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Asparagus Root Regulates Cholesterol Metabolism and Improves Antioxidant Status in Hypercholesteremic Rats  [PDF]
Nishant P. Visavadiya,A. V. R. L. Narasimhacharya
Evidence-Based Complementary and Alternative Medicine , 2009, DOI: 10.1093/ecam/nem091
Abstract: Hyperlipidemia/hypercholesteremia are major risk factors for atherosclerosis and cardiovascular diseases. Root of Asparagus racemosus (AR) is widely used in Ayurvedic system of medicine in India and is known for its steroidal saponin content. This study was designed to investigate the hypocholesteremic and antioxidant potential of AR root in both normo- and hypercholesteremic animals. Normal and hypercholesteremic male albino rats were administered with root powder of AR (5 and 10 g% dose levels) along with normal and hypercholesteremic diets, respectively, for a duration of 4 weeks. Plasma and hepatic lipid profiles, fecal sterol, bile acid excretion and hepatic antioxidant activity were assessed. Inclusion of AR root powder in diet, resulted in a dose-dependant reduction in plasma and hepatic lipid profiles, increased fecal excretion of cholesterol, neutral sterol and bile acid along with increases in hepatic HMG-CoA reductase activity and bile acid content in hypercholesteremic rats. Further, AR root also improved the hepatic antioxidant status (catalase, SOD and ascorbic acid levels). No significant changes in lipid and antioxidant profiles occurred in the normocholesteremic rats administered with AR root powder. AR root appeared to be useful as a dietary supplement that offers a protection against hyperlipidemia/hypercholesteremia in hypercholesteremic animals. The results of the present study indicate that the potent therapeutic phyto-components present in AR root i.e. phytosterols, saponins, polyphenols, flavonoids and ascorbic acid, could be responsible for increased bile acid production, elimination of excess cholesterol and elevation of hepatic antioxidant status in hypercholesteremic conditions.
Atherosclerosis and the Cholesterol Theory: A Reappraisal  [PDF]
Ang Peng Wong, Abdul Latiff Mohamed, Aleksandra Niedzwiecki
World Journal of Cardiovascular Diseases (WJCD) , 2016, DOI: 10.4236/wjcd.2016.611044
Abstract: Atherosclerosis is the precedent to ischemic heart disease, which may lead to angina, myocardial infarct, or heart failure; or to ischemic cerebrovascular disease, which may lead to stroke. The prevailing belief underlying conventional approaches to treatment of atherosclerosis and its sequel is that a diet high in cholesterol and saturated fat is the main contributory factor, triggering cholesterol build up in the intima of the blood vessels. Over the last 60 years, the blame has shifted from fats, to saturated fats, to low-density lipoprotein (LDL), and finally to oxidized LDL (Ox-LDL). Therapy has been predominantly aimed at lowering cholesterol and control of risk factors. However, there is an alternative hypothesis about the cause of heart disease linking it to the weakening of the vascular collagen matrix at the sites of high hemodynamic stress (coronary arteries) which triggers the infiltration of lipoprotein(apo) [Lp(a)] and plaque development. Accordingly, the vascular deposition of large molecules such as Lp(a) and atherosclerosis is the result of the body’s endogenous protective mechanism to reinforce the weakened artery walls. Understanding this mechanism may guide the natural prevention of this disease and form the basis for developing effective therapeutic strategies aiming at natural reversal of atherosclerosis through the reinforcement of the vascular wall structure as its primary goal. This reappraisal of atherosclerosis and the cholesterol theory looked at the historical development of the theory, and the Rath and Pauling unified theory of cardiovascular disease.
Atherosclerosis, cholesterol, nutrition, and statins – a critical review
Gebbers, Jan-Olaf
GMS German Medical Science , 2007,
Abstract: Atherosclerosis, which causes approximately half of all deaths of adults over age 60 in industrialized nations, is a pandemic among inappropriately nourished and/or physically hypoactive children, adolescents, and adults world wide. Although nowadays statins are widely prescribed to middle age and elderly adults with high blood lipid levels as pharmacological prevention for the late complications of atherosclerosis, from a critical point of view statins seem not to solve the problem, especially when compared with certain natural ingredients of our nutrition like micronutrients as alternative strategy. Statin ingestion is associated with lowering of serum cholesterol and low-density lipoprotein concentrations; some prospective studies have shown statistical associations with subsequent modest reduction of mortality from cardiovascular disease. However, specific biochemical pathways and pharmacological roles of statins in prevention of atherosclerosis, if any, are unknown. Moreover, there have been no systematic cost-benefit analyses of life-style prophylaxis versus statin prophylaxis versus combined life-style plus statin prophylaxis versus neither life-style nor statin prophylaxis for clinically significant complications of cardiovascular diseases in the elderly. Further, in the trials of effectiveness statins were not compared with management of nutrition, which is the most appropriate alternative intervention. Such studies seem to be important, as the ever increasing world population, especially in developing countries, now demand expensive statins, which may be unaffordable for mitigating the pandemic. Studies of this kind are necessary to identify more precisely those patients for whom cardiovascular benefits will outweigh the risks and costs of the statin treatment in comparison with nutritional interventions. Against the background of the current pathogenetic concept of atherogenesis some of its possible risk factors, particularly the roles of cholesterol and homocysteine, and the effects of statins versus nutritional (micronutrients) interventions in prevention and treatment of the disease are discussed. The prevailing opinion that serum cholesterol as a mediator of the disease is increased by eating saturated fats and decreased by eating polyunsaturated fats is being challenged. Evidently, the beneficial effects of statins in atherosclerosis are not mainly due to its cholesterol lowering effect, rather than to its “pleiotropic effects”. Other pathogenetic factors in atherosclerosis are involved, like inflammatory and immunologic processes, that
EKSTRAKSI DAN ANALISIS FITOSTEROL LEMBAGA GANDUM [Extraction and analysis of Phytosterol from wheat germ (Triticum sp.)]  [cached]
Sri Anna Marliyati1),Hidayat Syarief1),Deddy Muchtadi2),Latifah K Darusman3)
Jurnal Teknologi dan Industri Pangan , 2005,
Abstract: Phytosterol may reduce the absorption of cholesterol, and used for preventing atherosclerosis. It is limited in soybean, but potentially abundant in wheat germ. Research on the utilization of wheat germ sterol had not been reported so far. Many aspects of germ sterol extraction from wheat germ and its characteristics were still unknown. In this research, the best extraction method, kinds and content of phytosterol from wheat germ were investigated.This research consisted of two steps: (1) extraction of phytosterol directly form whole germ and ground germ using hexane, and indirect extraction through germ oil using hexane and mixed solvent of hexane and ethanol, and direct extraction from ground germ using ethanol; (2) analysis of the type and content of phytosterol in the crude extract through the following steps: preparation of crude extract, fractionation, and analysis.Results showed that indirect extraction through germ oil was considered as the best method which yielded 1.37% of phytosterol. The highest yield was obtained when extracted using a mixed solvent of hexane ¢a a€ ethanol 82:18. However, the odor of ethanol and hexane (gasoline like odor) was still detected. The solvent ¢a a ¢s ratio of hexane to ethanol at 1:2 resulted better odor of the extract. Extraction of sterol using ethanol yielded 18.39% of sterol when the ratio of germ to ethanol at 1:10 (w/v) was applied.Results of quantitative analysis on the main component of crude extract of wheat germ sterol showed that the total content of sterol extracted with mixed solvent was higher than those extracted with ethanol. The ratio of hexane to ethanol at 1:1 (v/v) gave higher content of total sterol, stigmasterol and campesterol, whereas higher content of -sitosterol was produced at the solvent ¢a a ¢s ratio of hexane to ethanol at 1:2 (v/v).
Effect of Dietary Cholesterol and Cholesterol Oxides on Blood Cholesterol, Lipids, and the Development of Atherosclerosis in Rabbits  [PDF]
Sun Jin Hur,Byungrok Min,Ki Chang Nam,Eun Joo Lee,Dong Uk Ahn
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms140612593
Abstract: Two studies were conducted to determine the effects of dietary cholesterol (CHO) and cholesterol oxides (COPs) on the development of atherosclerosis and the changes in fatty acid and blood characteristics in rabbits. In the first study, forty male New Zealand white rabbits were divided into 5 groups and fed commercial rabbit chow with no added CHO or COPs, 1 g CHO, 0.9 g CHO + 0.1 g COPs, 0.8 g CHO + 0.2 g COPs, or 0.5 g CHO + 0.5 g COPs per kg diet. In the second study, 24 male New Zealand White rabbits were divided into 3 groups and fed a diet containing 2 g CHO, 1.6 g CHO + 0.4 g COPs, or 1.2 g CHO + 0.8 g COPs per kg diet. All diets induced atherosclerotic lesions in the rabbits’ ascending thoracic aorta. The serum CHO and triglyceride levels ( p < 0.05) increased significantly with the increased levels of CHO in the diets. Dietary CHO or COPs did not influence high-density lipoprotein CHO levels. The ratio of saturated fatty acid to unsaturated fatty acid increased as the level of dietary CHO and COPs increased.
The Relation Between Diet, Plasma Cholesterol and Atherosclerosis in Pigeons, Quails and Chickens  [PDF]
F.J. Bavelaar,A.C. Beynen
International Journal of Poultry Science , 2004,
Abstract: A literature survey was conducted to determine the relationship between plasma cholesterol concentrations and the severity of diet-induced atherosclerosis in pigeons, quails and chickens. A direct relationship was found between plasma cholesterol and atherosclerosis as induced by cholesterol feeding. In general, dietary polyunsaturated fatty acids versus saturated fatty acids lowered plasma cholesterol concentrations in the three avian species
The “Mevalonate hypothesis”: a cholesterol-independent alternative for the etiology of atherosclerosis
Keizer Hiskias G
Lipids in Health and Disease , 2012, DOI: 10.1186/1476-511x-11-149
Abstract: The “cholesterol hypothesis” is the leading theory to explain the cause of atherosclerosis. The “cholesterol hypothesis” assumes that plasma (LDL) cholesterol is an important causal factor for atherosclerosis. However, data of at least seven placebo controlled randomized prospective trials with various cholesterol lowering drugs show that plasma cholesterol lowering does not necessarily lead to protection against cardiovascular disease. Therefore an alternative hypothesis for the etiology of cardiovascular disease is formulated. This alternative hypothesis, the “mevalonate hypothesis”, assumes that after stimulation of the mevalonate pathway in endothelial cells by inflammatory factors, these cells start producing cholesterol and free radicals. In this hypothesis, only the latter play a role in the etiology of atherosclerosis by contributing to the formation of oxidized cholesterol which is a widely accepted causal factor for atherosclerosis. Regardless of how the mevalonate pathway is activated (by withdrawal of statin drugs, by inflammatory factors or indirectly by reduced intracellular cholesterol levels) in all these cases free radical production is observed as well as cardiovascular disease. Since in the “mevalonate hypothesis” cholesterol is produced at the same time as the free radicals causing atherosclerosis, this hypothesis provides an explanation for the correlation which exists between cardiovascular disease and plasma cholesterol levels. From an evolutionary perspective, concomitant cholesterol production and free radical production in response to inflammatory factors makes sense if one realizes that both activities potentially protect cells and organisms from infection by gram-negative bacteria. In conclusion, data have been collected which suggest that activation of the mevalonate pathway in endothelial cells is likely to be a causal factor for atherosclerosis. This “mevalonate hypothesis” provides a better explanation for results obtained from recent clinical studies with cholesterol lowering drugs than the “cholesterol hypothesis”. Furthermore, this hypothesis explains how cholesterol can be correlated with cardiovascular disease without being a causal factor for it. Finally it provides a logical explanation for the etiology of this disease.
Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and on atherogenesis in apolipoprotein E knock-out mice
Portugal, L.R.;Gon?alves, J.L.;Fernandes, L.R.;Silva, H.P.S.;Arantes, R.M.E.;Nicoli, J.R.;Vieira, L.Q.;Alvarez-Leite, J.I.;
Brazilian Journal of Medical and Biological Research , 2006, DOI: 10.1590/S0100-879X2006000500010
Abstract: elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. several studies have reported a decrease in serum cholesterol during the consumption of large doses of fermented dairy products or lactobacillus strains. the proposed mechanism for this effect is the removal or assimilation of intestinal cholesterol by the bacteria, reducing cholesterol absorption. although this effect was demonstrated in vitro, its relevance in vivo is still controversial. furthermore, few studies have investigated the role of lactobacilli in atherogenesis. the aim of the present study was to determine the effect of lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and the possible hypocholesterolemic and antiatherogenic action of these bacteria using atherosclerosis-prone apolipoprotein e (apo e) knock-out (ko) mice. for this purpose, swiss/nih germ-free mice were monoassociated with l. delbrueckii and fed a hypercholesterolemic diet for four weeks. in addition, apo e ko mice were fed a normal chow diet and treated with l. delbrueckii for 6 weeks. there was a reduction in cholesterol excretion in germ-free mice, which was not associated with changes in blood or liver cholesterol concentration. in apo e ko mice, no effect of l. delbrueckii was detected in blood, liver or fecal cholesterol. the atherosclerotic lesion in the aorta was also similar in mice receiving or not these bacteria. in conclusion, these results suggest that, although l. delbrueckii treatment was able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or antiatherogenic effect was observed in apo e ko mice.
Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and on atherogenesis in apolipoprotein E knock-out mice  [cached]
Portugal L.R.,Gon?alves J.L.,Fernandes L.R.,Silva H.P.S.
Brazilian Journal of Medical and Biological Research , 2006,
Abstract: Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Several studies have reported a decrease in serum cholesterol during the consumption of large doses of fermented dairy products or lactobacillus strains. The proposed mechanism for this effect is the removal or assimilation of intestinal cholesterol by the bacteria, reducing cholesterol absorption. Although this effect was demonstrated in vitro, its relevance in vivo is still controversial. Furthermore, few studies have investigated the role of lactobacilli in atherogenesis. The aim of the present study was to determine the effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and the possible hypocholesterolemic and antiatherogenic action of these bacteria using atherosclerosis-prone apolipoprotein E (apo E) knock-out (KO) mice. For this purpose, Swiss/NIH germ-free mice were monoassociated with L. delbrueckii and fed a hypercholesterolemic diet for four weeks. In addition, apo E KO mice were fed a normal chow diet and treated with L. delbrueckii for 6 weeks. There was a reduction in cholesterol excretion in germ-free mice, which was not associated with changes in blood or liver cholesterol concentration. In apo E KO mice, no effect of L. delbrueckii was detected in blood, liver or fecal cholesterol. The atherosclerotic lesion in the aorta was also similar in mice receiving or not these bacteria. In conclusion, these results suggest that, although L. delbrueckii treatment was able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or antiatherogenic effect was observed in apo E KO mice.
Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes
Berti, J.A.;de Faria, E.C.;Oliveira, H.C.F.;
Brazilian Journal of Medical and Biological Research , 2005, DOI: 10.1590/S0100-879X2005000300010
Abstract: we determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) ai, lecithin-cholesterol acyl transferase (lcat) and cholesteryl ester transfer protein (cetp), or of their combinations influenced the development of diet-induced atherosclerosis. eight genotypic groups of mice were studied (ai, lcat, cetp, lcat/ai, cetp/ai, lcat/cetp, lcat/ai/cetp, and non-transgenic) after four months on an atherogenic diet. the extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. the relative influence (r2) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. whereas apo ai (r2 = 0.22, p < 0.001) and cetp (r2 = 0.13, p < 0.01) expression reduced lesion size, the lcat (r2 = 0.16, p < 0.005) and lcat/ai (r2 = 0.13, p < 0.003) genotypes had the opposite effect. logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo ai transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. these results show that apo ai overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of lcat when both transgenes were co-expressed. on the other hand, cetp expression was sufficient to eliminate the deleterious effect of lcat and lcat/ai overexpression. therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while cetp expression can change specific athero genic scenarios.
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