| Recently, hyperlipidemia and related cardiovascular disease are becoming a major health problem in the human and even in companion animals all over the world. There are many drugs which are used as hypolipidemic commonly known such as: statins, fibrates, ezetimibe and nicotinic acid. However, most of them are expensive and have undesirable side-effects. So there is a need to search other alternative medicine that can provide better safety and efficacy with less toxic and less expensive on a long term usage. The study was conducted to investigate the prevention and cure effect of aspirin eugenol ester(AEE) on hyperlipidemia. 1. The Preventive Effect of AEE on HyperlipidemiaThe experiment was conducted to evaluate the prevention effect of AEE on hyperlipidemia in SD male rats. To construct hyperlipidemia disease model, the rats were fed with high fat diet for six weeks. The drugs were administrated with the rat high fat diet at the same time to investigate the prevention effects. Intragastrical administration of the drug in each rat based on individual weekly body weight once weekly for six weeks, at the dosages of AEE 18, 36 and 54 mg/kg/day as low, medium and high dose respectively. Statin at the dosage of 10 mg/kg/day and CMC-Na at the dosage of 20 mg/kg/day was used as positive and negative control drug, respectively. Significant changes were observed on the levels of blood lipids indexes at the end of experiment. AEE at the dosage of 54 mg/kg/day for six weeks decreased TG, TC and LDL significantly(p<0.01), while statin decreased TC and LDL significantly(p<0.01), however, no effect on TG, which may suggested that AEE had prevention better effect on hyperlipidemia in SD rats than statin. AEE also showed significant change on body weight of rats during experiment which was interesting indicator for effect on obesity. 2. The Cure Effect of AEE on HyperlipidemiaTo investigate the cure effect of AEE on hyperlipidemia, Wistar rats as experimental animals were fed with high fat diet to induce hyperlipidemia for eight weeks. AEE were used in three different doses, and low, medium and high dose were selected as 18, 36 and 54 mg/kg/day, respectively. To compare the effects between AEE and its component, the mole of medium dose of AEE, aspirin, and eugenol is the same, at 0.3067 moles. In the experiment, aspirin and eugenol at the molar ratio 1:1(0.3067 mole) were set also. 0.5% of CMC-Na at the dose of 20 mg/kg was served as the vehicle control drug and the dosage of CMC-Na was close to equal in AEE and aspirin groups. Simvastatin 10 mg/kg was chosen as positive control drug to compare with AEE.The rats were divided in ten groups as blank, model groups and other eight treatment groups(n=10). Blood samples were taken for serum, which was used with conventional pharmacological methods to determine classical pathology biomarkers of hyperlipidemia, including TC, TG, LDL-C and HDL-C indexes. At the end of experiment after administrating the drug for five weeks, commercial assay kits were used and auto analyzer machine was used to measure the biomarkers of hyperlipidemia. There were significant differences in blood lipid indexes between each group.Under the present study conditions, AEE at dose 54 mg/kg/day for five weeks decreased TG, TC, LDL significantly(p<0.01) and increased HDL(p<0.05), while statin at dose 10 mg/kg and aspirin at dose 20 mg/kg decreased TG, TC, LDL significantly(p<0.01) and no increase in HDL. Eugenol at dose 18 mg/kg decreased TC and LDL significantly(p<0.01) and had no effect on TG and HDL. Integration of aspirin and eugenol at dose(20:18) mg/kg decreased TC and LDL significantly(p<0.01) and TG(p<0.05), however, no effect on HDL.Histopathological examinations for liver, stomach and intestine were performed. The results showed obviously changes on hepatic tissues among different groups. All sections from stomach and intestine showed no significant pathological changes. 3. Metabonomics of AEEHyperlipidemia with high blood lipid levels is a major risk factor for cardiovascular disease. In the present study, hyperlipidemia disease was induced by feeding rats with HFD. A sensitive ultra-performance liquid chromatography coupled with quadrupole time-of-flight synaptic high-definition mass spectrometry(UPLC-Q-TOF/MS) method was used for the analysis of plasma. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed to investigate the metabolic changes in rats. Potential biomarkers were detected using S-plot. 22 potential biomarkers in rat plasma for hyperlipidemia were screened out. Furthermore, metabonomic pathway analysis was performed with Met PA. The results revealed that the AEE treatment against hyperlipidemia may involve in regulating the lipid metabolism, amino acid metabolism and energy metabolism.In a conclusion, AEE at the dosage 54 mg/kg/day for six weeks had preventive effect on hyperlipidemia in SD male rats more than simvastatin. There were significant differences in blood lipid indexes throughout the experiment period after administrating the drug for five weeks. The AEE optimal dose for curing hyperlipidemia in Wistar rats was considered to be 54 mg/kg/day for five weeks. The AEE against hyperlipidemia may involve in regulating the lipid metabolism, amino acid metabolism and energy metabolism. |
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