الفهرس 
Introduction and aim of workOnly 14 pages are availabe for public view
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Abstract
Hyperlipidemia and its subsequent complications like atherosclerosis are great risk for cardiovascular disease (CVD) and major threat to global public. It is a silent killer as the patient does not know its progression since started many years ago even from childhood years. Cardiovascular disease due to atherosclerosis of the arterial vessel wall and liability to thrombosis formation is the foremost cause of premature mortality and of disability all over the world. Consequent activation of oxidation-sensitive mechanisms in the arterial wall, modulation of intracellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, quenching of nitric oxide (NO) and disturbance in coagulation-fibrinolysis homeostasis are marked steps. These will impair the functions controlled by the vascular wall and lead to the development of endothelial dysfunction and of atherosclerosis. Certain association between thrombus formation and atherosclerosis might exist where atherosclerotic lesions arose mainly from the arrangement of intravascular fibrin deposits.
The present work aimed mainly to:
1. Clarify the advers effect of hyperlipidemia in association to disturbance of coagulation/fibrinolysis in experimental rabbits.
2. Investigate the activity of the whole ginger extract (G-EX), curcuminoids (CURCUM) and 10-Dehydrogingerdione (DHGD) on some metabolic biomarkers.
3. Evaluate the atheroprotective effect of the natural products versus atorvastatin (ATOR) (synthetic standard drug).To fulfill such objectives, the following parameters were selected to be studied:
Serum Lipid profile include total cholesterol (TC), triacyglycerol (TAG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C).
Haemostatic parameters include serum prothrombin fragment 1+2(PF1+2), serum plasminogen activator inhibitor-1 (PAI-1) and plasma fibrinogen (FIB).
Inflammatory marker (serum C-reactive protein (CRP)).
Endothelial dysfunction markers serum endothelin-1 (ET-1) and nitric oxide (NO).
Oxidative stress marker (serum Ischemia modified albumin (IMA)).
Cholesteryl ester transfer protein (CETP).
Experimental design:
Thirty six New Zealand white male rabbits, 3-4 months old, weighing 1.75±0.25 kg.One week after acclimatization, rabbits were randomly assigned into 6 groups (n = 6 per group). One group received normal chow diet and other five groups were fed high cholesterol diet (HCD), freshly prepared, consisting of normal rabbit pellets containing 0.2% w/w cholesterol in coconut oil for 3 and 6 weeks. Rabbits were divided as following:
group (1): Normal control (NC) group, fed normal plain chow rabbit pellets (n=6).
group (2): Hypercholesterolemic control group (HCG), rabbits fed atherogenic diet HCD (n=6).
group (3): Atorvastatin-treated group (ATOR. group), received (20 mg /kg body weight/day) of freshly prepared ATOR suspended in water using 2% gum acacia orally along with HCD (n=6). group (4): 10-Dehydrogingerdione-treated group (DHGD group), received freshly prepared DHGD (10 mg/kg body weight, suspended in water using 2% gum acacia) daily along with HCD (n=6).
group (5): Curcuminoids–treated group (CURCUM. group) received freshly prepared CURCUM (50 mg/kg body weight suspended in water using 2% gum acacia) daily concurrently with HCD (n=6).
group (6): Ginger extract–treated group (G-EX. group) received freshly prepared G-EX (200 mg/kg body weight suspended in water using 2% gum acacia) daily along with HCD (n=6).
Results:
Hypercholesterolemic rabbits demonstrated a significant decrease in HDL-C and increased in TC, LDL-C, AI and CETP in comparison with normal values. Furthermore, concurrent administration of ATOR, DHGD, CURCUM or G-EX with HCD for 6 weeks modulated lipid profile, decreased markedly the serum levels of TC, TAG, LDL-C, AI and CETP along with HDL-C increase as compared to control group.
Observed hyperlipidemia was associated with inflammation (increase in CRP), oxidative stress (increase in IMA), vascular dysfunction (EN-1 increase and NO decrease) and disturbance in fibrinolysis (increased PAI-1, FIB, PF1+2) in comparison with normal values. Furthermore, concurrent administration of ATOR, DHGD, CURCUM or G-EX along with HCD for 6 weeks markedly decreased CRP, IMA, ET-1, PAI, PF1+2 and FIB levels along with activated of NO release as compared to control group.
Conclusion:
Feeding high cholesterol diet was associated with many adverse effects including dyslipidemia, oxidative stress, vascular endothelial dysfunctionand haemostatic impairment which are implicated in the development of atherosclerosis.
Atorvastatin produced significant improvement in hyperlipidemia and its related complications and this improvement attributed to its hypolipemic and pleiotropic effects.
Comparable with ATOR as synthetic standard drug, treatment with natural products DHGD, G-EX and CURCUM mitigates dyslipidemia and its related complications. This may be attributed to their hypolipemic activity, stimulation of NO release which oppose the vasoconstrictor effect of ET-1 and reduction of PAI-1, PF1+2, FIB, CRP and IMA levels.
Suppression of prethrombotic biomarkers by G-EX is better than CURCUM, while CURCUM demonstrated better effect regarding NO, ET-1 and IMA as compared to G-EX. Supplementation of both extracts may synergize their effects in dyslipidemia-induced haemostatic and vascular complications.
The amelioration of adverse effects of hyperlipidemia by DHGD mainly depended on its potential CETP inhibitory effect and increasing HDL-C.
10-Dehydrogingerdione, a new natural CETP inhibitor, represent a promising treatment for dyslipidemia and protective agent against hypercoagulability and vascular dysfunction.
Collectively, the findings of this study can support the recent evidence suggesting that the naturally occurring 1 0-DHGD may be a potential alternative to synthetic CETP inhibitor (not yet appeared and used) for the treatment of atherosclerosis. Thus, we believe that CETP inhibition could be a novel therapeutic means of controlling hyperlipidemia and it vascular complications through atheroprotective HDL-C elevation. Another point to be mentioned hereis that the atheroprotective effect of DHGD seems to be remarkable than ATOR.
Obviously, further studies including clinical and pharmacokinetic studies are urgently needed to validate these results.