{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:23:56Z","timestamp":1783596236468,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Oral ulcerations are complex pathological lesions with multifactorial etiology and diverse clinical manifestations. Current treatment options are mostly symptomatic with a different adverse effect. Therefore, this study aimed to develop a mucoadhesive oral gel containing Potentilla erecta L. ethanol extract (PEOG) and evaluate its healing effects in a rat model of oral ulceration. Dried rhizomes of Potentilla erecta were extracted with 70% ethanol using ultrasonic extraction, followed by low-pressure evaporation. The extract was incorporated into a gel base composed of poloxamer 407 and carbomer 934. Rheological characterization was performed to assess the viscoelastic and flow properties of the formulation. Therapeutic efficacy was evaluated through macroscopic assessment of ulcer healing, histopathological analysis, and determination of systemic oxidative stress biomarkers. Animals were assigned to three groups: untreated control, gel base (GB), and PEOG-treated. Rats were sacrificed on days 0, 3, 6, and 10 for blood and tissue sampling. PEOG treatment significantly accelerated ulcer healing, resulting in a marked reduction in ulcer size compared with controls. Histopathological findings indicated enhanced collagen deposition, while biochemical analyses suggested attenuation of oxidative stress. These results demonstrate that PEOG possesses considerable ulcer-healing potential and may represent a promising mucoadhesive formulation for the treatment of oral ulcerations.<\/jats:p>","DOI":"10.3390\/gels12070616","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:16:22Z","timestamp":1783592182000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unlocking Potential of Potentilla erecta: Development and Efficacy Evaluation of Oral Mucoadhesive Gel for Oral Ulcers"],"prefix":"10.3390","volume":"12","author":[{"given":"Tamara","family":"Rudic","sequence":"first","affiliation":[{"name":"Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-6085","authenticated-orcid":false,"given":"Jovana","family":"Bradic","sequence":"additional","affiliation":[{"name":"Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 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 the Study of Redox Balance in Cardiovascular and Metabolic Disorders, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, 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":"Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miona","family":"Vuletic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 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, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Petrusic","sequence":"additional","affiliation":[{"name":"Faculty of Management Herceg Novi, University Adriatic, 85348 Herceg Novi, Montenegro"}],"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 the Study of Redox Balance in Cardiovascular and Metabolic Disorders, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Pathophysiology, 1st Moscow State Medical University IM Sechenov, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-7953","authenticated-orcid":false,"given":"Aleksandra","family":"Stojanovic","sequence":"additional","affiliation":[{"name":"Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.coms.2022.10.001","article-title":"Ulcerative and inflammatory lesions of the oral mucosa","volume":"35","author":"Philipone","year":"2023","journal-title":"Oral Maxillofac. Surg. Clin. North Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41368-022-00178-0","article-title":"Difficult and complicated oral ulceration: An expert consensus guideline for diagnosis","volume":"14","author":"Zeng","year":"2022","journal-title":"Int. J. Oral Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, C., Wu, Y., Xie, Y., Zhang, Y., Jiang, S., Wang, J., Luo, X., and Chen, Q. (2022). Oral manifestations serve as potential signs of ulcerative colitis: A review. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1013900"},{"key":"ref_4","first-page":"1155","article-title":"Oral aphthous: Pathophysiology, clinical aspects and medical treatment","volume":"76","author":"Noor","year":"2021","journal-title":"Arch. Razi Inst."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Horvat Aleksijevi\u0107, L., Prpi\u0107, J., Muhvi\u0107 Urek, M., Pezelj-Ribari\u0107, S., Ivan\u010di\u0107-Joki\u0107, N., Per\u0161i\u0107 Bukmir, R., Aleksijevi\u0107, M., and Gla\u017ear, I. (2022). Oral mucosal lesions in childhood. Dent. J., 10.","DOI":"10.3390\/dj10110214"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/ijd.15986","article-title":"Eosinophilic ulcer of the oral mucosa: An update on clinicopathologic features, pathogenesis, and management","volume":"61","author":"Hamie","year":"2022","journal-title":"Int. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12105-018-0981-8","article-title":"Ulcerated lesions of the oral mucosa: Clinical and histologic review","volume":"13","author":"Fitzpatrick","year":"2019","journal-title":"Head Neck Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41415-022-5032-x","article-title":"Recognition and management of drug-associated oral ulceration: A review","volume":"233","author":"Ali","year":"2022","journal-title":"Br. Dent. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Didona, D., Caposiena Caro, R.D., Sequeira Santos, A.M., Solimani, F., and Hertl, M. (2022). Therapeutic strategies for oral lichen planus: State of the art and new insights. Front. Med., 9.","DOI":"10.3389\/fmed.2022.997190"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113412","DOI":"10.1016\/j.jep.2020.113412","article-title":"Recent phytochemical and pharmacological advances in the genus Potentilla L. sensu lato\u2014An update covering the period from 2009 to 2020","volume":"266","author":"Augustynowicz","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Russo, E., and Villa, C. (2019). Poloxamer hydrogels for biomedical applications. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120671"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Batista, D.G., Sganzerla, W.G., da Silva, L.R., Vieira, Y.G.S., Almeida, A.R., Dominguini, D., Ceretta, L., Pinheiro, A.C., Bertoldi, F.C., and Becker, D. (2024). Antimicrobial and cytotoxic potential of Eucalyptus essential oil-based nanoemulsions for mouthwashes application. Antibiotics, 13.","DOI":"10.3390\/antibiotics13100942"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"He, S., and Mu, H. (2023). Microenvironmental pH modification in buccal\/sublingual dosage forms for systemic drug delivery. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020637"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bradic, J., Petrovic, A., Nikolic, M., Nedeljkovic, N., Andjic, M., Baljak, J., Jakovljevic, V., Kocovic, A., Tadic, V., and Stojanovic, A. (2024). Potentilla tormentilla extract loaded gel: Formulation, in vivo and in silico evaluation of anti-inflammatory properties. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179389"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, B., and Chen, K. (2024). Advances in hydrogel-based drug delivery systems. Gels, 10.","DOI":"10.3390\/gels10040262"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pecora, T.M.G., Ragazzo, B., Bertin, W., Ragonese, A., Mascagni, M., Maffei, P., and Pignatello, R. (2021). Rheological behavior of a new mucoadhesive oral formulation based on sodium chondroitin sulfate, xyloglucan and glycerol. J. Funct. Biomater., 12.","DOI":"10.3390\/jfb12020028"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ghasemi, S., Farokhpour, F., Mortezagholi, B., Movahed, E., Ghaedi, A., Gargari, M.K., Khanzadeh, M., Bazrgar, A., and Khanzadeh, S. (2023). Systematic review and meta-analysis of oxidative stress and antioxidant markers in recurrent aphthous stomatitis. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-03636-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.jds.2022.11.016","article-title":"Serum levels of reduced glutathione, oxidized glutathione, and glutathione reductase activity in minor recurrent aphthous stomatitis patients","volume":"18","author":"Zhang","year":"2023","journal-title":"J. Dent. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1080\/14786419.2018.1488704","article-title":"Potentilla erecta (L.) rhizomes as a source of phenolic acids","volume":"33","author":"Sentkowska","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.3390\/molecules15074639","article-title":"Variation in total polyphenolics contents of aerial parts of Potentilla species and their anticariogenic activity","volume":"15","author":"Tomczyk","year":"2010","journal-title":"Molecules"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jep.2008.12.022","article-title":"Potentilla\u2014A review of its phytochemical and pharmacological profile","volume":"122","author":"Tomczyk","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hoffmann, J., Casetti, F., Bullerkotte, U., Haarhaus, B., Vagedes, J., Schempp, C.M., and W\u00f6lfle, U. (2016). Anti-Inflammatory Effects of Agrimoniin-Enriched Fractions of Potentilla erecta. Molecules, 21.","DOI":"10.3390\/molecules21060792"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.foodchem.2010.12.026","article-title":"A critical review of methods for characterisation of polyphenolic compounds in fruits and vegetables","volume":"126","author":"Ignat","year":"2011","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e71259","DOI":"10.1002\/fsn3.71259","article-title":"Antioxidant potential of polyphenolic compounds, sources, extraction, purification and characterization techniques: A focused review","volume":"13","author":"Ahmad","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_25","first-page":"264","article-title":"Phenolic, antioxidant, antimicrobial, and in-vivo wound healing properties of Potentilla erecta L. root extract in diabetic rats","volume":"19","author":"Kaltalioglu","year":"2020","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.foodres.2011.04.027","article-title":"Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health","volume":"44","author":"Landete","year":"2011","journal-title":"Food Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jug, U., Naumoska, K., and Vovk, I. (2021). (\u2212)-Epicatechin\u2014An important contributor to the antioxidant activity of Japanese knotweed rhizome bark extract as determined by antioxidant activity-guided fractionation. Antioxidants, 10.","DOI":"10.3390\/antiox10010133"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.identj.2024.08.003","article-title":"Dietary antioxidant index and the risk of recurrent aphthous stomatitis","volume":"75","author":"Mohseni","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1007\/s11756-022-01217-1","article-title":"The nephroprotective effect of ellagic acid against diclofenac-induced renal injury in male rats: Role of Nrf2\/HO-1 and NF-\u03baB\/TNF-\u03b1 pathways","volume":"77","author":"Namavari","year":"2022","journal-title":"Biologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.fct.2012.02.020","article-title":"Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes","volume":"50","author":"Hseu","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_31","first-page":"1067","article-title":"Wound healing: Future directions","volume":"6","author":"Appleton","year":"2003","journal-title":"iDrugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0002-9440(10)63297-X","article-title":"Effects of epicatechin gallate on wound healing and scar formation in a full thickness incisional wound healing model in rats","volume":"165","author":"Kapoor","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jep.2017.03.058","article-title":"Anti-inflammatory and vasoconstrictive properties of Potentilla erecta\u2014A traditional medicinal plant from the northern hemisphere","volume":"204","author":"Hoffmann","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"289","DOI":"10.21873\/invivo.11474","article-title":"Oxidative stress and oral mucosal diseases: An overview","volume":"33","author":"Sardaro","year":"2019","journal-title":"In Vivo"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, Y., Mei, Y., Zou, R., Niu, L., and Dong, S. (2022). Reactive oxygen species enlightened therapeutic strategy for oral and maxillofacial diseases\u2014Art of destruction and reconstruction. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112905"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dalessandri, D., Zotti, F., Laffranchi, L., Migliorati, M., Isola, G., Bonetti, S., and Visconti, L. (2019). Treatment of recurrent aphthous stomatitis (RAS; aphthae; canker sores) with a barrier forming mouth rinse or topical gel formulation containing hyaluronic acid: A retrospective clinical study. BMC Oral Health, 19.","DOI":"10.1186\/s12903-019-0850-1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/j.1468-3083.2007.02564.x","article-title":"The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: Comparison between recurrent aphthous ulcers and the oral ulcers of Beh\u00e7et\u2019s disease","volume":"22","author":"Lee","year":"2008","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vuleti\u0107, M., Jakovljevi\u0107, V., \u017divanovi\u0107, S., Papi\u0107, M., Papi\u0107, M., Mladenovi\u0107, R., \u017divkovi\u0107, V., Srejovi\u0107, I., Jeremi\u0107, J., and An\u0111i\u0107, M. (2022). The evaluation of healing properties of Galium verum-based oral gel in aphthous stomatitis in rats. Molecules, 27.","DOI":"10.3390\/molecules27154680"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Diaz-Salmeron, R., Toussaint, B., Huang, N., Bourgeois Ducournau, E., Alviset, G., Goulay Dufa\u00ff, S., Hillaireau, H., Dufa\u00ff Wojcicki, A., and Boudy, V. (2021). Mucoadhesive poloxamer-based hydrogels for the release of HP-\u03b2-CD-complexed dexamethasone in the treatment of buccal diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010117"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7394685","DOI":"10.1155\/2016\/7394685","article-title":"Development and evaluation of stability of a gel formulation containing the monoterpene borneol","volume":"2016","author":"Dantas","year":"2016","journal-title":"Sci. World J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Villegas, A., Fern\u00e1ndez-Ochoa, \u00c1., Rojas-Garc\u00eda, A., Ala\u00f1\u00f3n, M.E., Arr\u00e1ez-Rom\u00e1n, D., C\u00e1diz-Gurrea, M.L., and Segura-Carretero, A. (2023). The potential of Mangifera indica L. peel extract to be revalued in cosmetic applications. Antioxidants, 12.","DOI":"10.3390\/antiox12101892"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0378-5173(99)00464-0","article-title":"Determination of optimal combination of surfactants in creams using rheology measurements","volume":"197","author":"Korhonen","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9692","DOI":"10.1038\/s41598-017-08771-8","article-title":"Honey-based hydrogel: In vitro and comparative in vivo evaluation for burn wound healing","volume":"7","author":"Amer","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","first-page":"1","article-title":"Protective effects of Melissa officinalis ethanolic extract on doxorubicin-induced cardiotoxicity in a rat model","volume":"104","year":"2026","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Andji\u0107, M., Bo\u017ein, B., Dragini\u0107, N., Ko\u010dovi\u0107, A., Jeremi\u0107, J.N., Tomovi\u0107, M., Milojevi\u0107 \u0160amanovi\u0107, A., Kladar, N., \u010capo, I., and Jakovljevi\u0107, V. (2021). Formulation and evaluation of Helichrysum italicum essential oil-based topical formulations for wound healing in diabetic rats. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080813"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/7\/616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:47:54Z","timestamp":1783594074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/7\/616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["gels12070616"],"URL":"https:\/\/doi.org\/10.3390\/gels12070616","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]}}}