Inhibition Of LDL Oxidation Research Articles

Massa Medicata Fermentata, a Functional Food for Improving the Metabolic Profile via Prominent Anti-Oxidative and Anti-Inflammatory Effects.

Massa Medicata Fermentata (MMF) is a naturally fermented product used to treat indigestion and increase stomach activity in traditional medicine. This study examined the ability of the hydrothermal extract of MMF to scavenge free radicals corresponding to biological oxidative stresses, further protecting essential biomolecules. The anti-inflammatory effects of MMF were evaluated in LPS-induced RAW264.7 macrophages and zebrafish. In addition, the effects of MMF on the body mass index (BMI) and cholesterol accumulation in adult zebrafish fed a high-cholesterol diet (HCD) for three weeks were examined. MMF prevented the DNA and lipid damage caused by oxidative stress, inhibited LDL oxidation, and reduced the expression of cytokines and related proteins (MAPK and NFκB), with prominent anti-oxidative pathway (NRF2-HO-1) activation properties. LPS-induced NO production was reduced, and the increase in BMI and TC caused by the HCD diet was suppressed by MMF in zebrafish embryos or adult zebrafish. The bioactive aglycone of quercetin may be contributing to the mechanisms of systemic effects. MMF has excellent antioxidant properties and is useful for improving inflammation status and metabolic profile, thus highlighting its potential as a healthy, functional food.

Cuban Policosanol (Raydel®) Exerts Higher Antioxidant and Anti-Glycation Activities than Chinese Policosanol (BOC Sciences) in Reconstituted High-Density Lipoproteins: In Vivo Anti-Inflammatory Activities in Zebrafish and Its Embryos.

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel®) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and 1-tetratriacotanol (C34). After synthesizing rHDL with apolipoprotein A-I (apoA-I), the two policosanols bound well with phospholipid and apoA-I to form the discoidal rHDL. Notably, rHDL-1, containing Cuban policosanol, displayed the largest particle diameter at approximately 78 ± 3 nm. In contrast, both control rHDL (rHDL-0) and rHDL containing Chinese policosanol (rHDL-2) exhibited smaller particles, with diameters of approximately 58 ± 3 nm and 61 ± 2 nm, respectively. Furthermore, rHDL-1 demonstrated enhanced anti-glycation activity, safeguarding apoA-I from degradation within HDL, and displayed the antioxidant ability to inhibit LDL oxidation. A microinjection of each rHDL into zebrafish embryos in the presence of carboxymethyllysine (CML) revealed rHDL-1 to have the strongest antioxidant activity with the highest embryo survivability and normal developmental morphology. Dermal application to recover the wound revealed rHDL-1 to have the highest wound-healing activity (75%) and survivability (92%) in the cutaneous wound area in the presence of CML. In adult zebrafish, injecting CML (250 μg) caused acute death and hyperinflammation, marked by heightened neutrophil infiltration and interleukin (IL)-6 production in liver. However, co-administering rHDL-1 notably increased survival (85%) and exhibited strong anti-inflammatory properties, reducing IL-6 production while improving the blood lipid profile. However, a co-injection of rHDL-2 resulted in the lowest survivability (47%) with more hepatic inflammation. In conclusion, Cuban policosanol (Raydel®) has more desirable properties for the in vitro synthesis of rHDL with stronger anti-glycation and antioxidant activities than those of Chinese policosanol (BOC Sciences). Moreover, Raydel-policosanol-integrated rHDL demonstrates a noteworthy effect on accelerated wound healing and robust anti-inflammatory properties, leading to increased survivability in zebrafish embryos and adults by effectively suppressing CML-induced hyperinflammation.

Bioactive compounds from the leaves of Maytenus ilicifolia Mart. ex Reissek: Inhibition of LDL oxidation, glycation, lipid peroxidation, target enzymes, and microbial growth

Ethnopharmacological relevanceMaytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds—terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. Aims of the studyWe aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. Materials and methodsOrganic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. ResultsHPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 μg/mL and 7.95 μg/mL) compared to acarbose (0.144 μg/mL). Most organic fractions exhibited ∼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. ConclusionThis study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.

Abstract 13685: Eicosapentaenoic Acid (EPA) Inhibits Low-Density Lipoprotein (LDL) Oxidation Compared to Docosahexaenoic Acid (DHA) and Mineral Oil in vitro

Introduction: Oxidized LDL triggers inflammation during the initiation and progression of atherosclerotic plaque. The omega-3 fatty acid (n3-FA) EPA administered as icosapent ethyl (IPE), reduced cardiovascular (CV) events in REDUCE-IT due, in part, to potential antioxidant and anti-thrombotic activity. By contrast, mixed n3-FA containing docosahexaenoic acid (DHA) have failed to reduce CV events in similar high-risk patients (STRENGTH). Some have raised concerns over the relationship between these discordant outcomes and placebo choice (mineral oil) as well as DHA content. We compared the effects of these compounds on oxidation of LDL where such ingested fatty acids are concentrated and transported. Methods: LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL, and incubated at 37°C for 30 min with pharmaceutical grade mineral oil, EPA, DHA or vehicle at equimolar levels (10 μM). All samples were then subjected to copper sulfate-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Ascorbic acid at equimolar levels served as a control. Results: LDL oxidation increased 30-fold (0.28±0.03 vs 8.72±0.54 μM; p <0.001) after 4 h and the rate was unaffected by addition of mineral oil. By contrast, EPA significantly inhibited LDL oxidation; after 4 h, EPA inhibited MDA levels by 75% compared with vehicle (8.72±0.54 vs 2.20±0.36 μM; p <0.001). While DHA exhibited antioxidant activity at 2 hours at a level less than EPA (1.15±0.54 vs 3.00±1.08 μM; p <0.05), it exhibited no antioxidant activity after 4 h. Like DHA, ascorbic acid also reduced LDL oxidation only up to 2 h. Conclusions: These data support sustained LDL antioxidant effects for EPA compared with DHA, ascorbic acid, or mineral oil. The longer-term antioxidant actions of EPA may contribute to reduced events in outcome trials compared to mixed n3-FA formulations, independent of placebo selection.

Functional food in the primary prevention of cardiovascular diseases

Cardiovascular diseases, metabolic disorders and obesity are a serious threat to civilization, especially in highly developed countries. Due to the number of deaths and complications they are among the health priorities in Poland. The aim of the study is to review the literature on the role of functional food in the primary prevention of cardiovascular diseases. Functional food, thanks to its antioxidant, hypocholesterolemic and anti-inflammatory properties, has a beneficial effect on lowering blood pressure, cholesterol levels, inhibiting LDL oxidation or inhibiting platelet aggregation. It is necessary to promote this type of food, because its action has a significant impact on the prevention of various diseases, especially cardiovascular, diet-related and civilization. Proper nutritional education is a way to improve human potential and health. Therefore, it is worth educating in order to promote these products and increase the interest in them as well as raise the nutritional awareness of the society.

Inhibition of LDL Oxidation and Foam Cell Development of Tannin Methanol Extract from Citrus limon and Honey Formulation on Cell lines

Inhibition of LDL Oxidation and Foam Cell Development of Tannin Methanol Extract from Citrus limon and Honey Formulation on Cell lines

The beneficial effect of Adansonia digitata products success to modulate lipid profiles and inhibit LDL oxidation in-vitro: An associational study.

There is a growing interest in medicinal plants in recent years due to their many therapeutic benefits and low side effects. Among the medicinal plants is the African Adansonia digitata (baobab) that has edible fruit. In the current study, the effect of A. digitata juice consumption on the lipid profile was investigated. In addition, inhibition of the oxidation of low-density lipoprotein cholesterol (LDL-C) in-vitro by A. digitata essential oil (EO) was also investigated. In this cohort study, a total of 70 subjects of A. digitata users (AD group, 42 male and 28 female) and 70 non A. digitata users (Non-AD group, 44 male and 26 female) were recruited to participate in this study. We evaluated lipid profile, HbA1c, liver/kidney functions, and phytosterol contents in fasting blood samples of all participants. The present findings illustrated significantly lower levels of total cholesterol, triglycerides, and LDL in the AD group compared to Non-AD (p < 0.01). In addition, essential oil of A. digitata inhibited LDL oxidation in-vitro as shown by the significant decreases in the formation of malonaldehyde (MDA), protein carbonyl (PC), and lipid hydroperoxide (LHP) (P<0.05). No significant changes in fasting blood glucose, HbA1c, HDL, kidney function, and liver function enzymes between the two groups were detected (P>0.05). The juice of A. digitata has hypolipidemic and antioxidative effects and might be beneficial for the management of lipid levels in the body.

Larrea divaricata: anti-inflammatory and antioxidant effects on macrophages and low density lipoproteins

BackgroundThe oxidized low density lipoprotein (ox-LDL) contributes to inflammation and oxidative stress through the activation of macrophages under hyperglycemia contributing to the development of diabetes mellitus and to atherosclerosis. Plants are a source of effective and innocuous antioxidants. Larrea divaricata Cav. (Zygophyllaceae) is used in Argentina folk medicine for its anti-inflammatory properties.MethodsThe aim of this work was to study the antioxidant and anti-inflammatory effects of the aqueous extract (AE) of L. divaricata on macrophages under glucose stimulation and on human LDL and HDL particles under free radical generators. ResultsAE reduced the lipid peroxidation (17%), nitric oxide (NO) (47-50%), tumor necrosis factor-α (TNF-α) (32%) and free radicals (50%) induced by glucose on macrophages. Also prevented HDL nitration (28%), thus preserving its function and structure and inhibited LDL oxidation. The effect on the nitrosative stress was mainly driven by nordihydroguaiaretic acid (NDGA).ConclusionsThese results suggest a potential usefulness of AE as an adjuvant phytotherapy in patients with diabetes mellitus and atherosclerosis.

HDL and Oxidation.

In this chapter, we will focus on HDLs' activity of inhibiting LDL oxidation and neutralizing some other oxidants. ApoA-I was known as the main antioxidant component in HDLs. The regulation of antioxidant capacity of HDL is mainly exhibited in regulation of apoA-I and alterations at the level of the HDL lipidome and the modifications of the proteome, especially MPO and PON1. HDL oxidation will influence the processes of inflammation and cholesterol transport, which are important processes in atherosclerosis, metabolic diseases, and many other diseases. In a word, HDL oxidation might be an effective antioxidant target in treatment of many diseases.

Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.

The bioactive compounds content and antioxidant activities of some plant parts formulae distributed in Egyptian local markets

Plant parts are important source of bioactive compounds and have been used for folk medicine for many centuries. The present study aimed to determine the bioactive compounds and antioxidant activities of some plant parts formulae distributed in the Egyptian local markets. Also, the potential effect of the tested formulae as a promising tool in the prevention of cardiovascular diseases (CVD) including atherosclerosis will be in the scope of this investigation. The results showed that selected formulae possessed stronger antioxidant properties in inhibiting both lipid peroxidation (carotene bleaching assay) and CuSO4-induced LDL oxidation. The tested formulae showed slightly differences in antioxidant activity (AA= 92.74-94.56%). The high antioxidant properties of the tested formulae appeared to be attributed to its high bioactive compounds in particular phenolics content were 2275 and 38484 mg.100g-1 for formula I and II, respectively. The values of two tested formulae absorbances throught 120 min are coming well i.e. closing the line of 50 mg α-tocopherol and up to the line of 50 mg /L of butyhydroxy toluene (BHT). When all selected formulae were included in the statistical analysis, there was a positive and highly significant (r2= 0.9179 - 0.9462, p < 0.05) relationship between total phenolics and antioxidant activity. Finally, the tested formulae could be used successfully as a promising tool in the prevention of atherosclerosis by inhibiting LDL oxidation which merits further intensive studies. تعد الأجزاء النباتية مصدرا مهما للمرکبات النشطة بيولوجيا وقد استخدمت في الطب الشعبي لعدة قرون. لذلک هدفت الدراسة الحالية إلى تحديد المرکبات النشطة بيولوجيا وأنشطة مضادات الأکسدة لبعض ترکيبات أجزاء النبات المنتشرة في الأسواق المحلية المصرية. وکذلک دراسة مدى تأثيرها فى الوقاية من أمراض القلب والأوعية الدموية وتصلب الشرايين . أظهرت النتائج أن المجموعة النباتية المختارة تحتوى على مضادات أکسدة قوية تعمل على ايقاف کلا من أکسدة بيروکسيد الدهون والبروتينات الدهنية منخفضة الکثافة . أظهرت المجموعة النباتية المختارة فروقا طفيفة في درجة النشاط المضاد للاکسدة عندما تم حسابها والتى تراوحت بين 92.74 - 94.56 %. يرجع وجود مضادات الأکسدة العالية في المجموعات النباتية التى تم اختيارها إلى وجود مرکبات نشطة بيولوجية عالية فى محتواها من الفينولات والتى سجلت 2275 و 38484 ملجرام /100 جم للمجموعتين الأولى والثانية على التوالي.اظهرت مستخلصات الأجزاء النباتية المستخدمه زياده معنويه کبيرة بين الفينولات الکليه ونشاط مضادات الاکسده (r2= 0.9179 - 0.9462, p < 0.05 ). وفى النهاية نوصى باستخدام المستخلصات التى تم اختبارها بنجاح کاوسيلة في الوقاية من تصلب الشرايين عن طريق تثبيط أکسدة البروتين الدهني المنخفض الکثافة (LDL) الذي يستحق المزيد من الدراسات المکثفة.

Antioxidant and Pro-Oxidant Capacities as Mechanisms of Photoprotection of Olive Polyphenols on UVA-Damaged Human Keratinocytes.

A wide variety of polyphenols are reported to have considerable antioxidant and skin photoprotective effects, although the mechanisms of action are not fully known. Environmentally friendly and inexpensive sources of natural bioactive compounds, such as olive mill wastewater (OMWW), the by-product of olive-oil processing, can be considered an economic source of bioactive polyphenols, with a range of biological activities, useful as chemotherapeutic or cosmeceutical agents. Green strategies, such as the process based on membrane technologies, allow to recover active polyphenols from this complex matrix. This study aims to evaluate the antioxidant, pro-oxidant, and photoprotective effects, including the underlying action mechanism(s), of the ultra-filtered (UF) OMWW fractions, in order to substantiate their use as natural cosmeceutical ingredient. Six chemically characterized UF-OMWW fractions, from Italian and Greek olive cultivar processing, were investigated for their antioxidant activities, measured by Trolox Equivalent Antioxidant Capacity (TEAC), LDL oxidation inhibition, and ROS-quenching ability in UVA-irradiated HEKa (Human Epidermal Keratinocytes adult) cultures. The photoprotective properties of UF-OMWW were assayed as a pro-oxidant-mediated pro-apoptotic effect on the UVA-damaged HEKa cells, which can be potentially involved in the carcinogenesis process. All the UF-OMWW fractions exerted an effective antioxidant activity in vitro and in cells when administered together with UV-radiation on HEKa. A pro-oxidative and pro-apoptotic effect on the UVA-damaged HEKa cells were observed, suggesting some protective actions of polyphenol fraction on keratinocyte cell cultures.

Influence of enzyme concentrations in enzymatic bioprocessing of red rice bran: A detailed study on nutraceutical compositions, antioxidant and human LDL oxidation inhibition properties

Enzymes and their concentrations are crucial factors in improving the release of nutraceuticals bounded to rice bran's cell wall matrix. This study aims to investigate the optimal concentrations of Viscozyme and Fiberzyme at 3–30 beta-glucanase units/2 g in improving the release of phenolics, tocopherols, tocotrienols, and γ-oryzanol fractions and enhancing the bioactivities of red rice bran. At specific concentrations, Fiberzyme increased ferulic (301%) and caffeic acid (691%) in soluble phenolics, p-coumaric acid (98%), and catechin (161%) in bound phenolics as well as γ-oryzanol fractions(32%-134%) and increased ferric reducing power (90%), DPPH (41%), and hydroxyl (25%) radical scavenging activities. Viscozyme enhanced δ,γ,α-tocopherols (11%-164%) and tocotrienols (39%–271%) and scavenging activities against nitric oxide (144%), superoxide anion (120%), and inhibition of human LDL oxidation (40%). Cycloartenyl ferulate, ferulic acid, soluble phenolics, campesteryl ferulate, 24-methylenecycloartanyl ferulate, and α-tocotrienol showed a significant positive correlation with bioactivities. Thus, optimization of enzymatic processing will help process the red rice bran into a nutraceutical rich ingredient having higher biological activity.

Inhibición de la oxidación in vitro de lipoproteínas de baja densidad (LDL), por extractos acuosos de Camellia sinensis e Hibiscus sabdariffa

Introducción: el uso de bebidas funcionales como las infusiones de Camellia sinensis e Hibiscus sabdariffa, ha crecido en los últimos años a nivel mundial gracias a su contenido en compuestos bioactivos con un alto poder antioxidante, atribuyéndoles diversos efectos entre los que destaca su capacidad hipolipemiente.&#x0D; Objetivo: el estudio tuvo como propósito evaluar la capacidad de dos extractos acuosos de C. sinensis e H. sabdariffa en la inhibición de la oxidación de las LDL obtenidas de plasma.&#x0D; Material y métodos: se emplearon hojas de té verde orgánico y cálices deshidratados para la obtención de los extracto. Se determino el contenido de fenoles totales por el método de Folin-Ciocalteu y el ensayo de la oxidación de las LDL como modelo biológico para la evaluación de la capacidad inhibitoria de los extractos.&#x0D; Resultados: se observó inhibición de la oxidación de las LDL por ambos extractos con diferencia estadística respecto al control (p≤0,05), siendo el extractos de C. sinensis el mayor actividad.&#x0D; Conclusiones: las dos especies aportan un alto contenido de antioxidantes fundamentales para el organismo, por lo que la ingesta regulada y dirigida por expertos podría contribuir sin duda al tratamiento de hiperlipidemia.

A new analytical concept based on chemistry and toxicology for herbal extracts analysis: From phenolic composition to bioactivity

Studies regarding the bioactivity of teas are mainly based on the phenolic composition and in vitro antioxidant activity of the herbal species used in their preparation. The aim of this study was to compare the in vitro and ex vivo antioxidant activity, cytotoxic/antiproliferative activity against cancer cells, the inhibitory activity of α-amylase, α-glucosidase and angiotensin I-converting enzymes, as well as the inhibition of DNA-induced fission of the peroxyl radical, in relation to aqueous extracts of Camellia sinensis var. sinensis (CS), Ilex paraguariensis (IP), Aspalathus linearis (AL) and an optimised extract (OT) containing the three herb species. A bivariate and multivariate statistical approach was employed to associate functional activities with individual phenolic composition. The CS and OT extracts showed the highest levels of hesperidin, quercetin-3-rutinoside, (-)-epigallocatechin-3-gallate and isoquercitrin. The CS and OT extracts showed the highest antioxidant activity, greater ability to inhibit α-amylase and proliferation of HCT8 cells, and greater ability to reduce Folin-Ciocalteu reagent. The AL extract, which is the major source of quercetin-3-rutinoside, hesperidin and isoquercitrin, showed the highest ability to inhibit α-glucosidase, the inhibition of LDL oxidation and protection of human erythrocytes. The IP extract showed the highest inhibition of lipoperoxidation in brain homogenate of Wistar rats, antihypertensive activity, and A549 cell proliferation; chlorogenic acid was its major phenolic compound. In general, the in vitro functionality of each extract was dependent on its chemical composition and the OT extract presented the most varied phenolic composition, and biological activity similar to the CS sample. In conclusion, the mixture of CS, AL, and IP represents a chemical and functional-based strategy to develop functional teas.

Hdl From Diabetic Kidney Disease Patients Presents A Reduced Ability In Removing Macrophage Cholesterol And Inhibiting Ldl Oxidation According To The Stage Of Kidney Failure

Background and Aims: We analyzed in patients with DKD with different levels of kidney dysfunction but similar HbA1c levels the ability of HDL in removing cell cholesterol and inhibiting oxidation

Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users

Background and aimsAnabolic androgenic steroids (AAS) have been associated with coronary artery disease (CAD). AAS abuse leads to a remarkable decrease in high-density lipoprotein (HDL) plasma concentration, which could be a key factor in the atherosclerotic process. Moreover, not only the concentration of HDL, but also its functionality, plays a pivotal role in CAD. We tested the functionality of HDL by cholesterol efflux and antioxidant capacity. We also evaluated the prevalence of CAD in AAS users. MethodsTwenty strength-trained AAS users (AASU) age 29 ± 5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this cross-sectional study. Functionality of HDL was evaluated by 14C-cholesterol efflux and the ability of HDL in inhibiting LDL oxidation. Coronary artery was evaluated with coronary computed tomography angiography. ResultsCholesterol efflux was lower in AASU compared with AASNU and SC (20 vs. 23 vs. 24%, respectively, p < 0.001). However, the lag time for LDL oxidation was higher in AASU compared with AASNU and SC (41 vs 13 vs 11 min, respectively, p < 0.001). We found at least 2 coronary arteries with plaques in 25% of AASU. None of the AASNU and SC had plaques. The time of AAS use was negatively associated with cholesterol efflux. ConclusionsThis study indicates that AAS abuse impairs the cholesterol efflux mediated by HDL. Long-term AAS use seems to be correlated with lower cholesterol efflux and early subclinical CAD in this population.

Inhibition of LDL oxidation and inflammasome assembly by nitroaliphatic derivatives. Potential use as anti-inflammatory and anti-atherogenic agents

We have previously shown the antioxidant and anti-inflammatory properties of several para-substituted arylnitroalkenes. Since oxidative stress and inflammation are key processes that drive the initiation and progression of atherosclerosis, in the present work the antioxidant, anti-inflammatory and anti-atherogenic properties of an extended library of aryl-nitroaliphatic derivatives, including several newly designed nitroalkanes, was explored. The antioxidant capacity of the nitroaliphatic compounds, measured using the oxygen radical absorbance capacity assay (ORAC) showed that the p-methylthiophenyl-derivatives were about three times more effective than Trolox to prevent fluorescein oxidation, independently of the presence or the absence of the double bond next to the nitro group. The peroxyl radical scavenger capacity of the p-dimethylaminophenyl-derivatives was even higher, being the reduced form of these compounds even more active. In fact, while the antioxidant capacity of 1-dimethylamino-4-(2-nitro-1Z-ethenyl)benzene and 1-dimethylamino-4-(2-nitro-1Z-propenyl)benzene was 4.2 ± 0.1 and 5.4 ± 0.1 Trolox Eq/mol, respectively; ORAC values obtained with the ethyl and the propyl derivatives were 10 ± 1 and 13 ± 2 Trolox Eq/mol, respectively. The p-dimethylamino-derivatives, especially the nitroalkanes, were also able to prevent LDL oxidation mediated by peroxyl radicals. Oxygen consumption due to the oxidation of fatty acids was delayed in the presence of the dimethylamino substituted compounds, only the alkanes interrupted the chain of lipid oxidations decreasing the rate of oxygen consumption. Although the formation of foam cells in the presence of oxidized-LDL (oxLDL) remained unaffected, the molecules containing the dimethylamino moiety were able to decrease the expression of IL-1β in LPS/INF-γ challenged macrophages.

Protective effect of enzymatic hydrolysates from seahorse (Hippocampus abdominalis) against H2O2-mediated human umbilical vein endothelial cell injury.

Oxidative stress-mediated endothelial dysfunction and LDL oxidation have been implicated in the pathogenesis of atherosclerosis. Thus, the protection of the endothelial cells against oxidative stress-mediated injury and the inhibition of LDL oxidation by the use of antioxidants are a good strategy against atherosclerosis development. Here, we investigated the protective effect and the inhibition of LDL oxidation of seahorse H. abdominalia hydrolysates by Alcalase (SHAH). SHAH showed higher antioxidant activities by measuring DPPH, ABTS+, and ORAC assays than the other hydrolysates. SHAH reduced the formation of thiobarbituric acid reactive substance in Cu2+-induced LDL oxidation. In human umbilical vein endothelial cell (HUVEC), SHAH ameliorated H2O2-mediated HUVEC injury through the restoration of antioxidant enzyme activities and glutathione. In addition, SHAH inhibited HUVEC apoptosis through the down-regulation of caspase-3 and p53 and the increase bcl-2/bax ratio. These results suggested that seahorse H. abdominalia could be developed as potential agents for atherosclerosis.

Dapsone protects brain microvascular integrity from high-fat diet induced LDL oxidation

Atherosclerosis was considered to induce many vascular-related complications, such as acute myocardial infarction and stroke. Abnormal lipid metabolism and its peroxidation inducing blood–brain barrier (BBB) leakage were associated with the pre-clinical stage of stroke. Dapsone (DDS), an anti-inflammation and anti-oxidation drug, has been found to have protective effects on vascular. However, whether DDS has a protective role on brain microvessels during lipid oxidation had yet to be elucidated. We investigated brain microvascular integrity in a high-fat diet (HFD) mouse model. We designed this study to explore whether DDS had protective effects on brain microvessels under lipid oxidation and tried to explain the underlying mechanism. In our live optical study, we found that DDS significantly attenuated brain microvascular leakage through reducing serum oxidized low-density lipoprotein (oxLDL) in HFD mice (p < 0.001), and DDS significantly inhibited LDL oxidation in vitro (p < 0.001). Our study showed that DDS protected tight junction proteins: ZO-1 (p < 0.001), occludin (p < 0.01), claudin-5 (p < 0.05) of microvascular endothelial cells in vivo and in vitro. DDS reversed LAMP1 aggregation in cytoplasm, and decreased the destruction of tight junction protein: ZO-1 in vitro. We first revealed that DDS had a protective role on cerebral microvessels through preventing tight junction ZO-1 from abnormal degradation by autophagy and reducing lysosome accumulation. Our findings suggested the significance of DDS in protecting brain microvessels under lipid metabolic disorders, which revealed a novel potential therapeutic strategy in brain microvascular-related diseases.