Natural flavonoids in peptic ulcer disease: preclinical evidence for gastroprotection versus healing of established ulcers
5 affiliations
- 1Laboratory of Integrated Cancer Research, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca
- 2Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca
- 3Laboratory of Health, Environment and Biotechnology, Team of Physiopathology, Molecular Genetics and Biotechnology, Faculty of Sciences Ain Chock, Hassan II University of Casablanca
- 4Department of Cellular and Molecular Biology, Institute of Biosciences, São Paulo State University (Unesp)
- 5Higher Institute of Nursing Professions and Health Techniques
Abstract
Peptic ulcer disease (PUD) is a global health concern with a lifetime prevalence of 5%–10%. Current therapies may be limited by adverse effects and the increasing prevalence of drug-resistant Helicobacter pylori strains, highlighting the need for safer complementary approaches. Natural flavonoids have emerged as candidate bioactive compounds with gastroprotective properties in preclinical models. This systematic review, conducted according to PRISMA 2020, summarizes preclinical evidence published between 2020 and 2025 on the gastroprotective (preventive) and ulcer-healing effects of isolated and chemically characterized flavonoids. PubMed, Scopus, and ScienceDirect were searched, and eligible studies were restricted to in vitro and/or in vivo experimental investigations. Fourteen studies were included, and their risk of bias was assessed using the SYRCLE and ToxRTool tools. Gastric injury was induced mainly by ethanol, indomethacin, aspirin, or acetic acid in rats and mice, complemented by two gastric cell models. Seven of the 13 in vivo studies used preventive protocols, whereas only four evaluated the healing of established ulcers; the remaining studies used concurrent, post-injury, or mixed protocols. Quercetin (three studies), apigenin, and myricetin (two studies each) were the most frequently investigated, whereas luteolin, naringenin, acacetin, rhamnetin, fisetin, genistein, and malvidin were each evaluated in a single study. These compounds were associated with reduced mucosal damage and with changes in markers of oxidative stress, inflammation, apoptosis, and mucosal defense; potential anti- H. pylori mechanisms are discussed on the basis of previous reviews. Overall, the available evidence supports gastroprotective activity of natural flavonoids in preclinical models, whereas evidence for ulcer healing remains limited. Most studies were rated as having an unclear risk of bias, and differences in models, doses, treatment timing, and bioavailability limit direct comparison between compounds. These preclinical findings cannot be considered evidence of clinical efficacy, and pharmacokinetic, safety, and well-designed clinical studies are required before any therapeutic use in PUD can be considered.
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BibTeX
@article{segmani2026natural,
title = {{Natural flavonoids in peptic ulcer disease: preclinical evidence for gastroprotection versus healing of established ulcers}},
author = {Ibtihal Segmani and Fatima Mourabiti and Houda Filali and Imane Rahmoune and Ariane Leite Rozza and Mohammed Dalli},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1950919},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1950919/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Natural flavonoids in peptic ulcer disease: preclinical evidence for gastroprotection versus healing of established ulcers
AU - Ibtihal Segmani
AU - Fatima Mourabiti
AU - Houda Filali
AU - Imane Rahmoune
AU - Ariane Leite Rozza
AU - Mohammed Dalli
PY - 2026
DA - 2026/10/28
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1950919
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1950919/full
AB - Peptic ulcer disease (PUD) is a global health concern with a lifetime prevalence of 5%–10%. Current therapies may be limited by adverse effects and the increasing prevalence of drug-resistant Helicobacter pylori strains, highlighting the need for safer complementary approaches. Natural flavonoids have emerged as candidate bioactive compounds with gastroprotective properties in preclinical models. This systematic review, conducted according to PRISMA 2020, summarizes preclinical evidence published between 2020 and 2025 on the gastroprotective (preventive) and ulcer-healing effects of isolated and chemically characterized flavonoids. PubMed, Scopus, and ScienceDirect were searched, and eligible studies were restricted to in vitro and/or in vivo experimental investigations. Fourteen studies were included, and their risk of bias was assessed using the SYRCLE and ToxRTool tools. Gastric injury was induced mainly by ethanol, indomethacin, aspirin, or acetic acid in rats and mice, complemented by two gastric cell models. Seven of the 13 in vivo studies used preventive protocols, whereas only four evaluated the healing of established ulcers; the remaining studies used concurrent, post-injury, or mixed protocols. Quercetin (three studies), apigenin, and myricetin (two studies each) were the most frequently investigated, whereas luteolin, naringenin, acacetin, rhamnetin, fisetin, genistein, and malvidin were each evaluated in a single study. These compounds were associated with reduced mucosal damage and with changes in markers of oxidative stress, inflammation, apoptosis, and mucosal defense; potential anti- H. pylori mechanisms are discussed on the basis of previous reviews. Overall, the available evidence supports gastroprotective activity of natural flavonoids in preclinical models, whereas evidence for ulcer healing remains limited. Most studies were rated as having an unclear risk of bias, and differences in models, doses, treatment timing, and bioavailability limit direct comparison between compounds. These preclinical findings cannot be considered evidence of clinical efficacy, and pharmacokinetic, safety, and well-designed clinical studies are required before any therapeutic use in PUD can be considered.
SN - 1663-9812
ER -