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莰烯,一种植物来源的单萜烯,可降低高脂血症大鼠的血浆胆固醇和甘油三酯,而不依赖于 HMG-CoA 还原酶活性。

Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity.

机构信息

Department of Genetics, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

PLoS One. 2011;6(11):e20516. doi: 10.1371/journal.pone.0020516. Epub 2011 Nov 3.

Abstract

BACKGROUND

Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO).

METHODOLOGY/PRINCIPAL FINDINGS: The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins.

CONCLUSIONS

Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent and merits further evaluation.

摘要

背景

冠心病的病理学核心是胆固醇和甘油三酯等脂质在内皮的动脉血管中的积累。寻找治疗血脂异常的药物仍然是制药的主要焦点。在这项研究中,我们评估了奇欧乳香树胶(MGO)精油的降血脂特性。

方法/主要发现:在初发和易患去污剂诱导的高脂血症的大鼠中,研究了 MGO 的降血脂作用。使用商业试剂盒测定血清胆固醇和甘油三酯。用放射性测定法测定 HepG2 细胞提取物中的 HMG-CoA(3-羟基-3-甲基戊二酰辅酶 A)还原酶活性;用气相色谱法评估细胞内胆固醇和胆固醇酯。MGO 给药于初发大鼠导致血清胆固醇和甘油三酯的组成性合成呈剂量依赖性降低。在高脂血症大鼠中,MGO 治疗也具有很强的降血脂作用。通过测试 MGO 的各种成分,我们首次表明降血脂作用与莰烯有关。在高脂血症大鼠中,以 30μg/gr 体重的剂量给予莰烯可使总胆固醇降低 54.5%(p<0.001),LDL-胆固醇降低 54%(p<0.001),甘油三酯降低 34.5%(p<0.001)。用莰烯处理 HepG2 细胞可使细胞内胆固醇含量降低到与已知的 HMG-CoA 还原酶抑制剂洛伐他汀相同的程度。莰烯的降血脂作用独立于 HMG-CoA 还原酶活性,表明其降胆固醇和降甘油三酯作用与他汀类药物的作用机制不同。

结论

鉴于控制高血脂在心血管疾病中的关键作用,我们的研究结果为将莰烯用作替代降脂剂提供了新的见解,并值得进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4bb/3207810/c0732a9a6489/pone.0020516.g001.jpg

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