MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
Administration for Market Regulation of GuangDong Province Key Laboratory of Supervision for Edible Agricultural Products, Shenzhen Centre of Inspection and Testing for Agricultural Products, Shenzhen 518000, GuangDong Province, China.
J Nutr Biochem. 2019 Sep;71:110-121. doi: 10.1016/j.jnutbio.2019.05.015. Epub 2019 Jun 14.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver-related morbidity and mortality disease in the world. However, no effective pharmacological treatment for NAFLD has been found. In this study, we used a high fat diet (HFD)-induced NAFLD model to investigate hepatoprotective effect of apigenin (API) against NAFLD and further explored its potential mechanism. Our results demonstrated that gavage administration of API could mitigate HFD-induced liver injury, enhance insulin sensitivity and markedly reduce lipid accumulation in HFD-fed mice livers. In addition, histological analysis showed that hepatic steatosis and macrophages recruitment in the API treatment group were recovered compared with mice fed with HFD alone. Importantly, API could reverse the HFD-induced activation of the NLRP3 inflammasome, further reduced inflammatory cytokines IL-1β and IL-18 release, accompanied with the inhibition of xanthine oxidase (XO) activity and the reduction of uric acid and reactive oxygen species (ROS) production. The pharmacological role of API was further confirmed using free fatty acid (FFA) induced cell NAFLD model. Taking together, our results demonstrated that API could protect against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation. These protective effects may be partially attributed to the regulation of XO by API, which further modulated NLRP3 inflammasome activation and inflammatory cytokines IL-1β and IL-18 release. Therefore API is a potential therapeutic agent for the prevention of NAFLD.
非酒精性脂肪性肝病（NAFLD）是世界上导致肝相关发病率和死亡率的最常见原因。然而，尚未发现针对 NAFLD 的有效药物治疗方法。在这项研究中，我们使用高脂肪饮食（HFD）诱导的 NAFLD 模型来研究芹菜素（API）对 NAFLD 的保肝作用，并进一步探讨其潜在机制。我们的研究结果表明，API 灌胃给药可减轻 HFD 诱导的肝损伤，增强胰岛素敏感性，并显著减少 HFD 喂养小鼠肝脏中的脂质堆积。此外，组织学分析表明，与单独喂食 HFD 的小鼠相比，API 治疗组的肝脂肪变性和巨噬细胞募集得到恢复。重要的是，API 可逆转 HFD 诱导的 NLRP3 炎性小体的激活，进一步减少炎性细胞因子 IL-1β 和 IL-18 的释放，并伴有黄嘌呤氧化酶（XO）活性的抑制和尿酸和活性氧（ROS）产生的减少。使用游离脂肪酸（FFA）诱导的细胞 NAFLD 模型进一步证实了 API 的药理作用。总之，我们的研究结果表明，API 可通过改善肝脂质堆积和炎症来预防 HFD 诱导的 NAFLD。这些保护作用可能部分归因于 API 对 XO 的调节，进而调节 NLRP3 炎性小体的激活和炎性细胞因子 IL-1β 和 IL-18 的释放。因此，API 是预防 NAFLD 的一种潜在治疗药物。
