In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry

Yang

et al. 2015

PLoS ONE

Self Cite

Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na). AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5% CMC-Na (30 mg/kg) were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1) was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT). The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP)-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model

Yang

et al. 2015

PLoS ONE

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“…The metabolites of AEE had been confirmed in beagle dog and liver microsomes. AEE could be metabolized into aspirin and eugenol in vitro and in vivo , which could show their original activities and act synergistically [10]. AEE also reduced the side effects of its precursor such as the gastrointestinal damage of aspirin and irritation of eugenol [11].…”

Section: Introductionmentioning

confidence: 99%

Lowering effects of aspirin eugenol ester on blood lipids in rats with high fat diet

Karam¹,

et al. 2016

Lipids Health Dis

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BackgroundAspirin and eugenol were esterified to synthesize aspirin eugenol ester (AEE). As a pale yellow and odourless crystal, AEE reduced the gastrointestinal damage of aspirin and vulnerability of eugenol. The study was conducted to evaluate the preventive effects of AEE on blood lipids in rats with high fat diet (HFD).MethodsSuspensions of AEE and simvastatin were prepared in 5% carboxymethyl cellulose sodium (CMC-Na). In order to observe the intervention effects, the drugs and HFD were administrated at the same time. Based on individual weekly body weight (BW), AEE was intragastrically administrated at the dosage of 18, 36 and 54 mg/kg. Simvastatin (10 mg/kg) and CMC-Na (20 mg/kg) were used as control drug. After 6 weeks of administration, the changes of BW and blood lipid indices including triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol (TCH) were determined in the experiment.ResultsThe rat blood lipids profile in model group was remarkably different after feeding 6-weeks HFD. TG, TCH and LDL indexes in model group were increased significantly compared with those in control group (p < 0.01). AEE at the dosage of 54 mg/kg significantly decreased levels of TG, TCH and LDL (p < 0.01), and slowed the rate of BW gain in comparison with model group (p < 0.05). Moreover, high dose AEE showed better effects than simvastatin on reducing TCH level and similar effects on TG, HDL and LDL.ConclusionAEE could remarkably reduce levels of TG, TCH and LDL in rats with high fat diet, and slow the rate of body weight gain. It was conducted that AEE was a potential candidate on reducing blood lipids level. The mechanism of action of AEE should be investigated in further studies.

“…The acute toxicity of AEE is less than that of ASA and eugenol, only 0.02 times the toxicity of ASA and 0.27 times the toxicity of eugenol in mice [ 17 ]. AEE could be metabolized into ASA and eugenol in vitro and in vivo [ 18 ], and had the effects of anti-inflammation, antipyretic, analgesia, and antioxidant [ 15 , 19 ]. In addition, the previous research indicated that AEE (50 mg · kg −1 and 160 mg · kg −1 ) could reduce the serum TC and TG in rats with standard diet [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Regulation effect of Aspirin Eugenol Ester on blood lipids in Wistar rats with hyperlipidemia

Karam

et al. 2015

BMC Vet Res

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BackgroundAspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with less side effects. The experiment will be conducted to investigate the efficacy of AEE on curing hyperlipidemia in Wistar rats. The rats were fed with high fat diet (HFD) for 8 weeks to induce hyperlipidemia.ResultsCompared with the model group, the results showed that AEE at 54 mg/kg dosage could significantly decrease the hyperlipidemia indexes including triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (p < 0.01), increase high density lipoprotein (HDL) (p < 0.05) for five weeks drug administration. Meanwhile, simvastatin had same effect on hyperlipidemia indexes such as TG, LDL, TC, but no significant increase in HDL.ConclusionAEE was effective against hyperlipidemia and had better anti-hyperlipidemic effect than its component, acetylsalicylic acid (Aspirin, ASA), eugenol and integration of ASA and eugenol. Under the experimental circumstance, the optimal dose of AEE to cure hyperlipidemia is 54 mg/kg for five weeks in Wistar rats.