Résumé:
Oxidative stress is defined as an imbalance between productions of free radicals and reactive metabolites. This imbalance leads to damage of important biomolecules and cells, with potential impact on the whole organism. There is currently arenewed interest in phytochemicals as sources of natural antioxidants. Hyperhomocysteinemia is usually defined as an elevation of plasma tHcy. It is an important risk factor for premature cardiovascular disease. As a result, homocysteine metabolism abnormalities are now receiving increasing attention because of their potential role in the pathogenesis of atherosclerosis and other diseases such as venous thrombosis. In this study, we tested in vivo the antioxidant and anti-inflammatory effect of the Grape Leaves (Vitis vinifera) Algerian Variety on the cardiovascular inflammation induced by Hyperhomocysteinemia. The phenolic compounds (Anthocyanins and non anthocyanins) is identified by using HPLC-DAD/ESI-MS, total Homocysteine (t-Hcy) was estimated by competitive solid phase chemiluminescence immunoassay, the plasma hs-CRP is measured by immunoturbidimetric method and the concentration of the GSH measured by spectrophotometric method. In addition, the aorta histology examined in order to confirm the angiotoxic action of homocysteine and the reparative effect of grape leaves (Vitis vinifera) on the aorta. Results showed high levels of phenols, anthocyanins, flavonols and trans-caftaric acid in grape leaves (Vitis vinifera). The plasma hs-CRP and homocysteine levels were elevated significantly (p < 0.05) however the glutathione reduced significantly (p < 0.05) after the administration of L-methionine in high doses to mice. This was associated with the desquamation of endothelium and muscular lysis with transformation of spindle nuclei to oval nuclei; this is due to the angiotoxic action of homocysteine on the aorta. These changes were not observed in mice treated with L-methionine plus the antioxidant and anti-inflammatory extract of grape leaves (Vitis vinifera). So, the study proved the antioxidant and anti-inflammatory effects of the grape leaves (Vitis vinifera) on hyperhomocysteinemia induced inflammatory endothelial damage in cardiovascular diseases. Moreover, in the present thesis, we conducted a study in vitro to analyze the total phenols, anti-oxidative, anti-proliferative properties on MCF-7 and HepG2 Human Cancer Cell Lines and on modulate of Apoptosis-Related Gene Expression of water and ethanol crude extracts obtained by Accelerator Solvent Extractor from grape leaves (Vitis vinifera) grown in Algeria. The results revealed for the first time that accelerator solvent extraction yielded a higher extraction rate of total phenols and antioxidant activity in an extremely short time. The extract obtained from grape leaves (Vitis vinifera) grown in the Medea region (Algeria) exhibited an antiproliferative effect on MCF-7 breast cancer cells and HepG2 hepatocarcinoma cells. Moreover, considering previous reports by other authors and the present results that provides evidence for the modulation of Bax/Bcl2 mRNA levels by leaf extracts, which affects the balance between apoptosis and cell survival, it may be concluded that these extracts could be used as an easily accessible source of natural antioxidants, and as a matrix to prepare drugs counteracting distinctive cancer cells‟ proliferation.
