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Pharmaceuticals
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New and Emerging Treatment Strategies for Gastrointestinal Diseases
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New and Emerging Treatment Strategies for Gastrointestinal Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 October 2025 | Viewed by 15244

Special Issue Editor

Dr. Daniele Maria-Ferreira

E-Mail Website
Guest Editor
Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil
Interests: pharmacology; inflammatory bowel diseases; polysaccharides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastrointestinal homeostasis is orchestrated by complex regulatory mechanisms, including a protective epithelial barrier, a diverse microbiota and a highly regulated immune response controlled by different mucosal cell types. However, disruption of these mechanisms can lead to the development of acute and/or chronic pathological processes characterized by widely recognized problems, including gastroesophageal reflux, peptic ulcers, bile acid disorder, inflammatory bowel disease and others. Current treatment options for problems related to the gastrointestinal tract are limited and do not fully meet the needs of patients. In addition, prolonged use of some medications can have serious adverse effects. Therefore, the search for new treatment options is necessary.

Original papers and review articles are welcome for the Special Issue entitled “New and Emerging Treatment Strategies for Gastrointestinal Diseases”. Manuscripts must cover all aspects of the following:

  • Advances and challenges in the development of new and novel treatment strategies for gastrointestinal diseases
  • Extraction/isolation and identification of extracts or bioactive compounds for the treatment of gastrointestinal diseases
  • Benefits and safety of new treatment strategies for gastrointestinal diseases

Dr. Daniele Maria-Ferreira
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastrointestinal diseases
  • gastrointestinal homeostasis
  • gastrointestinal injuries
  • gastrointestinal disturbances
  • dysbiosis
  • bile acid
  • inflammatory bowel diseases
  • diarrhea

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Published Papers (7 papers)

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Research

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27 pages, 3509 KiB  
Article
A Comparative Study of N-Acetyl Cysteine, Rosuvastatin, and Vitamin E in the Management of Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Trial
by Amr Y. Zakaria, Rehab Badawi, Hasnaa Osama, Mona A. Abdelrahman and Asmaa M. El-Kalaawy
Pharmaceuticals 2025, 18(5), 650; https://doi.org/10.3390/ph18050650 - 29 Apr 2025
Viewed by 797
Abstract
Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, [...] Read more.
Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, randomized, controlled study was conducted and registered on clinicaltrials.gov (Identifier: NCT06105060), involving 135 NASH participants, who were divided into three groups: the control group (group 1), consisting of patients receiving standard therapy VE at a dosage of 400 IU twice daily. In the treated group (group 2), patients were administered NAC at a dosage of 1200 mg twice daily, while treatment (group 3) received RSV at a dosage of 20 mg once daily. FibroScan® examination of liver tissue and fibrosis scores, along with tests for liver aminotransferases, lipid profile, glycemic parameters, and renal and hepatic functions, were assessed before and after six months of treatment. Results: The analyzed groups demonstrated a significant reduction in steatosis and lipid peroxidation (p < 0.05). The NAC group demonstrated greater anti-inflammatory and anti-apoptotic effects compared to the RSV group, although this difference was not significant in the control group. NAC is conceded as the only significant antifibrotic agent in liver stiffness measurement (LSM), biological marker findings, and non-invasive liver fibrosis scores (p < 0.05), in addition to its improvement of several metabolic parameters and health-related quality of life. Conclusions: Patients receiving NAC demonstrated safety and efficacy in enhancing steatosis, fibrosis, and metabolic parameters, representing a novel strategy in the management of NASH. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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12 pages, 2219 KiB  
Article
Oxidized Low-Density Lipoprotein Induces Reactive Oxygen Species-Dependent Proliferation of Intestinal Epithelial Cells
by Eddy E. Gonzalez-Horta, Juan F. Burgueno, María J. Leiva, Carla Villavicencio, Fernando I. Kawaguchi, Hajar Hazime, Fátima Reyes, Viana Manrique-Suárez, Natalie C. Parra, Maria T. Abreu and Jorge R. Toledo
Pharmaceuticals 2024, 17(11), 1466; https://doi.org/10.3390/ph17111466 - 1 Nov 2024
Viewed by 1473
Abstract
Background/Objectives: Oxidized low-density lipoprotein (ox-LDL) is a proinflammatory particle associated with various diseases and affects cell proliferation and viability in multiple cell types. However, its impact on intestinal epithelial cells remains underexplored. This study investigates the effect of ox-LDL on colonic epithelial [...] Read more.
Background/Objectives: Oxidized low-density lipoprotein (ox-LDL) is a proinflammatory particle associated with various diseases and affects cell proliferation and viability in multiple cell types. However, its impact on intestinal epithelial cells remains underexplored. This study investigates the effect of ox-LDL on colonic epithelial cell proliferation and viability, as well as the underlying mechanisms involved. Methods: The expression levels of ox-LDL receptors in human colonoids were analyzed at baseline and in response to proinflammatory signals by qRT-PCR. The effect of ox-LDL on organoid proliferation was analyzed using morphometric measurements, viability assays, and the incorporation of a thymidine analog into DNA. The generation of reactive oxygen species (ROS) was determined by Amplex Red assays. Additionally, ox-LDL-induced ROS-dependent organoid proliferation was studied by exposing colonoids to an antioxidant or ROS inhibitors. Results: Colonic epithelial cells express ox-LDL receptors. Ox-LDL significantly induces the proliferation of colonic epithelial cells, which are dependent on ROS generation. Notably, ROS scavengers and NADPH inhibitors reduced ox-LDL-induced proliferation, highlighting the crucial role of oxidative stress in this process. Conclusions: This study demonstrates for the first time that ox-LDL stimulates CEC proliferation mediated by ROS production and validates that the colonic organoid model enables the analysis of potential pharmacological strategies for intestinal diseases characterized by oxidative stress and inflammation. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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Review

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26 pages, 794 KiB  
Review
Advances in Gastroesophageal Reflux Disease Management: Exploring the Role of Potassium-Competitive Acid Blockers and Novel Therapies
by Katarzyna Hossa and Ewa Małecka-Wojciesko
Pharmaceuticals 2025, 18(5), 699; https://doi.org/10.3390/ph18050699 - 9 May 2025
Viewed by 542
Abstract
Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors [...] Read more.
Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients’ quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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31 pages, 1014 KiB  
Review
New Interleukin-23 Antagonists’ Use in Crohn’s Disease
by Laura Biskup, Jan Semeradt, Jagoda Rogowska, Wiktoria Chort, Łukasz Durko and Ewa Małecka-Wojciesko
Pharmaceuticals 2025, 18(4), 447; https://doi.org/10.3390/ph18040447 - 22 Mar 2025
Viewed by 1590
Abstract
Crohn’s disease (CD) is a chronic inflammatory condition of the digestive tract, driven by an imbalance in immune system regulation, where proinflammatory interleukin-23 (IL-23) plays an essential role. Selective new IL-23 inhibitors, including risankizumab, guselkumab, and mirikizumab, block the IL-23p19 subunit to inhibit [...] Read more.
Crohn’s disease (CD) is a chronic inflammatory condition of the digestive tract, driven by an imbalance in immune system regulation, where proinflammatory interleukin-23 (IL-23) plays an essential role. Selective new IL-23 inhibitors, including risankizumab, guselkumab, and mirikizumab, block the IL-23p19 subunit to inhibit the Il-23 action and alleviate inflammation in CD. This review explores the effectiveness, safety, and therapeutic potential of anti-IL-23 treatment in CD management. Risankizumab, guselkumab, and mirikizumab demonstrated considerable effectiveness in inducing clinical remission and promoting endoscopic healing in patients with moderately to severely active CD, including those refractory to anti-TNF therapies. Risankizumab showed favorable results in pivotal trials like ADVANCE, MOTIVATE, and FORTIFY, achieving remission rates of up to 45% and sustained inflammatory biomarkers normalization. Guselkumab and mirikizumab similarly demonstrated substantial efficacy in the induction and maintenance phases, with promising long-term results. The safety profiles of IL-23 inhibitors were favorable, with low rates of serious adverse events, including infections and malignancies. Selective new IL-23 inhibitors represent a targeted and effective therapeutic class for moderately to severely active CD, offering high clinical and endoscopic remission rates, and favorable safety outcomes. Continued research, particularly on long-term efficacy and the selection of patients based on inflammatory biomarkers, will help optimize their role in personalized treatment strategies for refractory CD. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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12 pages, 263 KiB  
Review
Treatment Strategies for Chronic Pancreatitis (CP)
by Katarzyna Tłustochowicz, Agnieszka Krajewska, Adrianna Kowalik and Ewa Małecka-Wojciesko
Pharmaceuticals 2025, 18(3), 311; https://doi.org/10.3390/ph18030311 - 24 Feb 2025
Viewed by 2241
Abstract
Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are diseases with overlapping features, both requiring complex management strategies. CP is characterized by pancreatic exocrine insufficiency (PEI) and pain, with treatment focused on symptom relief through pancreatic enzyme replacement therapy (PERT), pain control, and lifestyle [...] Read more.
Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are diseases with overlapping features, both requiring complex management strategies. CP is characterized by pancreatic exocrine insufficiency (PEI) and pain, with treatment focused on symptom relief through pancreatic enzyme replacement therapy (PERT), pain control, and lifestyle and nutritional changes. However, the standard therapy does not address the underlying inflammation or fibrosis, which drives disease progression. AIP, on the other hand, presents with obstructive jaundice and fibrosis and is classified into two subtypes: Type 1 (AIP-1), linked to IgG4-related disease, and Type 2 (AIP-2), associated with inflammatory bowel disease. Treatment for AIP typically involves oral steroids. Immunomodulators and rituximab are used for recurrent or refractory cases. Novel therapies targeting the inflammation and fibrotic components of CP are being explored. A multidisciplinary approach is essential to optimize care and improve patients’ outcomes. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
16 pages, 999 KiB  
Review
Simulator of the Human Intestinal Microbial Ecosystem (SHIME®): Current Developments, Applications, and Future Prospects
by Wei Zhu, Xiaoyong Zhang, Dong Wang, Qinghua Yao, Guang-Lei Ma and Xiaohui Fan
Pharmaceuticals 2024, 17(12), 1639; https://doi.org/10.3390/ph17121639 - 6 Dec 2024
Cited by 4 | Viewed by 3355
Abstract
The human gastrointestinal microbiota plays a vital role in maintaining host health and preventing diseases, prompting the creation of simulators to replicate this intricate system. The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), a multicompartment dynamic simulator, has emerged as [...] Read more.
The human gastrointestinal microbiota plays a vital role in maintaining host health and preventing diseases, prompting the creation of simulators to replicate this intricate system. The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), a multicompartment dynamic simulator, has emerged as a pivotal in vitro model for studying the interactions and interferences within the human gut microbiota. The continuous and real-time monitoring hallmarks, along with the programmatically flexible setup, bestow SHIME® with the ability to mimic the entire human intestinal ecosystem with high dynamics and stability, allowing the evaluation of various treatments on the bowel microbiota in a controlled environment. This review outlines recent developments in SHIME® systems, including the M-SHIME®, Twin-SHIME®, Triple-SHIME®, and Toddle SHIME® models, highlighting their applications in the fields of food and nutritional science, drug development, gut health research, and traditional Chinese medicine. Additionally, the prospect of SHIME® integrating with other advanced technologies is also discussed. The findings underscore the versatility of SHIME® technology, demonstrating its significant contributions to current gut ecosystem research and its potential for future innovation in microbiome-related fields. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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16 pages, 586 KiB  
Review
Gastrointestinal Manifestations of Sarcoidosis: A State-of-the-Art, Comprehensive Review of the Literature—Practical Clinical Insights and Many Unmet Needs on Diagnosis and Treatment
by Salvatore Nicolosi, Maria Chernovsky, Darina Angoni, Michael Hughes, Giulia Bandini, Zsuzsanna McMahan, Marta Maggisano, Francesco Salton, Lucrezia Mondini, Mariangela Barbieri, Gianluca Screm, Marco Confalonieri, Elisa Baratella, Paola Confalonieri and Barbara Ruaro
Pharmaceuticals 2024, 17(9), 1106; https://doi.org/10.3390/ph17091106 - 23 Aug 2024
Cited by 4 | Viewed by 4405
Abstract
This comprehensive literature review explores the involvement of the gastrointestinal (GI) tract in sarcoidosis, a multisystem granulomatous disorder of unknown etiology. GI sarcoidosis presents a diagnostic and therapeutic challenge due to its rarity and nonspecific clinical manifestations, including overlap with other gastrointestinal diseases. [...] Read more.
This comprehensive literature review explores the involvement of the gastrointestinal (GI) tract in sarcoidosis, a multisystem granulomatous disorder of unknown etiology. GI sarcoidosis presents a diagnostic and therapeutic challenge due to its rarity and nonspecific clinical manifestations, including overlap with other gastrointestinal diseases. We conducted a comprehensive screening of articles addressing the clinical features, diagnostic approaches, and treatment strategies for GI sarcoidosis. Our findings reveal that GI sarcoidosis can affect any part of the gastrointestinal tract, with the stomach and small intestine being the most involved. Clinical presentations range from asymptomatic cases to severe complications such as obstruction and perforation, with reflux being a common symptom. Diagnosis is often delayed due to the nonspecific nature of symptoms and the need for histopathological confirmation. Therapeutic approaches are poorly defined, typically involving corticosteroids as the mainstay of treatment. However, the long-term efficacy and safety of these treatments remain uncertain in this patient group, given the significant risks and complications associated with prolonged glucocorticoid therapy. There is a clear need to develop accurate diagnostic protocols to distinguish GI sarcoidosis from other conditions and to establish standardized therapeutic guidelines to optimize patient outcomes. Further research is essential to enhance our understanding and management of this complex condition. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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