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Natural Compounds for Counteracting GI and Liver Diseases
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Natural Compounds for Counteracting GI and Liver Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 4842

Special Issue Editors

Dr. Daniela Gabbia

E-Mail Website
Guest Editor
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L. go Meneghetti 2, 35131 Padova, Italy
Interests: chronic liver disease; hepatocellular carcinoma; liver metabolism
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Raquel Abalo

E-Mail Website
Guest Editor
Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University (URJC), Alcorcón, 28922 Madrid, Spain
Interests: gastrointestinal motility; visceral pain; functional foods; cannabinoids; irritable bowel syndrome; nutraceuticals; enteric nervous system; brain–gut axis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue entitled “Natural Compounds for Counteracting GI and Liver Diseases” focuses on the role of natural compounds in promoting gastrointestinal (GI) and liver health. It aims to collect research articles, reviews, and perspectives that highlight the pharmacological potential of naturally derived substances to prevent and treat GI and hepatic disorders.

The following topics are welcome in the Special Issue:

  1. Studies on the efficacy of plant-derived compounds, such as polyphenols, flavonoids, and essential oils, in alleviating GI inflammation, ulceration, and microbial imbalances and chronic liver diseases, e.g., metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis.
  2. Research on beneficial bacteria, dietary fibers, probiotics, and prebiotics that could enhance gut microbiota composition, improve digestive and liver function, and boost the immune system.
  3. Studies investigating the molecular pathways through which natural compounds exert their therapeutic effects on the GI tract and the liver, including the modulation of signaling pathways, gene expression, and cellular processes.
  4. Summaries of clinical trials and preclinical evidence that validate the therapeutic potential of natural compounds for GI disorders and chronic liver diseases, along with discussions on safety, efficacy, and dosage considerations.
  5. Studies investigating newly discovered natural compounds and innovative delivery systems designed to enhance the bioavailability and effectiveness of these therapeutic agents.

This Special Issue aims to bridge the gap between traditional medicine and modern molecular science, providing a comprehensive overview of how natural compounds can be harnessed to improve gastrointestinal and liver health.

Dr. Daniela Gabbia
Prof. Dr. Raquel Abalo
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • natural compounds
  • gastrointestinal diseases
  • liver diseases
  • pharmacological potential

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Published Papers (4 papers)

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Research

17 pages, 4206 KiB  
Article
Anti-Steatotic Effect of Opuntia stricta var. dillenii Prickly Pear Extracts on Murine and Human Hepatocytes
by Irene Besné-Eseverri, Jenifer Trepiana, Lina Boutaleb, María Ángeles Martín, Stéphanie Krisa, María Gloria Lobo, M. Pilar Cano and María P. Portillo
Int. J. Mol. Sci. 2025, 26(7), 2864; https://doi.org/10.3390/ijms26072864 - 21 Mar 2025
Viewed by 386
Abstract
Opuntia stricta var. dillenii extracts exhibit anti-oxidative and anti-inflammatory properties, which are of significant interest for the prevention and management of metabolic dysfunction-associated fatty liver disease (MAFLD). The present study is the first to investigate the potential anti-steatotic effect of Opuntia stricta var. [...] Read more.
Opuntia stricta var. dillenii extracts exhibit anti-oxidative and anti-inflammatory properties, which are of significant interest for the prevention and management of metabolic dysfunction-associated fatty liver disease (MAFLD). The present study is the first to investigate the potential anti-steatotic effect of Opuntia stricta var. dillenii extracts. The aim is to evaluate the anti-steatotic effect of extracts from various parts of the plant (whole fruit, peel, pulp, and the industrial by-product, bagasse) in an in vitro model using both murine AML12 and human HepG2 hepatocytes. Results have demonstrated that all tested extracts, including those from the whole fruit, peel, pulp, and bagasse, exert an anti-steatotic effect. In murine hepatocytes, the whole fruit extract at 100 μg/mL and the peel extract at 10 μg/mL presented the highest capacity to reduce PA-induced triglyceride accumulation. In fact, the peel was the most potent extract, preventing lipid accumulation at the lowest dose used. In human HepG2 hepatocytes, the peel, pulp, and bagasse extracts at 100 μg/mL demonstrated the greatest triglyceride reduction, suggesting that the human model is less responsive. Regarding the main mechanism of action, the peel and pulp extracts seem to inhibit de novo lipogenesis. Additionally, the downregulation of the fatty acid transporter CD36 appears to contribute to the prevention of triglyceride accumulation in both extracts. Full article
(This article belongs to the Special Issue Natural Compounds for Counteracting GI and Liver Diseases)
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22 pages, 5040 KiB  
Article
Different Efficacy of Five Soluble Dietary Fibers on Alleviating Loperamide-Induced Constipation in Mice: Influences of Different Structural Features
by Zhiguo Zhang, Buyu Liu, Wei Liu, Xingquan Liu, Chengcheng Zhang, Weiwei Hu and Weicheng Wu
Int. J. Mol. Sci. 2025, 26(3), 1236; https://doi.org/10.3390/ijms26031236 - 31 Jan 2025
Viewed by 1094
Abstract
Different dietary fibers have distinct structures, leading to significant variations in their laxative effects. To explore how these structural differences impact constipation intervention, a 14-day study was conducted on loperamide-induced constipated mice using five dietary fibers: soluble dietary fiber from steamed sweet potato [...] Read more.
Different dietary fibers have distinct structures, leading to significant variations in their laxative effects. To explore how these structural differences impact constipation intervention, a 14-day study was conducted on loperamide-induced constipated mice using five dietary fibers: soluble dietary fiber from steamed sweet potato (SDF-S), oat β-glucan (OB), polydextrose (PD), arabinogalactan (AG), and inulin (IN). The results showed that four fibers, excluding PD, significantly improved gastrointestinal (GI) transit rate (p < 0.05), although PD had the highest fecal moisture, it was significantly different from the lowest IN (p < 0.05). AG and IN resulted in higher 6 h fecal weights compared to other fibers. SDF-S and OB were more effective in modulating serum levels of gastrointestinal hormones. The different monosaccharide compositions and glycosidic bonds of these fibers led to distinct changes in gut microbiota composition and SCFA profiles. Galactose and arabinose in AG were linked to increased abundance of Lachnospiraceae_UCG-006, Bacteroides, and Odoribacter, promoting butyrate fermentation, which is positively correlated with GI transit rate. Glucose in SDF-S, OB, and PD favored acetate fermentation positively correlated with fecal moisture. Fructose in IN encouraged the proliferation of Muribaculaceae_unclassified and Ruminococcus, associated with butyrate fermentation and increased 6 h stool weight, respectively. The β-glycosidic bonds in OB may lead to high butyrate production through the selective proliferation of Lachnospiraceae_unclassified. Minor components like fucose, rhamnose, and ribose were positively correlated with the abundance of Oscillospiraceae_unclassified, Anaerotignum, and Lachnospiraceae_unclassified. In conclusion, the unique monosaccharide compositions and glycosidic bond differences in dietary fibers selectively promote the proliferation of fiber-degrading and butyrate-producing bacteria, resulting in varied effects on constipation relief. Full article
(This article belongs to the Special Issue Natural Compounds for Counteracting GI and Liver Diseases)
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29 pages, 6986 KiB  
Article
A Non-Pharmacological Paradigm Captures the Complexity in the Mechanism of Action of Poliprotect Against Gastroesophageal Reflux Disease and Dyspepsia
by Sara Caterbi, Claudio Buttarini, Stefano Garetto, Isabelle Franco Moscardini, Stefano Ughetto, Angela Guerrini, Elena Panizzi, Cristiano Rumio, Laura Mattioli, Marina Perfumi, Anna Maidecchi, Andrea Cossu, Stanislas Bruley des Varannes, Jaroslaw Regula, Peter Malfertheiner, Claudia Sardi and Jacopo Lucci
Int. J. Mol. Sci. 2025, 26(3), 1181; https://doi.org/10.3390/ijms26031181 - 29 Jan 2025
Viewed by 1578
Abstract
When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of [...] Read more.
When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of endoscopy-negative patients with heartburn and/or epigastric pain or burning. Here, we provide preclinical data describing the mechanism of action of the Poliprotect formulation, a 100% natural, biodegradable, and environmental friendly medical device according to EU 2017/745 and containing UVCB (unknown or variable composition, complex-reaction products, or biological materials) substances of botanical and mineral origin, according to the REACH and European Chemical Agency definitions. Different in vitro assays demonstrated the capability of Poliprotect to adhere to mucus-secreting gastric cells and concomitantly deliver a local barrier with buffering and antioxidant activity. In studies conducted in accordance with systems biology principles, we evaluated the effects of this barrier on human gastric cells exposed to acidic stress. Biological functions identified via Ingenuity Pathway Analysis highlighted the product’s ability to create a microenvironment that supports the mucosal structural and functional integrity, promotes healing, and restores a balanced mucosal inflammatory status. Additionally, transepithelial electrical resistance and an Ussing chamber showed the product’s capability of preserving the integrity of the gastric and esophageal epithelial barriers when exposed to an acid solution. Two in vivo models of erosive gastropathy further highlighted its topical protection against ethanol- and drug-induced mucosal injury. Overall, our findings sustain the feasibility of a paradigm shift in therapeutics R&D by depicting a very innovative and desirable mode of interaction with the human body based on the emerging biophysical, rather than the pharmacological properties of these therapeutic agents. Full article
(This article belongs to the Special Issue Natural Compounds for Counteracting GI and Liver Diseases)
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17 pages, 3998 KiB  
Article
Poliprotect®, a Medical Device Made of Substances, Potently Protects the Human Esophageal Mucosa Challenged by Multiple Agents: Evidence from In Vitro and Ex Vivo Electrophysiological Models
by Mohamad Khalil, Valeria Perniola, Elisa Lanza, Laura Mahdi, Pierluca Sallustio, Valeria Idone, Daniela Semeraro, Maria Mastrodonato, Mario Testini, Jean-Francois Desaphy and Piero Portincasa
Int. J. Mol. Sci. 2025, 26(2), 791; https://doi.org/10.3390/ijms26020791 - 18 Jan 2025
Cited by 1 | Viewed by 1102
Abstract
The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect® (PPRO), a CE-marked [...] Read more.
The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect® (PPRO), a CE-marked medical device, on esophageal epithelial integrity using in vitro and ex vivo models. In vitro, the protective effects of PPRO were tested on Caco-2 cells. PPRO demonstrated safety and protection against oxidative damage induced by hydrogen peroxide. It also preserved epithelial integrity by maintaining transepithelial electrical resistance (TEER) against damage from calcium removal or bile acid exposure (taurodeoxycholic acid, TDCA). Ex vivo, esophageal biopsies from patients subjected to endoscopy were mounted in Ussing chambers and exposed to damaging agents (HCl or HCl + TDCA). Untreated biopsies (control) showed significant loss of epithelial resistance (up to −33%). In contrast, low concentrations of PPRO (50–100 µg/mL) provided strong protection against these damages (p < 0.001), even after 60 min of washing. Histological analysis confirmed the barrier-enhancing effect of PPRO. Overall, PPRO effectively protected the esophageal epithelium from damage in both models, suggesting its potential role in alleviating GERD or GERD-like symptoms by strengthening mucosal barriers and reducing epithelial sensitivity to reflux. Full article
(This article belongs to the Special Issue Natural Compounds for Counteracting GI and Liver Diseases)
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