{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:44:14Z","timestamp":1788867854314,"version":"build-2803163510"},"reference-count":98,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Innovative treatment strategies are required for stomach ulcers because of their multifactorial nature. Nanotechnology has emerged as a promising and transformative platform for the formulation and targeted delivery of therapeutic agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>The gastroprotective potential of both in its free form and encapsulated in calcium alginate beads was evaluated against ethanol-induced gastric ulceration in rats. Phytol-loaded nanoemulsions were incorporated into alginate beads to achieve controlled release. Alginate beads showed a pH-dependent release pattern. The release behavior showed a higher release rate at pH 6.8 than at pH 1.2. Phytol release kinetics followed the Korsmeyer\u2013Peppas model, indicating a release mechanism governed by diffusion and polymer relaxation. Rats were pretreated with Phytol and\/or nano-Phytol at 10 or 20\u2009mg\/kg doses administered one hour before ethanol exposure. Gastric ulcer was induced by administration of EtOH (1\u2009mL\/kg, p.o.) 0.5\u2009h after NG-nitro-L-Arginine Methyl Ester (L-NAME) or Aminoguanidine (AMG) injection. Phytol treatment led to a reduction in ulcer index and severity and improved stomach gross morphology. Also, interleukin-6 (IL-6) gastric contents were reduced, whereas transforming growth factor \u03b2 (TGF-\u03b21) was elevated, and histopathological features were ameliorated. Western blot analysis revealed that nano-Phytol exerted greater inhibitory effects on caspase-3 and Nuclear Factor kappa B (NF-\u03baB) than unformulated Phytol. Interestingly, Phytol\u2019s pharmacological effects on ulcers were enhanced by its nanoformulation in a dose-dependent way without exhibiting any toxicity symptoms. Confocal laser scanning microscopy (CLSM) confirmed significantly improved tissue penetration of nano-Phytol within the stomach layers compared to the Phytol. The Phytol or nano-Phytol gastroprotective effects were modified via the co-administration of L-NAME and AMG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The nano-Phytol formulation significantly enhanced the gastroprotective effect of Phytol against ethanol-induced gastric ulcers, primarily through modulation of the nitric oxide (NO) synthase pathway, suppression of inflammation, and upregulation of the growth factor TGF-\u03b21.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0327368","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T17:31:26Z","timestamp":1752255086000},"page":"e0327368","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phytol nanoemulsions encapsulated alginate hydrogel beads for the protection and management of alcohol-induced gastric ulcer via nitric oxide synthase and NF-\u03baB\/IL-6\/TGF-\u03b2 modulation"],"prefix":"10.1371","volume":"20","author":[{"given":"Tamer I. 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