Olive leaf extract inhibits lead poisoning-induced brain injury

Olive leaves have an antioxidant capacity, and olive leaf extract can protect the blood, spleen and hippocampus in lead-poisoned mice. However, little is known about the effects of olive leaf extract on lead-induced brain injury. This study was designed to determine whether olive leaf extract can inhibit lead-induced brain injury, and whether this effect is associated with antioxidant capacity. First, we established a mouse model of lead poisoning by continuous intragastric administration of lead acetate for 30 days. Two hours after successful model establishment, lead-poisoned mice were given olive leaf extract at doses of 250, 500 or 1 000 mg/kg daily by intragastric administration for 50 days. Under the transmission electron microscope, olive leaf extract attenuated neuronal and capillary injury and reduced damage to organelles and the matrix around the capillaries in the frontal lobe of the cerebral cortex in the lead-poisoned mice. Olive leaf extract at a dose of 1 000 mg/kg had the greatest protective effect. Spectrophotometry showed that olive leaf extract significantly in- creased the activities of superoxide dismutase, catalase, alkaline phosphatase and acid phes- phatase, while it reduced malondialdehyde content, in a dose-dependent manner. Furthermore, immunohistochemical staining revealed that olive leaf extract dose-dependently decreased Bax protein expression in the cerebral cortex of lead-poisoned mice. Our findings indicate that olive leaf extract can inhibit lead-induced brain injury by increasing antioxidant capacity and reducing apop- tosis.

Hydroxytyrosol and olive leaf extract exert cardioprotective effects by inhibiting GRP78 and CHOP expression

Myocardial infarction triggers massive biochemical changes, even cardiac cell death. Endoplasmic reticulum stress is involved in the pathology of myocardial infarction-mediated apoptosis. In the present study, myocardial cell line H9c2 cells were treated with cobalt chloride（CoCl_2） to induce hypoxia. Isoproterenol was used for two successive days to induce myocardial infarction in SD rats. The cardioprotective effect of olive leaf extract（OLE） and its main constituent hydroxytyrosol and the underlying mechanisms were evaluated. The results showed that hydroxytyrosol markedly protected H9c2 cells against CoCl2-induced apoptosis. Hydroxytyrosol could reduce the mRNA and protein expression of GRP78 and CHOP induced by CoCl2 in vitro. In vivo, the decreased ejection fraction and fractional shortening, increased heart weight/body ratio, the formation of infarction, disordered cardiac muscle fibers and infiltration of inflammatory cells induced by isoproterenol could be significantly ameliorated by pretreatment with OLE for a month. Similarly, OLE could also reverse the increase of GRP78 and CHOP expression induced by isoproterenol. Therefore, OLE and hydroxytyrosol exert a cardioprotective effect through endoplasmic reticulum stress, which could be a new target for the prevention and treatment of cardiovascular diseases.

An Optimum Dose of Olive Leaf Extract Improves Insulin Receptor Substrate-1,Tyrosine Kinase,and Glucose Transporters,While High Doses Have Genotoxic and Apoptotic Effects

Type 2 diabetes is the most common type of diabetes. Conventionally many drugs are used for the treatment of diabetes such as biguanides, sulfonylureas, meglitinides, etc. But the desired effective treatment is still not to be achieved. So researches are going on for the development of effective alternative therapy against diabetes. Olive leaves are traditionally used in the treatment of the disease. However, studies on its mechanism of action are not yet enough. The aim of this study was to investigate whether olive leaf extract (OLE) improves insulin receptor substrate-1 (IRS-1), tyrosine kinase (TK), GLUT-2, and GLUT-4. Oleuropein levels were analyzed from OLE obtained by using four different solvents, and the highest content of methanol extract was selected for the study. Different concentrations of OLE (2.5 to 320 μg/mL) were incubated with hepatocellular carcinoma (HepG2) cells for 24 hours. After incubation, cell viability was assessed based on luminometric ATP cell viability assay kit. Intracellular reactive oxygen species (ROS) generating level was detected using 2,7dichlorodihydrofluorescein-diacetate (H2DCF-DA) fluorescent probes. Apoptosis was evaluated by acridine orange/ethidium bromide double staining method. Genotoxicity was evaluated by alkaline single cell gel electrophoresis assay (Comet Assay). Protein expression levels of IRS-1, TK, GLUT-2, and GLUT-4 were analyzed by western blotting technique from the obtained cell lysates. Although an optimum doses of OLE (10 μg/mL) maximally increased cell proliferation, decreased ROS generation improved IRS-1, TK, GLUT-2, and GLUT-4 protein expression levels (about fivefold), higher doses (10 to 320 μg/mL) markedly decreased the cell viability, increased DNA damage, apoptosis and ROS generation in a concentration-dependent manner. OLE can be used in the treatment of type 2 diabetes. However, in order to find the most effective and non-toxic concentration, dose optimization is required.