Abstract
BackgroundCentral 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 FindingsThe 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.ConclusionsGiven 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.
Highlights
High levels of plasma cholesterol and triglycerides are strongly associated with the development of atherosclerosis and coronary heart disease [1,2,3,4] and clinical trials designed to reduce serum cholesterol levels by diet or pharmacological means have shown to lead to a reduction in the incidence of this disease [5]
We report that the hypolipidemic activity of camphene in hepatic cells is mediated via a metabolic process distinctly different than the process of inhibition of HMG-CoA reductase induced by statins
Effect of mastic gum essential oil (MGO) on plasma lipid levels in naıve animals We initially determined whether MGO could affect the lipid contents in the plasma of naıve rats prior to induction of hyperlipidemia
Summary
High levels of plasma cholesterol and triglycerides are strongly associated with the development of atherosclerosis and coronary heart disease [1,2,3,4] and clinical trials designed to reduce serum cholesterol levels by diet or pharmacological means have shown to lead to a reduction in the incidence of this disease [5]. It has been demonstrated that statins are the predominant inhibitors of HMG-CoA reductase [7] the enzyme that catalyzes the rate determining step of cholesterol biosynthesis. These drugs effectively lower LDL-cholesterol in humans [8] and reduce mortality and morbidity from coronary artery disease [9,10,11,12]. Several efforts aim to develop more effective hypolipidemic drugs that originate from natural agents. We evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO)
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