Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice.
Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice.
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异甘草素可减弱载脂蛋白 E 缺陷小鼠的动脉粥样硬化形成
DOI：
10.3390/ijms17111932
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发表时间：
2016-11-18
影响因子：
5.6
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Du F;Gesang Q;Cao J;Qian M;Ma L;Wu D;Yu H
异甘草素（Isoliquiritigenin，ISL）具有抗氧化和抗炎活性。我们试图研究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和机制。首先，我们确定了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，同时增加了几种脂蛋白相关基因的表达。脂多糖（LPS）处理的腹腔巨噬细胞。ISL还可提高氧化低密度脂蛋白（ox-LDL）处理的巨噬细胞过氧化物酶体增殖物激活受体γ（PPARγ）蛋白水平，逆转ATP结合盒转运体A（ABCA 1）和分化簇36（CD 36）的变化。然后，在一项体内研究中，雌性apoE−/−小鼠喂食添加ISL（0、20、100 mg/kg/天）的西方饮食12周。结果表明，ISL可降低极低密度脂蛋白（VLDL）/LDL的血浆胆固醇水平，提高血浆超氧化物歧化酶（SOD）和对氧磷酶-1（PON 1）活性，降低血浆IL-6、TNF-α和MCP-1水平。此外，ISL显著减少apoE−/−小鼠的动脉粥样硬化病变和肝脏脂肪变性。在肝脏中，ISL改变了几个关键基因（如SRBI、ABCA 1、ABCG 8、PPARγ和FXR）的表达，这些基因涉及胆固醇选择性摄取和排泄到胆汁中、甘油三酯（TG）生物合成和炎症。以上结果提示，ISL的抗动脉粥样硬化作用可能与其改善脂质代谢、抗氧化、抗炎等作用有关，这些作用与PPARγ信号通路有关。
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 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein-1 (MCP-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 SRBI, ABCA1, ABCG8, PPARγ, and FASN) 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.
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影响因子：
5.3
作者：
Fitzgerald ML;Mujawar Z;Tamehiro N
通讯作者：
Tamehiro N
DOI：
10.1161/atvbaha.112.300049
发表时间：
2013-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Maitra U;Li L
通讯作者：
Li L
影响因子：
3.1
作者：
Lin, Juntang;Kakkar, Vijay;Lu, Xinjie
通讯作者：
Lu, Xinjie
影响因子：
82.9
作者：
Chawla, A;Barak, Y;Evans, RM
通讯作者：
Evans, RM
影响因子：
7.4
作者：
Kim, Young Mi;Kim, Tae Hyun;Kim, Sang Geon
通讯作者：
Kim, Sang Geon