Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non-alcoholic fatty liver disease model.
Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non-alcoholic fatty liver disease model.
复制标题
大叶冬青中的粗三萜皂苷通过激活 AMPK 抑制 SREBP 表达，改善非酒精性脂肪肝模型中的脂质积累
DOI：
10.1186/s13020-015-0054-9
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发表时间：
2015
期刊：
影响因子：
4.9
通讯作者：
Ye WC
中科院分区：
文献类型：
--
作者：
Feng RB;Fan CL;Liu Q;Liu Z;Zhang W;Li YL;Tang W;Wang Y;Li MM;Ye WC
大叶冬青(Da叶冬青）用于减肥和抗糖尿病作用。本研究旨在探讨毛冬青三萜皂苷（CTS）的有益作用及其可能的作用机制。在高脂饮食（HFD）诱导的非酒精性脂肪性肝病（NAFLD）的小鼠模型中，观察到大叶冬青的抗氧化活性。将雄性C57 BL/6小鼠（n = 50）随机分为5组（每组n = 10）：对照组、HFD组、辛伐他汀组（10 mg/kg/天）和两个CTS治疗组（100和200 mg/kg/天）。除对照组外，所有小鼠均喂食HFD 4周。给药组动物分别口服辛伐他汀或CTS 8周。进行口服葡萄糖耐量试验和胰岛素耐量试验。在治疗结束时，使用商业测试试剂盒测量血浆脂质水平和肝脏中的氧化参数。Western blotting检测CTS是否诱导AMP活化蛋白激酶（AMPK）和乙酰辅酶A羧化酶的活化，定量PCR检测转录因子及其靶基因的表达。与HFD组相比，CTS（200 mg/kg/天）治疗组的血脂参数明显降低（甘油三酯、总胆固醇和低密度脂蛋白胆固醇分别为P < 0.001、P = 0.018和P = 0.005），并改善胰岛素抵抗（P = 0.006）。CTS（100和200 mg/kg/天）补充还通过降低丙二醛含量（分别为P < 0.001和P < 0.001）和恢复天冬氨酸转氨酶水平（分别为P <0.001和P < 0.001）降低肝脏脂质并保护肝脏免受氧化应激。此外，CTS（200 mg/kg/天）通过增强AMPK磷酸化和抑制固醇调节元件结合蛋白（SREBP）及其靶基因SREBP-1c、SREBP-2、脂肪酸合成酶和硬脂酰辅酶A去饱和酶的表达来减少脂质蓄积（分别为P = 0.013、P = 0.007、P = 0.011和P = 0.014）。我的CTS大叶黄杨改善HFD喂养小鼠的胰岛素抵抗和肝损伤，并通过激活AMPK和抑制SREBPs及其一些靶分子的基因表达来减轻NAFLD。
Ilex latifolia Thunb. (Da Ye Dong Qing) is used for weight loss and for its antidiabetic effects. This study aims to investigate the beneficial effects and potential mechanisms of action of crude triterpenoid saponins (CTS) from I. latifolia in a mouse model of high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6 mice (n = 50), were arbitrarily divided into five groups (n = 10 in each group): a control group, HFD group, simvastatin group (10 mg/kg/day), and two CTS treatment groups (100 and 200 mg/kg/day). All mice except those in the control group were fed an HFD for 4 weeks. Animals in the treatment groups were orally administered simvastatin or CTS for 8 weeks. Oral glucose tolerance tests and insulin tolerance tests were performed. At the end of treatment, plasma lipid levels, and oxidative parameters in the liver were measured using commercial test kits. Western blotting was used to evaluate whether CTS induced AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase activation, and the expression of transcription factors and their target genes was evaluated in a quantitative PCR assay. Compared with the HFD group, the CTS (200 mg/kg/day) treatment group showed significantly decreased plasma lipid parameters (P < 0.001, P = 0.018, and P = 0.005 for triglycerides, total cholesterol and low-density lipoprotein cholesterol, respectively), and improved insulin resistance (P = 0.006). CTS (100 and 200 mg/kg/day) supplementation also reduced hepatic lipids and protected the liver from oxidative stress by attenuating malondialdehyde content (P < 0.001 and P < 0.001, respectively) and restoring aspartate aminotransferase levels (P < 0.001 and P < 0.001, respectively). Moreover, CTS (200 mg/kg/day) reduced lipid accumulation by enhancing AMPK phosphorylation and inhibiting expression of sterol regulatory element-binding proteins (SREBPs) and their target genes SREBP-1c, SREBP-2, fatty acid synthase, and stearoyl-CoA desaturase (P = 0.013, P = 0.007, P = 0.011, and P = 0.014, respectively). CTS from I. latifolia improved insulin resistance and liver injury in HFD-fed mice, and attenuated NAFLD via the activation of AMPK and inhibition of the gene expression of SREBPs and some of their target molecules.