Du Fen, Gesang Quzhen, Cao Jia, Qian Mei, Ma Li, Wu Dongfang, Yu Hong
Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, 185 Donghu Road, Bldg. 2, 2-209, Wuhan 430071, China.
Medical College, Tibet University, Lhasa 850000, China.
Int J Mol Sci. 2016 Nov 18;17(11):1932. doi: 10.3390/ijms17111932.
Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (), tumor necrosis factor α (), and monocyte chemotactic protein-1 (), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS). ISL also enhanced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and reversed the changes of ATP-binding cassette transporter A (ABCA1) and cluster of differentiation 36 (CD36) in macrophages treated with oxidative low-density lipoprotein (ox-LDL). Then, in an in vivo study, female apoE mice were fed a Western diet with ISL (0, 20, 100 mg/kg/day) added for 12 weeks. We found that ISL decreased the plasma cholesterol levels of very low-density lipoprotein (VLDL)/LDL, promoted plasma superoxide dismutase (SOD) and paraoxonase-1 (PON1) activities, and decreased plasma IL-6, TNF-α, and MCP-1 levels. Moreover, ISL significantly reduced the atherosclerotic lesions and hepatic steatosis in apoE mice. In the liver, ISL altered the expression of several key genes (such as , , , , and ) involving cholesterol-selective uptake and excretion into bile, triglyceride (TG) biosynthesis, and inflammation. These results suggest that the atheroprotective effects of ISL are due to the improvement of lipid metabolism, antioxidation, and anti-inflammation, which involve PPARγ-dependent signaling.
异甘草素（ISL）具有抗氧化和抗炎活性。我们旨在研究ISL对载脂蛋白E缺陷（apoE）小鼠动脉粥样硬化病变发展的影响及其机制。首先，我们确定ISL降低了炎症因子白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）的mRNA水平，同时增加了脂多糖（LPS）处理的腹腔巨噬细胞中几种脂蛋白相关基因的表达。ISL还提高了过氧化物酶体增殖物激活受体γ（PPARγ）蛋白水平，并逆转了氧化型低密度脂蛋白（ox-LDL）处理的巨噬细胞中ATP结合盒转运体A（ABCA1）和分化簇36（CD36）的变化。然后，在一项体内研究中，给雌性apoE小鼠喂食添加了ISL（0、20、100mg/kg/天）的西式饮食12周。我们发现ISL降低了极低密度脂蛋白（VLDL）/低密度脂蛋白（LDL）的血浆胆固醇水平，提高了血浆超氧化物歧化酶（SOD）和对氧磷酶-1（PON1）的活性，并降低了血浆IL-6、TNF-α和MCP-1水平。此外，ISL显著减少了apoE小鼠的动脉粥样硬化病变和肝脂肪变性。在肝脏中，ISL改变了几个关键基因（如 、 、 、 和 ）的表达，这些基因涉及胆固醇选择性摄取和排入胆汁、甘油三酯（TG）生物合成以及炎症。这些结果表明，ISL的抗动脉粥样硬化作用归因于脂质代谢、抗氧化和抗炎的改善，这涉及PPARγ依赖性信号传导。
