Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways
Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways
复制标题
京尼平苷通过调节 Nrf2/AMPK/mTOR 信号通路缓解非酒精性脂肪肝
DOI：
10.1111/jcmm.15139
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发表时间：
2020-04-15
影响因子：
5.3
通讯作者：
Liu, Guowen
中科院分区：
文献类型：
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作者：
Shen, Bingyu;Feng, Haihua;Liu, Guowen
非酒精性脂肪性肝病（NAFLD）是一种常见的严重肝损害疾病。栀子苷（Geniposide，GEN）是从栀子果实中提取的一种环烯醚萜苷类化合物，具有抗细胞损伤、抗神经退行性疾病等多种生物学作用。与对照组相比，泰洛沙泊诱导的肝脏和油酸（OA）与棕榈酸（PA）诱导的HepG 2细胞中脂质积累明显，而GEN改善了增加的条件。GEN通过激活核因子红细胞2相关因子2（Nrf 2），降低总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、极低密度脂蛋白（VLDL）、髓过氧化物酶（MPO）、活性氧（ROS），升高高密度脂蛋白（HDL）、超氧化物歧化酶（SOD），血红素加氧酶（HO）-1和过氧化物酶体增殖物激活受体（PPAR）α可能影响小鼠和细胞中腺苷5 '-单磷酸激活蛋白激酶（AMPK）信号通路的磷酸化。GEN通过抑制磷脂酰肌醇3-激酶（PI 3 K）的表达，显著降低Nrf 2（-/-）小鼠脑组织中固醇调节元件结合蛋白（SREBP）-1c、雷帕霉素复合物磷酸化（P）-机制靶点（mTORC）、P-S6 K、P-S6和高迁移率族蛋白（HMGB）1的含量，并使其完全消失。本研究首次证实GEN通过上调Nrf 2/HO-1和AMPK信号通路的蛋白表达，抑制mTORC及其相关蛋白的磷酸化，增强抗氧化应激和抗炎能力，从而对脂质蓄积起到保护作用。
Non-alcohol fatty liver disease (NAFLD) is a common disease which causes serious liver damage. Geniposide (GEN), a kind of iridoid glycoside extracted from Gardenia jasminoides fruit, has many biological effects, such as resistance to cell damage and anti-neurodegenerative disorder. Lipid accumulation was obvious in tyloxapol-induced liver and oil acid (OA) with palmitic acid (PA)-induced HepG2 cells compared with the control groups while GEN improved the increasing conditions. GEN significantly lessened the total cholesterol (TC), the triglyceride (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), myeloperoxidase (MPO), reactive oxygen species (ROS) and increased high-density lipoprotein (HDL), superoxide dismutase (SOD) to response the oxidative stress via activating nuclear factor erythroid-2-related factor 2 (Nrf2), haeme oxygenase (HO)-1 and peroxisome proliferator-activated receptor (PPAR)alpha which may influence the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathway in mice and cells. Additionally, GEN evidently decreased the contents of sterol regulatory element-binding proteins (SREBP)-1c, phosphorylation (P)-mechanistic target of rapamycin complex (mTORC), P-S6K, P-S6 and high mobility group protein (HMGB) 1 via inhibiting the expression of phosphoinositide 3-kinase (PI3K), and these were totally abrogated in Nrf2(-/-) mice. Our study firstly proved the protective effect of GEN on lipid accumulation via enhancing the ability of antioxidative stress and anti-inflammation which were mostly depend on up-regulating the protein expression of Nrf2/HO-1 and AMPK signalling pathways, thereby suppressed the phosphorylation of mTORC and its related protein.