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Horm Metab Res
DOI: 10.1055/a-2256-6592
Review

Recent Advances in Molecular Pathways and Therapeutic Implications for Peptic Ulcer Management: A Comprehensive Review

Deepak Chandra Joshi
1   Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Ajmer, India
,
Nirmal Joshi
2   Department of Pharmacology, Amrapali Institute of Pharmacy and Sciences, Haldwani, India
,
Ajeet Kumar
3   Faculty of Pharmaceutical Sciences, Rama University, Kanpur, India
,
Shubhrat Maheshwari
3   Faculty of Pharmaceutical Sciences, Rama University, Kanpur, India
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Abstract

Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5–10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori-associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori-infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management.

Keywords

peptic ulcer - H. pylori - TNF- α - prostaglandins - vanoprazan


Publication History

Received: 21 December 2023

Accepted: 16 January 2024

Article published online:
11 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Narayanan M, Reddy KM, Marsicano E. et al. Peptic ulcer disease and Helicobacter pylori infection. Missouri Med 2018; 115: 219
    PubMedGoogle Scholar
  • 2 Abbasi-Kangevari M, Ahmadi N, Fattahi N. et al. Quality of care of peptic ulcer disease worldwide: a systematic analysis for the global burden of disease study 1990–2019. PloS one 2022; 17: e0271284
    CrossrefPubMedGoogle Scholar
  • 3 Maheshwari S, Tiwari RK, Singh L. et al. Green expertise: synthesis of silver nanoparticles for wound healing application an overview. Res J Pharm Technol 2021; 14: 1149-1154
    CrossrefPubMedGoogle Scholar
  • 4 Singh A, Ansari VA, Ahsan F. et al. Viridescent concoction of genstein tendentious silver nanoparticles for breast cancer. Res J Pharm Technol 2021; 14: 2867-2872
    CrossrefPubMedGoogle Scholar
  • 5 Maheshwari S, Singh A. et al. Navigating the dementia landscape: biomarkers and emerging therapies. Ageing Res Rev 2024; 10: 102193
    CrossrefPubMedGoogle Scholar
  • 6 Singh A, Ansari VA, Mahmood T. et al. Receptor for advanced glycation end products: dementia and cognitive impairment. Drug Res (Stuttg) 2023; 73: 247-150
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Joshi DC, Joshi N, Kumari H et al. To Evaluate Preliminary Pharmacological Screening of Plant Extract of Ficus auriculata Lour for Anti-ulcer Activity. JAMMR 2022; 34(22): 206–213
    PubMed
  • 8 Maheshwari S. Ferroptosis Signaling Pathways: Alzheimer's Disease. Horm Metab Res 2023; 55: 819-826
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Sharma N, Kumar P, Shukla KS. et al. AGE RAGE Pathways: cardiovascular disease and oxidative stress. Drug Res (Stuttg) 2023; 73: 408-411
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Lanas A, Chan FK. et al. Peptic ulcer disease. Lancet 2017; 390: 613-624
    CrossrefPubMedGoogle Scholar
  • 11 Kavitt RT, Lipowska AM, Anyane-Yeboa A. et al. Diagnosis and treatment of peptic ulcer disease. Am J Med 2019; 132: 447-456
    CrossrefPubMedGoogle Scholar
  • 12 Drini M. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Austr Prescrib 2017; 40: 91
    CrossrefPubMedGoogle Scholar
  • 13 Kuna L, Jakab J, Smolic R. et al. Peptic ulcer disease: a brief review of conventional therapy and herbal treatment options. J Clin Med 2019; 8: 179
    CrossrefPubMedGoogle Scholar
  • 14 Xie X, Ren K, Zhou Z. et al. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol 2022; 22: 58
    CrossrefPubMedGoogle Scholar
  • 15 Alsinnari YM, Alqarni MS, Attar M. et al. Risk factors for recurrence of peptic ulcer disease: a retrospective study in tertiary care referral center. Cureus 2022; 14: e22001
    PubMedGoogle Scholar
  • 16 Lv M, Cai Y, Hou W. et al. The RNA-binding protein SND1 promotes the degradation of GPX4 by destabilizing the HSPA5 mRNA and suppressing HSPA5 expression, promoting ferroptosis in osteoarthritis chondrocytes. Inflam Res 2022; 71: 461-472
    CrossrefPubMedGoogle Scholar
  • 17 Xu W, Zhang B, Xi C. et al. Ferroptosis plays a role in human chondrocyte of osteoarthritis induced by IL-1β in vitro. Cartilage 2023; 14 19476035221142011
    PubMedGoogle Scholar
  • 18 Riegger J. TRPV1 as an anti-ferroptotic target in osteoarthritis. EBioMedicine 2022; 84: 104279
    CrossrefPubMedGoogle Scholar
  • 19 Lv Z, Han J, Li J. et al. Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis. EbioMedicine 2022; 84: 104258
    CrossrefPubMedGoogle Scholar
  • 20 Gao L, Hua W, Tian L. et al. Molecular mechanism of ferroptosis in orthopedic diseases. Cells 2022; 11: 2979
    CrossrefPubMedGoogle Scholar
  • 21 Lu J, Yang J, Zheng Y. et al. Extracellular vesicles from endothelial progenitor cells prevent steroid-induced osteoporosis by suppressing the ferroptotic pathway in mouse osteoblasts based on bioinformatics evidence. Sci Rep 2019; 9: 16130
    CrossrefPubMedGoogle Scholar
  • 22 Zhang Y, Han S, Kong M. et al. Single-cell RNA-seq analysis identifies unique chondrocyte subsets and reveals involvement of ferroptosis in human intervertebral disc degeneration. Osteoarthr Cartil 2021; 29: 1324-1334
    CrossrefPubMedGoogle Scholar
  • 23 Luo H, Zhang R. et al. Icariin enhances cell survival in lipopolysaccharide-induced synoviocytes by suppressing ferroptosis via the Xc-/GPX4 axis. Exp Therap Med 2021; 21: 72
    CrossrefPubMedGoogle Scholar
  • 24 Joshi N, Arya RKK, Bisht D. et al. Role of Drug Metabolism & Disposition in Discovery and Development of New Drugs. 2021; 9(12): 180–190
    PubMedGoogle Scholar
  • 25 Xiong Z, Sun H, Liu M. et al. Roles of ferroptosis in intervertebral disc degeneration and osteoarthritis. Chin J Tissue Eng Res 2023; 27: 5884
    PubMedGoogle Scholar
  • 26 Xu G, Lu M, Fang L. et al. Quercetin suppresses ferroptosis in chondrocytes via activating the Nrf2/GPX4 signaling pathway. Nat Prod Commun 2023; 18 1934578X231194837
    PubMedGoogle Scholar
  • 27 Joo, M. K., Park, C. H., Kim, J. S., Park, J. M., Ahn, J. Y., Lee, B. E., Lee, J. H., Yang, H. J., Cho, Y. K., Bang, C. S., Kim, B. J., Jung, H. K., Kim, B. W., Lee, Y. C., & Korean College of Helicobacter Upper Gastrointestinal Research (2020). Clinical Guidelines for Drug-Related Peptic Ulcer, 2020 Revised Edition. Gut and liver, 14(6), 707–726.
    PubMed
  • 28 Guo Z, Lin J, Sun K. et al. Corrigendum: Deferoxamine alleviates osteoarthritis by inhibiting chondrocyte ferroptosis and activating the Nrf2 pathway. Front Pharmacol 2023; 14: 1199951
    CrossrefPubMedGoogle Scholar
  • 29 He Q, Yang J, Pan Z. et al. Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis. Biomed Pharmacother 2023; 157: 113915
    CrossrefPubMedGoogle Scholar
  • 30 Han T, Zhang Y, Qi B. et al. Clinical features and shared mechanisms of chronic gastritis and osteoporosis. Sci Rep 2023; 13: 4991
    CrossrefPubMedGoogle Scholar
  • 31 Zhou LP, Zhang RJ, Jia CY. et al. Ferroptosis: a potential target for the intervention of intervertebral disc degeneration. Front Endocrinol 2022; 13: 1042060
    CrossrefPubMedGoogle Scholar
  • 32 Li Y, Meng L, Zhao B. et al. The roles of N6-methyladenosine methylation in the regulation of bone development, bone remodeling and osteoporosis. Pharmacol Therapeut 2022; 238: 108174
    CrossrefPubMedGoogle Scholar
  • 33 Li M, He Q, Zeng J. et al. Iron overload in bone diseases. Chin J Tissue Eng Res 2023; 27: 2723
    PubMedGoogle Scholar
  • 34 Li Y, Li F. et al. Mechanism and Prospect of gastrodin in osteoporosis, bone regeneration, and osseointegration. Pharmaceuticals 2022; 15: 1432
    CrossrefPubMedGoogle Scholar
  • 35 Hu W, Liang K, Zhu H. et al. Ferroptosis and its role in chronic diseases. Cells 2022; 11: 2040
    CrossrefPubMedGoogle Scholar
  • 36 Miao R, Fang X, Zhang Y. et al. Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities. Cell Death Dis 2023; 14: 186
    CrossrefPubMedGoogle Scholar
  • 37 Chang S, Tang M, Zhang B. et al. Ferroptosis in inflammatory arthritis: a promising future. Front Immunol 2022; 13: 955069
    CrossrefPubMedGoogle Scholar
  • 38 Yan HF, Zou T, Tuo QZ. et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther 2021; 6: 49
    CrossrefPubMedGoogle Scholar
  • 39 Weiland A, Wang Y, Wu W. et al. Ferroptosis and its role in diverse brain diseases. Mol Neurobiol 2019; 56: 4880-4893
    CrossrefPubMedGoogle Scholar
  • 40 Vitalakumar D, Sharma A, Flora SJ. et al. Ferroptosis: a potential therapeutic target for neurodegenerative diseases. J Biochem Mol Toxicol 2021; 35: e22830
    CrossrefPubMedGoogle Scholar
  • 41 Bereda G. et al. Peptic Ulcer disease: definition, pathophysiology, and treatment. J Biomed Biol Sci 2022; 1: 10
    PubMedGoogle Scholar
  • 42 Paragomi P, Dabo B, Pelucchi C, Bonzi R. et al. The association between peptic ulcer disease and gastric cancer: results from the stomach cancer pooling (StoP) project consortium. Cancers 2022; 14: 4905
    CrossrefPubMedGoogle Scholar
  • 43 Mahmood S, Fareed MM, Ahmed G. et al. A robust deep model for classification of peptic ulcer and other digestive tract disorders using endoscopic images. Biomedicines 2022; 10: 2195
    CrossrefPubMedGoogle Scholar
  • 44 Li N, Yi X, He Y. et al. Targeting ferroptosis as a novel approach to alleviate aortic dissection. Int J Biol Sci 2022; 18: 4118-4134
    CrossrefPubMedGoogle Scholar
  • 45 Lei J, Chen Z, Song S. et al. Insight into the role of ferroptosis in non-neoplastic neurological diseases. Front Cell Neurosci 2020; 14: 231
    CrossrefPubMedGoogle Scholar
  • 46 Cheng Y, Song Y, Chen H. et al. Ferroptosis mediated by lipid reactive oxygen species: a possible causal link of neuroinflammation to neurological disorders. Oxid Med Cell Longev 2021; 2021: 1-3
    CrossrefPubMedGoogle Scholar
  • 47 Sun Y, Yan C, He L. et al. Inhibition of ferroptosis through regulating neuronal calcium homeostasis: An emerging therapeutic target for Alzheimer’s disease. Ageing Res Rev 2023; 87: 101899
    CrossrefPubMedGoogle Scholar
  • 48 Tang M, Chen Z, Wu D. et al. Ferritinophagy/ferroptosis: Iron-related newcomers in human diseases. J Cell Physiol 2018; 233: 9179-9190
    CrossrefPubMedGoogle Scholar
  • 49 Qiu Y, Cao Y, Cao W. et al. The application of ferroptosis in diseases. Pharmacol Res 2020; 159: 104919
    CrossrefPubMedGoogle Scholar
  • 50 Rogers JT, Cahill CM. Iron-responsive-like elements and neurodegenerative ferroptosis. Learn Memory 2020; 27: 395-413
    CrossrefPubMedGoogle Scholar
  • 51 Stockwell BR, Angeli JP, Bayir H. et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 2017; 171: 273-285
    CrossrefPubMedGoogle Scholar
  • 52 Wang S, Liao H, Li F. et al. A mini-review and perspective on ferroptosis-inducing strategies in cancer therapy. Chin Chem Lett 2019; 30: 847-852
    CrossrefPubMedGoogle Scholar
  • 53 Musheshe N, Oun A, Sabogal-Guáqueta AM. et al. Pharmacological inhibition of epac1 averts ferroptosis cell eath by preserving mitochondrial integrity. Antioxidants 2022; 11: 314
    CrossrefPubMedGoogle Scholar
  • 54 Plascencia-Villa G, Perry G. Implication of ferroptosis iron-dependent programmed cell death mechanism in neurodegeneration: molecular and cell biology/oxidative stress. Alzheimer Dement 2020; 16: e043978
    CrossrefPubMedGoogle Scholar
  • 55 Zhang Z, Yan W, Zhang X. et al. Peptic ulcer disease burden, trends, and inequalities in 204 countries and territories, 1990–2019: a population-based study. Therap Adv Gastroenterol 2023; 16 17562848231210375
    PubMedGoogle Scholar
  • 56 Yokoyama M, Usuda D, Sugita M. et al. Multiple peptic ulcers. Visual J Emerg Med 2023; 32: 101646
    CrossrefPubMedGoogle Scholar
  • 57 Miao Y, Chen Y, Xue F. et al. Contribution of ferroptosis and GPX4’s dual functions to osteoarthritis progression. EBioMedicine 2022; 76: 103847
    CrossrefPubMedGoogle Scholar
  • 58 Al-Hetty HR, Abdulameer SJ, Alghazali MW. et al. The role of ferroptosis in the pathogenesis of osteoarthritis. J Memb Biol 2023; 256: 223-228
    CrossrefPubMedGoogle Scholar
  • 59 Zhou X, Zheng Y, Sun W. et al. D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner. Cell Prolif 2021; 54: e13134
    CrossrefPubMedGoogle Scholar
  • 60 Yang J, Hu S, Bian Y. et al. Targeting cell death: pyroptosis, ferroptosis, apoptosis and necroptosis in osteoarthritis. Front Cell Develop Biol 2022; 9: 789948
    CrossrefPubMedGoogle Scholar
  • 61 Liu H, Deng Z, Yu B. et al. Identification of SLC3A2 as a aotential therapeutic target of osteoarthritis involved in ferroptosis by integrating bioinformatics, clinical factors and experiments. Cells 2022; 11: 3430
    CrossrefPubMedGoogle Scholar
  • 62 Distéfano AM, López GA, Bauer V. et al. Ferroptosis in plants: regulation of lipid peroxidation and redox status. Biochem J 2022; 479: 857-866
    CrossrefPubMedGoogle Scholar
  • 63 Shan K, Feng N, Zhu D. et al. Free docosahexaenoic acid promotes ferroptotic cell death via lipoxygenase dependent and independent pathways in cancer cells. Eur J Nutr 2022; 61: 4059-4075
    CrossrefPubMedGoogle Scholar
  • 64 Chen Q, Zheng Q, Yang Y. et al. 12/15-Lipoxygenase regulation of diabetic cognitive dysfunction is determined by interfering with inflammation and cell apoptosis. Int J Mol Sci 2022; 23: 8997
    CrossrefPubMedGoogle Scholar
  • 65 Mishima E, Ito J, Wu Z. et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 2022; 608: 778-783
    CrossrefPubMedGoogle Scholar
  • 66 Liao EC, Yu CH, Lai JH. et al. A pilot study of non-invasive diagnostic tools to detect Helicobacter pylori infection and peptic ulcer disease. Sci Rep 2023; 13: 22800
    CrossrefPubMedGoogle Scholar
  • 67 Srivastav Y, Kumar V, Srivastava Y. et al. Peptic ulcer disease (PUD), diagnosis, and current medication-based management options: schematic overview. J Adv Med Pharm Sci 2023; 25: 14-27
    PubMedGoogle Scholar
  • 68 He Y, Koido M, Sutoh Y. et al. East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease. Nature Genet 2023; 55: 2129-2138
    CrossrefPubMedGoogle Scholar
  • 69 Li ZW, Tong Y, Liu F. et al. A comparative study on laparoscopic and open surgical approaches for perforated peptic ulcer repair: efficacy and outcomes analysis. Langenbeck Archiv Surg 2023; 408: 435
    CrossrefPubMedGoogle Scholar
  • 70 Beran A, Al-Abboodi Y, Majzoub AM. et al. Endoscopic versus conservative therapy for bleeding peptic ulcer with adherent clot: a comprehensive systematic review and meta-analysis. Digest Dis Sci 2023; 68: 3921-3934
    CrossrefPubMedGoogle Scholar
  • 71 Mahajan KC, Ghodake SS, Mantry S. et al. An alternative therapy for improvement of efficacy and safety of polyherbal formulation for treatment of peptic ulcer. Acta Biomed 2023; 94: e2022268
    PubMedGoogle Scholar
  • 72 Gaynes RP. Barry Marshall and pylori in peptic ulcer disease. In: Germ theory: Medical Pioneers in Infectious Diseases. New York: Wiley; 2023. Chap. 16, 295
    Google Scholar
  • 73 Chankseliani G. Peptic ulcer – treatment methods. Exp Clin Med Georgia 2023; Issue No 6 DOI: 10.52340/jecm.2023.06.02.
    CrossrefPubMedGoogle Scholar
  • 74 Dahiya DS, Mandoorah S, Gangwani MK. et al. A comparative analysis of bleeding peptic ulcers in hospitalizations with and without end-stage renal disease. Gastroenterol Res 2023; 16: 17
    CrossrefPubMedGoogle Scholar
  • 75 Tartaglia D, Strambi S, Coccolini F. et al. Laparoscopic versus open repair of perforated peptic ulcers: analysis of outcomes and identification of predictive factors of conversion. Updates Surg 2023; 75: 649-657
    CrossrefPubMedGoogle Scholar
  • 76 Nivetha G, Unnikrishnan S, Ramalingam K. et al. Medicinal plant treatments for peptic ulcers: applications and future perspectives. Pharmacol Benefits Nat Agents 2023; 172-199 IGI Global
    CrossrefPubMedGoogle Scholar
  • 77 Kim H. U. (2015). Diagnostic and Treatment Approaches for Refractory Peptic Ulcers. Clinical endoscopy, 48(4), 285–290
    PubMed
  • 78 Chan S, Pittayanon R, Wang HP. et al. Use of over-the-scope clip (OTSC) versus standard therapy for the prevention of rebleeding in large peptic ulcers (size ≥ 1.5 cm): an open-labelled, multicentre international randomised controlled trial. Gut 2023; 72: 638-643
    CrossrefPubMedGoogle Scholar
  • 79 Starup-Linde J, Langdahl B, Vestergaard P. et al. Incident peptic ulcers and concomitant treatment of direct oral anticoagulants and oral bisphosphonates–a real-world cohort study. Osteoporos Int 2022; 33: 1323-1334
    CrossrefPubMedGoogle Scholar