الفهرس 
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Abstract
This work was conducted to investigate the prophylactic, protection and treated effect of Artemisia monosperma and Artemisia herba-alba on hypercholesterolemic rats in order to prove its claim in folklore practice against lipid profile disorders and to evaluate its possible mechanism of actions by investigating its effect on biochemical and immunological aspects on the hyperlipidemia induced in rats, pre-and post treated with oral administration of 0.39 g/kg Artemisia extracts were for 2 weeks. In addition to the identification of phytoconstituents present in both extracts using HPLC/DAD/MS analysis which may be responsible for the hypolipidemic activity observed in this study in order to hit upon multiple mechanisms of action of each identified compounds in the observed hypolipidemic activity. The high unexpected antioxidant activity of both extracts in comparison to trolox may represent another clue for their ability to inhibit atherosclerosis. The results obtained from our study indicates that Artemisia monosperma posses a significantly higher antioxidant potential than that of Artemisia herba alba this may refer to the difference in the phytochemical constituents identified in each extract. The compounds identified in Artemisia monosperma such as rutin, catechin, diosmetin and pentagalloyl-glucopyranose are known to have strong antioxidant properties while Artemisia herba-alba contain other compounds with moderate antioxidant activity such as, rhamnetin , naringenin , apigenin , catechin and 5,7-dihydroxy-3’,4’,5’-trimethoxyflavone which have ordered the scavenging activity of flavonoids as following: rutin > rhamnetin > diosmetin > naringenin > apigenin > catechin > 5,7-dihydroxy-3’,4’,5’-trimethoxyflavone > flavones. This suggested that Artemisia monosperma and Artemisia herba alba may act through multiple mechanisms. In the present study, feeding rats on high cholesterol diet exhibited a significant increase in triglycerides (TG) and total cholesterol (TC) as compared to normal control. Moreover, level of low density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index (AI) and body weight were increased, while high density lipoprotein (HDL) was decreased.These results are demonstrated that similar hyperlipidemia pattern and further suggesting initiation of atherosclerotic process consequent to lipid changes in atherogenic rats. In light of the results, both extract of Artemisia monosperma and Artemisia herba alba on high fat fed hypercholesterolemic rats exhibited significant hypolipidemic activity as indicated by the decrease of each of the following measured parameters like body weight, serum lipid profiles, albumin, total protein, liver enzymes, blood sugar level, antioxidant activity (SOD & CAT) and lipid peroxidation (MDA) IgG, while total lymphocytes count and phagocytic index increase. The hypolipidemic activity may be attributed to the presence of a number of phytoconstituents that had been identified in the phytochemical part of this study using HPLC/DAD/MS analysis. According to the phtyochemical studies the presence of chlorogenic acid (CGA) was found to be responsible for the decrease in total cholesterol (TC), triglycerides (TGs) and LDL levels, through a multiple mechanisms including: 1- The activation of vascular Lipoprotein lipase (LPL): its primary role is the hydrolysis of core triglycerides (TG) in circulating triglyceride-rich lipoproteins (TGRL), converting these into remnant particles. This process generates free fatty acids which may be taken up and used for energy or for storage, and also results in the generation of surface remnants which form the basis of high density lipoprotein (HDL) 2- Regulation of lipoprotein lipase (LPL) in skeletal muscles inhibiting the mobilization of fats suggesting that chlorogenic acid can strengthen the ability to dispose cholesterol in the liver and these is associated with protection against atherosclerosis. 3- By its inhibitory effects on intestinal glucose uptake and hepatic glucose 6-phosphatase activity. Such enzymes play a major role in the intestinal absorption of dietary fats leading to a decrease in serum lipid and glucose level, increasing insulin sensitivity and modifies lipid metabolism in the liver and skeletal muscle. The present data revealed that pre- and post treatment with Artemisia extracts show, significant decreases in serum AST and ALT activities compared to those of hypercholesterolemic group. According to the results obtained from the biochemical and histopathological investigations Artemisia monosperma Artemisia herba alba were found to reduces the liver enzyme whereas Artemisia monosperma exerts a highly significant hepatoprotective effect which is probably due to the presence of flavonoids including rutin, hesperetin, isorhamnetin, naringenin, isorhamnetin. Artemisia monosperma water extracts through reduction the activities of ALT and AST enzymes. Whereas in case of Artemisia herba-alba extract contain 4,5 di-O-caffoeylquinic acid, which has biological activities including hepatoprotective effect of apigenin, quercetin, and naringenin. It was found to be the most effective one is rutin. Rutin showed regenerative and hepato-protective effects against microcrystin LR- induced hepatotoxicity in experimental cirrhosis. Results of the current study also indicated that a decreased serum total protein contents and albumin concentration after induction of hypercholesterolemia. Additionally, the decrement in protein content is usually accompanied by an increase in the amount of ROS under hypercholesterolemic states, which induces cellular damage associated with protein oxidation. Malondialdehyde (MDA) is a highly toxic product resulting from lipid peroxidation initiated by free radicals. Results showed that MDA activities were significantly increases in hypercholesterolemic rats when compared to those of normal control group. While, treatment of hypercholesterolemic rats with Artemisia at dose of 0.39 g/kg for two weeks resulted in a significant decrease in MDA level as compared to those of hypercholesterolemic group. MDA is significantly increased in hypercholesterolemic group and this may be due to the excessive production of reactive oxygen species (ROS). It had been reported that the high-fat diet would induce free radical production, followed by hypercholesterolemia and oxidative stress. Artemisia momosperma extract contains flavonoids include quercetin derivatives and isorhamnetin. These constituents have roles in stimulating the immune potentials. Hypercholesterolemia may affect the function of cells involved in host defense. In vitro studies show that incubation with hyperlipidemic serum or isolated lipoproteins influences the production of reactive oxygen species by macrophages and polymorphonuclear neutrophils, inhibits the chemotactic responses of neutrophils to N-formyl-methionyl-leucylphenyloalanine (fMLP) and suppresses the lymphocyte activation by polyclonal T cell mitogens. Similarly, phagocytic cells isolated from hypercholesterolemic animals and patients showed several functional abnormalities, such as increased release of oxygen species and vasoconstrictive products as well as enhanced aggregability of neutrophils or decreased cytokine production by macrophages. Adherence and chemotaxis were shown to be impaired in neutrophils.