Low-density Lipoprotein Inhibition Research Articles

Antioxidant Capacity of Caffeic Acid Phenethyl Ester in Scavenging Free Radicals by a Computational Insight

The free radicals, due to having a single free electron, are highly reactive in the body and cause irreversible damage to the macromolecules of living organisms. Propolis or bee glue is known as a substance with various biological properties, including antioxidant effects. The most important function of propolis is to inhibit free radicals, and inhibition of low-density lipoprotein (LDL) cholesterol oxidation and DNA scission activities, cardioprotective, anti-atherosclerotic, strengthen the immune system, their antimicrobial, antioxidant and anti-cancer effects. Caffeic acid phenethyl ester (CAPE) is a natural phenolic chemical compound in propolis. The antioxidant activity of CAPE is calculated by inhibiting free radicals of DPPH, peroxide, carboxyl and hydroxide. Performance calculations of CAPE on free radicals are done by the method of B3LYP/6-31 + G*. The results show that the caffeic acid phenethyl ester (CAPE) can have a strong antioxidant effect on the above radicals. In comparison between radicals, CAPE antioxidant effect on free radicals of .COOH is more than other radicals. This result can be related to the spatial structure and the greater tendency of radicals to share free electrons. The data show the effective role of the number of hydroxyl groups, intermolecular hydrogen bonds and the position of hydroxyl functional groups in the CAPE, which determines the inhibition of free radicals by it.

Antioxidant, anti-proliferative, and anti-atherosclerotic effect of phytochemicals isolated from Trachyspermum ammi with honey in RAW 264.7 and THP-1 cells

Background: Trachyspermum ammi is a common spice with vital medicinal properties used in Ayurveda to treat many ailments. Furthermore, natural Honey is said to have high levels of antioxidants and anti-inflammatory properties. While the combination of both T. ammi and Honey is unexplored in anti-atherosclerotic activity. Materials and Methods: Assays guided isolation of carotenoids, phenolics, and tannins were performed by methanol and aqueous extraction from T. ammi seed powder and honey mixture. Phytochemical screening for antioxidant activity (superoxide radical scavenging activity, nitric oxide radical scavenging activity, and 2, 2-diphenyl-1-picrylhydrazyl scavenging activity) and antilipidemic activity by inhibition of low-density lipoprotein (LDL) oxidation were investigated. Sample showing highest activity with lowest IC50 value from antioxidant and antilipidemic activity was further evaluated on RAW 264.7, THP-1 cells for foam cell inhibition activity, anti-proliferation, antiapoptotic activity, and nitric oxide assay. The sample was characterized using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Results: Out of the phytochemicals screened, tannin methanol extract (TME) showed the highest antioxidant activity with IC50 value having 7.11 μg/mL in superoxide scavenging assay, the IC50 value of 1.46 μg/mL by nitric oxide scavenging assay, and followed by IC50 value of 20.83 μg/mL in 2, 2-diphenyl-1-picrylhydrazyl activity. The results showed that it also efficiently inhibited LDL oxidation at 240 μg/mL (71.29% at 5 h)., thus inhibiting foam cell development, preventing proliferation, apoptosis, and nitrate production in cultured RAW 264.7 and THP-1 cells. HPLC analysis showed the presence of tannin in the extract. TME was characterized in GC-MS, which showed 13 prominent compounds. Conclusion: The scientific evidence in the present study showed that the TME from T. ammi seed powder and honey act as an antioxidant and antiatherogenic properties in inhibiting foam cell formation. Hence, this phytochemical can be used for the treatment of atherosclerosis.

Quercetin and its ester derivatives inhibit oxidation of food, LDL and DNA

Quercetin was esterified with fatty acids (FA) in order to expand its application in a wide range of food and biological systems. The antioxidant potential of the esters were examined using hydroxyl radical scavenging activity, antioxidation in oil-in-water emulsion and bulk oil, inhibition of low-density lipoprotein (LDL) oxidation and deoxyribonucleic acid (DNA) scission. Except for oil-in-water emulsion system, quercetin derivatives demonstrated similar and/or better antioxidant activity than quercetin itself in bulk oil (quercetin with C18:1 and C22:6), hydroxyl radical scavenging assay (quercetin with C3:0-C8:0), DNA scission (quercetin with C3:0-C8:0), and LDL oxidation (quercetin with C14:0-C22:6, except C18:0). These results suggest that esterification did not compromise the antioxidant activity of the parent compound and quercetin derivatives might be useful as possible antioxidants in food and biological systems.

Antioxidant paraoxonase 1 activity in children with celiac disease. Impact of gluten free diet

Background and Aims: There is evidence, that celiac disease (CD) could be associated with non-traditional atherogenic risk factors. High density lipoproteins (HDL) constitute the only antiatherogenic fraction, being the inhibition of low density lipoprotein (LDL) oxidation one of its main functions. This capacity depends on different HDL-associated components, such as the antioxidant enzyme paraoxonase (PON1). To assess the relationship between CD and the activity of PON1 in recently diagnosed children compared to healthy controls, and the effect of gluten-free diet (GFD).

Antioxidants and Atherosclerosis: Mechanistic Aspects.

Atherosclerosis is a chronic inflammatory disease which is a major cause of coronary heart disease and stroke in humans. It is characterized by intimal plaques and cholesterol accumulation in arterial walls. The side effects of currently prescribed synthetic drugs and their high cost in the treatment of atherosclerosis has prompted the use of alternative herbal medicines, dietary supplements, and antioxidants associated with fewer adverse effects for the treatment of atherosclerosis. This article aims to present the activity mechanisms of antioxidants on atherosclerosis along with a review of the most prevalent medicinal plants employed against this multifactorial disease. The wide-ranging information in this review article was obtained from scientific databases including PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Natural and synthetic antioxidants have a crucial role in the prevention and treatment of atherosclerosis through different mechanisms. These include: The inhibition of low density lipoprotein (LDL) oxidation, the reduction of reactive oxygen species (ROS) generation, the inhibition of cytokine secretion, the prevention of atherosclerotic plaque formation and platelet aggregation, the preclusion of mononuclear cell infiltration, the improvement of endothelial dysfunction and vasodilation, the augmentation of nitric oxide (NO) bioavailability, the modulation of the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, and the suppression of foam cell formation.

The effect of exenatide (a GLP-1 analog) and sitagliptin (a DPP-4 inhibitor) on plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and concentration in normal and fructose-fed rats

Inflammation and oxidative stress are the two processes crucial in atherogenesis. Platelet-activating factor acetylhydrolase (PAF-AH), a plasma lipoprotein-associated enzyme, degrades pro-inflammatory lipids generated within oxidatively modified lipoproteins. Extensive evidence shows that incretin-based drugs, a new class of anti-diabetic agents, can provide cardiovascular protection that cannot be attributed to their glucose-lowering effects. The present study was undertaken to determine whether the antiatherogenic effects of the GLP-1(glucagon-like peptide-1) receptor agonist (exenatide) and DPP-4(dipeptidyl peptidase-4) inhibitors (sitagliptin) may occur via the regulation of platelet-activating factor acetylhydrolase (PAF-AH) activity/mass and inhibition of low-density lipoprotein (LDL) oxidation in the fructose-fed rats.Normal and fructose-fed rats (8 wk) were treated (4 wk) with sitagliptin (5 and 10 mg/kg p.o.) or with exenatide (5 and 10 µg/kg, s.c.). Plasma PAF-AH activity and phosphatidylcholine (PC) concentration were measured colorimetrically. Plasma PAF-AH concentration, oxidized LDL (oxLDL), hexanoyl-Lys adduct (HEL), lyso-PC, apolipoprotein A-I (apoA-I), apoB, platelet-activating factor (PAF), monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were measured by ELISA.The four-week exenatide (5 µg/kg, sc.) treatment of fructose fed-rats significantly increased plasma PAF-AH activity (+33%, P < 0.001) and decreased the level of circulating oxLDL (-42%, P < 0.05) and MCP-1 (-23%, P < 0.01). These changes were accompanied by the decrease in plasma PC/lyso-PC (-47%, P < 0.001) and apoB/apoA-I ratio (-75%, P < 0.001). The effect of exenatide on enzyme activity was associated with only a minor effect on metabolic parameters and was independent of weight reduction.Exenatide but not sitagliptin inhibits oxidative modification of LDL probably due to favorable effect on plasma PAF-AH activity.

DNA scission and LDL cholesterol oxidation inhibition and antioxidant activities of Bael (Aegle marmelos) flower extracts

Phenolic compounds and other antioxidants have been implicated in protection against non-communicable diseases (NCDs) in which oxidative stress is a main contributor. The extracts of Bael (Aegle marmelos) flower were examined for their phenolic content, free radical scavenging efficacy and inhibition of low density lipoprotein (LDL) cholesterol oxidation and DNA scission activities. The extracts of Bael flowers were prepared using different solvent systems and their total phenolic content (TPC) and total flavonoid content (TFC) determined. Selected extracts which showed high TPC were subsequently used to determine their efficacy in scavenging hydroxyl, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, using electron paramagnetic resonance (EPR) spectroscopy. The corresponding peroxyl radical scavenging activity was measured using oxygen radical absorbance capacity (ORAC) assay. The potency of the extracts in inhibiting hydroxyl and peroxyl radical-induced supercoiled DNA scission and inhibition of LDL cholesterol oxidation was also evaluated. The chemical identity of phenolic compounds present in the extracts was tentatively unraveled using HPLC-MS. Phenolic extracts of Bael flowers effectively inhibited hydroxyl, and peroxyl radicals. Phenolic extracts demonstrated notable inhibitory activity against hydroxyl and peroxyl radical-induced DNA scission and LDL oxidation. Vanillic, p-coumaric, chlorogenic, caffeic, and gentisic acids were identified as major phenolic acids, along with flavonoids, mainly catechin, and quercetin. The knowledge gained here may help better use of Bael flower extracts as functional herbal beverage ingredients in the prevention of NCDs.

Chemical Analysis of Polyphenols with Antioxidant Capacity from Pinus durangensis Bark

The most active phenolics in Pinus durangensis residual bark were identified and evaluated following a chromatographic fractionation. Bark powder was defatted with hexane, and a crude extract (CE) was obtained by extraction with aqueous acetone (67%). A liquid partition with ethyl acetate was performed to produce an organic extract (OE), which was subsequently purified by column chromatography (Toyopearl HW-40F, methanol), resulting in ten fractions (MF1 to MF10) and an oligomeric fraction eluted with acetone 67% (OLF). Subfraction MF6-1 was obtained by a second chromatographic purification of MF6. Extraction yields, total phenolics, flavonoids, and flavanols contents were determined in CE and OE. The antioxidant activity of bark extracts was measured by DPPH and ABTS assays at 100 µg/mL, expressed in percentage, median effective concentration (IC50), and TEAC (mM). Also the low density lipoprotein inhibition was evaluated. Identification of major phenolics was carried out by HPLCESI–MS and HPLC–DAD instruments. Bioactive taxifolin (dihydroquercetin), dihydromyricetin, myricetin, quercetin, pinomyricetin (myricetin-methoxy), pinoquercetin (quercetin-methoxy), trimeric, and tetrameric procyanidins were detected and identified in P. durangensis bark extracts. Polyphenols found are similar to those contained in Pycnogenol and other Pinus species.

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.

Phenolics of selected lentil cultivars: Antioxidant activities and inhibition of low-density lipoprotein and DNA damage

Free, esterified, and insoluble-bound phenolics were extracted from selected lentil cultivars. Total phenolics, flavonoids and proanthocyanidin contents were determined. Catechin, epicatechin and procyanidins B were predominant in all fractions of all tested samples as evaluated using HPLC-DAD-ESI-MSn. Methyl vanillate, procyanidin dimer A, and prodelphinidin dimer A were identified and quantified in lentils for the first time. Procyanidin dimer A was detected only in the insoluble-bound form, methyl vanillate was present in the esterified and insoluble-bound one and prodelphinidin dimer A was found in all forms. The presence of unrevealed compounds present only in the insoluble-bound form shows that ignoring the presence of phenolics linked to the cell wall of lentils may underestimate their potential health benefits. The antioxidant activities and the inhibition of cupric ion-induced human low-density lipoprotein peroxidation and peroxyl radical induced supercoiled plasmid DNA strand scission demonstrated that lentil seeds may be considered as a functional food.

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.

Grape skin and loquat leaf extracts and acai puree have potent anti-atherosclerotic and anti-diabetic activity in vitro and in vivo in hypercholesterolemic zebrafish

Three major sources of flavonoids and phenolic compounds, which are commonly used in food industry, namely loquat leaf (LL), grape skin (GS) and acai puree, were tested in regard to their potential anti-atherosclerotic and anti-diabetic activity. The compounds were evaluated by in vitro antioxidant assay using a macrophage model and for in vivo hypolipidemic activity using zebrafish. In assays in vitro, all extracts demonstrated potent ferric ion reductive capacity, radical-scavenging activity and inhibition of low-density lipoprotein (LDL) oxidation at a final concentration of 0.1 mg/ml. Extracts could also abrogate fructose-mediated protein glycation and mildly inhibit cholesteryl ester transfer protein (CETP). Cellular uptake of oxidized or acetylated LDL into macrophages was inhibited by acai treatment (final concentration, 0.1 mg/ml) and moderately diminished by GS and LL extracts. After 4 weeks of feeding on a high cholesterol diet (HCD), zebrafish exhibited serum total cholesterol (TC) and triglyceride (TG) levels 2.5-fold higher than those fed a normal diet (ND). Within the experimental group, those fed acai demonstrated the lowest serum TC and CETP activity, while the LL-consuming group showed a reduction in serum TC and TG relative to HCD-fed fish. Serum glucose levels also increased in the HCD group, to threefold above the ND group; GS and LL feeding elicited the greatest reduction in hyperglycemia. The groups consuming acai and LL showed much less hepatic inflammation, as well as attenuation of fatty liver and a reduced content of oxidized species. In conclusion, extracts of LL, GS, and acai shared antioxidant, anti-inflammatory and anti-atherosclerotic activity in cellular assays and in a hypercholesterolemic zebrafish model.

ANTIOXIDATIVE EFFECTS OF TWO NATIVE BERRY SPECIES,EMPETRUM NIGRUMVAR. JAPONICUM K. KOCH ANDRUBUS BUERGERIMIQ., FROM THE JEJU ISLAND OF KOREA

The extracts of two native berries from the Jeju Island of Korea were used to assess polyphenolics and flavonol levels, superoxide dismutase (SOD)-like enzyme activity, free radical scavenging activity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide cell viability, protective effects against H2O2-induced cow pulmonary artery endothelium (CPAE) cell cytotoxicity and inhibition of low density lipoprotein (LDL) peroxidation. The total content of the flavonols and phenolic compounds in the leaves was higher than the fruit for both berries. In the free radical scavenging and SOD-like enzyme assay, all extracts showed strong antioxidative effects. The CPAE viability was greatly reduced and the survival rate was near 37% when the cells were treated with 1.0 mM H2O2 for 24 h. The extracts also inhibited lipid peroxidation in human LDL, measured as reduction in malondialdehyde production. The results showed that the leaf extracts of Empetrum nigrum significantly protected human LDL from Cu2+-induced oxidation. E. nigrum is suggested as an excellent potential source of natural antioxidants. PRACTICAL APPLICATIONS The results of these two Korean native berry species, especially Shiromi species, showed very strong effects on the inhibition of low density lipoprotein (LDL) oxidation and free radical scavenging. The LDL and free radicals have known close relations with coronary artery and cerebrovascular atherosclerosis. The antioxidative effects of these berries were stronger than existing commercial products. From these results, Korean native berry species might be very useful for the development of functional food for antioxidants preventing oxidative stress-related diseases like atherosclerosis. Making a new commercial product with Korean Shiromi berry will have good prospects.

Coincubation of PON1, APO A1, and LCAT increases the time HDL is able to prevent LDL oxidation

The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown. LDL was incubated with apolipoprotein A1 (apo A1), lecithin:cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON1) alone or in combination, in the presence or absence of HDL under oxidizing conditions. LDL lipid peroxide concentrations were determined. Apo A1, LCAT, and PON1 all inhibit LDL oxidation in the absence of HDL and enhance the ability of HDL to inhibit LDL oxidation. Their effect was additive rather than synergistic; the combination of these proteins significantly enhanced the length of time LDL was protected from oxidation. This seemed to be due to the ability of PON1 to prevent the oxidative inactivation of LCAT. Apo A1, LCAT, and PON1 can all contribute to the antioxidant activity of HDL in vitro. The combination of apo A1, LCAT, and PON1 prolongs the time that HDL can prevent LDL oxidation, due, at least in part, to the prevention LCAT inactivation.

Relationships between Lipophilicity and Biological Activities in a Series of Indoline-based Anti-oxidative Acyl-CoA:Cholesterol Acyltransferase (ACAT) Inhibitors

A novel series of 1-alkyl-7-amido-indoline-based anti-oxidative acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors have been reported and are expected to lower plasma cholesterol levels due to the inhibition of intestinal and hepatic ACAT, and to inhibit cholesterol accumulation in macrophages due to the inhibition of low density lipoprotein (LDL) oxidation. In the present study, relationships between lipophilicity and biological activities were examined in 13 derivatives. Lipophilicity (logP) increased and water solubility decreased with dependence on the number of carbons in the 1-alkyl chain. Inhibitory activity against both in vitro intestinal ACAT and LDL oxidation positively correlated with logP; however, the optimum logP, at which the level of activity is maximal, differed between these two effects. Inhibitory activity against in vitro plasma oxidation was weakly dependent on logP. Plasma concentrations of the derivatives after oral administration at 10 mg/kg correlated negatively with logP and positively with water solubility. Hypocholesterolemic activity in rats fed a high-cholesterol diet, and the ratio of Cmax and IC50 values for ACAT inhibition, an index of effective plasma concentration, positively and highly correlated with logP, while ex vivo inhibitory activity against plasma oxidation in rats, and the ratio of Cmax and IC50 values for the inhibition of plasma oxidation negatively correlated with logP. In conclusion, in vitro ACAT inhibitory and anti-oxidative activity were differently dependent on logP, and intestinal absorption was inversely dependent on lipophilicity in indoline-based anti-oxidative ACAT inhibitors. The hypocholesterolemic effect positively correlated and the ex vivo anti-oxidative effect negatively correlated with lipophilicity. Optimum logP as a bioavailable dual inhibitor against in vivo ACAT and lipid peroxidation was estimated to be 3.8 (1-pentyl and 1-isopentyl derivatives) in the present series of derivatives.

비정제유 첨가가 참치유 보강 에멀젼의 산화방지활성에 미치는 영향

This study was conducted to evaluate the effects of adding unrefined oil on the antioxidant activity of a tuna oil-enriched emulsion by determining DPPH radical scavenging activity, reducing power, and inhibition of low-density lipoprotein (LDL) oxidation in vitro. The emulsion consisted of tocopherol-stripped canola (18.3 g) and tuna (9.1 g) oil, one of the unrefined oils (4.6 g), such as extra virgin olive, mustard, perilla, or sesame oil, 0.5% acetic acid (64 g), and egg yolk powder (4 g). The control emulsion contained only canola (21.4 g) and tuna oil (10.6 g), as oil sources,with the same composition of the remaining ingredients. The emulsion with added unrefined oil, particularly mustard oil, showed higher radical scavenging activity and reducing power than those of the control emulsion. The radical scavenging activity and reducing power of the emulsion with added unrefined oil were higher at 1,000 ppm than at 500 ppm thus, the effect was concentration-dependent. Adding sesame or perilla oil to the tuna oil-enriched emulsion resulted in higher inhibition of LDL oxidationwhereas adding olive oil increased LDL oxidation. The results clearly showed that adding roasted mustard, sesame, or perilla oil improved the antioxidant activity of a tuna oil-enriched emulsion by increasing free radical scavenging activity, reducing power, and inhibiting LDL oxidation. The results also suggest that adding unrefined oils produces a healthier fish oil-enriched salad dressing recipe.

Inhibition of Low Density Lipoprotein-oxidation, ACAT-1, and ACAT-2 by Lignans from the Bark of Machilus thunbergii

The bark of Machilus thunbergii was extracted with 80% aqueous methanol (MeOH), and the concentrated extract was partitioned using ethyl acetate (EtOAc), butanol (n-BuOH), and <TEX>$H_2O$</TEX>, successively. From the EtOAc fraction, five lignans were isolated through the repeated silica gel, octadecyl silica gel (ODS) and, Sephadex LH-20 column chromatography. Based on nuclear magnetic resonance (NMR), mass spectroscopy (MS), and infrared spectroscopy (IR) spectroscopic data, the chemical structures of the compounds were determined to be machilin A (1), machilin F (2), licarin A (3), nectandrin A (4), and nectandrin B, (5). This study presents comparative account of five lignans from M. thunbergii bark contributing inhibition of low density lipoprotein (LDL), ACAT-1, and ACAT-2. Compounds 2-5 showed varied degree of antioxidant activity on LDL with <TEX>$IC_{50}$</TEX> values of 2.1, 11.8, 15.3, and <TEX>$4.1{\mu}M$</TEX>. Compounds 1, 2, and 3 showed inhibition activity on ACAT-1 with values <TEX>$63.4{\pm}6.9%$</TEX> (<TEX>$IC_{50}=66.8{\mu}M$</TEX>), <TEX>$53.7{\pm}0.9%$</TEX> (<TEX>$IC_{50}=109.2{\mu}M$</TEX>), and <TEX>$78.7{\pm}0.2%$</TEX> (<TEX>$IC_{50}=40.6{\mu}M$</TEX>), respectively, at a concentration of 50 mg/mL, and on ACAT-2 with values <TEX>$47.3{\pm}1.5%$</TEX> (<TEX>$IC_{50}=149.7{\mu}M$</TEX>), <TEX>$39.2{\pm}0.2%$</TEX> (<TEX>$IC_{50}=165.2{\mu}M$</TEX>), and <TEX>$52.1{\pm}1.0%$</TEX> (<TEX>$IC_{50}=131.0{\mu}M$</TEX>, respectively, at a concentration of 50 mg/mL.

Biochemical, Environmental, and Genetic Factors Associated with Paraoxonase (PON1) Activity

Paraoxonase (PON1, EC 3.1.8.1) is tightly linked to high-density lipoprotein (HDL) and shows significant correlation with apo AI concentrations. It plays an important role in functions such as protection against vascular disease (e.g., atherosclerosis) through its inhibition of low-density lipoprotein (LDL) oxidation and detoxification of organophosphorus compounds by hydrolyzing the bioactive oxons (Mackness et al. 1991). The activity of PON1 is modulated by genetic and environmental factors. Two coding region polymorphisms of the PON1 gene result in amino acid substitutions at position 192 (PON1 Q192R, glutamine to arginine) and at position 55 (PON1 L55 M, leucine to methionine). PON1 Q192R has been reported to account for 73–76% of the variation in hydrolysis activity of paraoxon (paraoxonase activity) and 12–25% of the variation in activity for the hydrolysis of diazoxon (diazonase activity) in vitro (Jarvik et al. 2000). The L55 M polymorphism also contributes to PON1 protein stability and activity (Leviev et al. 2001). PON1 polymorphisms have been studied in many populations of the world; the frequency of the low-activity

Anthocyanin-Rich Black Currant Extract Suppresses the Growth of Human Hepatocellular Carcinoma Cells

Dietary antioxidants, such as anthocyanins, are helpful in the prevention and control of various diseases by counteracting the imbalance of oxidative and antioxidative factors in the living systems. Black currant (Ribes nigrum L., Grossulariaceae) is known to contain high amounts of anthocyanins (250 mg/100 g fresh fruit). Black currant fruits have been used in Asian and European traditional medicine for the treatment of a variety of diseases. Black currant extract has recently been found to be the second most effective amongst nine different berry extracts studied for their free radical scavenging activity. Constituents present in black currant juice have been found to exert a number of health-promoting effects, including immunomodulatory, antimicrobial and antiinflammatory actions, inhibition of low-density lipoprotein, and reduction of cardiovascular diseases. Although antioxidant and antiinflammatory effects of black currant juice could be of value in preventing and treating oxidative stress- and inflammation-driven cancers, no experimental evidence is available to now. The objective of the present study was to evaluate the potential antiproliferative effects of black currant fruit skin extract against HepG2 human liver cancer cells. The aqueous extract yielded an anthocyanin-rich fraction with cyanidin-3-O-rutinoside as one of the major anthocyanins. This fraction exhibited a potent cytotoxic effect on HepG2 cells and this effect was more pronounced than that of delphinidin and cyanidin, two major aglycones of anthocyanins present in black currant. Our results indicate, for the first time, that black currant skin containing an anthocyanin-rich fraction inhibits the proliferation of liver cancer cells, possibly due to additive as well as synergistic effects. This product could be useful in the prevention and treatment of human hepatocellular carcinoma.

Structure/Function Relationships of Apolipoprotein A-I Mimetic Peptides

Apolipoprotein (apoA)-I mimetic peptides are a promising type of anti-atherosclerosis therapy, but how the structural features of these peptides relate to the multiple antiatherogenic functions of HDL is poorly understood. To establish structure/function relationships of apoA-I mimetic peptides with their antiatherogenic functions. Twenty-two bihelical apoA-I mimetic peptides were investigated in vitro for the capacity and specificity of cholesterol efflux, inhibition of inflammatory response of monocytes and endothelial cells, and inhibition of low-density lipoprotein (LDL) oxidation. It was found that mean hydrophobicity, charge, size of hydrophobic face, and angle of the link between the helices are the major factors determining the efficiency and specificity of cholesterol efflux. The peptide with optimal parameters was more effective and specific toward cholesterol efflux than human apoA-I. Charge and size of hydrophobic face were also the major factors affecting antiinflammatory properties, and the presence of cysteine and histidine residues was the main factor determining antioxidant properties. There was no significant correlation between capacities of the peptides to support individual functions; each function had its own optimal set of features. None of the peptides was equally effective in all the antiatherogenic functions tested, suggesting that different functions of HDL may have different mechanisms and different structural requirements. The results do suggest, however, that rationalizing the design of apoA-I mimetic peptides may improve their therapeutic value and may lead to a better understanding of mechanisms of various antiatherogenic functions of HDL.