Silent mating type information regulation 2 homolog 1 (SIRT1) is an important inflammatory regulator, which epigenetically reprograms inflammation by altering the acetylation of NF-κB. Hesperetin, as a common flavonoid, has been proven to have a significant effect on acute inflammatory diseases. However, the detailed molecular mechanism by which hesperetin alleviates inflammatory response and accompanied tissue injury is poorly understood. Our results show that SIRT1 is required for the inhibitory effect of hesperetin on inflammation. Hesperetin suppresses the acetylation of RelA/p65 to reduce NF-κB activity by inducing SIRT1 expression. Mechanistically, hesperetin increases SIRT1 expression through AMPK/CREB pathway. Additionally, the protective effect of hesperetin against LPS/D-GalN-induced hepatitis in mice is also dependent on SIRT1. Our study suggests that hesperetin is an SIRT1 activator and could be potential candidates for the treatments of inflammatory conditions.

沉默交配型信息调节因子2同源物1（SIRT1）是重要的炎症调节因子，通过改变NF-κB的乙酰化，在表观遗传上重编程炎症。橙皮素作为一种常见的类黄酮，已被证明对急性炎症性疾病具有显著作用。但是，人们对橙皮素减轻炎症反应和伴随组织损伤的详细分子机制了解甚少。我们的结果表明，SIRT1是橙皮素对炎症的抑制作用所必需的。橙皮素通过诱导SIRT1表达抑制RelA / p65的乙酰化，从而降低NF-κB活性。机械上，橙皮素通过AMPK / CREB途径增加SIRT1表达。此外，橙皮素对LPS / D-GalN诱导的小鼠肝炎的保护作用也取决于SIRT1。