Department of Pharmacology, Pharmacy College, Xinxiang Medical University, Xinxiang, Henan, China.
Department of Pathology, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
J Biochem Mol Toxicol. 2020 Jul;34(7):e22497. doi: 10.1002/jbt.22497. Epub 2020 Mar 27.
We investigated the effects of chrysin (CHR) on nonalcoholic fatty liver disease (NAFLD) in mice. The NAFLD mouse model was established using a diet deficient in methionine and choline (MCD). CHR was shown to attenuate MCD-induced hepatic fat accumulation, increase very low-density lipoprotein (VLDL) secretion, and decrease hepatic oxidative stress in NAFLD mice. Inhibition of oxidative stress or direct suppression of protein kinase C (PKC) by CHR significantly reduced PKC activity in the liver, leading to a decrease in inhibitory phosphorylation of hepatocyte nuclear factor 4α (HNF4α). The resulting activation of HNF4α led to induced transcription of apolipoprotein B and VLDL secretion. Together, these results show that CHR effectively ameliorates MCD-induced fatty liver in NAFLD mice by targeting the hepatic oxidative stress/PKC/HNF4α signaling pathway.
我们研究了白杨素（CHR）对非酒精性脂肪性肝病（NAFLD）小鼠的作用。使用蛋氨酸和胆碱缺乏的饮食（MCD）建立了 NAFLD 小鼠模型。结果表明，CHR 可减轻 MCD 诱导的肝脂肪堆积，增加极低密度脂蛋白（VLDL）分泌，并降低 NAFLD 小鼠的肝氧化应激。CHR 抑制氧化应激或直接抑制蛋白激酶 C（PKC）可显著降低肝脏中 PKC 的活性，导致肝细胞核因子 4α（HNF4α）的抑制性磷酸化减少。由此激活的 HNF4α导致载脂蛋白 B 的转录诱导和 VLDL 的分泌。总之，这些结果表明，CHR 通过靶向肝氧化应激/蛋白激酶 C/肝细胞核因子 4α 信号通路有效改善 MCD 诱导的 NAFLD 小鼠的脂肪肝。
