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Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico\n                    <jats:italic>,<\/jats:italic>\n                    in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-\u03b21), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-\u03b21, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-\u03b21 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Highlights<\/jats:bold>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-\u03b21 and collagen both in vitro and in vivo<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-\u03b21 and improved mouth opening in OSF rat model.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1007\/s10787-023-01212-1","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T12:01:41Z","timestamp":1682596901000},"page":"2349-2368","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Polyphenol-based targeted therapy for oral submucous fibrosis"],"prefix":"10.1007","volume":"31","author":[{"given":"Chetan Hasmukh","family":"Mehta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivangi","family":"Paliwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjunatha S.","family":"Muttigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raviraja N.","family":"Seetharam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alevoor Srinivas Bharath","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogendra","family":"Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1995-3114","authenticated-orcid":false,"given":"Usha Yogendra","family":"Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"1212_CR1","doi-asserted-by":"publisher","DOI":"10.1111\/JICD.12208","author":"PN Adtani","year":"2017","unstructured":"Adtani PN, Narasimhan M, Punnoose AM, Kambalachenu HR (2017) Antifibrotic effect of Centella asiatica Linn and Asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts. 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Institutional Animal Ethical Committee (IAEC), Kasturba Medical College, MAHE, Manipal, was obtained before the experiments (# IAEC\/KMC\/112\/2018).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}