The Phytochemical Profile of Areca Nut and Its Role in Oral Potentially Malignant Disorders and Oral Carcinogenesis: A Review

Areca nut (Areca catechu) remains one of the most widely consumed psychoactive substances in South and Southeast Asia, deeply entrenched in cultural and social traditions. Despite its historical significance, chronic exposure is associated with severe deleterious consequences on oral health, as classified by the International Agency for Research on Cancer. This review explores the complex phytochemical profile of the areca nut and its role in the pathogenesis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). The biological impact is driven by a synergistic interaction between pyridine-derived alkaloids, such as arecoline, and polyphenolic tannins, which disrupt the extracellular matrix by promoting fibroblast proliferation and inhibiting collagen degradation. Furthermore, high concentrations of soluble copper act as a biochemical catalyst for lysyl oxidase, accelerating mucosal rigidity in oral submucous fibrosis (OSF). On a molecular level, carcinogenesis is facilitated through the formation of DNA adducts, chronic oxidative stress, and the induction of the epithelial-mesenchymal transition (EMT) within a hypoxic microenvironment. These processes culminate in invasive malignancy, characterised by characteristic anatomical distributions in the oral cavity. Given the high malignant transformation rates of areca-induced lesions, this review emphasises the urgent need for a paradigm shift in public health strategies, integrating advanced molecular diagnostics with culturally empathetic cessation programs and proactive clinical surveillance to mitigate this global cancer burden.