Oral phytochemicals as photoprotectants in UVR exposed hairless mice: A study of hesperidin methyl chalcone, phloroglucinol, and syringic acid

Ultraviolet radiation is the primary risk factor for keratinocyte carcinoma. Because of increasing incidence rates, new methods of photoprotection must be explored. Oral supplementation with photoprotective compounds presents a promising alternative. Phytochemical compounds like hesperidin methyl chalcone, phloroglucinol, and syringic acid are particularly of interest because of their antioxidant properties. Our primary outcome was to evaluate the effects of oral phytochemicals on photocarcinogenesis with time until tumour onset as the primary endpoint. A total of 125 hairless C3.Cg-Hr^hr/TifBom Tac mice were randomised to receive tap water supplemented with either 100 mg/kg hesperidin methyl chalcone, phloroglucinol, or syringic acid, 600 mg/kg nicotinamide as a positive control, or no supplementation. The mice were irradiated with 3.5 standard erythema doses thrice weekly to induce photocarcinogenesis. Supplementation with the phytochemicals phloroglucinol and syringic acid and nicotinamide delayed tumour onset from a median of 140 days to 151 (p = 0.036), 157 days (p = 0.02), and 178 (p = 2.7·10⁻⁵), respectively. Phloroglucinol and nicotinamide supplementation reduced tumour number. Nicotinamide increased UV-induced pigmentation and reduced oedema formation, while phloroglucinol supplementation reduced epidermal thickness. These results indicate that oral supplementation with phloroglucinol and syringic acid protects against photocarcinogenesis in hairless mice, but not to the same extent as nicotinamide.