Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes

Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7–9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably.     

Olive tree wood phenolic compounds with human platelet antiaggregant properties

Oleuropein and (+)-cycloolivil are natural polyphenolic compounds with a significant radical scavenging activity present in olive tree. We have investigated the antiaggregant effects of oleuropein and (+)-cycloolivil isolated from an ethyl acetate extract of olive tree wood. Oleuropein and (+)-cycloolivil reduced the ability of thrombin to stimulate platelet aggregation. Both compounds reduced thrombin-evoked Ca²⁺ release and entry to a similar extent to hydroxytyrosol. This effect was greater in platelets from patients with type 2 diabetes mellitus than in controls. Thrombin-, thapsigargin- and 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ)-evoked protein tyrosine phosphorylation, which is involved in Ca²⁺ signalling and platelet aggregation, is inhibited by oleuropein and (+)-cycloolivil. oleuropein and (+)-cycloolivil are natural oxygen radical scavengers that reduce thrombin-induced protein tyrosine phosphorylation, Ca²⁺ signalling and platelet aggregation. These observations suggest that oleuropein and (+)-cycloolivil may prevent thrombotic complications associated to platelet hyperaggregability and be the base for the development of antiaggregant therapeutic strategies.     

橄榄苦苷在大鼠体内药代动力学研究

目的 建立测定大鼠血浆中橄榄苦苷浓度的HPLC方法,研究橄榄苦苷在大鼠体内的药代动力学过程.方法 雄性Wistar大鼠,灌胃给予橄榄苦苷100 mg·kg-1,于不同时间点收集血液.以甲醇-水-甲酸( 63:37:1)为流动相,Agi-lent C18为色谱柱,在紫外波长276 nm下检测,应用药代动力学软件3p97拟合房室模型,并进行药代动力学参数的计算.结果 选定条件下橄榄苦苷峰形良好,线性范围为0.052～0.263 mg/ml,日内日间精密度RSD均小于3％,准确度RE为-0.190％,加样回收率为96.900％ ～ 102.700％.大鼠灌胃橄榄苦苷100 mg·kg-1后,体内药代动力学过程符合二室模型,Tmax为5.440 h,t1/2(α)为2.164 h,t1/2(β)为35.292 h,Cmax为0.113 μg/μl,AUC为6.254,CL为15.990.结论 该方法灵敏,简便,选择性强,适用于橄榄苦苷血药浓度的测定,及其药代动力学研究.     

Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity.     

RP-HPLC测定不同来源油橄榄叶中的橄榄苦苷

目的采用HPLC法测定橄榄叶中橄榄苦苷的含量。方法采用SHIM-PACK VP-ODS色谱柱(150 mm×4.6 mm,5μm),流动相为乙腈-水(22:78),柱温30℃,流速1 ml.min-1,检测波长282 nm。结果橄榄苦苷的标准曲线为:Y=3.125×106X 179.37(r=0.9997,n=5),1~10μg线性关系良好,平均回收率98.7%,RSD=1.39%。四川达州栽培的不同品种不同生长年限的橄榄叶中橄榄苦苷的含量为1.86%~8.25%,一年生的橄榄叶中橄榄苦苷较两年生者高。结论所建方法稳定、可靠,可用于橄榄叶的质量控制。     

Hypoglycemic,hypolipidemic and antiatherogenic effects of oleuropein in alloxan-induced Type 1 diabetic rats

ObjectiveTo assess effect of oleuropein on hemoglobin A1C, serum glucose, lipid profile and atherogenic index in alloxan-induced Type 1 diabetic rats.MethodsThirty Sprage-Dawley male rats were divided into three groups randomly; group one as control, group two diabetic untreatment, and group three treatments with oleuropein by 15 mg/kg i.p. daily, respectively. Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of hemoglobin A1C, fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein, high density lipoprotein and atherogenic index of all groups were analyzed.ResultsOleuropein significantly decreased hemoglobin A1C, fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein. High density lipoprotein level was significantly increased when treated with oleuropein.ConclusionsThe findings of the present study suggest that oleuropein exert beneficial effects on serum glucose, hemoglobin A1C, lipid profile and atherogenic index in alloxan-induced Type 1 diabetic rats.     

Olea europaea leaf extract exerts L-type Ca(2+) channel antagonistic effects

Ethnopharmacological relevance

In Southern Europe Olea europaea leafs are known as a folk remedy for hypertension. Cardiovascular diseases are still the leading causes of morbidity and mortality in industrialized countries with hypertension being one of the main risk factors.

Aim of the study

We investigated effects of a commercial Olea europaea leaf extract (OLE) on isolated hearts and cultured cardiomyocytes.

Materials and methods

Isolated rabbit hearts were perfused according to the Langendorff technique and connected to a 256-channel epicardial mapping system. Voltage clamp experiments were performed in cultured neonatal rat cardiomyocytes using a perforated-patch technique.

Results

OLE caused a concentration-depended decrease in systolic left ventricular pressure and heart rate as well as an increase in relative coronary flow and a slight, but not significant prolongation of PQ-time. There were no significant changes between the groups in the activation-recovery interval and its dispersion, total activation time, peak-to-peak amplitude, percentage of identical breakthrough-points and similar vectors of local activation. Voltage clamp experiments in cultured neonatal rat cardiomyocytes showed a significant decrease in maximum I_Ca,L by OLE which was reversible upon wash-out.

Conclusions

OLE suppresses the L-type calcium channel directly and reversibly. Our findings might help to understand the traditional use of OLE in the treatment of cardiovascular disease.