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作 者:吴崇明[1] 栾红[1] 王帅[1] 张小坡[2] 刘海涛[1] 郭鹏[1]
机构地区:[1]中国医学科学院药用植物研究所,北京100094 [2]海南医学院药学院,海南海口571101
出 处:《药学学报》2015年第3期278-283,共6页Acta Pharmaceutica Sinica
基 金:国家自然科学基金资助项目(81402983);北京市自然科学基金资助项目(7102111)
摘 要:前期研究证明,露兜树(Pandanus tectorius Soland.)的果实露兜簕富含咖啡酰奎宁酸类成分并具有显著降血脂作用。为探究露兜簕发挥降脂作用的有效成分和潜在机制,用油酸诱导的Hep G2肝癌细胞脂质积聚模型对7种露兜簕来源的咖啡酰奎宁酸类成分进行了筛选。结果显示,3-咖啡酰奎宁酸(3-CQA)、3,5-二咖啡酰奎宁酸(3,5-CQA)和3,4,5-三咖啡酰奎宁酸(3,4,5-CQA)可显著降低Hep G2肝细胞脂质积聚和细胞内总胆固醇和甘油三酯水平,并且无显著细胞毒性。实时定量PCR结果表明,这三种咖啡酰奎宁酸化合物能够显著抑制脂质合成相关基因的表达,同时3-CQA和3,5-CQA还可显著提高脂质氧化相关基因的表达。结果提示,3-CQA、3,5-CQA和3,4,5-CQA可能是露兜簕发挥降脂作用的主要活性成分,它们可以通过调节脂代谢相关基因的表达发挥降脂活性。The fruit of Pandanus tectorius (PTF) has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province, South China. Our previous studies have shown that the n-butanol extract of PTF is rich in caffeoylquinic acids and has an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet. In this work, seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity in HepG2 hepatoma cells. Oil-Red O staining, microscopy and intracellular triglyceride (TG) and total cholesterol (TC) quantification showed that 3-O-caffeoylquinic acid (3-CQA), 3, 5-di-O-caffeoylquinic acid (3,5-CQA), and 3,4, 5-tri-O-caffeoylquinic acid (3, 4, 5-CQA) significantly inhibited lipid accumulation induced by oleic acid and decreased intracellular levels of TC and TG in a dose-dependent manner. These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1-50 μmol·L^-1 as determined by MTT assay. Realtime quantitative PCR revealed that 3-CQA and 3, 5-CQA significantly increased the expression of lipid oxidation-related genes PPARa, CPT-1 and ACOXI while 3-CQA, 3, 5-CQA and 3,4,5-CQA decreased the expression of lipogenic genes SREBP-1c, SREBP-2, HMGR, ACC, FAS. Overall, 3-CQA, 3, 5-CQA and 3, 4, 5-CQA may be the principal hypolipidemic components in PTF which can decrease intracellular lipid accumulation through up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.
分 类 号:R963[医药卫生—微生物与生化药学]
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