4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1–100 μM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.
Background 4-hexylresorcinol (4HR) has been shown to have anti-oxidant activity similar to that of resveratrol. As resveratrol increases sirtuin (SIRT) activity, 4HR might behave similarly to resveratrol. Method In this study, the expression levels of SIRT1, SIRT3, and SIRT6 were evaluated after 4HR administration (1–100 μM). As NAD+ is a substrate for SIRTs, its levels with SIRT activity were also studied. Results In the results, SIRT3 (100 μM at 24 h) and SIRT6 (1–100 μM at 24 h and 10 μM at 8 h) were shown to have significantly higher expression levels compared to untreated control (p < 0.05). Pan-SIRT activity and the NAD+ level was significantly increased compared to that of the untreated control (p < 0.05; 10 and 100 μM at 24 h). Conclusion 4HR administration increased SIRT activity and the NAD+ level in Saos-2 cells.
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