Herbal Phytochemicals as Molecular Modulators of Oral Submucous Fibrosis: A Narrative Review of Mechanisms, Clinical Evidence, and Priorities for South Asian Research

Abstract

Oral submucous fibrosis (OSF) is a chronic, potentially malignant disorder driven mainly by areca nut chewing, common across South Asia, including Pakistan. Research has increasingly mapped the molecular pathways underlying OSF, while a growing body of work has tested plant-derived compounds such as curcumin, lycopene, EGCG and astaxanthin against these same targets. The objective of this study was to bring together the molecular pathogenesis of OSF and the phytochemical approach to treatment, matching compounds to molecular targets with attention to research gaps in Pakistan and other high-burden settings. Review of literature was conducted on studies published between 2012 and 2026 using PubMed, Google Scholar, and ScienceDirect, focusing on molecular mechanism studies, randomised controlled trials, and reviews addressing herbal or nutraceutical compounds in OSF. Curcumin, lycopene, EGCG and astaxanthin produce measurable clinical benefit in OSF through suppression of TGF-β1/Smad signalling, reduced CTGF, and antioxidant activity. Key gaps remain; most trials measure symptoms rather than molecular endpoints, bioavailability is a practical barrier, and oral microbial dysbiosis in OSF is largely untouched by phytochemical research. Locally conducted research accounting for the genetic and exposure profile of Pakistani patients represents a clear and timely priority.