Epigenetic Potential of Melatonin in Preventing Malignant Transformation of Oral lichen Planus: A Randomized Clinical Trial

Introduction and Aim Oral lichen planus (OLP) is a chronic inflammatory disorder with a known risk of malignant transformation, often linked to epigenetic changes like DNA hypermethylation. This study aimed to evaluate the epigenetic potential of melatonin in preventing the malignant transformation of OLP. Methods A randomized clinical trial was conducted on 50 patients with OLP. Patients were assigned to either a control group, which received conventional treatment with topical corticosteroids and antifungals, or a test group, which received melatonin for 8 weeks. All patients were assessed for DNA hypermethylation levels of the ZNF582 gene. Epigenetic evaluations were conducted before and after the 8‐week treatment period. Results A notable reduction in the methylation index (MI) was observed in the melatonin group ( p = 0.001). Furthermore, only the melatonin group showed a significant intragroup change in MI before and after treatment ( p = 0.011). Conclusion When combined with conventional therapy, melatonin may help prevent the malignant transformation of OLP by reducing DNA hypermethylation of the ZNF582 gene in a period of 8 weeks. Trial Registration: ClinicalTrials.gov number: NCT06533033