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Background: Oral squamous cell carcinoma (OSCC) is a malignant tumor that can rapidly infiltrate the oral epithelial tissue and cause high mortality worldwide because the available therapies are less effective. Chrysanthemum cinerariifolium leaf contains secondary metabolites as anti-inflammatory, antioxidant, anticancer, and antimutagenic.

Aims: The study aimed to analyze the ethanolic extract of C. cinerariifolium leaf in reducing proliferation (Ki-67) and the degree of dysplasia in OSCC rats.

Methods: This study used male Sprague Dawley induced by 7, 12-dimethylbenz (a) anthracene (DMBA) 0.5% and divided into five treatment groups, namely positive control/C+(sick), negative control/C-(healthy), and treatment group induced with DMBA and given extract C. cinerariifolium leaf with successive doses of T1, T2, and T3 (50, 100, and 200 mg/kg bw). The oral epithelium was stained with hematoxylin and eosin and immunohistochemically stained with a Ki-67 monoclonal antibody. The statistical analysis utilizes the one-way analysis of variance test.

Results: The results showed that T1 at a dose of 200 mg/kg bw could significantly reduce Ki-67 expression and the degree of oral epithelial dysplasia (OED; p< 0.05) close to healthy controls.

Conclusion: The conclusion shows that C. cinerariifolium leaf extract can be a therapy against OSCC by decreasing cell proliferation and the degree of OED.