, 16 (2), 135-9 (1976) https://doi.org/10.1089/neu.2023.0314

Alkofahi A, Atta AH. Pharmacological screening of the anti-ulcerogenic effects of some Jordanian medicinal plants in rats. Journal of Ethnopharmacology, 67 (3), 341-5 (1999) https://doi.org/10.1016/S0378-8741(98)00126-3

Chen J, Wang H, Zhu J. Extract from Falcaria vulgaris loaded with exosomes for the treatment of hypertension in pregnant mice: In vitro and In vivo investigations. Bio-Medical Materials and Engineering, 35(6), 509-21 (2024) https://doi.org/10.3233/BME-240053

Keyvanara AH, Yegdaneh A, Talebi A. Evaluating anti-inflammatory effect of hydroalcoholic extracts of Citrus medica L. pulp and peel on rat model of acute colitis. Research Journal of Pharmacognosy, 10 (2), 29-38 (2023) https://doi.org/10.22127/rjp.2023.377466.2027

Balaky ST. Anti H. pylori, anti-secretory and gastroprotective effects of Thymus vulgaris on ethanol-induced gastric ulcer in Sprague Dawley rats. Plos one, 19(1), e0287569 (2024) https://doi.org/10.1371/journal.pone.0287569

Li W, Huang H, Niu X, Fan T, Mu Q, Li H. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice. Toxicology and applied pharmacology, 272 (1), 21-9 (2013) https://doi.org/10.1016/j.taap.2013.05.035

Byeon S, Oh J, Lim JS, Lee JS, Kim JS. Protective effects of Dioscorea batatas flesh and peel extracts against ethanol-induced gastric ulcer in mice. Nutrients, 10 (11), 1680 (2018) https://doi.org/10.3390/nu10111680

Al-Qarawi AA, Abdel-Rahman H, Ali BH, Mousa HM, El-Mougy SA. The ameliorative effect of dates (Phoenix dactylifera L.) on ethanol-induced gastric ulcer in rats. Journal of ethnopharmacology, 98 (3), 313-7 (2005) https://doi.org/10.1016/j.jep.2005.01.023

Pan LR, Tang Q, Fu Q, Hu BR, Xiang JZ, Qian JQ. Roles of nitric oxide in protective effect of berberine in ethanol-induced gastric ulcer mice. Acta Pharmacologica Sinica, 26 (11), 1334-8 (2005) https://doi.org/10.1111/j.1745-7254.2005.00186.x

Bremshey S, Groß J, Renken K, Masseck OA. The role of serotonin in depression—A historical roundup and future directions. Journal of Neurochemistry, 168 (9), 1751-79 (2024) https://doi.org/10.1111/jnc.16097

Mózsik G, Past T, Abdel Salam OM, Kuzma M, Perjési P. Interdisciplinary review for correlation between the plant origin capsaicinoids, non-steroidal anti-inflammatory drugs, gastrointestinal mucosal damage and prevention in animals and human beings. Inflammopharmacology, 17, 113-50 (2009) https://doi.org/10.1007/s10787-009-0002-3

Li T, Shi M, Zhao Y, He Z, Zong Y, Chen W, Du R. Mechanism of action of vinegared Cornu Cervi Degelatinatum in suppressing spleen kidney yang deficient ulcerative colitis through NCK2-JNK pathway. Heliyon, 10 (2) (2024) https://doi.org/10.1016/j.heliyon.2024.e24782

Glavin GB, Szabo S. Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies. The FASEB journal, 6 (3), 825-31 (1992) https://doi.org/10.1096/fasebj.6.3.1740232

Qian Y, Li GJ, Zhu K, Suo HY, Sun P, Zhao X. Effects of three types of resistant starch on intestine and their gastric ulcer preventive activities in vivo. Journal of the Korean Society for Applied Biological Chemistry, 56 (6), 739-46 (2013) https://doi.org/10.1007/s13765-013-3229-z

Zhou YL, Wang R, Feng X, Zhao X. Preventive effect of insect tea against reserpine induced gastric ulcers in mice. Experimental and Therapeutic Medicine, 8 (4), 1318-24 (2014) https://doi.org/10.3892/etm.2014.1859

Yi R, Wang R, Sun P, Zhao X. Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers. Experimental and Therapeutic Medicine, 10 (1), 338-44 (2015) https://doi.org/10.3892/etm.2015.2473

Pfeiffer CJ, Cho CH, Cheema A, Saltman D. Reserpine-induced gastric ulcers: protection by lysosomal stabilization due to zinc. European Journal of Pharmacology, 61 (4), 347-53 (1980) https://doi.org/10.1016/0014-2999(80)90073-4

Ogle CW, Cho CH. Protection by zinc sulphate against reserpine-induced ulceration and other gastric effects in the rat. Pharmacology, 17 (5), 254-61 (1978) https://doi.org/10.1159/000136864

Li T, Shi M, Zhao Y, He Z, Zong Y, Chen W, Du R. Mechanism of action of vinegared Cornu Cervi Degelatinatum in suppressing spleen kidney yang deficient ulcerative colitis through NCK2-JNK pathway. Heliyon, 10 (2) (2024) https://doi.org/10.1016/j.heliyon.2024.e24782

Sandu, R., Singh, J. A comprehensive review on calcitonin gene-related peptide in the management of gastrointestinal disorders. Inflammopharmacol, 33, 1043–1059 (2025) https://doi.org/10.1007/s10787-025-01657-6

Vane JR, Botting RM. Anti-inflammatory drugs and their mechanism of action. Inflammation Research, 47, 78-87 (1998) https://doi.org/10.1007/s000110050284

Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacological reviews, 56 (3), 387-437 (2004) https://doi.org/10.1124/pr.56.3.3

Slomiany BL, Slomiany A. Role of endothelin-converting enzyme-1 in the suppression of constitutive nitric oxide synthase in rat gastric mucosal injury by indomethacin. Scandinavian journal of gastroenterology, 35 (11), 1131 (2004) https://doi.org/10.1080/003655200750056583

Maity B, Banerjee D, Bandyopadhyay SK, Chattopadhyay S. Regulation of arginase/nitric oxide synthesis axis via cytokine balance contributes to the healing action of malabaricone B against indomethacin-induced gastric ulceration in mice. International immunopharmacology, 9 (4), 491-8 (2004) https://doi.org/10.1016/j.intimp.2009.01.028

Suzuki T, Yoshida N, Nakabe N, Isozaki Y, Kajikawa H, Takagi T, Handa O, Kokura S, Ichikawa H, Naito Y, Matsui H. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. Journal of pharmacological sciences, 106 (3), 469-77 (2008) https://doi.org/10.1254/jphs.FP0071422

Doma I, Haruna I, Hamza A. Antipyretic and Antinociceptive Effect of the Methanol Leaf Extract of Ficus asperifolia in Murine Models. Journal of Current Biomedical Research, 4 (1), 1436-53 (2024) https://doi.org/10.54117/jcbr.v4i1.2

Abdel‐Raheem IT. Gastroprotective effect of rutin against indomethacin‐induced ulcers in rats. Basic & clinical pharmacology & toxicology, 107 (3), 742-50 (2010) https://doi.org/10.1111/j.1742-7843.2010.00568.x

Eraslan E, Tanyeli A, Güler MC, Kurt N, Yetim Z. Agomelatine prevents indomethacin-induced gastric ulcer in rats. Pharmacological Reports., 72 (4), 984-91 (2020) https://doi.org/10.1007/s43440-019-00049-2

El-Ashmawy NE, Khedr EG, El-Bahrawy HA, Selim HM. Nebivolol prevents indomethacin-induced gastric ulcer in rats. Journal of immunotoxicology, 13 (4), 580-9 (2016) https://doi.org/10.3109/1547691X.2016.1142488

Tiwari D, Alam A, Dhoundiyal S, Sharma S, Yadav S. Medicinal Herbs for the Treatment of Peptic Ulcers. Current Traditional Medicine, 10 (7), 106-18 (2024) https://doi.org/10.2174/0122150838262681230920054706

Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK. Healing properties of some Indian medicinal plants against indomethacin-induced gastric ulceration of rats. Journal of Clinical Biochemistry and Nutrition., 41 (2), 106-14 (2007) https://doi.org/10.3164/jcbn.2007015

Aleid IS, Alfheeaid HA, Aljutaily T, Alhomaid RM, Alharbi HF, Althwab SA, Abdel-Rahman HA, AlGeffari MA, Barakat H. Gastroprotective effects of spirulina platensis, golden kiwifruit flesh, and golden kiwifruit peel extracts individually or in combination against indomethacin-induced gastric ulcer in rats. Nutrients., 13 (10), 3499 (2021) https://doi.org/10.3390/nu13103499

Wang XY, Wang M, Yin JY, Song YH, Wang YX, Nie SP, Xie MY. Gastroprotective activity of polysaccharide from the fruiting body of Hericium erinaceus against acetic acid-induced gastric ulcer in rats and structure of one bioactive fraction. International Journal of Biological Macromolecules, 210, 455-64 (2022) https://doi.org/10.1016/j.ijbiomac.2022.04.153

Shen C, Zhang S, Di H, Wang S, Wang Y, Guan F. The Role of Triterpenoids in Gastric Ulcer: Mechanisms and Therapeutic Potentials. International Journal of Molecular Sciences, 26 (7), 3237 (2025) https://doi.org/10.3390/ijms26073237

Devaraj VC, Krishna BG, Viswanatha GL, Prasad VS, Babu SV. Protective effect of leaves of Raphinus sativus Linn on experimentally induced gastric ulcers in rats. Saudi Pharmaceutical Journal, 19 (3), 171-6 (2011) https://doi.org/10.1016/j.jsps.2011.03.003

da Silva LM, Pezzini BC, Somensi LB, Mariano LN, Mariott M, Boeing T, Dos Santos AC, Longo B, Cechinel-Filho V, de Souza P, de Andrade SF. Hesperidin, a citrus flavanone glycoside, accelerates the gastric healing process of acetic acid-induced ulcer in rats. Chemico-biological interactions, 308, 45-50 (2019) https://doi.org/10.1016/j.cbi.2019.05.011

da Silva LM, Allemand A, Mendes DA, Dos Santos AC, André E, de Souza LM, Cipriani TR, Dartora N, Marques MC, Baggio CH, Werner MF. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system. Food and chemical toxicology, 51, 179-87 (2013) https://doi.org/10.1016/j.fct.2012.09.026

Garabadu D, Singh S, Gautam T. Manilkara hexandra (Roxb.) Dubard Ameliorates Acetic Acid-induced Rat Gastric Ulcer. Journal of Dietary Supplements, 18 (3), 278-92 (2021) https://doi.org/10.1080/19390211.2020.1770393

Viana AF, Lopes MT, Oliveira FT, Nunes PI, Santos VG, Braga AD, Silva AC, Sousa DP, Viana DA, Rao VS, Rita de Cássia MO. (−)-Myrtenol accelerates healing of acetic acid-induced gastric ulcers in rats and in human gastric adenocarcinoma cells. European Journal of Pharmacology, 854, 139-48 (2019) https://doi.org/10.1016/j.ejphar.2019.04.025

Fan HP, Zhou Y, Chen ML, Qiu KH, Feng X, Zhou C, Zhu ML, Huang RZ, Hu TY. Effect of proton pump inhibitors versus histamine‐2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 44 (7), 539-48 (2024) https://doi.org/10.1002/phar.2947

Jily J. Noor A, Qazi NG, Nadeem H, Khan AU, Paracha RZ, Ali F, Saeed A. Synthesis, characterization, anti-ulcer action and molecular docking evaluation of novel benzimidazole-pyrazole hybrids. Chemistry Central Journal, 11, 1-3 (2017) https://doi.org/10.1186/s13065-017-0314-0

Hosoda S, Ikedo H, Saito T. Praomys (Mastomys) natalensis: Animal model for study of histamine-induced duodenal ulcers. Gastroenterology, 80 (1), 16-21 (1981) https://doi.org/10.1016/0016-5085(81)90184-0

Pu L, Jia T, Su S, Yang L, Yao H, Su Y, Chen Z. Proton Pump Inhibitors Versus Histamine-2 Receptor Blockers for Stress Ulcer Prophylaxis on In-Hospital Mortality Among Intensive Care Unit Patients Hospitalized for Major Adverse Cardiovascular and Cerebrovascular Events: Retrospective Cohort Study. Clinical Therapeutics, 46 (9),677-82 (2024) https://doi.org/10.1016/j.clinthera.2024.06.020

Fulga S, Pelin AM, Ghiciuc CM, Lupușoru EC. Particularities of experimental models used to induce gastric ulcer. ARS Medica Tomitana, 25 (4), 179-84 (2020) https://doi.org/10.32819/2021.94026

Yin R, R Hamblin M. Antimicrobial photosensitizers: drug discovery under the spotlight. Current medicinal chemistry, 22 (18), 2159-85 (2015) https://doi.org/10.2174/0929867322666150319120134

Chrétien NM, Zenab Linda FN, Brice Junior NN, Marcelle Olga FY, Vanessa Mba MM, Stephanie Flore DN, Yacine Karelle MK, Elvira NA, Marius M, Gilbert A. Anti-inflammatory, anti-oxidant and anti-ulcer activities of aqueous lyophilizate of Markhamia lutea (Bignoniaceae). Journal of Complementary and Integrative Medicine, 10 (0) (2024) https://doi.org/10.1515/jcim-2024-0059

Anderson G, Noorian AR, Taylor G, Anitha M, Bernhard D, Srinivasan S, Greene JG. Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease. Experimental neurology, 207 (1), 4-12 (2007) https://doi.org/10.1016/j.expneurol.2007.05.010

Shah DI, Santani DD, Goswami SS. A novel use of methylene blue as a pharmacological tool. Journal of pharmacological and toxicological methods, 54 (3), 273-7 (2006) https://doi.org/10.1016/j.vascn.2005.12.003

Lynch SR, Stoltzfus RJ. Iron and ascorbic acid: proposed fortification levels and recommended iron compounds. The Journal of nutrition, 133 (9), 2978S-84S (2003) https://doi.org/10.1093/jn/133.9.2978S

Teleanu RI, Niculescu AG, Roza E, Vladâcenco O, Grumezescu AM, Teleanu DM. Neurotransmitters—key factors in neurological and neurodegenerative disorders of the central nervous system. International journal of molecular sciences, 23 (11), 5954 (2022) https://doi.org/10.3390/ijms23115954

Thanoon TB, Althanoon ZA. Ketamine role in the treatment of Maternal depression: effects on offspring behaviour.Research square, 28 (2), (2024) https://doi.org/10.21203/rs.3.rs-3969981/v1

Lüscher TF, Vanhoutte PM. Endothelium-dependent responses to platelets and serotonin in spontaneously hypertensive rats. Hypertension, 8 (6_pt_2), II55 (1986) https://doi.org/10.1161/01.HYP.8.6_Pt_2.II55

Boakye-Yiadom M, Kumadoh D, Adase E, Woode E. Medicinal plants with prospective benefits in the management of peptic ulcer diseases in Ghana. BioMed Research International, 2021 (1), 5574041 (2021) https://doi.org/10.1155/2021/5574041

Buynitsky T, Mostofsky DI. Restraint stress in biobehavioral research: recent developments. Neuroscience & Biobehavioral Reviews., 33 (7), 1089-98 (2009) https://doi.org/10.1016/j.neubiorev.2009.05.004

Guo Jiang Q, Guo M, Guo L, Ling Q, Xie C, Li X, Zhao G, Tu W. Electroacupuncture pretreatment at ST36 alleviates acute gastric mucosal lesions induced by water immersion restraint stress through the TRPV1/SP/CGRP/NO pathway in rats. Acupuncture in Medicine, 43 (1), 3-13 (2025) https://doi.org/10.1177/09645284241300177

Fulga S, Pelin AM, Ghiciuc CM, Lupușoru EC. Particularities of experimental models used to induce gastric ulcer. ARS Medica Tomitana, 25 (4), 179-84 (2020) https://doi.org/10.2478/arsm-2019-0035

Janssen, H.J.B., Geraedts, T.C.M., Fransen, L.F.C. et al. Electrical vagus nerve stimulation is a promising approach to reducing pulmonary complications after an esophagectomy: an experimental rodent model. Immunol Res, 72, 1247–1258 (2024) https://doi.org/10.1007/s12026-024-09523-3

Khan N, Khushtar M, Rahman MA, Kaish M, Ajmal M. Amelioration of gastric ulcer using a hydro-alcoholic extract of Mangifera indica in Sprague Dawley rats by prevention of muco-oxidative stress. Pharmacological Research-Modern Chinese Medicine, 11, 100442 (2024) https://doi.org/10.1016/j.prmcm.2024.100442

Clark JD, Gebhart GF, Gonder JC, Keeling ME, Kohn DF. The 1996 guide for the care and use of laboratory animals. ILAR journal, 38 (1), 41-8 (1997) https://doi.org/10.1093/ilar.38.1.41

Al-Gabri N, Elnagar GM, Saghir SA, El-Shaibany A, Alnomasy SF, Althafar ZM, Elkomy NM, Elaasser MM, Abdoh MS, Yosri M. Preliminary Study of Gastroprotective Effect of Aloe perryi and Date Palm Extracts on Pyloric Ligation‐Induced Gastric Ulcer in Experimental Rats. BioMed Research International, 2022 (1), 9246785 (2022) https://doi.org/10.1155/2022/9246785

Yismaw Haritha M, Leena Lavanya D, Muthukumar T. Morphological, Anatomical, and Histochemical Study of Cordia diffusa KC Jacob—A Steno Endemic Plant. Microscopy Research and Technique, 88 (5), 1273-91 (2025) https://doi.org/10.1002/jemt.24791

Rajakrishnan R, Alfarhan AH, Al-Ansari AM, Lekshmi R, Sreelakshmi R, Benil PB, Kim YO, Tack JC, Na SW, Kim HJ. Therapeutic efficacy of the root tubers of Aconitum heterophyllum and its substitute Cyperus rotundus in the amelioration of pylorus ligation induced ulcerogenic and oxidative damage in rats. Saudi Journal of Biological Sciences, 27 (4), 1124-9 (2020) https://doi.org/10.1016/j.sjbs.2019.12.025

Elazab ST, Hsu WH. α-Bisabolol alleviates doxorubicin-induced cognitive dysfunction in rats via enhancing the hippocampal BDNF/TrKB signaling and inhibiting neuroinflammation. Frontiers in Pharmacology, 16, 1549009 (2025) https://doi.org/10.3389/fphar.2025.1549009

Andargie Y, Sisay W, Molla M, Norahun A, Singh P. Evaluation of the antiulcer activity of methanolic extract and solvent fractions of the leaves of Calpurnia aurea (Ait.) Benth.(Fabaceae) in rats. Evidence‐Based Complementary and Alternative Medicine, 2022 (1), 4199284 (2022) https://doi.org/10.1155/2022/4199284

Odukanmi OA, Salami AT, Ashaolu OP, Adegoke AG, Olaleye SB. Kolaviron attenuates ischemia/reperfusion injury in the stomach of rats. Applied Physiology, Nutrition, and Metabolism, 43 (1), 30-7 (2018) https://doi.org/10.1139/apnm-2017-0138

Fagundes FL, Piffer GD, Périco LL, Rodrigues VP, Hiruma-Lima CA, Dos Santos RD. Chrysin modulates genes related to inflammation, tissue remodeling, and cell proliferation in the gastric ulcer healing. International Journal of Molecular Sciences, 21 (3), 760 (2020) https://doi.org/10.3390/ijms21030760

Ohara R, Périco LL, Rodrigues VP, Bueno G, Zanatta AC, Dos Santos LC, Vilegas W, Constatino FB, Justulin LA, Hiruma-Lima CA. Terminalia catappa L. infusion accelerates the healing process of gastric ischemia-reperfusion injury in rats. Journal of ethnopharmacology, 256, 112793 (2020) https://doi.org/10.1016/j.jep.2020.112793

Bajramagic S, Sever M, Rasic F, Staresinic M, Skrtic A, Beketic Oreskovic L, Oreskovic I, Strbe S, Loga Zec S, Hrabar J, Coric L. Stable Gastric Pentadecapeptide BPC 157 and Intestinal Anastomoses Therapy in Rats—A Review. Pharmaceuticals, 17 (8), 1081 (2024) https://doi.org/10.3390/ph17081081

Dos Santos RD, Bonamin F, Périco LL, Rodrigues VP, Zanatta AC, Rodrigues CM, Sannomiya M, dos Santos Ramos MA, Bonifácio BV, Bauab TM, Tamashiro J. Byrsonima intermedia A. Juss partitions promote gastroprotection against peptic ulcers and improve healing through antioxidant and anti-inflammatory activities. Biomedicine & pharmacotherapy, 111, 1112-23 (2019) https://doi.org/10.1016/j.biopha.2018.12.132

Salami AT, Odukanmi OA, Faniyan OF, Omayone TP, Olaleye SB. Seeds of Buchholzia coriacea in diet mitigate ischemic reperfusion–induced gastric ulceration in experimental rats. Journal of dietary supplements, 15 (6), 842-59 (2018) https://doi.org/10.1080/19390211.2017.1404544

Sung JJY, Kuipers EJ, El-Serag HB. Systematic review: The global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther, 29 (9), 938–46 (2009) https://doi.org/10.1111/j.1365-2036.2009.03960.x

Borao Laguna C, Lanas A. Advances in the pharmacotherapeutic management of refractory peptic ulcers. Expert Opinion on Pharmacotherapy, 24 (7), 825-33 (2023) https://doi.org/10.1080/14656566.2023.2199922

Wu, Y., Murray, G.K., Byrne, E.M. et al. GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression. Nat Commun, 12, 1146 (2021) https://doi.org/10.1038/s41467-021-21280-7

Mozaffari S, Mousavi T, Nikfar S, Abdollahi M. Common gastrointestinal drug-drug interactions in geriatrics and the importance of careful planning. Expert Opinion on Drug Metabolism & Toxicology, 19 (11), 807-28 (2023) https://doi.org/10.1080/17425255.2023.2273384

Tang B, Li P, Mao X. Precision Diagnosis of Helicobacter pylori Infection and Its Drug Resistance. iLABMED, 3 (1), 106-23 (2025) https://doi.org/10.1002/ila2.73

Yuan Y, Dong SX. Social and natural environmental factors cause the birth-cohort phenomenon of peptic ulcers by superposition mechanism. International Journal of Environmental Health Research, 35 (2), 424-38 (2025) https://doi.org/10.1080/09603123.2024.2359069

Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology, 153 (2), 420–9 (2017) https://doi.org/10.1053/j.gastro.2017.04.022

Ford AC, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer: Systematic review and meta-analysis. Gut, 69 (12), 2113–21 (2020) https://doi.org/10.1136/gutjnl-2020-320839

Bafna PA, Balaraman R. Anti-ulcer and antioxidant activity of DHC-1, a herbal formulation. J Ethnopharmacol, 97 (2), 273–80 (2005) https://doi.org/10.1016/j.jep.2003.09.036

Szabo S, Hollander D. Pathways of gastrointestinal protection and repair: mechanisms of action of sucralfate. Am J Med, 86 (6A), 23–31 (1989) https://doi.org/10.1016/0002-9343(89)90153-8

Mamache W, Amira S, Benchikh F, Benabdallah H, Bencheikh A, Amira H, Ounis R, Torki MA, Kaoudoune C. The therapeutic potential of Salvia aegyptiaca extracts in ethanol-induced gastric ulcer: insights into macroscopic, histopathological, and biochemical mechanisms. Turkish Journal of Biology, 49 (1), 40-51 (2025) https://doi.org/10.55730/1300-0152.2722

Suden A. Management of Ulcerative Colitis Vis-À-Vis Atisara and Its Manifestations: An Ayurvedic Review. International research journal of ayurveda and yoga, 3 (8) (2020) https://doi.org/10.47223/IRJAY.2020.3818

Wang X, Tang Q, Hou H, Zhang W, Li M, Chen D, Gu Y, Wang B, Hou J, Liu Y, Cao H. Gut microbiota in NSAID enteropathy: new insights from inside. Frontiers in cellular and infection microbiology, 11, 679396 (2021) https://doi.org/10.3389/fcimb.2021.679396

Muayad HA, AlQadhi HI. The Cytoprotective Effects of Melatonin on Gastric Ulcer: A Rat Model. Journal of the Faculty of Medicine Baghdad, 67 (1), 78-84 (2025) https://doi.org/10.32007/jfacmedbaghdad2467

Okabe S, Pfeiffer CJ. Chronicity of acetic acid ulcer in the rat stomach. Am J Dig Dis, 17 (7), 619–29 (1972) https://doi.org/10.1007/BF02231748

Fokou PV, Nyarko AK, Appiah-Opong R, Yamthe LR, Addo P, Asante IK, Boyom FF. Ethnopharmacological reports on anti-Buruli ulcer medicinal plants in three West African countries. Journal of ethnopharmacology, 172, 297-311 (2015) https://doi.org/10.1016/j.jep.2015.06.024

Kavitt RT, Lipowska AM, Anyane-Yeboa A, Gralnek IM. Diagnosis and treatment of peptic ulcer disease. The American journal of medicine, 132 (4), 447-56 (2019) https://doi.org/10.1016/j.amjmed.2018.12.009

Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther, 29 (9), 938–46 (2009) https://doi.org/10.1111/j.1365-2036.2009.03960.x

Nyssen OP, Bordin D, Tepes B, Pérez-Aisa Á, Vaira D, Caldas M, Bujanda L, Castro-Fernandez M, Lerang F, Leja M, Rodrigo L. European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients. Gut, 70 (1), 40-54 (2021) https://doi.org/10.1136/gutjnl-2020-321372

Bardhan KD, Strugala V, Dettmar PW. Reflux revisited: advancing the role of pepsin. Int J Otolaryngol, 2012, 646901 (2012) https://doi.org/10.1155/2012/646901

Ko KA, Lee DK. Nonsteroidal Anti-Inflammatory Drug-Induced Peptic Ulcer Disease. The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 25 (1), 34-41 (2025) https://doi.org/10.7704/kjhugr.2025.0004

Wallace JL, Syer S, Denou E, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology., 141 (4), 1314–22 (2011) https://doi.org/10.1053/j.gastro.2011.06.075

Tourrette E, Torres RC, Svensson SL, Matsumoto T, Miftahussurur M, Fauzia KA, Alfaray RI, Vilaichone RK, Tuan VP, Helicobacter GenomicsConsortium, Wang D. An ancient ecospecies of Helicobacter pylori found in Indigenous populations and animal adapted lineages. bioRxiv, 2023 (04) (2023) https://doi.org/10.1101/2023.04.28.538659

Shanahan F, Ghosh TS, O'Toole PW. The gut microbiome in health and disease: A clinical perspective. Lancet Gastroenterol Hepatol, 6 (3), 260–70 (2021) https://doi.org/10.1146/annurev-med-051223-031809

Liu JZ, Öztekin M, Yılmaz B, Ağagündüz D, Capasso R. Overview of Helicobacter pylori infection: clinical features, treatment, and nutritional aspects. Diseases, 9 (4), 66 (2021) https://doi.org/10.3390/diseases9040066

Tarnawski AS, Ahluwalia A. Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers. Curr Med Chem, 19 (1), 16–27 (2012) atoon A, Sachan V, Kori P, Khushtar M, Pujari NM. Current Practices and Emerging Technologies in Animal Models for Gastric Ulcer Research. Journal of Drug Discovery and Health Sciences, 1 (3), 153-60 (2024) https://doi.org/10.21590/jddhs.01.03.05

Wallace JL, Sharkey KA. Pharmacotherapy of gastric acid-related disorders: Pathways of gastric protection and healing. Trends Pharmacol Sci, 42 (4), 276–88 (2021) https://doi.org/10.3390/ijms25021311

Zatorski H, Mukherjee P, Roy S, Ghosh D. et al. Role of animal models in biomedical research: a review. Lab Anim Res, 38, 18 (2022) https://doi.org/10.1186/s42826-022-00128-1

Mills JC, Shivdasani RA. Gastric epithelial stem cells and their roles in cancer and mucosal regeneration. Gastroenterology, 140 (2), 412–24 (2011) https://doi.org/10.1053/j.gastro.2010.12.001

Malfertheiner P, Schulz C, Hunt RH. Helicobacter pylori Infection: A 40-year journey through shifting the paradigm to transforming the management. Digestive Diseases, 42 (4), 299-308 (2024) https://doi.org/10.1159/000538079

Published

2025-04-30

How to Cite

Singh, L. P. ., Chatterjee, S., & Kar, S. K. . (2025). A comprehensive review of peptic ulcer disease: epidemiology, experimental models, and mechanistic insights. Journal of Applied Pharmaceutical Research, 13(2), 39-54. https://doi.org/10.69857/joapr.v13i2.953

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