NOVEL COMPOSITIONS FOR THE TREATMENT OF ATHEROSCLEROSIS AND RELATED CONDITIONS

Abstract: The present invention is related to novel ginger-based compositions for the treatment of atherosclerosis and related conditions. Standardized ginger extracts included as components of the proprietary composition, "ROZ20", were tested in-vivo for their effect on reducing atherogenic modifications of low-density lipoprotein (LDL) and on reducing or substantially preventing the development of atherosclerosis. The study was performed in apolipoprotein E deficient (Eo) mice. At the end of 10 weeks of consumption of 250 microgram/day, "ROZ20", the entire aorta of the mice were examined for atherosclerotic lesions. The mean lesion area of the ROZ20-treated mice was reduced by 67 % in comparison to the lesion area of placebo-treated mice. These results clearly demonstrate that administration of "ROZ20" for a period of 10 weeks to the atherosclerotic Eo mice has a significant beneficial effect in substantially reducing the size and rate of development of atherosclerotic lesions.

Description: NOVEL COMPOSITIONS FOR THE TREATMENT OF ATHEROSCLEROSIS AND RELATED CONDITIONS FIELD AND BACKGROUND The present invention is related to novel compositions for the treatment of atherosclerosis and related conditions, and in particular, is related to novel compositions which include 6-shogaol, 6-gingerol or a mixture thereof, or one or more of 8-gingerol, 10-gingerol, 8-shogaol or 10-shogaol, dried ginger rhizome, or a novel combination of an extract and dried ginger rhizome, as well as methods for the use of these novel compositions. Atherosclerosis is the major cause of morbidity and mortality in the western world and its pathogenesis involves complicated interactions between cells of the arterial wall, blood cells, and plasma lipoproteins (1). The early atherosclerotic lesion is characterized by foam cells, which are derived from cholesterol loaded macrophages (2,3). Macrophage cholesterol accumulation and foam cell formation are the hallmark of early atherogenesis and most of the cholesterol in these cells is derived from plasma low-density lipoprotein (LDL). Native LDL however, has to undergo some modifications in order to cause extensive macrophage cholesterol accumulation (4-6). Two major modifications with potential pathological significance are LDLoxidation (7,8) and lipoprotein aggregation (9, 10). Both of these modifications lead to increased macrophage uptake of the modified lipoprotein, followed by cellular cholesterol accumulation and foam cell formation (7-10). Both oxidized LDL (Ox-LDL) and aggregated LDL (Agg-LDL) were shown to be present in the atherosclerotic lesion of humans and of the apolipoprotein - E deficient (E ) mice ( 1 1 , 12). While the increased uptake of Ox-LDL is mediated via scavenger receptor(s), which are not regulated by the cellular cholesterol content (4. 13), the enhanced uptake of aggregated LDL involves phagocytosis, which is mediated via the LDL receptor (9, 10) The involvement of Ox-LDL in atherosclerosis is suggested from its presence in the atherosclerotic lesion, from the increased susceptibility to oxidation of LDL derived from atherosclerotic patients, such as hypercholesterolermic, as well as from the atherosclerotic apolipoprotein E-deficient (E ) mice, and also from the anti- atherogenicity of several dietary antioxidants (8). The involvement of LDL aggregation in atherosclerosis is also suggested from the presence of such modified LDL in human atherosclerotic lesion, as well as in the aortas from E mice (12). Oxidative modification of LDL in the arterial wall can also lead to acceleration of the atherosclerotic process, secondary to macrophage foam cell formation. Macrophage foam cell formation involves the transport of both LDL and monocytes into the arterial wall. Monocytes can adhere to the endotheluim under certain pathological conditions, followed by migration into the arterial wall and differentiation to macrophages (Figure 1). Plasma LDL can also be transported into the arterial wall, where arterial wall cells and matrix components can lead to its oxidation and aggregation (Figure 1). Oxidative modification of LDL in the arterial wall during early atherogenesis is probably mediated mainly by the action of monocyte-derived macrophages. Arterial wall macrophages were shown to accumulate oxidized lipids in areas of the atherosclerotic lesion and these cells can oxidize LDL m the vascular interstitial space. Activation of the cellular oxygenases can result in the release of reactive oxygen species (ROS), which can induce the oxidation of extracellular LDL. LDL oxidation by macrophages depends on the oxidative status of the macrophages (the balance between cellular oxygenases and cellular antioxidants), as well as by the LDL oxidative status (the balance between the LDL substrates which are prone to oxidation and LDL-associated antioxidants). In the arterial wall, macrophage oxygenases such as NADPH oxidase and lipoxygenase (14-16), and cellular antioxidants such as the glutathione system, including reduced glutathione (GSH) and the enzymes gluthatione peroxidase, reductase and transferase (8), determine the capacity of the cells to oxidatively modify LDL. In addition to the cellular oxidative status, LDL polyunsaturated fatty acids and cholesterol content, and the antioxidants in the LDL environment (intrinsic constituents such as vitamin E, β-carotene, lycopene and polyphenolic flavonoids, and extrinsic components such as vitamin C) also affect LDL oxidation. Vitamin E is the most abundant antioxidant in LDL, and dietary supplementation of vitamin E was shown to increase the resistance of LDL to oxidation (17, 18). The carotenoids β- carotene and lycopene possess some oxidative capabilities, though to a limited extent and probably only in unique oxidative systems, such as those producing singlet oxygen radicals (19-23). In addition, the phenolic flavonoids are also anti-oxidants which appear to be able to prevent certain of the pathogenic processes associated with atherosclerosis. The polyphenolic flavonoids constitute a large class of related compounds consisting of two phenylbenzene (chromanol) rings linked through a pyran ring. Consumption of phenolic flavonoids in the diet was shown to be inversely associated with morbidity and mortality from coronary heart disease (24-27). Different classes of flavonoids are present in different fruits, vegetables, and beverages such as tea and wine. Flavonoids may prevent coronary artery disease by reducing platelet aggregation, by reducing damage from ischemia and reperfusion, or by inhibiting LDL oxidation. The antioxidant activity of the flavonoids is related to their chemical structure (28,29). Polyphenol constituents in olive oil were shown to contribute to the inhibition of LDL oxidation (30, 31). Consumption of black or green tea, which are rich in another subclass of polyphenols, was shown to be associated with an increase in plasma antioxidant potential (32). The "French paradox", i.e. the low incidence of cardiovascular events in the general French population despite the high level of saturated fat in the diet, was attributed to regular drinking of red wine, a dietary source of polvphenols. Ingestion of red wine was shown to be associated with increased antioxidant activity in serum (33, 34). Frankel et al. reported (35) that flavonoids extracted from Califonian red wine protected LDL against oxidation when added in vitro. Furthermore, the long-term consumption of red wine was shown to inhibit LDL oxidation ex vivo (36). The inventors of the present Application have recently demonstrated that consumption of red wine rich in catechin (flavanol) and quercetin (flavonol) with meals results in reduced susceptibility of LDL to oxidation (37), and in reduced progression of atherosclerosis in the atherogenic apolipoprotein E deficient mice (38). Crude extract of licorice, derived from the rhizomes of the Asian plant Glycyrrhiza glabra, which is also a nutrient rich in polyphenols (mainly glabridin), was recently shown to protect LDL against lipid peroxidation in vitro and in vivo in normal healthy human volunteers (39). Ginger (Zingiber Officinale Roscoe) is one of the world best known spices, and has also been universally used throughout history for its health benefits. The dried extract of ginger includes many different substances, such as essential oils containing monoterpenes and sesquiterpenes. As shown in Figure 2A, the gingerols and shogaols, and related phenolic ketone derivatives, can also be found in ginger. Ginger extract was shown to possess antioxidative characteristics, and can significantly scavenge superoxide anion and hydroxyl radical (40). Gingerols isolated from Z. officinale was shown to inhibit platelet function due to inhibition of thromboxane formation (41), and the compounds found in ginger also appeared to interfere with the process of inflammation 1 9 (42). High concentrations of gingerols inhibited ascorbate/Fe -induced lipid peroxidation in rat liver microsomes (43). Furthermore, feeding ginger to rats significantly elevated the activity of hepatic cholesterol-7-alpha-hydroxylase, the rate limiting enzyme of bile and biosynthesis. This elevated activity stimulated the conversion of cholesterol to bile acids, and thus the elimination of cholesterol from the body (44). Furthermore, a pure constituent from ginger (E-8 beta, -17 epoxylabd- 12-ene- 15, 16-dial (ZT)) was shown to inhibit cholesterol biosynthesis in homogenated rat liver (45). However, none of the components of ginger has been shown to alter or prevent the pathogenesis of atherosclerosis in an experimental animal model. Even whole ginger has not been shown to have any such effects on the process of atherosclerosis. Since ginger has been consumed as a spice for thousands of years, if any of the components of ginger were shown to have such favorable anti-atherosclerotic activity, the relative safety of such components would be quite likely. Thus, determining if any component or components of ginger is able to exert such effects would be very useful for the treatment and prevention of coronary disease. There is thus a need for, and it would be useful to have, a composition for the treatment or prevention of atherosclerosis and related conditions, such as coronary disease, strokes and cardiac arrest, which would be derived from a foodstuff such as ginger, and which would include one or more components of ginger or even whole dried ginger. SUMMARY OF THE INVENTION According to the present invention there is provided a composition for treating an atherosclerotic condition, comprising a component selected from the group consisting of 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8-gingerol and 10-gingerol, and a mixture thereof. Preferably, the component is selected from the group consisting of 6-shogaol and 6-gingerol. More preferably, the component is 6-shogaol. Alternatively and preferably, the component is 6- gingerol. According to another embodiment of the present invention there is provided a method for the treatment of an atherosclerotic condition in a subject, comprising the step of administering a pharmaceutically effective amount of a component selected from the group consisting of a 6-shogaol, 8-shogaol, 10- shogaol, 6-gingerol, 8-gingerol and 10-gingerol, and a mixture thereof; dried ginger rhizome alone or in combination with one of the aforementioned ingredients; and ROZ20, alone or in combination with one of the aforementioned ingredients. Preferably, the component includes ROZ20. More preferably, the component is selected from the group consisting of a 6-shogaol, 8-shogaol, 10- shogaol, 6-gingerol, 8-gingerol and 10-gingerol, and a mixture thereof. Also preferably, the component includes dried ginger rhizome. According to yet another embodiment of the present invention, there is provided a method for preparation of a ginger extract, the method comprising the steps of: (a) extracting ginger rhizome with a first volume of an ethanol solvent to form a first extract and a first residue; (b) separating the first extract and the first residue; (c) evaporating the first extract to form a dried extract; and (d) mixing the dried extract with dried, powdered ginger rhizome to form the standardized ginger extract. Preferably, the step of mixing the dried extract with the dried, powdered ginger rhizome is performed by microencapsulating the dried extract and the dried, powdered ginger rhizome. Also preferably, the ethanol solvent is 90% (VW) ethanol. Preferably, the method further comprises the steps of: (e) extracting the first residue with a second volume of the ethanol solvent to form a second extract and a second residue; (f) separating the second extract and the second residue; (g) extracting the second residue with a third volume of the ethanol to form a third extract and a third residue; (h) separating the third extract and the third residue; (i) combining the first extract, the second extract and the third extract to form a combined extract; (j) evaporating the combined extract to form a combined dried extract; and (k) mixing the combined dried extract with the dried, powdered ginger rhizome to form the ginger powder extract. Preferably, the ginger rhizome is milled ginger rhizome. According to still another embodiment of the present invention, there is provided a composition for the treatment of atherosclerosis, comprising a composition prepared according to any of the above methods. Hereinafter, the term "ginger" refers to any part of the plant Zingiber Officinale Roscoe. Hereinafter, the term "whole dried ginger" refers to any portion of the ginger rhizome itself which has been dried to remove at least a portion of the moisture present in the rhizome when harvested, but specifically excludes extracts of the ginger rhizome. Hereinafter, the term "component of ginger" refers to a molecule selected from the group consisting of 6-shogaol, 8- SUBSTΓΠJTE SHEET (RULE 26) shogaol, 10-shogaol, 6-gingerol, 8-gingerol and 10-gingerol, but preferably 6- shogaol and 6-gingerol. Hereinafter, the term "6-shogaol" refers to 5-hydroxy-l-(4-hydroxy-3- methoxyphenyl)-4-decen-3-one [C 17 H ?4 0 4 ]. Hereinafter, the term "6-gingerol" refers to 5-hydroxy-l -(4-hydroxy-3-methoxyphenyl)-3-decanone [C 17 H 26 0 4 ]. BRIEF DESCRIPTION OF THE DRAWINGS The invention is herein described, by way of example only, with reference to the accompanying drawings, wherein: FIG. 1 shows a schematic diagram of oxidative modifications of LDL and atherosclerosis; FIG. 2A shows the gingerols and shogaols found in ginger, while FIG. 2B shows an illustrative analysis of the ginger extract of the present invention; FIGS. 3 A and 3B show the effect of administration of ROZ20 for two weeks on VLDL oxidative state as measured by TBARS (Figure 3A) or lipid peroxide level (Figure 3B ); FIGS. 4A and 4B show the effect of administration of ROZ20 for two weeks on copper ion-induced VLDL oxidation as measured by TBARS (Figure 4A) or lipid peroxide level (Figure B); * FIG. 5 shows the effect of the administration of ROZ20 for ten weeks on conjugated diene formation; FIGS. 6A and 6B show the effect of administration of ROZ20 for ten weeks on copper ion-induced VLDL oxidation as measured by TBARS (Figure 6A) or lipid peroxide level (Figure 6B); FIGS. 7A and 7B show the effect of administration of ROZ20 for two weeks on AAPH-induced VLDL oxidation as measured by TBARS (Figure 7A) or lipid peroxide level (Figure 7B); FIGS. 8 A and 8B show the effect of administration of ROZ20 for ten weeks on AAPH-induced VLDL oxidation as measured by TBARS (Figure 8A) or lipid peroxide level (Figure 8B); FIGS. 9A and 9B show the effect of administration of ROZ20 for two weeks (Figure 9A) or ten weeks (Figure 9B) on LDL oxidative state; FIGS. 10 A- IOC show the effect of administration of ROZ20 for two weeks on copper ion-induced LDL oxidation as measured by conjugated diene formation (Figure 10A), TBARS (Figure 10B) or lipid peroxide level (Figure 10C); FIGS. 11A-1 1C show the effect of administration of ROZ20 for ten weeks on copper ion-induced LDL oxidation as measured by conjugated diene formation (Figure 1 1 A), TBARS (Figure 1 IB) or lipid peroxide level (Figure 1 1C); ' FIGS. 12 A and 12B show the effect of administration of ROZ20 for two weeks on AAPH-induced LDL oxidation as measured by TBARS (Figure 12 A) or lipid peroxide level (Figure 12B); FIGS. 13A and 13B show the effect of administration of ROZ20 for ten weeks on AAPH-induced LDL oxidation as measured by TBARS (Figure 13 A) or lipid peroxide level (Figure 13B); FIG. 14 shows a kinetic study of the effect of ROZ20 on copper ion- induced LDL oxidation; FIGS. 15A and 15B show the in vitro effect of ROZ20 on copper ion- induced LDL oxidation as shown by TBARS (Figure 15 A) or lipid peroxide level (Figure 15B); FIG. 16 demonstrates the capacity of ROZ20 for scavenging of free radicals; FIGS. 17A and 17B show the effect of ROZ20 on VLDL aggregation after administration for two weeks (Figure 17A) or ten weeks (Figure 17B); FIGS. 18A and 18B show the effect of ROZ20 on LDL aggregation after administration for two weeks (Figure 18 A) or ten weeks (Figure 18B); FIGS. 19A and 19B show the effect of ROZ20 administration on macrophage-mediated LDL oxidation as shown by TBARS (Figure 19 A) or lipid peroxide level (Figure 19B); FIG. 20 shows the effect of ROZ20 administration on cholesterol synthesis in macrophages; FIGS. 21 A and 2 IB show the effect of ROZ20 administration on LDL uptake by macrophages; FIGS. 22 A and 22B show the effect of ROZ20 administration on Ox- LDL uptake by macrophages; FIG. 23 shows the effect of ROZ20 administration on aortic arch lesion area; and FIGS. 24A and 24B illustrate aortic arch cross-sections taken from control (Figure 24 A) and ROZ20-treated (Figure 24B) mice. DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is related to novel compositions for the treatment of atherosclerosis and related conditions, and methods for their use thereof. The compositions of the present invention include the ROZ20 composition of the present invention, as well as 6-shogaol, 6-gingerol or a mixture thereof, or one or more other components of ginger, or whole dried gmger rhizome, or mixtures of whole dried ginger rhizome and one or more components of ginger thereof. As described in further detail in the Examples below, a standardized ginger extract included as a component of the ROZ20 composition of the present invention was first analyzed to determine the identity of the components of the extract. The results of this analysis are shown in Example 1. These results demonstrate that the main components of the ginger extract, and hence of the ROZ20 composition of the present invention, are 6-shogaol and 6- gingerol, which are the particularly preferred components of ginger in the composition of the present invention. Next, ROZ20 was tested in vivo for its effect on reducing atherogenic modifications of LDL and on reducing or substantially preventing the development of atherosclerosis. The atherogenic modifications examined included oxidation and aggregation of LDL. The study was performed in apolipoprotein E deficient (E ) mice. These mice have a "knockout" for the apolipoprotein E gene, and are used as an animal model for atherosclerosis. The mice develop atherosclerosis through a pathogenic process which is highly similar to the equivalent process in humans. This pathogenic process is substantially accelerated by a high cholesterol diet, and the resultant atherosclerotic plaque resembles the atherosclerotic lesions found in humans. Example 1 Preparation and Analysis of ROZ20 The extract of ginger described herein was prepared and then analyzed to determine the identity of the major components. This analysis was done by HPLC (high pressure liquid chromatography). The extract of ginger was then mixed with dried, powdered ginger to form the ROZ20 composition of the present invention. The preparative and analytical methods were as follows. First, the ginger extract of the present invention was prepared from the ginger raw material, ginger rhizomes, as follows. Approximately 250 kg of ginger raw material was milled with a mill screen of 10 mm. The first extraction was performed by adding a minimum of 1000 liters of ethanol 90% (VYV) to the ginger raw material, which was then allowed to stand at 50 °C for 1 hour. The extract was then separated from the remaining particulate material by filtration. At this point, the first extract could have been evaporated, substantially as descπbed below, to form an oleoresin extract, which could also have been microencapsulated, substantially as described below. However, preferably the second extraction was performed on the remaining particulate material with a similar volume of ethanol, but the mixture was only allowed to stand for one half of an hour. A third extraction was also preferably performed. The third extraction was similar to the second extraction, except that only a minimum of 750 liters of ethanol 90% (VYV) was added. The extracts were preferably combined and then were concentrated under a vacuum pressure of 500 mm Hg with gradual heating to a maximum temperature of 60 °C until a minimum of 90% TDS (Total Dissolved Substances) has been reached. The extract was then concentrated further by evaporation at a temperature which does not exceed 60 °C. The evaporation continued for one additional hour until no more liquid was visible, thereby forming a dried combined extract. At this point, the extract was at least 95% TDS and was then cooled to room temperature. After cooling, the extract was analyzed for gingerols and shogaols substantially as described below. The ginger extract was then combined by being microencapsulated with dried, powdered ginger rhizome which contained known concentrations of gingerols and shogaols to form the ROZ20 composition of the present invention. The weight percent ratio of the amount of extract to the amount of powdered rhizome was in a range of a ratio of from about 1 to about 9, to a ratio of from about 2 to about 8. The microencapsulation was performed by spheronizing ginger extract and powdered rhizome with a binder, preferably a water soluble cellulose derivative, to form small spheres,, preferably of about 1000 microns diameter. The spheres were then preferably further coated with a cellulose derivative. In the prefeπed embodiment, the complete ROZ20 extract was a combination of from about 90 percent to about 95 percent material derived from ginger and from about 5 percent to about 10 percent cellulose derivatives, weight per weight. The HPLC (high pressure liquid chromatography) analysis was performed substantially as described in the Seventh Supplement, USP - NF , Official Monographs, NF 18 page 4095 (United States Pharmacopeial Convention Inc., Rockville, Maryland, USA). Briefly, the mobile phase featured acetonitrile, dilute phosphoric acid (1 in 1000) and methanol (55:44: 1). The column was a 4.6 mm x 25 cm Lichrocart column, RP - 18 endcapped, which was packed with LI (Lichrospher 100 (5 microns); catalog number 50838, Merck, USA). The flow rate was 1 ml/min. As a standard for quantification, a standard solution of 0.25 mg per milliter of USP capsaicin RS was prepared. Fifty milligrams of the ginger extract of the present invention was then dissolved in 10 milliliters of methanol to form a ginger extract solution. Ten microliters of the standard solution and ten microliters of the ginger extract solution were then separately injected into the HPLC after preparation of the column. Figure 2B shows the results of the HPLC analysis. As shown, peak number 2 is 6-gingerol and peak number 4 is 6-shogaol, both of which are clearly the major components of the gmger extract and hence of the ROZ20 composition of the present invention. In addition, a peak for 8-gingerol is seen at 13.81 minutes, a peak for 6-gιngerodiol at 23.83 minutes, a peak for 10-gingerol at 30.65 minutes and a peak for 8-shogaol at 37.63 minutes. However, it should be noted that other peaks are also present, and are not necessarily excluded as being one or more of the active component or components of ROZ20 responsible for the effects of the ROZ20 composition of the present invention (see Example 2 for a descπption of the effects). These other peaks are believed also to be potentially effective as a treatment for atherosclerosis and as such lie within the scope of the present Application. In particular, ginger rhizome has been shown to contain gingerols and shogaols, as shown in Figure 2A. Both gingerols and shogaols are families of structurally related compounds as shown. Ginger rhizome contains 6-, 8- and 10-gingerol and -shogaol. As described previously for Figure 3, all of these compounds are clearly contained within the ROZ20 extract of the present invention. Thus, all of these compounds may be described as a "component of ginger" and therefore lie within the scope of the present invention. Furthermore, since the ROZ20 composition of the present invention is a mixture of both the ginger extract, prepared as described above, and dried, powdered ginger, dried ginger rhizome also contains one or more components of ginger and as such also lies within the scope of the present invention. Example 2 Testing the Effect of ROZ20 on Atherosclerosis in E ~ Mice The effect of the composition of the present invention, ROZ20, on the pathogenesis of atherosclerosis in E (apolipoprotein E-deficient) mice was tested. Briefly, the mice were fed ROZ20 in the diet for varying lengths of time. The mice were then sacrificed and various parameters of atherosclerosis were analyzed, including the visual inspection of the arteries for the formation of atherosclerotic plaques. ROZ20 was shown to be highly effective for preventing the formation of atherosclerotic plaques in these mice. The experimental method was as follows. METHODS Sixty apolipoprotein E deficient (E ) mice, 6 weeks of age, were divided into 3 groups, with 20 mice in each group. The study was performed in two consecutive experiments, each experiment using 60 mice. The mice received a dietary supplement in their drinking water which was selected from one of the following: a) placebo (control group); b) 25 μg/day/mouse of ROZ20; or c) 250 μg/day/mouse of ROZ20. LDL was isolated from blood samples drawn from the E mice before administration of the composition, and at two and ten weeks after administration, by discontinuous density gradient ultracentrifugation (48). The resultant fraction was dialyzed against saline with EDTA ( 1 mmol/L). Before the oxidation study was performed, the fraction containing LDL was diluted in phosphate buffered saline (PBS) to 200 mg protein/L and dialyzed overnight against PBS at 4 °C to remove EDTA. LDL protein concentration in the fraction was determined with the Folin phenol reagent (49). LDL oxidation and aggregation Oxidation of LDL was carried out in a shaking water bath at 37 C under air, in plastic tubes, 1 cm in diameter. For metal ion-dependent oxidation, LDL was incubated for 4h at 37 °C with freshly prepared CuS0 4 (5μmol/L). Oxidation was terminated by refrigeration at 4 °C and by the addition of 0.1 mmol/L EDTA to chelate the copper ions. LDL oxidation was determined by measuring the amount of thiobarbituric acid reactive substances (TBARS) (50). Formation of conjugated dienes was continuously monitored by measuring the increase in absorbance at 234 nm (51 ). Incubations were carried out in the spectrophotometer cuvette at 37 °C in a temperature-controlled six cell holder in a spectrophotometer (Ultrospec 3000, Pharmacia, Biotech). The reference cell contained 5 μmol/L CuS0 4 in PBS, or 1 mmol/L of AAPH together with 0.1 mM EDTA in PBS, for the examination of metal ion dependent or metal ion-independent oxidation, respectively. The initial background of the different samples ranged between 0.1-0.2 O.D. as recorded at 234nm. However, after recording the initial absorbance, the spectrophotometer was set to zero against the blank, and the increase in absorbance occurring during LDL oxidation was recorded over time every ten minutes. The extent of LDL associated lipid peroxide formation was determined with a commercially available kit (cholesterol color reagent, CHOD iodide method, Diagnostica Merck, Darmstadt, Germany) (52). This assay is based on the oxidative activity of lipid peroxides which convert iodide to iodine, and which can be measured spectrophotometrically. The assay was performed with 100 μl of lipoprotein solution ( 100 mg protein/ml) which was mixed on a vortex with 1 ml of color reagent from the manufacturer. The sample was allowed to stand for 30 minutes in the dark followed by the measurement of absorbance at 365 nm against a blank. LDL aggregation was induced by vigorous vortexing of the sample. The optical density at 680 nm was measured every 10 seconds. Increased optical density of the sample indicated the presence of LDL aggregation. Mouse peritoneal macrophage preparation Mouse peritoneal macrophages (MPM) were harvested from the peritoneal fluid of the E mice (15-25g) 4 days after intraperitoneal injection into each mouse of 3ml of thioglycolate (24g/l) in saline. The cells (10-20 x 10 cells per mouse) were washed and centrifuged three times with phosphate- buffered saline (PBS) at lOOOg for 10 min, then re-suspended in DMEM containing 15% horse serum (heat-inactivated at 56° C for 30min), 100 U/ml penicillin, 100 μg/ml streptomycin, and 2 mM glutamine for a final concentration of 10 cells per liter. The cell suspension was dispensed into 35 mm plastic Petri dishes and incubated in a humidified incubator (5% C0 2 , 95% air) for 2 hours. The dishes were washed once with 5 ml DMEM to remove nonadherent cells, and the monolayer was then incubated under similar conditions for 18 hours prior to the beginning of the experiment. LDL oxidation bv macrophages Cells (10 cells per 35 mm dish) were incubated in the incubator with the fraction containing LDL (0.2 mg protein/ml) in DMEM supplemented with 1 μM CuS0 4 for 18 hours at 37 °C. Oxidation was terminated by the addition of 1 mM EDTA and refrigeration at 4 C. The extent of LDL oxidation was measured directly in the medium. Free radical scavenging capacity The free radical scavenging capacity of ROZ20 was analyzed by the 1, 1 -diphenyl-2-picryl-hydrazyl (DPPH) assay. Aliquots of the ROZ20 composition were mixed at the indicated concentration, with 1 ml of 0.1 mmol DPPH/L (in ethanol) in a cuvette. The time course of the change in the optical density at 517 nm was then kinetically monitored (53 Histopathology of aortic atherosclerotic lesion The histopathological analysis of the lesions was performed as follows. At the end of the experimental period the mice were anesthetized with ethyl ether in a local nasal container. The heart and entire aorta were rapidly dissected out and immersion fixed in 3% glutaraldehyde in 0.1M sodium cacodylate buffer with 0.0 1% calcium chloride, pH 7.4 at room temperature. After approximately one hour, under a binocular stereomicroscope, the aortic arch was dissected free from the surrounding fatty tissue and the first four millimeters of the ascending aorta (beginning with the aortic valves) was removed and cut transversely with razor blades into four blocks of approx. 1 mm each. The samples were kept in the fixative at room temperature overnight. The samples were then rinsed and stored in 0.1M sodium cacodylate buffer containing 7.5% w/v sucrose prior to treatment with an unbuffered 1% aqueous solution of osmium tetroxide for 4 hours. This was followed by cacodylate rinse and dehydration in ascending ethanols, prior to propylene oxide and embedding in epoxy resin ("Eponate 12", Pelco Int., Redding, CA). The blocks were orientated so that the transverse section of the aorta could be cut. After heat polymerization for 18 hours at 60 °C, the blocks were trimmed and one micron sections were cut with glass or diamond knives on an LKB "Nova" ultramicrotome (LKB, Bromma, Sweden). The sections were mounted on glass slides and stained with 0. 1% toluidine blue in 1% borax (sodium tetraborate). In these toluidine blue stained sections, the lipid deposits appear to have a green color and are easily visualized. When sufficient semi- thin sections were sampled from all the blocks, the remainder of the blocks were then cut into much thicker sections ( 150-200μm) for more macroscopic observation. The lipid content of the lesions of these thicker sections was stained an intense black from the prolonged osmium treatment, so that the delineation of the areas of atherosclerotic lesions was easily determined histomorphometrically. (The thinner toluidine blue sections, as seen in the micrographs, permitted observations on the histopathological development of the lesions at a higher resolution and also allowed further cutting for transmission electron microscopy). Only the area of the aortic arch was examined as previous studies have shown that this area is especially prone to atherosclerosis in the Apolipoprotein E-deficient mice. Statistical analyses The student t-test was used in order to analyze the significance of the results. Results are given as mean + S.D. RESULTS I. The effect of the composition of the present invention, ROZ20. on plasma and lipoprotein levels Consumption of ginger extract for 2 weeks had no effect on the levels of total cholesterol and triglycerides in plasma, whether administered at a low concentration of 25 μg/day/mouse (Z-25), or at a higher concentration (by 10 fold) of 250 μg/day/mouse (Z-250), as shown in Table 1. However, after 10 weeks of ginger extract consumption, a significant (pO.O l) 29% and a 27% decrease in plasma levels of cholesterol and triglycerides, respectively, was obtained in those mice which consumed 250 μg of ginger extract per day (Table 1). Consumption of ginger extract for 2 weeks did not affect the triglyceride concentration in the isolated VLDL fraction at any concentration administered. The cholesterol level in VLDL was slightly decreased by 17% after 2 weeks consumption of 25 μg/day or 250 μg/day of ginger extract, as shown in Table 1. However, after 10 weeks of 250 μg/day of ginger extract consumption, a significant (p<0.01) reduction in VLDL-cholesterol level (by 33%), and VLDL triglyceride level (by 36%) was obtained (Table 1). No significant decrease in the level of cholesterol or triglyceride level in LDL was observed following consumption of the composition of the present invention for 2 weeks at any concentration administered. However, following consumption of 25 μg/day or 250 μg/day of ginger extract for a period of 10 weeks, a concentration-dependent reduction in the triglyceride level in LDL of 27% and 58 % respectively (pO.OOl), and an 18% and 54% (pO.OOl) reduction in the LDL cholesterol levels, respectively, were obtained as shown in Table 1. II The effect of ROZ20 on VLDL oxidation VLDL and VLDL-remnant are the main lipid earners in the apolipoprotein E deficient mice (E -mice). These lipoproteins are susceptible to oxidative modification, similar to LDL, and may result in increased cellular uptake by macrophages (54), and foam cell formation. Therefore the effect of ROZ20 on the oxidation of VLDL was examined. LDL derived from control mice receiving placebo for 2 weeks was minimally oxidized, as shown by 4.9 Nome MDA/mg protein (Figure 3A) and 155 Nome VLDL-associated lipid peroxides per mg of protein (Figure 3B). However, consumption of 25 μg/day or 250μg/day of ginger extract for a period of 2 weeks significantly (pO.Ol) reduced the basal TBARS level associated with the VLDL by 74% and 75%, respectively (Figure 3A), and the basal VLDL -lipid peroxide level by 38% and 33%, respectively (Figure 3B). Surprisingly, after 10 weeks of ginger extract consumption, the VLDL isolated from the control group, as well as the VLDL isolated from the mice treated with ROZ20, was not oxidized at a detectable level, thus no effect of the ginger extract could be determined. Administration of 25 μg/day or 250μg/day of ginger extract to E mice for a period of 2 weeks resulted in a marked reduction in their VLDL susceptibility to copper ion-induced oxidation, as measured by decreases of 24% and 26% in TBARS formation, respectively (Figure 4A), and a reduction of 20%o and 56% in lipid peroxide formation (Figure 4B). VLDL isolated from E mice at the early age of 6-8 weeks does not exhibit a lag phase, which is the time needed for oxidation of polyunsaturated fatty acids within the VLDL, therefore no effect of ginger extract consumption for 2 weeks on this parameter could be recorded. However, 2 months later, after 10 weeks of consumption of the ROZ20 composition of the present invention, a lag time of 80 minutes was recorded for the onset of oxidation of VLDL taken from mice of the placebo group. Consumption of 25 μg/day or 250 μg/day of the ROZ20 composition of the present invention resulted in prolongation of the lag phase by 40 minutes, and a slight reduction in the maximal level of conjugated diene formation (Figure 5). Measurement of the extent of copper ion-induced VLDL oxidation by measurement of the formation of TBARS (Figure 6 A) or lipid peroxides (Figure 6B), revealed that consumption of 25 μg/day or 250 μg/day of the ROZ20 composition of the present invention for a period of 10 weeks had no significant effect on the susceptibility of VLDL to oxidation, in comparison to VLDL derived from the placebo group. Thus, the consumption of the ROZ20 composition of the present invention for a short period of 2 weeks had a significant inhibitory effect on the oxidizabihty of VLDL, but this effect did not persist after supplementation for longer period of time. VLDL from mice which consumed the ROZ20 composition of the present invention for 2 weeks showed a decrease of 34% and 49%> in the formation of TBARS respectively, in comparison to VLDL derived from the placebo group, upon radical-induced oxidation with 5mM AAPH (Figure 7A). Similarly, AAPH-induced VLDL oxidation, measured as the formation of lipid peroxides, was significantly (p<0.01 ) inhibited in VLDL from mice fed 25 μg/day or 250 μg/day of the ROZ20 composition of the present invention for two weeks, by 34% and 48%, respectively (Figure 7B). However, these inhibitory effects were not found when the VLDL was isolated from mice after 10 weeks of dietary consumption of the ROZ20 composition of the present invention (Figure 8). Since the oxidative stress progresses during aging in these mice, at the age of 4 months the dietary supplementation of 250 μg/day of ginger extract may not be enough to overcome the oxidative stress, and thus cannot further protect the VLDL from oxidative modification. III. The effect of the ROZ20 composition of the present invention on LDL oxidation The basal oxidative state of LDL isolated from mice fed placebo (control), 25 μg/day (Z-25) or 250 μg/day (Z-250) of the ROZ20 composition of the present invention for 2 weeks or for 10 weeks was estimated by measuring LDL-associated lipid peroxides. Figure 9A demonstrates that the administration of ROZ20 for 2 weeks reduced the LDL-associated lipid peroxides by 13% and by 22% when administered at a low (25μg/day) or high (250 μg/day) concentration, respectively, in comparison to LDL isolated from the control mice. Similarly, consumption of 25 μg/day of ginger extract for a period of 10 weeks reduced the basal level of LDL-associated lipid peroxides by 10%), whereas consumption of 250 μg/day of the ginger extract for 10 weeks resulted in a significant (p<0.01) reduction in the basal level of LDL-associated lipid peroxides by 62% in compaπson to LDL from the placebo group (Figure 9B). In order to determine if ROZ20 increased the resistance of LDL to transition metal ion-induced, or to free radical-induced oxidation, LDL isolated from the control mice, and the mice treated with ROZ20 for 2 and for 10 weeks, underwent ex vivo oxidation. The oxidation process was induced by LDL incubation with copper ions or with the radical initiator AAPH at 37 °C. Continuous monitoring of the formation of conjugated dienes revealed that incubation of LDL isolated from mice that consumed low or high concentration of ginger extract for 2 weeks with 5 μM CuS0 4 , resulted in LDL-lipid peroxidation which propagated after a lag phase of 50 minutes, similar to the LDL isolated from the placebo group (Figure 10A). The lag phase of the LDL oxidation process represents the phase during which the lipoprotein is protected by antioxidants against lipid peroxidation. Without wishing to be limited by a single mechanism, since these antioxidants are consumed orally, the LDL- lipids, and more precisely the polyunsaturated fatty acids within the LDL, may be rapidly oxidized in a self propagation phase. Thus administration of ROZ20 for 2 weeks did not increase the resistance of the LDL to copper ion-induced oxidation. This result was further supported by determination of the LDL oxidation by measuring formation of TBARS or lipid peroxides. Figure 10B demonstrates that the formation of TBARS, following incubation of the LDL with 5 μM copper ions for 2 hours at 37 °C, was not inhibited when the LDL was obtained from mice treated for 2 weeks with either 25 μg/ml or 250 μg/ml of the ROZ20 composition of the present invention. Figure IOC, however, shows that a slight decrease of 19%o in the formation of lipid occurred only in LDL isolated from mice treated with 250 μg/day of ROZ20 for 2 weeks. Consumption for a longer period of 10 weeks did not increase significantly the resistance of LDL to copper ion-induced oxidation. However, a 40 minute prolongation of the lag phase was observed only in LDL from mice treated with 250 μg/day of ginger extract for 10 weeks, in comparison to LDL derived from the control group (Figure 1 IA). In addition, a significant (p<0.01) decrease in copper ion- induced lipid peroxide formation of 15% was also observed only with LDL from mice treated for 10 weeks with 250 μg/day of ginger extract (Figure 1 1C). These results suggest that administration of the ROZ20 composition of the present invention to E mice for a period of 10 weeks did not markedly increase the resistance of LDL to metal ion-induced lipid peroxidation. Similarly, the susceptibility of LDL to free radical-induced oxidation did not appear to have been reduced by ROZ20, whether consumed for 2 weeks (Figure 12) or for 10 weeks (Figure 13). IV. Possible mechanisms for the antioxidative effect of ROZ20 ' In order to establish if the antioxidative effects of treatment with the ROZ20 composition of the present invention can be attributed to a direct antioxidative effect of the extract, in vitro incubations of human LDL with copper ions in the absence (control) or presence of increasing concentrations of ROZ20 was performed. Continuous monitoπng of the formation of conjugated dienes in LDL revealed that at the lowest concentration studied (2.5 μg/ml), an increase of 30 minutes of the lag phase was observed. Incubation with 5 μg/ml of ROZ20 retarded the onset of LDL oxidation by 60 minutes, whereas 10 μg/ml ROZ20 completely inhibited the initiation of copper ion-induced oxidation by up to 120 minutes (Figure 14). Measurement of LDL oxidation by determination of TBARS or of lipid peroxides revealed that ROZ20 inhibited LDL oxidation with an IC 50 (the concentration needed to inhibit LDL oxidation by 50%>) of 5μg/ml for TBARS, (Figure 15A) and 5.4 μg/ml for lipid peroxide formation (Figure 15B). The capacity of ROZ20 to scavenge free radicals was then examined with the DPPH assay, as described in the "Methods" section above. The DPPH radical has a deep violet color, and radical scavenging can be followed spectrophotometrically by the loss of absorbency at 517 nm, as the pale yellow non-radical form of DPPH is produced. Vitamin E (25 μM) served as a positive control in this experiment, since vitamin E is known to scavenge free radicals. The addition of 25 μM of vitamin E to the DPPH solution induced a rapid decrease in the optical density at 517 nm, which reached a plateau within 50 seconds. The addition of 40 μg/ml of ROZ20 to the DPPH solution induced a 38%> decrease in the optical density at 517 nm within 100 seconds, whereas lOOμg/ml of ROZ20 reduced the optical absorbance of DPPH at 517 nm by 65% (Figure 16). These results demonstrate that ROZ20 possesses antioxidative capacity and the ability to scavenge free radicals. V. The effect of the ROZ20 composition of the present invention on lipoprotein aggregation Aggregation of LDL represents another lipoprotein modification with atherogenic properties, since aggregated LDL is taken up by macrophages at increased rate, leading to foam cell formation (9, 10). Furthermore, oxidation of LDL leads to its aggregation (46). Since treatment of apolipoprotein E- deficient mice with ROZ20 was shown to reduce the basal oxidative state and the oxidizabihty of VLDL, and to a lesser extent of LDL, the effect of treatment with ROZ20 on lipoprotein aggregation was examined. Aggregation was induced by vigorous vortexing of the lipoprotein solution for different periods of time, as described in "Methods" above. Since VLDL is the main lipid carrier lipoprotein in E° mice, and ROZ20 was shown above to increase the resistance of this lipoprotein to oxidation, the effect of treatment with ROZ20 on the susceptibility of VLDL to vortex- induced aggregation was examined. The optical density at 68 nm of VLDL derived from the placebo (control) group reached a value of 0.7 O.D within 170 seconds of vortexing (Figure 17). Aggregation of VLDL from mice treated with 25 μg/day or 250 μg/day ROZ20 for 2 weeks (Figure 17A) or for 10 weeks (Figure 17B) was reduced by more than 50% or 25%, respectively. These results are in accordance with the results presented in the previous section, which demonstrated that the administration of the ROZ20 composition of the present invention markedly affected VLDL oxidation following 2 weeks of dietary administration, whereas after 10 weeks the inhibitory effects were reduced. Figure 18 demonstrates that vortex-induced LDL self-aggregation was slightly reduced following administration of 25μg/day or 250μg/day of the ROZ20 composition of the present invention for 2 weeks (Figure 18 ). Administration of ROZ20 for 10 weeks, however, resulted in a greater inhibition of LDL aggregation (by 30%) at both concentrations tested (Figure 18B). Furthermore, the inhibitory effect of treatment with ROZ20 on LDL and VLDL aggregation could not be associated with a direct effect on the lipoproteins, since the treatment did not inhibit aggregation of LDL or of VLDL when added in vitro. Thus the reduced susceptibility to aggregation of both LDL and VLDL isolated from animals treated with the ROZ20 composition of the present invention may be related to the reduced oxidizabihty of these lipoproteins after treatment. VI. The effect of treatment with the ROZ20 composition of the present invention on the capacity of peritoneal macrophages to oxidativelv modify LDL. Cells of the arterial well, including macrophages, are known to oxidize LDL in vivo. The ability of the cells to oxidize the lipoprotein is the result of the balance between cellular oxidants and antioxidants. Consumption of ROZ20 resulted in reduced susceptibility of isolated LDL and VLDL to oxidation. However, when ingested, antioxidant components in the ROZ20 composition of the present invention may become incorporated into cells, thus affecting their oxidative status. Thus, after 10 weeks of treatment with ROZ20, peritoneal macrophages were harvested from E mice which consumed placebo, 25μg/day ROZ20, or 250μg/day ROZ20. The cells were then incubated with lOOμg of protein of human LDL/ml under conditions of oxidative stress generated by adding 5μM CUS0 4 to the incubation medium. LDL incubated under similar conditions but without cells served as a control. Figure 19A shows that when LDL was incubated with peritoneal macrophages (MPM) derived from mice which consumed 25 μg/day or 250μg/day ROZ20, respectively, as compared to LDL incubated with MPM from the placebo group, a significant (p<0.01) reduction in LDL oxidation of 60% and 45%, respectively, was obtained from the TBARS assay. Furthermore, a reduction in LDL oxidation of 36% and 47%, respectively, was found as measured by the amount of lipid peroxide formation (Figure 19B). These results suggest that treatment with ROZ20 may also affect cells in the arterial wall by reducing their capacity to oxidatively modify native LDL. Since strong evidence suggests that the oxidation of LDL in vivo occurs in extracellular spaces in the arterial wall, and is probably mediated by cells of the arterial wall, reduction in the oxidative capacity of the cells by oral administration of ROZ20 may represent an important intervention to reduce the rate of development of atherosclerosis. VII. The effect of ROZ20 consumption on cholesterol metabolism in macrophages Cholesterol is an essential component of all animal cell membranes. Excess accumulation of cholesterol in cells is avoided by maintaining a balance between external sources via the receptor-mediated endocytosis of lipoproteins, and the internal sources from de novo cellular synthesis. Cellular uptake of LDL is mediated via the LDL receptor, whose activity is regulated by the cellular cholesterol level. However, as was mentioned before, oxidative modification of LDL leads to its recognition and endocytosis via the scavenger receptors, which are not subjected to cellular cholesterol regulation. This process therefore can lead to cholesterol accumulation in the cells and to foam cell formation. Therefore, the effect of treatment with ROZ20 on the cholesterol metabolism in macrophages was examined. First, the effect of treatment with ROZ20 on the cellular cholesterol synthesis rate was examined. As shown in Figure 20, demonstrates macrophages derived from mice which consumed 25μg/day or 250μg/day of ginger extract for 10 weeks were shown to have a reduction of 36% or 16% in the rate of cellular cholesterol synthesis, respectively. Next, the effect of ROZ20 consumption on the cellular uptake of LDL and of oxidized - LDL (Ox- LDL) was examined. Figure 21 demonstrates that the incubation of radio- iodinated LDL with macrophages derived from mice which consumed 25μg/day or 250μg/day of ROZ20 resulted in decreased cellular degradation of LDL of 66% or 61%, respectively (Figure 21 A), and decreased cellular association of the LDL of 65% and 59%, respectively (Figure 2 IB), in compaπson to cellular degradation and cell association of LDL by macrophages derived from control mice. Although the Ox-LDL receptor is not regulated by the cellular cholesterol level, a 50% inhibition in cellular deactivation (Figure 22A) and cellular association (Figure 22B) of OX-LDL was found in macrophages from mice treated with ROZ20, in comparison to Ox-LDL uptake by macrophages from mice given the placebo. Thus, treatment with ROZ20 appears to affect cellular lipoprotein uptake, probably by mechanisms independent of the cellular cholesterol level. III. Histopathologv of the aortic arch atherosclerotic lesion in E ~ mice after treatment with the ROZ20 composition of the present invention At the end of 10 weeks of consumption of 250μg/day ROZ20, the mice were sacrificed and the entire aorta was rapidly dissected as described in "Methods". Aortic arches obtained from all mice studied (control and those treated with ROZ20) showed atherosclerotic lesions. However, in all cases the lesion areas in the aortic arches of ROZ20 treated mice were considerably smaller than the lesions in the arches of mice treated with placebo (Figure 23). Histomorphometric data confirmed qualitatively that the area of the lesions of the ROZ20-treated mice was considerably reduced in comparison with that of the placebo-treated mice. The mean lesion area of the ROZ20-treated mice was reduced by 67% in comparison to the lesion area of placebo-treated mice (Figure 24). These results clearly demonstrate that administration of ROZ20 for a period of 10 weeks to the atherosclerotic E mice has a significant beneficial effect in substantially reducing the size and rate of development of atherosclerotic lesions. Example 3 Suitable Formulations for Administration of the Compositions of the Present Invention As noted previously, the components of ginger of the present invention include compounds selected from the group consisting of 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8-gingerol and 10-gingerol, but preferably 6-shogaol and 6-gingerol. The compositions of the present invention include at least one component of ginger, or a mixture thereof, and may also include dried ginger rhizome alone or in combination with one of the components of ginger, or ROZ20, alone or in combination with one of the aforementioned ingredients. All of these ingredients may be described as a "component". The compositions of the present invention can be administered to a subject in a number of ways, which are well known in the art. Hereinafter, the term "subject" refers to the human or lower animal to whom the composition of the present invention was administered. For example, administration may be done topically (including ophtalmically, vaginally, rectally, intranasally), orally, or parenterally, for example by intravenous drip or intraperitoneal, subcutaneous, or intramuscular injection. Formulations for topical administration may include but are not limited to lotions, ointments, gels, creams, suppositories, drops, liquids, sprays and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, sachets, capsules or tablets. Thickeners, diluents, flavorings, dispersing aids, emulsifϊers or binders may be desirable. Formulations for parenteral administration may include but are not limited to sterile aqueous solutions which may also contain buffers, diluents and other suitable additives. Dosing is dependent on the severity of the symptoms and on the responsiveness of the subject to the composition of the present invention. Persons of ordinary skill in the art can easily determine optimum dosages, dosing methodologies and repetition rates. Example 4 Method of Treatment of Atherosclerosis and Related Conditions As noted above, the ROZ20 composition of the present invention has been shown to be effective for the treatment of atherosclerosis. The compositions of the present invention are generally contemplated as useful for the treatment of atherosclerotic conditions. Hereinafter, the term "treatment" includes ameliorating or substantially eliminating an existing condition, as well as substantially preventing such a condition from arising. Hereinafter, the term "atherosclerotic condition" includes, but is not limited to, the constellation of clinical manifestations of atherosclerosis, such as deposition of cholesterol in the arterial walls and the formation of plaques; oxidation and aggregation of LDL; any type of naπowing of the blood vessels through the deposition of cholesterol; and the physical conditions for which atherosclerosis may be at least one rhizome cause, such as angina, stroke and cardiac arrest. The following example is an illustration only of a method of treating atherosclerosis with a composition of the present invention, and is not intended to be limiting. The method includes the step of administering the composition of the present invention, in a pharmaceutically acceptable carrier as described in Example 3 above, to a subject to be treated. The composition of the present invention is administered according to an effective dosing methodology, preferably until a predefined endpoint is reached, such as a reduction in the size of arterial atherosclerotic lesions taken from the subject. While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications and other applications of the invention may be made. APPENDIX - REFERENCES 1) Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990. Nature. 1993. 362:-801-809. 2) Gerrity R.G. The role of monocytes in atherogenesis. Am. J. Pathol. 1981.103:. 181-190. 3) Schaffner T., Taylor K., Bartucci E.J., Fischer-Dzoga K., Beenson J.H., Glagov S. and Wissler R. 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Claims: WHAT IS CLAIMED IS: 1. A composition for treating an atherosclerotic condition, comprising a component selected from the group consisting of 6-shogaol, 8-shogaol, 10- shogaol, 6-gingerol, 8-gingerol and 10-gingerol, and a mixture thereof. 2. The composition of claim 1 , wherein said component is selected from the group consisting of 6-shogaol and 6-gingerol. 3. The composition of claim 2, wherein said component is 6-shogaol. 4. The composition of claim 2, wherein said component is 6-gingerol. 5. The composition of claim 1 , further comprising a dried ginger extract. 6. The composition of claim 5, further comprising powdered rhizome. 7. The composition of claim 6, wherein said dried ginger extract is microencapsulated with said powdered rhizome. 8. A composition for treating an atherosclerotic condition, comprising a dried gmger extract. 9. The composition of claim 8, further compπsing powdered rhizome. 10. The composition of claim 9, wherein said dried ginger extract is microencapsulated with said powdered rhizome. 1 1. The composition of claim 8, wherein the composition includes ROZ20. 12. A method for the treatment of an atherosclerotic condition in a subject, comprising the step of administering a pharmaceutically effective amount of a component selected from the group consisting of a 6-shogaol, 8- shogaol, 10-shogaol, 6-gingerol, 8-gingerol and 10-gingerol, and a mixture thereof; dried ginger rhizome alone or in combination with one of the aforementioned ingredients; and ROZ20, alone or in combination with one of the aforementioned ingredients. 13. The method of claim 12, wherein said component includes ROZ20. 14. The method of claim 12, wherein said component is selected from the group consisting of a 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8- gingerol and 10-gingerol, and a mixture thereof. 15. The method of claim 14, wherein said component includes dried ginger rhizome. 16. A method for preparation of a ginger extract, the method comprising the steps of: (a) extracting ginger rhizome with a first volume of an ethanol solvent to form a first extract and a first residue; (b) separating said first extract and said first residue; (c) evaporating said first extract to form an oleoresin extract; and (d) mixing said oleoresin extract with dried, powdered ginger rhizome to form the ginger extract. 17. The method of claim 16, wherein the step of mixing said oleoresin extract with said dried, powdered ginger rhizome is performed by microencapsulating said oleoresin extract and said dried, powdered ginger rhizome. 18. The method of claim 16, wherein said ethanol solvent is 90% (VYV) ethanol. 19. The method of claim 16, further comprising the steps of: (e) extracting said first residue with a second volume of said ethanol solvent to form a second extract and a second residue; (f) separating said second extract and said second residue; (g) extracting said second residue with a third volume of said ethanol to form a third extract and a third residue; (h) separating said third extract and said third residue; (i) combining said first extract, said second extract and said third extract to form a combined extract; (j) evaporating said combined extract to form a combined dried extract; and (k) mixing said combined dried extract with said dried, powdered ginger rhizome to form the ginger extract. 20. The method of claim 19, wherein said ginger rhizome is milled ginger rhizome. 21. A composition for the treatment of atherosclerosis, comprising a composition prepared according to the method of claim 16. 22. A composition for the treatment of atherosclerosis, comprising a composition prepared according to the method of claim 19.

Inventors: AVIRAM MICHAEL, FUHRMAN BIANCA, ROSENBLAT MIRA, TENNE MEIR, AVIRAM, MICHAEL, FUHRMAN, BIANCA, ROSENBLAT, MIRA, TENNE, MEIR
Applicants: AVIRAM MICHAEL, DALIDAR PHARMA ISRAEL 1995 LTD, FUHRMAN BIANCA, ROSENBLAT MIRA, TEFF JENNIFER, TENNE MEIR, AVIRAM, MICHAEL, DALIDAR PHARMA ISRAEL (1995) LTD., FUHRMAN, BIANCA, ROSENBLAT, MIRA, TEFF, JENNIFER, TENNE, MEIR
Application year: 1999
Main classification: A61K35
IPC codes: A61K31, A61K35, A61K36