Atherosclerosis is a dynamic and reversible process [¹]. In animals fed a cholesterol-rich diet, lowering of plasma cholesterol levels promotes the regression of atherosclerotic lesions [^1-3]. Evidence for atherosclerosis regression in humans has also been reported [^4-6]. Although plasma lipid lowering is a major driving force, the mechanisms that promote lesion regression and stabilization are not clear [⁷]. Recent reports indicate that the reversal or regression of lesions can be achieved by aggressive lipid lowering or drug treatment [⁸,⁹]. Hypercholesterolemia induces oxidative stress, which is known to have adverse effects on the integrity of cells [¹⁰]. Antioxidants and hypolipidemic agents suppress the development of hypercholesterolemic atherosclerosis and induce regression of atherosclerosis. Suppresses the development of atherosclerosis is associated with decreases in oxidative stress and serum lipids [^11-13].

Amaranthus Caudatus L.( A.Caudatus) which is synonym with Amaranthus Paniculatus L. was used in some studies. Grain and leaves of Amaranthus are utilized as food for human beings as well as for animals [¹⁴] and their nutritional value have been extensively studied [¹⁵]. Amaranthus leaves are an excellent source of protein, fiber, squalene, anthocyanins and tocotrienols [^16-18]. Squalene is an intermediate in cholesterol biosynthesis and is found in humans under the skin and inside the adipose tissue [¹⁷]. The physiological effects of dietary flavonols are of current interest due to their in vitro anti-oxidative and anti-inflammatory activities [¹⁸]. It was recently shown positive effect of A. caudatus extract to decrease of cholesterol level, reduced serum lipid levels to atheromatous plaque formation [¹⁹,²⁰]. Qureshi et al. (1991), shows that A. caudatus extracts contains tocotrienol and tocopherol [²¹]. Recently, it has shown that these two substance regulate cholesterol metabolism [²²].

This study assessed the ability of Amaranthus Caudatus L. to reduce atheromatous plaque formation and also its ability to regress atheromatous lesions in hypercholesterolemic rabbits by analysing biochemical markers such as total cholesterol, triglyceride and LDL-cholesterol, apolipoproteinB, malondialdehyde inflammatory markers such as C-reactive protein (CRP) and lesion in the aorta by histochemical analysis.

The results presented above indicate that Amaranthus, has significant antihyperlipidemic and antiatherogenic effects and promoted the regression of atheromatous lesions. This was evidenced by decrease in the extent of accumulation of cholesterol and triglycerides in serum and aorta of rabbits to slow lipid peroxidation process (lower Ox-LDL and MDA), and finally to enhance the inflammatory response of the endothelial cells and accelerated the regression of atheromatous lesions in the aorta as evidenced by significantly low sudanophilic staining. Andrea et al. (2002), shows positive effect of A. caudatus extract to decrease of cholesterol level, LDL-C, VLDL-C and TG [¹⁹]. Recent studies has shown A. caudatus extract decreased the most important risk factors of cardiovascular diseases the serum lipoproteins, apoB and Ox-LDL and inflammatory factors prevented atherosclerosis [²⁰]. Amaranthus have Certain particularly soluble fibers, which have a high water holding capacity, appear to be effective in lowering the serum levels of total and LDL cholesterol in both normal and hyperlipidemic subjects [²⁸]. Among the dietary interventions, dietary fibers play a crucial role in lipid lowering [²⁹]. The effect of dietary fiber on cholesterol metabolism has been studied extensively. These effects are associated with increased excretion of bile acids and neutral sterols, increased catabolism of cholesterol, and reduced absorption of cholesterol and fat [³⁰]. Squalene is an intermediate in cholesterol biosynthesis acts as a hyocholesterolemic agent by inhibiting HMG-CoA reductase, a necessary enzyme in cholesterol biosynthesis [¹⁷].

Atherosclerosis is widely viewed as an inflammatory disease [³¹]. Therefore, the reported inverse association between fruits and vegetable consumption(eight vs. two servings/day) and the selected proinflammatory gene expression and significantly reduced CRP levels [³²,³³]. The anti-inflammatory mechanisms related to fruit and vegetable consumption are still unclear. Fruits and vegetables also are important sources of dietary fiber [³⁴], contain several flavonoids and carotenoids with recognized antioxidant properties which appears to have an anti-inflammatory role flavonoids and carotenoids, by an inhibition of NFκB activity, through suppressing the activation-related phosphorylation, and inhibiting the nuclear translocation [³⁴,³⁵]. Also, dietary fiber intake could participate in weight control and favor weight loss, hypoglycemic actions and hypolipidemic effects [³⁶].

The flavanols and anthocyanins, and their role in the modulation or reduction of risk factors and the prevention of cardiovascular health problems through different aspects of bioeficacy in vascular health platelet agregation, atherosclerosis, blood pressure, antioxidant status, inflammation-related markers, etc.) are consistent. Anthocyanins seem to have a clear effect on endothelial function and myocardium protection [³⁷], Anthocyanins have an effect on cholesterol distribution, protecting endothelial cells from CD40- induced proinflammatory signalling [³⁸]. In macrophages, blackberry anthocyanins inhibit LPS induced nitric oxide biosynthesis [³⁹]. Anthocyanins have anti inflammatory and free radical scavenging activity [³⁹]. A great number of studies have shown that, anthocyanins prevents endothelial damages and act as an inhibitor of endothelial cell death [³⁹,⁴⁰]. Anthocyanins protect endothelial cell by inhibition peroxynitrites that it leads to oxidative damages [³⁹]. The mechanism by which the Amaranthus reduces atheromatous lesion formation and accelerates the rate of lesion regression has not been examined in detail. The hypolipidemic action of the Amaranthus contributes to this. Although the mechanism of the antiinflammatory effect is not clear, the antiinflammatory effect as evidenced by a decrease in inflammatory markers such as CRP may also contribute to the protective effect stress oxidative.

The objectives of the present investigation were Amaranthus produces regression of hypercholesterolemic atherosclerosis and regression is associated with reductions in serum lipids and oxidative stress. An investigation was therefore made of the effects of Amaranthus on the regression of atherosclerosis and serum lipids (cholesterol, triglyceride and LDL-cholesterol, HDL-C, ApolipoproteinB(apoB), apolipoproteinA(apoA), malondialdehyde (MDA), hs-C-reactive protein (hs-CRP) as well as atherosclerosis index (AI) and OX-LDL in rabbits. Oxidative stress parameters were assessed by measuring serum malondialdehyde (MDA) an index of levels of oxygen radicals, aortic antioxidant reserve and the oxygen radical-producing activity of white blood cells cells (WBC-CL). Our studies indicate that Amaranth can be considered as an effective natural antioxidant supplement capable of protecting cellular membranes against oxidative.

The authors declare that they have no competing interests.

NK Participated in the study design of study, interpretation of results, wrote the manuscript and proof read paper and made changes. SA designed and organized the research, contributed wrote the manuscript and proof read paper and made changes. MS contributed with the conception and design. All authors: read and approved the final manuscript.

The work was supported by a grant number 84143 from Isfahan Cardiovascular Research Center (ICRC). We would like to thank Isfahan Cardiovascular Research Center and staff of ICRC Basic Science Laboratory