{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:15:44Z","timestamp":1790691344216,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Gastric ulcer (GU) is a common gastrointestinal disorder that impacts quality of life. Currently, several drugs are available for GU treatment, including proton pump inhibitors like omeprazole (OMP); however, their use is limited by numerous potential adverse effects. Glycyrrhizic acid (GLY), a natural anti-inflammatory agent, exhibits promising gastroprotective properties; however, its use is likewise limited by numerous potential adverse effects. This study aimed to synthesize GLY nanoparticles (GLY-NPs) to enhance their therapeutic potential and to comparatively evaluate their efficacy against OMP in an ethanol-induced GU in male Wistar rats. GLY-NPs were synthesized via a hydrothermal method and characterized using TEM, XRD, FTIR, and zeta potential analyses. In vivo, GLY-NPs significantly attenuated gastric mucosal damage compared to OMP, as evidenced by macroscopic and histopathological analyses. Biochemical assays revealed that GLY-NPs markedly improved antioxidant defenses by elevating SOD, catalase, and glutathione peroxidase activities while reducing MDA levels, surpassing the effects of OMP. Furthermore, GLY-NPs modulated inflammatory responses by downregulating p38 MAPK, NF-\u03baB, and TNF-\u03b1 expression, concomitant with upregulation of the anti-inflammatory cytokine IL-10. Mechanistic insights indicated that GLY-NPs favorably regulated key signaling pathways implicated in gastric mucosal protection, including suppression of the JAK2\/STAT3 and TGF-\u03b21\/Smad3 pathways, alongside activation of the SIRT1\/FOXO1\/PGC-1\u03b1 axis. In conclusion, these findings indicate that GLY-NPs offer higher gastroprotective effects relative to traditional OMP therapy through comprehensive modulation of oxidative stress, inflammation, and molecular signaling pathways. This study highlights GLY-NPs as a potent nanotherapeutic candidate for the effective management of GU.<\/jats:p>","DOI":"10.3390\/antiox14080990","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T09:43:01Z","timestamp":1755078181000},"page":"990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development of Glycyrrhizic Acid Nanoparticles for Modulating Gastric Ulcer Healing: A Comparative In Vivo Study Targeting Oxidative Stress and Inflammatory Pathways"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4955-5705","authenticated-orcid":false,"given":"Mody","family":"Albalawi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-7247","authenticated-orcid":false,"given":"Sahar","family":"Khateeb","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Biochemistry Division, Department of Chemistry, Faculty of Science, Fayoum University, Fayoum 63514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00535-021-01769-0","article-title":"Evidence-Based Clinical Practice Guidelines for Peptic Ulcer Disease 2020","volume":"56","author":"Kamada","year":"2021","journal-title":"J. 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