Polyphenols as multi-target anti-fibrotic agents in oral submucous fibrosis: a scoping review
Abstract
Abstract Background Oral submucous fibrosis (OSF) is a chronic, potentially malignant fibrotic disorder of the oral mucosa driven by areca-nut arecoline, for which current therapy is palliative, toxic, and non–disease-modifying. Four dietary polyphenols - curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, and quercetin - offer multi-target anti-fibrotic potential, but the evidence remains fragmented. This scoping review maps their mechanistic convergence and translational barriers in OSF. Methods and Materials: Following PRISMA-ScR and JBI guidance, Scopus, Embase, and PubMed/MEDLINE were searched from inception to July 2026 using a Population–Concept–Context framework. Preclinical studies (in vitro, in vivo, ex vivo, in silico) evaluating the four polyphenols against arecoline or its downstream mediators (TGF-β1, thrombin, S1P) were included. Two reviewers screened and charted data independently; findings underwent narrative synthesis. Results Twenty-one studies (2009–2026) were included-EGCG (12), curcumin (6), resveratrol (2), quercetin (1) - overwhelmingly in vitro, with no clinical trial. The polyphenols converged on a shared pro-fibrotic network, intercepting the ROS/HIF-1α/TGF-β1-Smad axis and its CTGF/CCN2 and Egr-1 hubs, while resveratrol uniquely repressed ZEB1 epigenetically. Critically, epithelial–mesenchymal transition (EMT) emerged as the node linking fibrosis to malignant transformation. Low oral bioavailability limited in vivo efficacy, best overcome…
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Evidence Hub reads this as a preprint, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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