Effect Of Sitosterol Research Articles

Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis

Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.

Efficacy of different primers on growth and yield of tulip (Tulipa gesneriana L.)

Tulip (Tulipa gesneriana L.) is an important and highly valuable flower of the cut flower industry. The most critical step in its cultivation is to break dormancy in order to initiate the growth, especially in tropical and sub-tropical areas of the world. Therefore, the current research was conducted to break bulb dormancy and foster the growth of tulip in Potohar region with the help of different primers. The objective of this study was the selection of best primer at appropriate concentration level to enhance growth, yield and vase life of the flower. Tulip bulbs were treated with different primers: T0 (distilled water), T1 (chitosan @ 5 g/L), T2 (gibberellic acid @ 0.15 g/L), T3 (humic acid 160 g/L), T4 (imidacloprid 19 g/L) and T5 (salicylic acid 0.1 g/L) for 24 hours, respectively. The experiment was laid out using Complete Randomized Design (CRD) with three replications. Statistical results revealed that characteristics including early germination, plant height, number of leaves, stalk length, fresh and dry weight of flower, weight of bulbs, diameter of bulbs and number of daughter bulbs were significantly increased in T2. Whereas, leaf area, diameter of stem and flower was maximum in T0. Plants under T3 showed an increase in chlorophyll content of leaves. While floral characteristics like early formation and opening of flower bud, more number of flowers and vase life were improved in T1. Thus, statistical results showed that priming can effectively help to improve morpho-physiological attributes of tulip.

In vitro effects of sitosterol and sitostanol on mitochondrial respiration in human brown adipocytes, myotubes and hepatocytes

PurposeLowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also lower triacylglycerol (TG). However, it is not fully understood how reduction in TG is achieved and what the full potential of plant sterols and stanols is on whole-body metabolism. We here hypothesize that high levels of plant sterols and stanols stimulate whole-body energy expenditure, which can be attributed to changes in mitochondrial function of brown adipose tissue (BAT), skeletal muscle and liver.MethodsPhytosterolemic mice were fed chow diets for 32 weeks to examine whole-body weight gain. In vitro, 24-h incubation were performed in adipocytes derived from human BAT, human myotubes or HepG2 human hepatocytes using sitosterol or sitostanol. Following mitochondrial function was assessed using seahorse bioanalyzer.ResultsChow feeding in phytosterolemic mice resulted in diminished increase in body weight compared to control mice. In vitro, sitosterol or sitostanol did not change mitochondrial function in adipocytes derived from human BAT or in cultured human myotubes. Interestingly, maximal mitochondrial function in HepG2 human hepatocytes was decreased following sitosterol or sitostanol incubation, however, only when mitochondrial function was assessed in low glucose-containing medium.ConclusionsBeneficial in vivo effects of plant sterols and stanols on lipid and lipoprotein metabolism are well recognized. Our results indicate that alterations in human mitochondrial function are apparently not involved to explain these beneficial effects.

Effect of Sitosterol on Root Formation of Cotton Cuttings

Effect of Sitosterol on Root Formation of Cotton Cuttings

3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity is inhibited by cholesterol and up-regulated by sitosterol in sitosterolemic fibroblasts

Sitosterolemia is an inherited recessive disease characterized by abnormally increased plasma and tissue plant sterol concentrations. Patients hyperabsorb sitosterol. In addition, hepatic, ileal, and mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-controlling enzyme in the cholesterol biosynthetic pathway, is markedly suppressed in this disease. It is still controversial whether the down-regulation is due to accumulated sitosterol, but the effect of sitosterol on HMG-CoA reductase activity has not been studied in sitosterolemic tissues. To investigate whether sitosterol inhibits HMG-CoA reductase activity in sitosterolemia, we measured the enzyme activities in liver and cultured skin fibroblasts from patients. Hepatic HMG-CoA reductase activities in patients were decreased 76% (P <.05) as compared with results in control subjects. In contrast, HMG-CoA reductase activities in sitosterolemic fibroblasts were not decreased as compared with results in control fibroblasts, and the activities in all cells were up-regulated similarly when they were exposed to delipidated medium. Because the cultured sitosterolemic fibroblasts contained only trace amounts of plant sterols, we added 20 μg/mL sitosterol directly to the cell medium. Raising the intracellular sitosterol concentration to 7% of cellular cholesterol level increased HMG-CoA reductase activity 23% (P <.05), while the addition of the same amount of cholesterol to the cells reduced the activity 46% (P <.05). Thus, when sitosterolemic skin fibroblasts were used, it was possible to distinguish between the effects of cholesterol and those of sitosterol on the activity of HMG-CoA reductase. These results suggest that reduced HMG-CoA reductase activity in this disease is caused by secondary effects of unknown regulator(s) other than sitosterol. (J Lab Clin Med 2000;135:174-9)

Cholesterol-lowering action of plant sterols.

Plant sterols have an extended history of use as cholesterol-lowering agents. Until the 1970s, the principal interest in plant sterols lay in effects of sitosterol, but over the past decade interest has reemerged in using plant sterols in functional foods. Hydrogenated plant sterols have been shown efficacious in lowering lipid levels, inhibiting cholesterol absorption and regressing plaque in animals. Hydrogenated versus unhydrogenated plant sterol esters have been demonstrated to possess equal efficacy in low-density lipoprotein cholesterol lowering in humans. Unhydrogenated plants sterol esters show consistency in cholesterol-lowering across dosage levels in humans. Unhydrogenated, unesterifed plant sterols yield similar low-density lipoprotein cholesterol lowering efficacy as achieved with hydrogenated sitostanol esters. Solubility and miscibility are likely more important determinants in cholesterol-lowering potential of plant sterols than their specific composition.

Long-term Treatment of Severe Familial Hypercholesterolemia in Children: Effect of Sitosterol and Bezafibrate

Seven prepubertal children (age range 5.3 to 10.8 years) with severe heterozygous familial hypercholesterolemia (serum cholesterol concentration 416 +/- 85 mg/dL and low-density lipoprotein [LDL] cholesterol concentration 360 +/- 90 mg/dL) were first treated by dietary intervention, second by sitosterol (3 x 2 g/d), and third by bezafibrate (2 x 200 mg/d). Each treatment period lasted 3 months. Subsequently, a treatment combining half the dose of sitosterol and bezafibrate was administered for the following 24 months. Diet alone reduced total and LDL cholesterol values by 4.5% (not significant) and 6.6% (P less than .05), respectively. Sitosterol lowered total and LDL cholesterol values by 17% (P less than .05) when compared with diet alone. Compared with sitosterol, bezafibrate produced a more pronounced effect on total and LDL cholesterol values (-18% and -28%, P less than .05), and high-density lipoprotein cholesterol concentration increased significantly from 48 mg/dL to 55 mg/dL. Combined treatment with half the dose each of sitosterol and bezafibrate was as effective as the higher dose of bezafibrate, and reduction averaged almost 40% and 50% for total and LDL cholesterol values; this lipid-lowering effect persisted for the next 24 months. Laboratory safety parameters and physical examination revealed no obvious side effects. This study indicates that the combination of sitosterol (3 x 1 g/d) plus bezafibrate (1 x 200 mg/d) is an alternate, acceptable, safe, and effective therapeutic approach for treatment of severe hypercholesterolemia in children with high-risk familial hypercholesterolemia.

Toxicity of sitosterol to human umbilical vein endothelial cellsin vitro

The pathogenesis of the early development of atherosclerosis in sitosterolaemia is unknown. The effect of sitosterol on vascular endothelial cells in vitro was investigated by culturing human umbilical vein endothelial cells in the presence of up to 0.7 mmol l-1 of sitosterol. Liposomes were used to supply the high sterol concentrations. Exposure to 0.7 mmol l-1 of sitosterol for 72 h caused contraction of the endothelial cells and increased release of intracellular lactate dehydrogenase. After 96 h incubation the cells were partly detached from the substrate. At this time-point 0.35 mmol l-1 of sitosterol also caused perturbation of the endothelial cells. However, we could not confirm previous reports that tissue plasminogen activator production was enhanced by sitosterol.

Effect of sitosterol on the rate-limiting enzymes in cholesterol synthesis and degradation.

Attempts were made to develop an animal model for phytosterolemia. Infusion of Intralipid containing 0.2% sitosterol in rats gave circulating levels of sitosterol of about 2.5 mmol/l, which is similar to or higher than those present in patients with untreated phytosterolemia. In addition, the infusions gave serum levels of cholesterol nearly twice those obtained in rats infused with Intralipid alone or Intralipid containing 0.2% cholesterol. The hepatic HMG-CoA reductase activity was unaffected or slightly increased by the sitosterol infusions (not statistically significant). The cholesterol 7 alpha-hydroxylase activity was slightly depressed (ca. 30%). In the case of 7 alpha-hydroxylation of endogenous cholesterol, the depression reached statistical significance (p less than 0.05). The microsomal content of sitosterol in the sitosterol-infused rats was about 30% of that of microsomal cholesterol. The effect of sitosterol on 7 alpha-hydroxylation of cholesterol was investigated by incubations of acetone powder of rat liver microsomes with mixtures of cholesterol and sitosterol. Sitosterol mixed with cholesterol to a composition similar to that found in the above microsomal fraction had a depressing effect on 7 alpha-hydroxylation of cholesterol. This degree of depression was of the same magnitude as that found in the sitosterol infusion experiments. The possibility is discussed that the hypercholesterolemia obtained in the beta-sitosterol-infused rats is due to the inhibitory effect of sitosterol on the cholesterol 7 alpha-hydroxylase.

Effect of sitosterol on autoxidation rate and product composition in a model lipid system

AbstractThe effect of 5% sitosterol on the autoxidation of tristearin at 120°C was investigated. It was found that sitosterol caused a two‐fold increase in the process rate; this effect was unchanged at peroxide concentrations of up to 350 mEq kg−‐1. It was established that introduction of 5% sitosterol considerably increased the concentration of oxidised products in tristearin (from 0.5 to 6.5%) after oxidation at 120°C for 7h. The degree of oxidation of sitosterol in the system was found to be 56%. The structure and composition of oxidised products in the two lipid systems (tristearin, and tristearin+5% sitosterol) were determined. Conclusions were drawn concerning the effect of the lipid medium on the composition and structure of the products of sitosterol autoxidation.

The effect of sitosterol on radioactive fat absorption patterns

1. 1. Concomitant administration of a plant sterol (cytellin) with radioactive triolein did not decrease the absorption of the tagged fat. 2. 2. In a group of patients with coronary artery disease and hypercholesterolemia prolonged treatment with this preparation produced no appreciable change in their radioactive fat tolerance even when the serum cholesterol level decreased to normal. 3. 3. Reliance on blood cholesterol levels alone is probably an incomplete guide as to the effectiveness of “antiatherogenic” medication.

Effect of sitosterol on the concentration of serum lipids in patients with coronary atherosclerosis.

The oral administration of large amounts of sitosterol to patients with coronary atherosclerosis has resulted in statistically significant decrease in serum cholesterol in one half of the trial periods. However, because of the fluctuation of the serum cholesterol that occurs in patients with coronary atherosclerosis, further study will be necessary to demonstrate that the decrease in serum cholesterol coincident with sitosterol administration is not due to the lability of the serum lipids in this group of individuals.

Effects of sitosterol on the cholesterol concentration in serum and liver in hypothyroidism.

The effects of the administration of the plant sterol, β-sitosterol, on the elevated serum lipids of hypothyroidism and on the cholesterol content of the liver have been investigated. In patients with hypothyroidism sitosterol administration, without dietary restriction, resulted in a reduction of serum cholesterol and other lipids. In the hypothyroid rat the addition of sitosterol to the diet prevented the increase in serum lipids and in the cholesterol content of the liver which otherwise occurs on a high-cholesterol diet.

Effects of Beta-sitosterol and ferric chloride on accumulation of cholesterol in mouse liver.

Summary1. Increasing the cholic acid content of a diet rich in cholesterol, significantly increased total liver cholesterol. 2. The addition of β-sitosterol to diets containing cholic acid and cholesterol, decreased total liver cholesterol. 3. Addition of ferric chloride, in varying amounts, to diets rich in cholesterol and cholic acid, resulted in practically no change in total cholesterol content of mouse liver.

The effects of sitosterol on serum lipids

1. 1. The effects of the plant sterol, beta-sitosterol, on serum cholesterol, other lipids and lipoproteins have been studied. Twenty to 25 gm. of sitosterol per day was administered for prolonged periods to fourteen patients on free diets. 2. 2. A sustained lowering of serum total cholesterol results from the prolonged administration of sitosterol. A concomitant reduction in serum total lipid, neutral fat and, to a lesser degree, lipid phosphorus occurs. 3. 3. A trend toward lower levels of S f 3–10, 10–30 and 30–100 classes of lipoproteins occurs during sitosterol administration but this effect is less consistent than the reduction of serum cholesterol. 4. 4. The effects of sitosterol are attributable to its interference with absorption of cholesterol. They are not identical with those of dietary cholesterol restriction, since sitosterol would seem to reduce absorption of cholesterol present in the bile as well as that present in the diet. 5. 5. It is suggested that sitosterol interferes with cholesterol absorption by competing for esterification, a step in the transport mechanism by which cholesterol is absorbed. 6. 6. The changes in serum lipids and lipoproteins resulting from sitosterol administration are in the direction generally considered desirable in atherosclerosis, and the absence of any toxic or adverse side effects permits its further study in man.