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Towards Application of Bioactive Natural Products Containing Isoprenoids for the Regulation of hmg-coa Reductase—A Review

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American Journal of Plant Sciences 2013年第5期4卷 1116-1126页

作者： Sepideh Pakpour Department of Biology University of British Columbia Kelowna Canada.

Recognition of the biological properties of numerous “natural products” has fueled the current focus of this field, namely, the search for new drugs, antibiotics, insecticides, and herbicides. Based on their biosynthetic origins, natural products can be divided into three major groups: the isoprenoids, alkaloids, and phenolic compounds. Isoprenoids are structurally the most diverse group of secondary natural metabolites with different roles in the growth, development, and reproduction of a diverse range of prokaryotic and eukaryotes cells. Mevalonate and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathways are known to be responsible for biosynthesis of numerous isoprenoids. hmg-coa reductase is a rate-determining enzyme in mevalonate pathway, producing intermediates such as farnesyl and geranylgeranyl pyrophosphates, which lead to by-products such as cholesterol. Earlier studies have demonstrated that the inhibition of hmg-coa reductase is one of the most effective approaches for treating hypercholesterolemia and eventually cardiovascular disease (CVD). Statins are hmg-coa reductase inhibitors and the most prescribed group of drugs worldwide in treating hypercholesterolemia;however the application of this group of drugs may be expensive and has side effects including rashes and gastrointestinal symptoms. For these reasons, there is an important need to examine the viability of natural products as an alternative to statin treatment. This article is a review of different aforementioned areas with a focus on isoprenoids that can be used for the regulation of hmg-coa reductase.

关键词： Isoprenoids hmg-coa Reductase Mevalonate Pathway Hypercholesterolemia

hmg-coa还原酶抑制剂治疗高胆固醇血症

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中国临床药理学杂志 1990年第3期6卷 151-157页

作者：陆宗良中国医学科学院阜外医院心血管病研究所北京100034

以低密度脂蛋白(LDL)及极低密度脂蛋白(VLDL)残基血清水平升高为特征的高胆固醇血症,是人类早发冠心病(CHD)的主要危险因素之一。设法使高胆固醇血症患者的血清总胆固醇(TC)水平降低,能明显地降低CHD的发病率及死亡率。

关键词： hmg-coa 还原酶抑制剂胆固醇 CHD

Inhibitory roles of protein kinase B and peroxisome proliferator-activated receptor gamma coactivator on hepatic hmg-coa reductase promoter activity

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Advances in Bioscience and Biotechnology 2013年第10期4卷 1-5页

作者： Gene C. Ness Jeffrey L. Edelman Department of Molecular Medicine Morsani College of Medicine University of South Florida Tampa USA

Since we had previously demonstrated that siRNAs to tristetraprolin (TTP) markedly inhibited insulin stimulation of hepatic hmg-coa reductase (hmgR) transcription, we investigated the effects of transfecting rat liver with TTP constructs. We found that transfecting diabetic rats with TTP did not increase hmgR transcription but rather led to modest inhibition. We then investigated whether co-transfection with protein kinase B, hepatic form (AKT2), might lead to phosphorylation and result in activation of hmgR transcription. We found that this treatment resulted in near complete inhibition of transcription. Transfection with peroxisome proliferator-activated receptor g coactivator (PGC-1a) also inhibited hmgR transcription. These results show that although TTP is needed for activation of hmgR transcription, it cannot by itself activate this process. AKT2 and PGC-1a, which mediate the activation of gluconeogenic genes by insulin, exert the opposite effect on hmgR.

关键词： In Vivo Electroporation hmg-coa Reductase Insulin Protein Kinase B Peroxisome Proliferator-Activated Receptor γ coactivator Tristetraprolin

hmg-coa还原酶抑制剂对2型糖尿病病人的血脂影响

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中华内分泌代谢杂志 1997年第4期13卷 229-232页

作者：梁奕铨余斌杰肖亦斌中山医科大学附属第一医院内分泌科

我们观察了羟甲基戊二酰辅酶Ａ（ＨＭＧＣｏＡ）还原酶抑制剂乐瓦停对３１例胆固醇增高的２型糖尿病病人的降胆固醇作用，结果显示每日睡前服乐瓦停２０ｍｇ，３个月后平均降低血清总胆固醇３０．５％、低密度脂蛋白胆固醇２９．８％... 详细信息

我们观察了羟甲基戊二酰辅酶Ａ（ＨＭＧＣｏＡ）还原酶抑制剂乐瓦停对３１例胆固醇增高的２型糖尿病病人的降胆固醇作用，结果显示每日睡前服乐瓦停２０ｍｇ，３个月后平均降低血清总胆固醇３０．５％、低密度脂蛋白胆固醇２９．８％，并对高密度脂蛋白胆固醇降低者有升高其高密度脂蛋白胆固醇的作用；同时也有明显的降低载脂蛋白Ｂ１００（Ｐ＜０．０１）和载脂蛋白ＣＩＩＩ（Ｐ＜０．０５）的作用，但对载脂蛋白ＡＩ与载脂蛋白ＡＩＩ水平无影响。在观察期间未发现对血糖与糖基化血红蛋白Ａ１ｃ有影响，提示在２型糖尿病病人中。

关键词：糖尿病载脂蛋白还原酶抑制剂 hmg-coa

hmg－coa还原酶抑制剂新进展及其临床应用

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华西药学杂志 1996年第3期11卷 168-169页

作者：王利彦李红宝车胜荣青海医学院药理教研究室青海医学院附属医院

ＨＭＧ－ＣＯＡ还原酶抑制剂是近十年内出现的一类新型的降血脂药，发展很快，临床应用疗效好，副作用少，是治疗高脂血症一大进展，很受欢迎。

关键词： hmg-coa 还原酶抑制剂高脂血症

De novo assembly and comparative analysis of root transcriptomes from different varieties of Panax ginseng C. A. Meyer grown in different environments

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Science China(Life Sciences) 2015年第11期58卷 1099-1110页

作者： ZHEN Gang ZHANG Lei DU YaNan YU RenBo LIU XinMin CAO FangRui CHANG Qi DENG Xing Wang XIA Mian HE Hang State Key Laboratory of Protein and Plant Gene Research College of Life Sciences Peking University School of Advanced Agricultural Sciences Peking University Frontier Laboratories of Systems Crop Design Co. Ltd. Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College

Panax ginseng C. A. Meyer is an important traditional herb in eastern Asia. It contains ginsenosides, which are primary bioactive compounds with medicinal properties. Although ginseng has been cultivated since at least the Ming dynasty to increase production, cultivated ginseng has lower quantities of ginsenosides and lower disease resistance than ginseng grown under natural conditions. We extracted root RNA from six varieties of fifth-year P. ginseng cultivars representing four different growth conditions, and performed Illumina paired-end sequencing. In total, 163,165,706 raw reads were obtained and used to generate a de novo transcriptome that consisted of 151,763 contigs(76,336 unigenes), of which 100,648 contigs(66.3%) were successfully annotated. Differential expression analysis revealed that most differentially expressed genes(DEGs) were upregulated(246 out of 258, 95.3%) in ginseng grown under natural conditions compared with that grown under artificial conditions. These DEGs were enriched in gene ontology(GO) terms including response to stimuli and localization. In particular, some key ginsenoside biosynthesis-related genes, including hmg-Co A synthase(hmgS), mevalonate kinase(MVK), and squalene epoxidase(SE), were upregulated in wild-grown ginseng. Moreover, a high proportion of disease resistance-related genes were upregulated in wild-grown ginseng. This study is the first transcriptome analysis to compare wild-grown and cultivated ginseng, and identifies genes that may produce higher ginsenoside content and better disease resistance in the wild; these genes may have the potential to improve cultivated ginseng grown in artificial environments.

关键词：人参皂苷生长条件人工环境转录组品种差异表达基因抗病相关基因 hmg-coa

青钱柳多糖对3T3-L1脂肪细胞CAP、ATGL、FTO和hmg-coa表达的影响

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青钱柳多糖对3T3-L1脂肪细胞CAP、ATGL、FTO和HMG-CoA表达的影响

作者：傅凌韵江西农业大学

学位级别：硕士

在世界范围内，肥胖症已经成为一个主要的公共健康问题，它会导致糖尿病、高血压、心脏疾病以及其他健康问题。这就除了需要更多的临床降脂药物外，还需更多开发具有降脂效用的食品。而青钱柳叶被誉为“神茶”，近年来已有一些研究发现... 详细信息

在世界范围内，肥胖症已经成为一个主要的公共健康问题，它会导致糖尿病、高血压、心脏疾病以及其他健康问题。这就除了需要更多的临床降脂药物外，还需更多开发具有降脂效用的食品。而青钱柳叶被誉为“神茶”，近年来已有一些研究发现具有显著降糖降脂作用。现本文以青钱柳叶中提取纯化出的不同青钱柳多糖组分为研究对象，通过体外试验探讨青钱柳多糖降血脂作用。采用Q-PCR法检测青钱柳多糖各组分对3T3-L1脂肪细胞中的原癌基因c-Cbl相关蛋白(CAP)、甘油三酯脂肪酶(ATGL)和3-羟基-3-甲基戊二酸单酰辅酶A还原酶（hmg-coa）基因表达的影响。采用Western-blot法检测青钱柳多糖不同组分对3T3-L1脂肪细胞中的脂肪量和肥胖相关基因（FTO）、甘油三酯脂肪酶(ATGL)和3-羟基-3-甲基戊二酸单酰辅酶A还原酶（hmg-coa）蛋白表达的影响。主要试验结果如下：（1）通过对脂肪细胞内形成的脂滴进行油红O染色并测定细胞内甘油三酯的含量探讨青钱柳多糖对3T3-L1前脂肪细胞增殖分化影响，结果表明，青钱柳多糖对3T3-L1前体脂肪细胞分化影响较小。（2）基因表达的结果表明，青钱柳多糖作用四天后各组分脂肪细胞中CAPmRNA表达显著提高;青钱柳多糖组分Ⅰ、Ⅱ都能极显著提高3T3-L1前脂肪细胞ATGL mRNA表达水平，青钱柳多糖组分Ⅲ、Ⅳ在作用八天时能显著提高ATGLmRNA表达水平;青钱柳多糖组分Ⅰ能极显著降低3T3-L1前脂肪细胞hmg-coamRN表达水平;青钱柳多糖组分Ⅱ、Ⅲ、Ⅳ在作用四天时都能显著降低3T3-L1前脂肪细胞中hmg-coa mRN表达水平。（3）蛋白表达的结果表明，青钱柳多糖作用四天后，青钱柳多糖组分Ⅰ作用后3T3-L1脂肪细胞中FTO蛋白表达量下降;青钱柳多糖组分Ⅰ和Ⅲ对3T3-L1脂肪细胞作用八天时，FTO蛋白的表达显著或极显著减少;青钱柳多糖各组分都能使ATGL蛋白表达量显著或极显著的提高;随着时间的增加，青钱柳多糖组分Ⅰ各实验组细胞及组分Ⅳ中浓度为30μg/ml时，hmg-coa蛋白表达量显著下降，青钱柳多糖组分Ⅱ和Ⅲ则无统计学上差异，但与空白组相比，青钱柳多糖作用四天和八天后各青钱柳多糖组分实验细胞中hmg-coa蛋白表达显著提高或无统计学上的差异。

关键词：青钱柳多糖 3T3-L1脂肪细胞 FTO ATGL hmg-coa CAP