Inhibition Of Low-density Lipoprotein Oxidation Research Articles

Inhibitory effects of compounds isolated from roots of Cynanchum wilfordii on oxidation and glycation of human low-density lipoprotein (LDL)

Abstract Low-density lipoprotein (LDL) modification such as oxidation and glycation has been known to play a significant role in the initiation and progression of atherosclerosis. The inhibitors on LDL modification have been emerged as a new strategy to be a supplement for prevention of atherosclerosis. In an effort to discover inhibitors on LDL modification from natural products, phytochemical investigation on Cynanchum wilfordii roots were performed, leading to isolation of acetophenones (1–6) including a new one (1) and nine pregnane-type steroids (7–15). The structure of the compound 1 was determined by analysis of 1D and 2D NMR spectral data analysis. All the isolated compounds were evaluated for their inhibitory activities against LDL modification. Among them, compounds 2 and 5 strongly inhibited LDL oxidation and glycation. These results suggest that compounds 2 and 5 from C. wilfordii may provide potential protective effects against atherosclerosis via inhibition of LDL oxidation and glycation.

Positively charged peptides from casein hydrolysate show strong inhibitory effects on LDL oxidation and cellular lipid accumulation in Raw264.7 cells

Inhibiting low-density lipoprotein (LDL) oxidation and cellular lipid accumulation to reduce foam cell formation plays a key role in preventing atherosclerosis. Casein hydrolysate (66% < 1 kDa) was separated into four different charged fractions. The inhibitory effect of peptide fractions on LDL oxidation and cellular lipid accumulation was analysed using a CuSO4 cell-free system and a Cu2+-mediated and ox-LDL-induced Raw264.7 macrophage cell-based system. Casein peptide fractions not only significantly inhibited LDL oxidation but also prevented cellular lipid accumulation. Positively charged fractions exhibited stronger inhibitory effects than negatively charged fractions. Seven peptides with different charge properties were synthesised. With the increase in net positive charge, the ability of peptides to inhibit LDL oxidation was enhanced. Peptides containing lysine presented better inhibition than those that contained histidine. This study suggests that casein hydrolysate, especially positively charged peptide fractions, could be used as a natural antioxidant in functional foods to prevent atherosclerosis.

Antioxidants inhibit low density lipoprotein oxidation less at lysosomal pH: A possible explanation as to why the clinical trials of antioxidants might have failed

Oxidised low density lipoprotein (LDL) was considered to be important in the pathogenesis of atherosclerosis, but the large clinical trials of antioxidants, including the first one using probucol (the PQRST Trial), failed to show benefit and have cast doubt on the importance of oxidised LDL. We have shown previously that LDL oxidation can be catalysed by iron in the lysosomes of macrophages. The aim of this study was therefore to investigate the effectiveness of antioxidants in preventing LDL oxidation at lysosomal pH and also establish the possible mechanism of oxidation. Probucol did not effectively inhibit the oxidation of LDL at lysosomal pH, as measured by conjugated dienes or oxidised cholesteryl esters or tryptophan residues in isolated LDL or by ceroid formation in the lysosomes of macrophage-like cells, in marked contrast to its highly effective inhibition of LDL oxidation at pH 7.4. LDL oxidation at lysosomal pH was inhibited very effectively for long periods by N,N'-diphenyl-1,4-phenylenediamine, which is more hydrophobic than probucol and has been shown by others to inhibit atherosclerosis in rabbits, and by cysteamine, which is a hydrophilic antioxidant that accumulates in lysosomes. Iron-induced LDL oxidation might be due to the formation of the superoxide radical, which protonates at lysosomal pH to form the much more reactive, hydrophobic hydroperoxyl radical, which can enter LDL and reach its core. Probucol resides mainly in the surface monolayer of LDL and would not effectively scavenge hydroperoxyl radicals in the core of LDL. This might explain why probucol failed to protect against atherosclerosis in various clinical trials. The oxidised LDL hypothesis of atherosclerosis now needs to be re-evaluated using different and more effective antioxidants that protect against the lysosomal oxidation of LDL.

Syzygium cumini leaf extract inhibits LDL oxidation, but does not protect the liproprotein from glycation

Etnopharmacological relevanceSyzygium cumini (L.) Skeels is a plant widely used in folk medicine to treat diabetes mellitus (DM). The tea from its leaves is frequently used by diabetics for lowering hyperglycemia. There is a close relationship between DM and atherosclerosis, a chronic immuno-inflammatory disease, were the early stages encompass oxidative and glycative modifications in the structure of low density lipoprotein (LDL). Aim of this studyTo investigate the potential protective effects of aqueous-leaf extract from Syzygium cumini (S.cExt) against CuSO4-induced oxidation and methylglyoxal (MG)-induced glycation of human LDL in vitro. Materials and methodsLDL oxidative changes were evaluated by measuring conjugated dienes (CD) formation, thiobarbituric acid reactive substances (TBARS) levels, quenching of tryptophan (Trp) fluorescence and structural modifications in LDL particle. In LDL glycated by MG (glyLDL), we determined the levels of fluorescent advanced glycation end products (AGEs) and mobility by agarose gel electrophoresis. ResultsS.cExt blocked oxidative events induced by CuSO4 in human LDL, plasma and serum. Fourier transform infrared spectroscopy (FT-IR) revealed that specific regions of apoB100 were oxidized by CuSO4 in human LDL and that S.cExt reduced these oxidations. Unlike, the increased AGEs levels and eletrophoretic mobility observed in LDL MG-glycated were not modified by S.cExt. ConclusionThe findings herein indicate that S.cExt could be tested in atherogenesis models as potential protective agent against LDL oxidation.

ANTIDYSLIPIDEMIA AND ANTIOXIDANT ACTIVITY OF ANDROGRAPHOLIDE COMPOUND FROM SAMBILOTO (ANDROGRAPHIS PANICULATA) HERB

Objective: The aim of this study was to observe the antidyslipidemic and antioxidant activity of andrographolide (AND) compound from Sambiloto (Andrographis paniculata) herb. The antidyslipidemic activity could be described by lowering TC (total cholesterol), TG (triglyceride), and LDL (low-density lipoprotein) level in the blood and by increasing HDL (high-density lipoprotein) level in the blood. The antioxidant activity could be described by inhibiting the ox-LDL (oxidized low-density lipoprotein) formation.Methods: AND was separated from the sambiloto ethanolic extract. Atherosclerosis in rats was induced by rich fat food (5% yolk, 10% lard), 1% calcium and 20.000 IU vitamin D3 for 90 d. The rats were treated with AND compound on the 61st day for 30 d. On the 90th day, the blood of rats had been collected, and its blood vessel was also extracted. Antidyslipidemic activity was measured by estimating the level of TC, TG, LDL and HDL in the blood. Antioxidant activity was measured by calculating the ox-LDL concentration in blood and histopathology parameter.Results: 18 mg/kg BW AND could reduce the level TC, TG, and LDL in blood, and could increase HDL blood level significantly (p&lt;0.05). This compound can also significantly inhibit LDL oxidation (p&lt;0.05), and the histopathology result showed that this compound could protect the vessel from adhesive lipid plaques.Conclusion: AND compound from sambiloto herb showed the antidyslipidemic and antioxidant effect in atherogenic rats.

The Health Benefits of Jeju Gamgyul ( Citrus unshiu Marc.) Brandy and Wine

Beneficial health effects of fruits and vegetables in the diet have been attributed to the reduction of risk for some diseases, such as diabetes, chronic diseases, cancer, or cardiovascular diseases. Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and the fact that their pulp are usually consumed like juice or jam, although their functional effects are much higher than those of fruit peels. This investigation inquired into the effects of Gamgyul wine, which is derived from whole fruits of Citrus unshiu, with respect to antioxidant property, anti-diabetic activity, low density lipoprotein (LDL) oxidative inhibition and flavanones. In particular, antioxidant and antidiabetic activities of both Gamgyul wine and brandy were measured. However, the differences of the antioxidant and antidiabetic effects of Gamgyul wine were trifling between dynamite and microfiltration processes. In particular, the effect of antidiabetic activity was rather significant as demonstrated in the Gamgyul brandy. The results showed that α-glucosidase inhibition rates at 20 µL/mL for Gamgyul brandy and wine were 50% and 20%, respectively. Almost 100% inhibition rate was shown at 80 µL/mL treatment for all the samples. Antioxidant activities and LDL oxidative inhibition were also measured. Gamgyul wine showed increased concentration-dependent antioxidant activities, while epigallocatechin gallate (EGCG) revealed an almost same level of activities. On the other hand, Gamgyul brandy presented little activity at any treatment concentration. Gamgyul wine in 20 µL/mL inhibited LDL oxidation approximately three times more than that of the comparative negative control, D.W. Flavanone analysis showed detections of both narirutin and hesperidin, while narirutin was the most abundant flavanone in Gamgyul wine. These overall results suggest that Gamgyul wine has the potential to be used as a functional dietary supplement and is an effective α-glucosidase inhibitor, which may be beneficial only for low to moderate intake.

Evaluación química y capacidad antioxidante de extractos polifenólicos de cortezas

Se evaluó la concentración de fenoles totales, flavonoides y proantocianidinas en extractos de acetona acuosa 70% (extracto crudo) y extractos semipurificados por partición líquido-líquido con acetato de etilo (extracto orgánico), de cortezas de Pinus cooperi, Pinus engelmannii, Pinus leiophylla y Pinus teocote, asimismo se determinó la actividad antioxidante de los extractos por las técnicas de radical ácido 2,2´-azinobis-3-etilbenzotiazolin-6-sulfónico (ABTS•+), desoxi-d-ribosa (atrapamiento de radical hidroxilo), y por la inhibición de la oxidación de lipoproteínas de baja densidad (LDL). Se realizó una comparación cromatográfica de los extractos por Cromatografía Líquida de Alta Resolución (HPLC). La concentración de fenoles fue de 491 mg g-1 a 604 mg g-1, los extractos orgánicos presentaron mayor concentración de flavonoides (292 mg g-1 a 385 mg g-1) que los extractos crudos (259 mg g-1 a 314 mg g-1) , mientras que la concentración de proantocianidinas fue mayor en el extracto crudo (186 mg g-1a 286 mg g-1) que en el orgánico (70 mg g-1a 151 mg g-1) . La capacidad de captura del radical ABTS fue de 49,48% a 57,44%, similares al que presentó el estándar catequina (57,92 %). La capacidad de captura del radical hidroxilo varió de 25,85% a 48,46% y fue mayor en el extracto orgánico en todas las especies. La inhibición de oxidación de LDL fue de 64,41% a 89,39%, con valores más altos en el extracto orgánico. Los cromatogramas de HPLC muestran semejanza de los compuestos químicos en las cuatro especies. Se identificó el flavanol catequina a baja concentración en todas las especies. El compuesto principal en P. cooperi, P. engelmannii, y P. teocote, es similar en las tres especies y por espectro de UV corresponde a una flavanona.

Protective effects of 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitors on oxidative modification of human low density lipoproteins in vitro.

It has been suggested that 2,3-diaryl-substituted indole-based cyclooxygenase-2 (COX-2) inhibitors (2,3-diaryl-indole coxibs) do not only appear as potent anti-inflammatory agents but also show the ability to scavenge reactive oxygen species (ROS). This led to the hypothesis that 2,3-diaryl-indole coxibs also may act as potent inhibitors of oxidative modification of low-density lipoprotein (LDL), which is considered a key factor in atherogenesis. The aim of this study was to explore i) the reactivity of a series of new synthesized 2,3-diaryl-indoles with several well characterized LDL oxidation systems and ii) subsequent effects on an inflammatory/atherogenic microenvironment. The results demonstrate that under the present experimental conditions 2,3-diaryl-indoles showed potent ROS scavenging activity and were able to markedly inhibit LDL oxidation. Subsequently, this led to a substantial decrease of modified LDL uptake by scavenger receptors in THP-1 macrophages in vitro and in rats in vivo. Moreover, modified LDL-mediated monocyte/neutrophil adhesion to endothelial cells, macrophage NFκB activation, as well as macrophage and endothelial cell cytokine release was diminished in vitro. The reduction of modified LDL-induced atherogenic effects by antioxidant 2,3-diaryl-indole coxibs may widen the therapeutic window of COX-2 targeted treatment.

Cardio-Protecting Effect of Natural Bioactive Compound (Polyphenol) by Inhibiting LDL Oxidation with the Scavenging of Reactive Oxygen Species (ROS)

Reduction in plasma low-density lipoprotein is a fundamental treatment for the prevention of acute coronary syndromes (ACS). Oxidization of low-density lipoprotein (LDL) particles leads to formation of atherosclerotic lesions and increased risk of cardiovascular disease (CVD) via a complex cascade of biochemical events occurring mostly within the arterial wall. The major advantage of drug those are treating with hypertension, hyperglycemia and hyperlipidemias to reduce the CVD morbidity and mortality are well established. However, the epidemiological evidences support that ingestion of certain foods in regular diet chart results to a reduction in of myocardial infarction markers and other CVD. Many reviews supported that the dietary antioxidants pertained to LDL oxidation and to vascular endothelial dysfunction. Polyphenol consumption is beneficial to maintain the plasma LDL level. This short commentary emphasising on health aspect depending on the published literature, which may provide some guidance for researchers in further investigations of cardiovascular health agents

Sorghum–cowpea composite porridge as a functional food, Part II: Antioxidant properties as affected by simulated in vitro gastrointestinal digestion

The effect of compositing red non-tannin sorghum with brownish-cream cowpea and in vitro gastrointestinal digestion on total phenolic and flavonoid contents and antioxidant properties of a sorghum–cowpea composite porridge was studied. Maize–soybean composite porridge was used as a reference sample. Antioxidant properties were studied using radical scavenging activities against the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), peroxyl and NO radicals as well as inhibition of low density lipoprotein (LDL) oxidation and oxidative damage of vector DNA. Hydroperoxide content of the samples was also measured. All the samples demonstrated radical scavenging activity. Simulated duodenal digests of the porridges had hydroperoxides and therefore caused LDL oxidation. The undigested porridges and simulated gastric digests inhibited LDL oxidation. Compositing the cereals with legumes increased total phenolic and flavonoid contents and NO scavenging activity of their porridges. In vitro gastrointestinal digestion of the porridges increased their total phenolic and flavonoid contents, radical scavenging activities and LDL oxidation inhibitory activity.

Antiatherogenic and antitumoral properties of Opuntia cladodes: inhibition of low density lipoprotein oxidation by vascular cells, and protection against the cytotoxicity of lipid oxidation product 4-hydroxynonenal in a colorectal cancer cellular model.

Opuntia species have been used for thousands of years as a folk medicine in the treatment of diseases. However, the components and protective mechanisms are still unclear. We make the hypothesis that Opuntia species may protect the development of oxidative stress-associated diseases, such as atherosclerosis or colon cancer, via their antioxidant properties. We investigated the protective effect of Opuntia cladode powder against the oxidation of low-density lipoprotein (LDL) evoked by vascular endothelial cells, an important risk factor for atherosclerosis development, and the toxicity of 4-hydroxynonenal (a major lipid peroxidation product) on normal (Apc +/+) and preneoplastic (Apc min/+) immortalized epithelial colon cells. Various Opuntia species classified according to their degree of domestication, from the wildest (Opuntia streptacantha, Opuntia hyptiacantha, Opuntia megacantha), medium (Opuntia albicarpa), to the most domesticated (Opuntia ficus-indica) were tested. Cladode powders prepared from these Opuntia species significantly inhibited LDL oxidation induced by incubation with murine endothelial cells and the subsequent foam cell formation of RAW 264.7 murine macrophages and cytotoxicity on murine endothelial cells. Moreover, Opuntia cladode powder blocked the promotion of colon cancer development on an in vitro model of colonocytes. It may be noted that the phenolic acid and flavonoids content, the antioxidant capacity, and the protective effect were relatively similar in all the cladode powders from wild (O. streptacantha) and domesticated Opuntia. Altogether, these data confirm the therapeutic potential of Opuntia cladodes in diseases associated with oxidative stress.

Effects of lactic acid bacteria on low-density lipoprotein susceptibility to oxidation and aortic fatty lesion formation in hyperlipidemic hamsters.

We investigated the effects of Streptococcus thermophilus YIT 2001, a strain of lactic acid bacteria, on the susceptibility of low-density lipoprotein (LDL) to oxidation and the formation of aortic fatty lesions in hyperlipidemic hamsters. S. thermophilus YIT 2001 had the highest in vitro antioxidative activity against LDL oxidation among the 79 strains of lactic acid bacteria and bifidobacteria tested, which was about twice that of S. thermophilus YIT 2084. The lag time of LDL oxidation in the YIT 2001 feeding group was significantly longer than in controls, but was unchanged in the YIT 2084 group. After the feeding of YIT 2001, lag times were prolonged and areas of aortic fatty lesions were dose-dependently attenuated, although there were no effects on plasma lipid levels. These results suggest that YIT 2001 has the potential to prevent the formation of aortic fatty lesions by inhibiting LDL oxidation.

Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism

Lipid oxidation leads to endothelial dysfunction, inflammation, and foam cell formation during atherogenesis. Glucose also contributes to lipid oxidation and promotes pathologic changes in membrane structural organization, including the development of cholesterol crystalline domains. In this study, we tested the comparative effects of eicosapentaenoic acid (EPA), an omega-3 fatty acid indicated for the treatment of very high triglyceride (TG) levels, and other TG-lowering agents (fenofibrate, niacin, and gemfibrozil) on lipid oxidation in human low-density lipoprotein (LDL) as well as membrane lipid vesicles prepared in the presence of glucose (200mg/dL). We also examined the antioxidant effects of EPA in combination with atorvastatin o-hydroxy (active) metabolite (ATM). Glucose-induced changes in membrane structural organization were measured using small angle x-ray scattering approaches and correlated with changes in lipid hydroperoxide (LOOH) levels. EPA was found to inhibit LDL oxidation in a dose-dependent manner (1.0–10.0µM) and was distinguished from the other TG-lowering agents, which had no significant effect as compared to vehicle treatment alone. Similar effects were observed in membrane lipid vesicles exposed to hyperglycemic conditions. The antioxidant activity of EPA, as observed in glucose-treated vesicles, was significantly enhanced in combination with ATM. Glucose treatment produced highly-ordered, membrane-restricted, cholesterol crystalline domains, which correlated with increased LOOH levels. Of the agents tested in this study, only EPA inhibited glucose-induced cholesterol domain formation. These data demonstrate that EPA, at pharmacologic levels, inhibits hyperglycemia-induced changes in membrane lipid structural organization through a potent antioxidant mechanism associated with its distinct, physicochemical interactions with the membrane bilayer.

The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes.

It was found that glucose in the range of concentrations 12.5-100mM stimulated Cu(2+)-mediated free radical peroxidation of low-density lipoproteins (LDL) from human blood plasma. Considering the kinetic parameters of LDL peroxidation we proposed that intensification of this process may be caused by formation of free radical intermediates of glucose auto-oxidation. Addition of SOD to the medium inhibited LDL oxidation, indicating the formation of superoxide anion-radicals under autoxidation of glucose. Similarly, SOD inhibited free radical peroxidation of liposomes from egg lecithin in the presence of glucose that confirms the generation of superoxide radicals under co-oxidation of unsaturated lipids and glucose. Normalization of glucose level in the blood of patients with type 2 diabetes mellitus during therapy was accompanied by a significant decrease in LDL oxidation in vivo (the decrease in primary and secondary lipoperoxidation products). The formation of superoxide anion-radicals was observed during interaction of aminoacid L-lysine with a product of glucose oxidative metabolism-methylglyoxal, but not with a product of lipoperoxidation malonyldialdehyde. In accordance with the foregoing the administration of sugar-lowering drug metformin, which binds and utilizes methylglyoxal, caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals. Based on the results we set out the hypothesis about autocatalytic mechanism of free radical reactions involving natural dicarbonyls and suppose the common molecular mechanism of vascular wall injury in atherosclerosis and diabetes.

Antioxidative properties and ability of phenolic compounds of Myrtus communis leaves to counteract in vitro LDL and phospholipid aqueous dispersion oxidation.

Antioxidant activities of Myrtus communis leaf phenolic compounds (McPCs) were investigated on 2,2'-9-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS(+) •) and oxygen radical absorbance capacity (ORAC) tests or on oxidation of biological models, human low-density lipoprotein (LDL) and phospholipid aqueous dispersion (L-α-phosphatidylcholine stabilized by bile salts). Two extraction techniques, microwave-assisted (MAE) and conventional (CE), were used to isolate McPCs, producing similar results of phenolic compound content. ABTS(+) • assay showed clearly that myrtle extracts exhibited a stronger scavenging effect than butylated hydroxyanisole and α-tocopherol, with a slight advantage for myrtle CE extract. In ORAC assay, the both McPC extracts were similarly less effective than the pure compounds as caffeic acid and myricitrin (myricetin 3-O-rhamnoside) but stronger than butylated hydroxytoluene. Moreover, myrtle CE and MAE extracts, and myricitrin were able to inhibit similarly the production of conjugated dienes and to prolong the lag phase (Tlag) during Cu(2+)-induced LDL oxidation with a dose-response effect. The cryo-electron microscopy observations on studied phospholipid dispersion stabilized by bile salts (BS) revealed the presence of bilayer vesicles and micelles. In 2,2'-azobis (2-amidinopropane) hydrochloride-induced phospholipid/BS oxidation, myrtle CE and MAE extracts gave similar effects to α-tocopherol and caffeic acid but myricitrin showed a higher protective effect than myrtle extracts. We showed also that no synergic or additive effect between α-tocopherol and myrtle extracts or caffeic acid in α-tocopherol-enriched phospholipid/BS dispersion, but myricitrin showed an additive effect and thus promoted the total antioxidant activity. These data showed that myrtle extract could be used as potential natural antioxidants, food stabilizers, or natural health products. We show that microwave-assisted extraction could be an alternative method for plant phenolic compound recovery allowing important gain in time extraction.We report inhibition of low-density lipoprotein oxidation in vitro initiated by Cu(2+) ions. We report that myrtle extract may be a source of natural antioxidants to counteract phospholipid peroxidation as well as α-tocopherol.

Poster #T161 AN OPEN-LABEL TRIAL OF ADJUNCTIVE TOCILIZUMAB IN SCHIZOPHRENIA

Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating potential anti-atherogenic properties. The aim of this study was to investigate how the inhibition of low density lipoprotein (LDL) oxidation was influenced by common apoA-IV isoforms. Recombinant wild type apoA-IV (100 μg/ml) significantly inhibited the oxidation of LDL (50 μg protein/ml) by 5 μM CuSO4 (P < 0.005), but not by 100 μM CuSO4, suggesting that it may act by binding copper ions. ApoA-IV also inhibited the oxidation of LDL by the water-soluble free-radical generator 2,2′-azobis(amidinopropane) dihydrochloride (AAPH; 1 mM), as shown by the two-fold increase in the time for half maximal conjugated diene formation (T1/2; P < 0.05) suggesting it can also scavenge free radicals in the aqueous phase. Compared to wild type apoA-IV, apoA-IV-S347 decreased T1/2 by 15% (P = 0.036) and apoA-IV-H360 increased T1/2 by 18% (P = 0.046). All apoA-IV isoforms increased the relative electrophoretic mobility of native LDL, suggesting apoA-IV can bind to LDL and acts as a site-specific antioxidant. The reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV may account for the previous association of the APOA4 S347 variant with increased CHD risk and oxidative stress.

Inhibition of Human Low-Density Lipoprotein Oxidation In Vitro by Ginger Extracts

Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in atherosclerotic plaque formation. Currently, there is a renewed interest in ginger because of its antioxidants and cardioprotective properties. The effects of ethanol, methanol, ethyl acetate, and hexane solvent extracts of ginger and pure major ginger constituents on Cu(2+)-induced oxidation of human LDL in vitro were examined. The LDL oxidation inhibition by ethanol, methanol, ethyl acetate, and hexane extracts of ginger was 71%, 76%, 67%, and 67%, respectively, at their optimum extraction conditions. Inhibition of LDL oxidation by water extracts of ginger, which was prepared by ultrasonic-assisted extraction conditions of 52°C for 15 min, was about 43%. Phenolic bioactives of ginger-6-gingerols, 8-gingerols, 10-gingerols, and 6-shogaol-seem to be strong inhibitors of Cu(+2)-induced LDL oxidation. Overall, ginger extracts, including the water extract possess the antioxidant activities to inhibit human LDL oxidation in vitro.

Simvastatin and bezafibrate increase cholesterol efflux in men with type 2 diabetes

The importance of functional properties of high-density lipoproteins (HDL) for atheroprotection is increasingly recognized. We determined the impact of lipid-lowering therapy on 3 key HDL functionalities in Type 2 diabetes mellitus (T2DM). A placebo-controlled, randomized cross-over study (three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), alone and in combination) was carried out in 14 men with T2DM. Cholesterol efflux was determined using human THP-1 monocyte-derived macrophages, HDL antioxidative capacity was measured as inhibition of low-density lipoprotein oxidation in vitro, and HDL anti-inflammatory capacity was assessed as suppression of thrombin-induced monocyte chemotactic protein 1 expression in human umbilical vein endothelial cells. Pre-β-HDL was assayed using crossed immunoelectrophoresis. While cholesterol efflux increased in response to simvastatin, bezafibrate and combination treatment (+12 to +23%; anova, P = 0.001), HDL antioxidative capacity (P = 0.23) and HDL anti-inflammatory capacity (P = 0.15) did not change significantly. Averaged changes in cellular cholesterol efflux during active treatment were correlated positively with changes in HDL cholesterol, apoA-I and pre-β-HDL (P < 0.05 to P < 0.001). There were no inter-relationships between changes in the three HDL functionalities during treatment (P > 0.10). Changes in HDL antioxidative capacity and anti-inflammatory capacity were also unrelated to changes in HDL cholesterol and apoA-I, while changes in HDL antioxidative capacity were related inversely to pre-β-HDL (P < 0.05). Simvastatin and bezafibrate increase cholesterol efflux, parallel to HDL cholesterol and apoA-I responses. The antioxidative and anti-inflammatory properties of HDL are not to an important extent affected by these therapeutic interventions.

Recognition Functions of Pentameric C-Reactive Protein in Cardiovascular Disease

C-reactive protein (CRP) performs two recognition functions that are relevant to cardiovascular disease. First, in its native pentameric conformation, CRP recognizes molecules and cells with exposed phosphocholine (PCh) groups, such as microbial pathogens and damaged cells. PCh-containing ligand-bound CRP activates the complement system to destroy the ligand. Thus, the PCh-binding function of CRP is defensive if it occurs on foreign pathogens because it results in the killing of the pathogen via complement activation. On the other hand, the PCh-binding function of CRP is detrimental if it occurs on injured host cells because it causes more damage to the tissue via complement activation; this is how CRP worsens acute myocardial infarction and ischemia/reperfusion injury. Second, in its nonnative pentameric conformation, CRP also recognizes atherogenic low-density lipoprotein (LDL). Recent data suggest that the LDL-binding function of CRP is beneficial because it prevents formation of macrophage foam cells, attenuates inflammatory effects of LDL, inhibits LDL oxidation, and reduces proatherogenic effects of macrophages, raising the possibility that nonnative CRP may show atheroprotective effects in experimental animals. In conclusion, temporarily inhibiting the PCh-binding function of CRP along with facilitating localized presence of nonnative pentameric CRP could be a promising approach to treat atherosclerosis and myocardial infarction. There is no need to stop the biosynthesis of CRP.

Polyphenolic content and antioxidant activity of leaf extracts from Quercus durifolia, Quercus eduardii, Quercus sideroxyla and Quercus resinosa

The phenolic content and antioxidant activities of extracts from Quercus durifolia, Quercus resinosa, Quercus eduardii and Quercus sideroxyla leaves were studied. Extracts were obtained by successive extraction with aqueous acetone (70%) followed by methanol (50%). Antioxidant activities were determined using a single electron transfer (SET) and hydrogen atom transfer (HAT) based assays. For SET-based the assays performed were, 2,2-diphenyl-1-picryl hydrazine (DPPH) inhibition expressed as IC50, redox potential, as mV, inhibition of the low density lipoprotein (LDL) oxidation, as % of inhibition. For HAT-based assay, crocin bleaching technique was applied; a kinetics approach was used for the evaluation of total antioxidant capacity and the results presented in terms of equivalence by weight of a reference antioxidant. Acetone extracts (PFQA) from leaves of all Quercus species showed the best antioxidant capacity. Q. resinosa (PFQr) exhibited the best antioxidant capacity among the Quercus species analyzed either in acetone or methanol extracts (PFQM). Distinctive results are: DPPH IC50, PFQrA = 78.3 µg/g, PFQrM = 250.7 µg/g; In Redox potential, PFQrA = 147.0 mV, PFQrM = 201.6 mV; In LDL oxidation inhibition: 98.2% and in inhibition of crocin bleaching, PFQrA = 1.08 g, PFQrM = 0.98 g. In conclusion, Quercusleaves might be used as potential source of polyphenolic antioxidants. Key words: Quercus sp., SET-based assay, HAT-based assay, phenolic compounds, antioxidant activity.