Preferential Efflux of Phytosterols over Cholesterol from Macrophages

Phytosterols are structurally similar to cholesterol. Increased dietary intake of phytosterols effectively lowers LDL-cholesterol. Since phytosterols are incorporated in a growing number of foods and some of the ingested phytosterols reach the circulation, accumulation of phytosterols in foam-cell-prone cells such as macrophages might occur. Therefore we examined the influx and efflux of phytosterols by human THP-1 macrophages. The influx rates of methyl-β-cyclodextrin delivered phytosterols did not significantly differ from that of cholesterol (~3.8 pmol/min per mg cellular protein), neither did the total influx of oxidised LDL delivered phytosterols differ from that of cholesterol. The efflux of β-sitosterol and sitostanol from preloaded THP-1 cells to HDL was more efficient than the efflux of campesterol and cholesterol (rate constants of 0.41 ± 0.04/h, 0.62 ± 0.08/h, 0.23 ± 0.05/h and 0.29 ± 0.03/h, respectively). The efflux of β-sitosterol was not associated with a dominant transfer to ApoA-I, nor did ABCA1 induction-promoted cholesterol efflux to the level observed for β-sitosterol. Our data show that THP-1 macrophages take up phytosterols, but have efficient mechanisms to remove phytosterols from their cellular compartments. Consequently, it is less likely that macrophages preferentially accumulate phytosterols over cholesterol and hence promote foam-cell formation in vivo.     

Parenteral Lipid Emulsions in Guinea Pigs Differentially Influence Plasma and Tissue Levels of Fatty Acids,Squalene, Cholesterol,and Phytosterols

Lipid emulsions are made by mixing vegetable and/or fish oils with egg yolk and contain different types and amounts of fatty acids and sterols. This study assessed the effects of oral diet, soybean oil (SO)-, fish oil (FO)-, a mixture of olive and soybean oil (OOSO)-, and a mixture of fish, olive, coconut, and soybean oil (FOCS)-based emulsions on plasma triacylglycerols and plasma and tissue fatty acid and sterol content following acute and chronic intravenous administration in the guinea pig. Upon acute administration, peak triacylglycerols were highest with SO and lowest with OOSO. Upon chronic administration, the plasma triglyceride levels did not increase in any group over that of the controls. Fatty acid levels varied greatly between organs of animals on the control diets and organs of animals following acute or chronic lipid administration. Squalene levels increased in plasma following acute administration of OOSO, but plasma squalene levels were similar to control in all emulsion groups following chronic administration. Total plasma phytosterol levels were increased in the SO, OOSO, and FOCS groups following both acute and chronic infusions, whereas phytosterols were not increased following FO infusion. Total phytosterol levels were higher in liver, lung, kidney and adipose tissue following SO and OOSO. Levels were not increased in tissues after FO and FOCS infusion. These results indicate that fatty acid and sterol contents vary greatly among organs and that no one tissue reflects the fatty acid or sterol composition of other tissues, suggesting that different organs regulate these compounds differently.     

Phytosterols and human lipid metabolism: efficacy,safety, and novel foods

Plant sterols have been known for several decades to cause reductions in plasma cholesterol concentrations. These plant materials have been granted a conditional health claim in the United States regarding their effects in the prevention of cardiovascular disease and are being sold in functional foods in several countries in Europe as well as in the United States and Australia. It is generally suggested that daily consumption of ∼2 g of plant sterols can lower cholesterol concentrations as part of a dietary prevention strategy. However, phytosterols have been added and tested for their cholesterol-lowering effects mainly in spreads. Consumption of these high-fat foods seemingly flies in the face of current recommendations for the promotion of heart health, which suggest lowering total fat and energy intake to maintain weight. Hence, new food formulations are being evaluated using phytosterols incorporated into low-fat and reduced-fat food items. The purpose of this review is to examine the cholesterol-lowering efficacy of plant sterols, focusing on novel food applications, their mechanism of action, and safety. These novel food formulations include new solubilization processes that lead to improved uses for plant sterols, as well as new foods into which phytosterols have been incorporated, such as breads, cereals, and beef. Such new foods, and formulations should pave the way for greater use of phytosterols in heart health promotion, increasing the longer-term potential for the creation of innovative functional foods containing plant sterols and their derivatives.     

天然植物甾醇的应用与提取工艺

文章对天然植物甾醇的分类，应用，提取工艺，分析方法等作了比较系统，详尽的论述。     

Effect of Dietary Cholesterol and Cholesterol Oxides on Blood Cholesterol,Lipids, and the Development of Atherosclerosis in Rabbits

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.     

Phytosterols in human nutrition: Type,formulation, delivery,and physiological function

Phytosterols are a family of compounds similar to cholesterol which have been shown to lower cholesterol levels when supplemented in the diet. A daily dose of 2–3 g of phytosterols has been shown to reduce LDL‐cholesterol levels by 5–15%. Phytosterol supplementation can be undertaken using phytosterol enriched functional foods or nutraceutical preparations. The type of phytosterol supplemented, such as plant sterol or saturated plant stanol appear to be equally effective in lowering cholesterol levels. Phytosterols, whether in esterified or free form have both been shown to lower cholesterol levels, with esterified phytosterol formulations having a greater number of clinical trials demonstrating efficacy. The functional food or nutraceutical matrix which is used to deliver supplemental phytosterols can significantly affect cholesterol lowering efficacy. Effective cholesterol lowering by phytosterols depends on delivery of phytosterols to the intestine in a form which can compete with cholesterol for absorption. New phytosterol functional food and nutraceuticals products should always be tested to demonstrate adequate delivery of phytosterol dose and effective total and LDL‐cholesterol lowering. Phytosterol products which do not effectively lower cholesterol will negatively impact the perception and use of phytosterols, and must not be allowed on the marketplace.     

Phytosterols,triterpene alcohols,and phospholipids in seed oil from white lupin

This study was conducted to determine effects of genotypes and growing environment on phytosterols, triterpene alcohols, and phospholipids (PL) in lupin (Lupinus albus L.) oil from seven genotypes grown in Maine and Virginia. The unsaponifiable lipid (UNSAP) and phospholipid (PL) fractions ranged from 2.1 to 2.8% and from 2.6 to 2.8% of oil, respectively. UNSAP in lupin oil contained 19.9 to 28.7% sterols and 17.3 to 22.0% triterpene alcohols. Growing location significantly affected contents of total PL, PS, phosphatidylglycerol, β-sitosterol, campesterol, and β-amyrin. Genotypic effects were significant for stigmasterol. PC (32.6 to 46.3% of PL), PE (21.6 to 32% of PL), and PS (11.2 to 17.9% of PL) were the major PL in lupin oil. The concentration of PL classes in lupin oil were in the following descending order: PC>PE>PS>PI>phosphatidic acid > lysophosphatidylcholine > phosphatidylglycerol > diphosphatidylglycerol. In descending order of abundance, the sterols present in lupin oil were: β-sitosterol > campesterol > stigmasterol > Δ⁵-avenasterol > Δ⁷-stigmastenol Lupeol was the most prominent triterpene alcohol in lupin seed oil. In general, growing environment had a much greater influence on lupin oil characteristics than the genotypes.     

Sea Anemones,Actinoporins, and Cholesterol

Spanish or Spanish-speaking scientists represent a remarkably populated group within the scientific community studying pore-forming proteins. Some of these scientists, ourselves included, focus on the study of actinoporins, a fascinating group of metamorphic pore-forming proteins produced within the venom of several sea anemones. These toxic proteins can spontaneously transit from a water-soluble fold to an integral membrane ensemble because they specifically recognize sphingomyelin in the membrane. Once they bind to the bilayer, they subsequently oligomerize into a pore that triggers cell-death by osmotic shock. In addition to sphingomyelin, some actinoporins are especially sensible to some other membrane components such as cholesterol. Our group from Universidad Complutense of Madrid has focused greatly on the role played by sterols in this water–membrane transition, a question which still remains only partially solved and constitutes the main core of the article below.     

Phytosterols and steryl esters in diverse Cucurbita,Cucumis and Citrullus seed oils

Δ⁷‐Phytosterols present in pumpkin seed oil are significant for the prevention of prostate disorders. Herbal medicines are increasingly offered as dried kernels or concentrated ethanolic extracts of Cucurbita pepo seeds. Until now, the pumpkin seeds of C. pepo have almost exclusively been used for this purpose. Only a few data concerning the sterol content of other Cucurbitoideae seeds are available. Therefore, we isolated, identified, and quantified the free and esterified phytosterols of 12 Cucurbita, 3 Cucumis, and 3 Citrullus seed oils. The total sterol content of these seeds ranged from 297 mg per 100 g oil in Cucurbita maxima ‘Turk's Turban’ to 814 mg per 100 g oil in Citrullus lanatus ‘Sugar Baby Watermelon’, equivalent to 64 to 193 mg per 100 g seeds respectively. These were mainly Δ⁷‐sterols (˜82%) with the steryl esters acounting for ˜32% of the total sterol content.     

Egg‐Yolk Sphingomyelin and Phosphatidylcholine Attenuate Cholesterol Absorption in Caco‐2 Cells

Phospholipids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is regulated by several transporter proteins. Of these proteins, Niemann–Pick C1‐Like 1 (NPC1L1) is a major contributor to this process. The mechanism by which phospholipids modulate cholesterol absorption remains unknown. Here, we evaluate the effects of egg‐yolk phospholipids on cholesterol absorption and transport in human colon carcinoma cell line (Caco‐2 cells) and on the expression of NPC1L1 and others proteins associated with cholesterol absorption (ABCG5, ABCG8, ABCA1, ACAT2, MTP, CAV‐1, ANX‐2). The roles of SREBP‐1 and SREBP‐2 in this process were also investigated. The results show that egg‐yolk sphingomyelin (CerPCho) and phosphatidylcholine (PtdCho) inhibit cholesterol transport in the Caco‐2 monolayer in a dose‐dependent manner. These might be due to the decrease of the cholesterol solubility in micelles as well as to the increases in the micellar sizes and the bile acid‐binding capacity. Furthermore, the treatments with egg‐yolk CerPCho or PtdCho at 1.2 mmol/L reduced the expression levels of NPC1L1 protein to 21 or 22%, respectively, and its mRNA to 9 or 31% of that in the control group (p < 0.05). Moreover, there was a general inhibitory effect of egg‐yolk PtdCho and CerPCho on the mRNA levels of SREBP‐1, and SREBP‐2. These results suggest that the inhibitory effect of egg‐yolk CerPCho and PtdCho on cholesterol transport might be due to their interference with the physicochemical properties of micelles and their regulations on the expression of the NPC1L1 gene.     

NPC1L1 and SR-BI are Involved in Intestinal Cholesterol Absorption from Small-Size Lipid Donors

In the human intestinal content after a meal, cholesterol is dispersed in a complex mixture of emulsified droplets, vesicles, mixed micelles and precipitated material. The aim of this study was to determine the contribution of the main intestinal cholesterol transporters (NPC1L1, SR-BI) to the absorption processes, using different cholesterol-solubilizing donors. Cholesterol donors prepared with different taurocholate concentrations were added to an apical medium of differentiated TC7/Caco-2 cells. As the taurocholate concentrations increased, cholesterol donor size decreased (from 712 to 7 nm in diameter), which enhanced cholesterol absorption in a dose-dependent manner (38-fold). Two transport processes were observed: (1) absorption from large donors exhibited low-capacity transport with no noticeable transporter contribution; (2) efficient cholesterol absorption occurs from small lipid donors (相似文献   

Absorption of Dietary Cholesterol Oxidation Products and Their Downstream Metabolic Effects Are Reduced by Dietary Apple Polyphenols

Exogenous and endogenous cholesterol oxidation products (COPs) perturb various metabolic processes, and thereby they may induce various homeostasis-related disorders. Here, we observed that procyanidin-rich dietary apple polyphenol (APP) from unripe apples alleviates the perturbation of lipid metabolism by decreasing the exogenous COP levels in rats. Dietary COPs may be the greatest source of COPs found in the human body. Rats (4 weeks of age) were fed AIN-purified diets containing 0.3% COPs supplemented with 0.5 or 2.5% APP for 3 weeks. Dietary APP alleviated the growth inhibition action of the exogenous COPs. The modulations of the liver lipid profile by COPs remained unchanged. However, serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels increased following the intake of dietary APP. Further, dietary APP inhibited the increase in lipid peroxide levels in the liver and serum by COPs. The activity of hepatic Δ6 desaturase was lowered by dietary APP in a dose-dependent manner, although exogenous COPs generally increased the activity of this enzyme. In keeping with this observation, Δ6 desaturation indices in the phospholipids and cholesteryl esters of the liver and serum lipids were lower in the APP-fed groups than those in the control group. Dietary APP also promoted the excretion of exogenous COPs, cholesterol, and acidic steroids in feces. Therefore, the inhibition of intestinal absorption of COPs may partly contribute to the alleviation of the perturbation of lipid metabolism and lipid peroxidation levels. Thus, APP may be an important removal agent of exogenous toxic material such as COPs contained in processed or fast foods.     

Glycosidic Bond Cleavage is Not Required for Phytosteryl Glycoside-Induced Reduction of Cholesterol Absorption in Mice

Phytosteryl glycosides occur in natural foods but little is known about their metabolism and bioactivity. Purified acylated steryl glycosides (ASG) were compared with phytosteryl esters (PSE) in mice. Animals on a phytosterol-free diet received ASG or PSE by gavage in purified soybean oil along with tracers cholesterol-d₇ and sitostanol-d₄. In a three-day fecal recovery study, ASG reduced cholesterol absorption efficiency by 45 ± 6% compared with 40 ± 6% observed with PSE. Four hours after gavage, plasma and liver cholesterol-d₇ levels were reduced 86% or more when ASG was present. Liver total phytosterols were unchanged after ASG administration but were significantly increased after PSE. After ASG treatment both ASG and deacylated steryl glycosides (SG) were found in the gut mucosa and lumen. ASG was quantitatively recovered from stool samples as SG. These results demonstrate that ASG reduces cholesterol absorption in mice as efficiently as PSE while having little systemic absorption itself. Cleavage of the glycosidic linkage is not required for biological activity of ASG. Phytosteryl glycosides should be included in measurements of bioactive phytosterols.     

脱臭馏出物中植物甾醇的回收和精制

以脱臭馏出物为原料，采用甲醇酯化、结晶分离、溶剂重结晶净化精制工艺，对回收和精制植物甾醇的过程进行了研究. 实验结果表明，应用该工艺从油脂脱臭馏出物中提取的植物甾醇含量大于95%，过程总收率达80%以上，为从脱臭馏出物中提取植物甾醇的工业化生产提供了技术依据.     

Viral Hepatitis,Cholesterol Metabolism,and Cholesterol-Lowering Natural Compounds

Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis.     

Lipase-Catalyzed Esterification of Triterpene Alcohols and Phytosterols with Oleic Acid

Oleic acid esters of phytosterols (PSs) and triterpene alcohols (TAs), derived from rice bran, were synthesized using lipases under mild conditions. Some lipases, especially from Candida rugosa, type VII, showed very high substrate specificity towards both PSs and TAs, when a mixture of PS and TA (PS/TA mixture) was used as the substrate source. The maximum yield of PS esters was ca. 80 % in each case; however, the maximum yield of TA esters was much lower when the reaction was continued for 7 days. Due to the difficulty in purifying the esters obtained when the PS/TA mixture was used as source of substrate, free PSs and TAs were separated from the PS/TA mixture by silica-gel and reverse-phase chromatography prior to esterification. The pure PSs or TAs were esterified with oleic acid to obtain the corresponding esters with high purity. Differential scanning calorimetric analysis of the resulting esters revealed that their melting points ranged from 7.0 to 42 °C. These values were at least 100 °C lower than those of the free PSs and TAs.     

Fatty Acids,Tocopherols, Tocotrienols,Phytosterols, Carotenoids,and Squalene in Seed Oils of Hyptis suaveolens,Leonotis nepetifolia,and Ocimum sanctum

The oil yield and composition of fatty acids, tocopherols, tocotrienols, sterols, carotenoids, and squalene in the seeds of three species—Hyptis suaveolens, Leonotis nepetifolia, Ocimum sanctum—belonging to the Lamiaceae family, are studied. The oil yields are 12.1%, 16.1%, and 29.0% in O. sanctum, H. suaveolens, and L. nepetifolia, respectively. The unsaturated fatty acids are a predominant group (86.8–92.1%) in all three investigated plants; however, the profile for each species is unique. The main fatty acid differs as follows: H. suaveolens—linoleic acid (85.8%), L. nepetifolia—oleic acid (58.3%), and O. sanctum—α‐linolenic (48.6%). γ‐Tocopherol accounts for over 97%, 90%, and 93% of the total tocochromanol content (sum of tocopherols and tocotrienols) in H. suaveolens, L. nepetifolia, and O. sanctum, respectively. Two tocotrienol homologues, α and γ, are detected only in L. nepetifolia. β‐Sitosterol is the main detected sterol (38–59%) in all three species. High levels of campesterol (18–20%), Δ5‐stigmasterol (9–21%), and Δ5‐avenasterol (7–12%) are also detected. Squalene is detected only in O. sanctum (45.8 mg/100 g oil). The content of sterols, tocochromanols, and carotenoids in the investigated Lamiaceae plant seed oils ranges between 279.5–576.3, 54.5–66.7, and 0.3–3.1 mg/100 g oil, respectively. Practical Applications: Lamiaceae plants are of medicinal interest due to the presence of a broad spectrum of bioactive molecules. The present study demonstrates that seeds of the species H. suaveolens, L. nepetifolia, and O. sanctum are rich sources of bioactive compounds of lipophilic nature. There is limited knowledge associated with the composition of tocopherols, tocotrienols, sterols, carotenoids, and squalene. The results of the studied medicinal plants may enhance future targeted applications in various sectors.