{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T08:24:48Z","timestamp":1784708688561,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-137\/2025-03\/200111"],"award-info":[{"award-number":["451-03-137\/2025-03\/200111"]}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200111"],"award-info":[{"award-number":["451-03-136\/2025-03\/200111"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Encouraged by the traditional use of Cotinus coggygria Scop. (European smoketree) for its anti-inflammatory and antioxidant properties, and considering the limitations of current therapies for recurrent aphthous stomatitis (RAS), we aimed to develop and evaluate a mucoadhesive oral gel containing C. coggygria stem bark extract. Methods: A thermosensitive gel was formulated using Carbopol\u00ae 974P NF and poloxamer 407, enriched with 5% C. coggygria extract (CC gel), and characterized for its organoleptic properties, pH, electrical conductivity, and storage stability over six months. Therapeutic efficacy was assessed in a Wistar albino rat model of chemically induced oral ulcers. Animals were divided into three groups: untreated controls (CTRL), rats treated with gel base (GB), and those treated with CC gel over a 10-day period. Healing progression was monitored macroscopically (ulcer size reduction), biochemically (oxidative stress markers in plasma and tissue), and histologically. Results: The CC gel demonstrated satisfactory physicochemical stability and mucosal compatibility. Moreover, it significantly accelerated ulcer contraction and achieved complete re-epithelialization by day 6. Biochemical analyses revealed reduced TBARS and increased SOD, CAT, and GSH levels in ulcer tissue, indicating enhanced local antioxidant defense. Histological evaluation confirmed early resolution of inflammation, pronounced fibroblast activity, capillary proliferation, and full epithelial regeneration in the CC group, in contrast to delayed healing and persistent inflammatory infiltration in the GB and CTRL groups. Conclusions: These findings indicate that the CC gel has potential as a natural, topical formulation with antioxidant and regenerative properties for RAS, although further studies, including clinical evaluation, are required to confirm its overall efficacy and long-term safety.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101293","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:07:48Z","timestamp":1759417668000},"page":"1293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Oral Gel Formulation of Cotinus coggygria Scop. Stem Bark Extract: Development, Characterization, and Therapeutic Efficacy in a Rat Model of Aphthous Stomatitis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-6085","authenticated-orcid":false,"given":"Jovana","family":"Bradic","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Singidunum University, Danijelova 32, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miona","family":"Vuletic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0071-8376","authenticated-orcid":false,"given":"Vladimir","family":"Jakovljevic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5849-1998","authenticated-orcid":false,"given":"Jasmina","family":"Sretenovic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Zivanovic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1307-6915","authenticated-orcid":false,"given":"Marina","family":"Tomovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Singidunum University, Danijelova 32, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-2637","authenticated-orcid":false,"given":"Jelena","family":"Zivkovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Singidunum University, Danijelova 32, 11000 Belgrade, Serbia"},{"name":"The Institute for the Study of Medicinal Plants \u201cDr. Josif Pan\u010di\u0107\u201d, Tadeu\u0161a Ko\u0161\u0107ukog 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9906-436X","authenticated-orcid":false,"given":"Aleksandar","family":"Kocovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Svetozara Makovi\u0107a 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2111-8943","authenticated-orcid":false,"given":"Nina","family":"Dragicevic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Singidunum University, Danijelova 32, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.2298\/JSC0711045N","article-title":"Chemical Composition, Antibacterial and Antifungal Activity of the Essential Oils of Cotinus coggygria from Serbia","volume":"72","year":"2007","journal-title":"J. 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