LDL Oxidation Research Articles

Exploiting the beneficial effects of Salvia officinalis L. extracts in human health and assessing their activity as potent functional regulators of food microbiota

Salvia officinalis L. has attracted scientific and industrial interest due to its pharmacological properties. However, its detailed phytochemical profile and its correlation with beneficial effects in the human microbiome and oxidative stress remained elusive. To unveil this, S. officinalis was collected from the region of Epirus and its molecular identity was verified with DNA barcoding. Phytochemical profile for both aqueous and ethanol-based extracts was determined by high-pressure liquid chromatography-tandem mass spectrometry and 103 phytochemicals were determined. The effect of S. officinalis extracts as functional regulators of food microbiota by stimulating the growth of Lacticaseibacillus rhamnosus strains and by suppressing evolution of pathogenic bacteria was verified. Furthermore, we recorded that both extracts exhibited a significant cellular protection against H2O2-induced DNA damage. Finally, both extracts exhibited strong inhibitory effect towards LDL oxidation. This study provides a comprehensive characterization of S. officinalis on its phytochemical components as also its potential impact in human microbiome and oxidative stress.

Effect of alkyl‐chain unsaturation on the antioxidant potential of chlorogenic acid derivatives in food and biological systems

SummaryChlorogenic acid (CGA) was modified using acyl chlorides with different levels of unsaturation (C18:0–C18:3) to enhance the lipophilicity and promote its application. The antioxidant activity of CGA derivatives in food and biological models was evaluated. All CGA derivatives had significantly greater antioxidative activity than CGA in fish oil and β‐carotene/linoleic acid emulsions (P < 0.05), but there was no linear relationship between antioxidative activity and unsaturation. The effectiveness of CGA‐C18:0 was significantly greater than that of CGA in scavenging H2O2 and reducing copper‐induced human low‐density lipoprotein (LDL) oxidation (P < 0.05). Furthermore, the H2O2 scavenging activity, inhibitions of copper‐induced human LDL oxidation and hydroxyl or peroxyl radical‐induced DNA oxidation were all linearly related to the unsaturation of the alkyl chains, mainly with the free radical chain reactions of the unsaturated bonds. Our findings showed that CGA derivatives could potentially be used as antioxidants in food and biological systems.

Increased 12/15-lipoxygenase by disturbed flow promotes endothelial dysfunction and the development of atherosclerosis

Abstract Introduction Atherosclerosis is predisposed at bifurcations, branch points and arterial curvatures where the blood flow is disturbed. Deposition and oxidative modification of low-density lipoprotein (LDL) in the subendothelial intima is an early event in the pathogenesis of atherosclerosis. However, the effect of disturbed flow (d-flow) on LDL oxidation and the underlying mechanisms remain unclear. Purpose In this study, we investigated the role of 12/15-lipoxygenase (LOX) in LDL oxidation in endothelial cells (EC) and the development of atherosclerosis at d-flow sites. Methods En face immunofluorescence was performed to analyze the expression of 12/15-LOX in EC under exposure to different flow patterns. Protein expression and LDL oxidation was studied in vitro by using 2 different flow apparatuses. Animal model of d-flow was established by partial ligation of the carotid artery. Results En face staining exhibited a significant increase in 12/15-LOX protein expression in EC in areas exposed to d-flow than those exposed to steady flow (s-flow). Carotid partial ligation in ApoE knockout mice led to substantially increased deposition of oxidized LDL in the subendothelial intima and formation of atherosclerotic plaques in the carotid artery, whereas these detrimental effects by d-flow were markedly attenuated in ApoE/12/15-LOX double knockout mice. In cultured EC, d-flow generated by a reversal flow pump markedly promoted the expression of 12/15-LOX and translocation of the protein onto the cell membrane. Inhibition of 12/15-LOX in EC, either by knockdown with its specific siRNA or a pharmacological inhibitor, suppressed production of 15s-HETE and LDL oxidation in response to d-flow. Mechanically, we found d-flow induced the expression of 12/15-LOX by activating a specific responsive element in the 12/15-LOX promoter through recruiting a shear stress-sensitive transcriptional factor SREBP2. Chromatin immunoprecipitation further confirmed the interaction of SREBP2 with the promoter of 12/15-LOX upon d-flow exposure. Conclusions These data define an essential role of 12/15-LOX in promoting the pathogenesis of atherosclerosis under d-flow by increasing LDL oxidation in EC through SREBP2 signaling.

Abstract 16934: Eicosapentaenoic Acid Inhibits Lipoprotein(a) With Higher Rates of Oxidation Compared to Non-Modified Low-Density Lipoprotein in vitro

Background: Lp(a) synthesis is the result of covalent binding of apolipoprotein a to apolipoprotein B on LDL particles. Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Atherogenic mechanisms for Lp(a) include increased inflammation due to its associated oxidized lipids. The omega-3 fatty acid (n3-FA) EPA administered as icosapent ethyl reduced CV events in REDUCE-IT. As a potential mechanism, EPA inhibits oxidation of different sized ApoB-containing lipoproteins compared to other n3-FAs. We tested EPA effects on oxidation of lipoprotein samples enriched with Lp(a) compared to control LDL samples. Methods: Lp(a) was enriched to 40% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) (100 μg/mL) and non-modified LDL were incubated at 37°C for 30 min with EPA (50 μM). Samples were then subjected to copper sulfate-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Results: Lp(a) enriched ApoB particles underwent increased oxidation by 18% after 2 h which was significantly higher than non-modified LDL (13.24 ± 0.47 vs 11.23 ± 0.44 μM, p<0.001). EPA significantly inhibited Lp(a) and non-modified LDL oxidation; after 2 h, EPA inhibited MDA levels by 56% and 76%, respectively (p<0.001). The inhibition of oxidation in both particles with EPA was time dependent. Conclusions: Lp(a) enriched plasma underwent oxidation to a greater extent than non-modified LDL and this process was inhibited in a dose-dependent fashion by EPA. The antioxidant actions of EPA may contribute to reduced events in outcome trials, including in subjects with elevated Lp(a).

An Overview of Dietary Flavonoids as a Nutraceutical Nanoformulation Approach to Life-Threatening Diseases.

Obesity, heart disease, diabetes, and cancer are just a few chronic diseases for which proper nutrition has been demonstrated to be a crucial factor in preven-tion. Flavonoids, found in many fruits and vegetables, are a type of dietary polyphenol with potent antioxidant activity and anti-carcinogenic characteris-tics. Flavonoids and foods rich in flavonoids have been shown in recent years to have profound effects on cognitive function, aging, and neurodegenerative diseases like Alzheimer's. Foods high in flavonoids, such as green tea, choco-late, blueberries, and other fruits and vegetables, have ameliorated symptoms of cognitive impairment, Alzheimer's disease, and dementia in several animal models. As a result of their ability to prevent neuronal death generated by neu-rotoxic chemicals such as free radicals and β-amyloid proteins. Furthermore, flavonoids are also effective in slowing the evolution of clinical signs of neuro-degenerative illnesses. In addition, flavonoids can improve lipid profiles by preventing the oxidation of low-density lipoproteins, and these antioxidant ca-pabilities are responsible for their therapeutic impacts. Finally, the potential of flavonoids to induce vasodilation and control apoptotic processes in the endo-thelium is another way in which they benefit the cardiovascular system. This review aims to offer up-to-date information on categorizing these compounds, their primary methods of action in the human body, and their positive impacts on the management of neurodegenerative diseases, cardiovascular disorders, and other life-threatening diseases.

Quercetin and Heart Health: From Molecular Pathways to Clinical Findings

Cardiovascular diseases (CVD) are the leading causes of global death, increasing over time. Despite current novel improvements, it is still a major medical challenge. Quercetin (QU) is a flavonoid with anti-inflammatory, vasodilatory, antihypertensive, antiarrhythmogenic, and antiapoptotic effects. It can reduce low-density lipoprotein (LDL) and cholesterol oxidation and prevent endothelial dysfunction in CVD. Also, it can protect myocardial cells against oxidative stress and inflammation caused by free radicals. An updated review of the literature on the cardiovascular effects of quercetin was performed using PubMed, Embase, and Science Direct databases. The aim of this review is to summarize the various effects of quercetin on the cardiovascular system.

Simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) by probe-type ultrasound-assisted natural deep eutectic solvents and their inhibition effects on low density lipoprotein oxidation

The simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) was performed by integrating natural deep eutectic solvents (NADES) and ultrasound-assisted extraction (UAE). Among the eight kinds of NADES screened, choline chloride-1,2-propylene glycol was the most suitable extractant. The probe-type ultrasound-assisted NADES extraction system (pr-UAE-NADES) demonstrated higher extraction efficiency compared with plate-type ultrasound-assisted NADES extraction system (pl-UAE-NADES). Orthogonal experimental design and a modified multi-index synthetic weighted scoring method were adopted to optimize pr-UAE-NADES extraction process. The optimal extraction conditions that had a maximum synthetic weighted score of 29.46 were determined to be 25 °C for extraction temperature, 600 W for ultrasonic power, 20 min for extraction time, and 25% (w/w) for water content in NADES, leading to the maximum yields (7.39 ± 0.20 mg/g and 57.99 ± 0.91 mg/g, respectively) of crocin and geniposide. Thirty-three compounds including iridoids, carotenoids, phenolic acids, flavonoids, and triterpenes in the NADES extract were identified by LC-Q-TOF-MS2 coupled with a feature-based molecular networking workflow. The kinetics evaluation of the conjugated dienes generation on Cu2+-induced low density lipoprotein (LDL) oxidation via the four-parameter logistic regression model showed that crocin increased the lag time of LDL oxidation in a concentration-dependent manner (15 μg/mL, 30 μg/mL, 45 μg/mL) by 12.66%, 35.44%, and 73.42%, respectively. The quantitative determination for fluorescence properties alteration of the apolipoprotein B-100 exhibited that crocin effectively inhibited the fluorescence quenching of tryptophan residues and the modification of lysine residues caused by reactive aldehydes and malondialdehydes. The pr-UAE-NADES showed significant efficiency toward the simultaneous extraction of crocin and geniposide from gardenia fruits. And this study demonstrates the potential utility of gardenia fruits in developing anti-atherogenic functional food.

Elevated glycosylation of CD36 in platelets is a risk factor for oxLDL-mediated platelet activation in type 2 diabetes.

Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS-based identification of differentially expressed platelet proteins with a focus on glycosylated forms. Glycosylation is considered one of the common post-translational modifications in T2D, and N/O-linked glycosylation of glycoproteins (GPs)/integrins is known to play crucial roles in platelet activation. Our platelet proteome data revealed elevated levels of GPs GPIbα, GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had elevated N-linked glycosylation of CD36 at asparagine (Asn)408,417 . Enrichment analysis revealed a close association of glycosylated CD36 with thrombospondin-1, fibrinogen and SERPINA1 in T2D platelets. The glycosylation of CD36 has previously been reported to increase cellular uptake of long-chain fatty acids. Our in silico molecular docking data also showed a favorable binding of cholesterol with glycosylated Asn417 CD36 compared to the non-glycosylated form. We further investigated the CD36:LDL cholesterol axis in T2D. Elevated levels of oxidized-low density lipoprotein (oxLDL) were found to cause significant platelet activation via CD36-mediated stimulation of Lyn-JNK signaling. Sulfo-N-succinimidyl oleate, an inhibitor of CD36, effectively inhibited oxLDL-mediated platelet activation and adhesion in vitro. Our study suggests increased glycosylation of CD36 in T2D platelets as a potential route for oxLDL-mediated platelet activation. The oxLDL:CD36 axis may thus be exploited as a prospective target to develop therapeutics against thrombosis in T2D.

Plant & its Bioactive Components Uses in Cardio-Potential Diseases: A Sectional Study for Different Herbs

Thirty percent of all deaths that occur each year can be attributed to heart disease, stroke, and other forms of cardiovascular disease. The World Health Organisation (WHO) predicts that by the year 2030, the annual death toll from cardiovascular diseases will have increased to 22.2 million, up from the present annual total of 17.9 million. Mortality rates tend to go up in populations as they get older. The chance of dying from cardiovascular disease is significantly higher for females (51%) than it is for males (42%). The majority of people treat and prevent cardiovascular disease by using plant-based medications (also known as phytochemicals), either in addition to or in instead of pharmaceuticals that are readily available on the market. In this study, the efficacy of treating cardiovascular illness is evaluated using 92 different plants, including 15 terrestrial plants. A number of different medicinal herbs, including Daucus carota, Nerium oleander, Amaranthus Viridis, Ginkgo biloba, Terminalia arjuna, Picrorhiza kurroa, Salvia miltiorrhiza, Tinospora cordifolia, Mucuna pruriens, Hydrocotyle asiatica, Bombax ceiba, and Andrographis paniculate, are utilised to treat cardiovascular disease. There are a variety of active phytochemicals found in these plants, some of which include flavonoids, polyphenols, plant sterols, plant sulphur compounds, and terpenoids. Flavonoids, in general, are known to increase vasodilation by inhibiting the oxidation of low-density lipoprotein (LDL). Plant sterols reduce the amount of cholesterol in the blood, which in turn protects against cardiovascular disease. Plant sulphur compounds protect against cardiovascular disease in addition to their role in the activation of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and the inhibition of cholesterol formation. The incidence of cardiovascular disease can be reduced by increasing the synthesis of ATP in mitochondria, and terpenoids can diminish atherosclerotic lesion in the aortic valve. Even though several physiologically active compounds with acknowledged biological functions have been found in a wide variety of plants, the prevalence of cardiovascular disease continues to rise, making it imperative that effective CVD prevention and treatment strategies be developed. More research is required to understand both the mechanism and the individual phytochemicals in plants that treat CVD.
 GRAPHICAL ABSTRACT 

Dyslipidemia in rheumatoid arthritis: the possible mechanisms

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, of which the leading cause of death is cardiovascular disease (CVD). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) in RA decrease especially under hyperinflammatory conditions. It is conflictive with the increased risk of CVD in RA, which is called “lipid paradox”. The systemic inflammation may explain this apparent contradiction. The increased systemic proinflammatory cytokines in RA mainly include interleukin-6(IL-6)、interleukin-1(IL-1)and tumor necrosis factor alpha(TNF-α). The inflammation of RA cause changes in the subcomponents and structure of HDL particles, leading to a weakened anti-atherosclerosis function and promoting LDL oxidation and plaque formation. Dysfunctional HDL can further worsen the abnormalities of LDL metabolism, increasing the risk of cardiovascular disease. However, the specific mechanisms underlying lipid changes in RA and increased CVD risk remain unclear. Therefore, this article comprehensively integrates the latest existing literature to describe the unique lipid profile of RA, explore the mechanisms of lipid changes, and investigate the impact of lipid changes on cardiovascular disease.

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.

Endoplasmic Reticulum Stress Promotes the Expression of TNF-α in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1α and MAPK/NF-κB Pathways.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 cells and primary human monocytes by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of the ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress were determined by qRT-PCR, TNF-α protein by ELISA, reactive oxygen species (ROS) by DCFH-DA assay, hypoxia-inducible factor 1-alpha (HIF-1α), p38, extracellular signal-regulated kinase (ERK)-1,2, and nuclear factor kappa B (NF-κB) phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed using qRT-PCR/IHC and plasma TNF-α, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and oxidized low-density lipoprotein (OX-LDL) via ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CCAAT-enhancer-binding protein homologous protein (CHOP), activating transcription factor 6 (ATF6), superoxide dismutase 2 (SOD2), and nuclear factor erythroid 2-related factor 2 (NRF2) expression (p ≤ 0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α stabilization and p38 MAPK/p65 NF-κB phosphorylation, while the MAPK/NF-κB pathway inhibitors and antioxidants/ROS scavengers such as curcumin, allopurinol, and apocynin attenuated the TNF-α production (p ≤ 0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (p ≤ 0.05). Our findings support a metabolic-ER stress cooperativity model, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also highlights the therapeutic potential of antioxidants in inflammatory conditions involving metabolic/ER stresses.

Blue mussel (Mytilus edulis) hydrolysates attenuate oxidized-low density lipoproteins (ox-LDL)-induced foam cell formation, inflammation, and oxidative stress in RAW264.7 macrophages

Seafood consumption has a great demand in the world due to its array of health benefits. Marine-derived bioactive peptides and hydrolysates have been found to have multifunctional health benefits. In this study, inhibitory effects of blue mussel hydrolysates, including blue mussel Alcalase® hydrolysate (BMAH) and blue mussel-pepsin hydrolysate (BMPH), on foam cell formation in ox-LDL-induced RAW264.7 macrophages were investigated. BMAH inhibited lipid accumulation evidenced by Oil Red O staining. Its inhibitory effect was higher than that of BMPH. BMAH positively modulated levels of total cholesterol, free cholesterol, and cholesterol ester in model cells. It suppressed cholesterol influx by downregulating SR-A1 and CD36 expression, but increased cholesterol efflux by upregulating ABCA-1 and ABCG-1 expression. In addition, ox-LDL treated RAW264.7 macrophages produced inflammatory responses and oxidative stress during foam cell formation. However, BMAH treatment significantly ameliorated proinflammatory cytokines production (TNF-α, IL-6, and IL-1β) by inhibiting NF-κB nuclear translocation. Moreover, BMAH inhibited intracellular reactive oxygen species (ROS) generation by activating HO-1/Nrf2 signaling pathway in ox-LDL-treated RAW264.7 macrophages. Taken together, these results suggest that BMAH might be useful as an ingredient of functional foods to ameliorate the development of atherosclerosis.

Efektivitas Ekstrak Daun Salam (Syzygium polyanthum) Dalam Mencegah Kenaikan Kadar Kolesterol LDL Tikus Putih (Rattus norvegicus) Diinduksi Kuning Telur Puyuh

Quail egg yolk contains high cholesterol which can trigger dyslipidemia. If Cholesterol is consumed in excess, will increase lipid profile, which can increase LDL cholesterol levels. Bay leaf extract contains several active compounds, like quercetin, a class of flavonoids with antioxidants that can prevent LDL oxidation. The aim of this study is to ensure the effectiveness of bay leaf extract on LDL cholesterol levels in white rats induced by quail egg yolk. The animal tested in this study were male white rats (Rattus norvegicus) with the Sprague Dawley strain. Samples were randomly selected and divided into five groups: three groups given quail egg yolk and bay leaf extract in various doses of 0.18 g/day, 0.36 g/day and 0.72 g/day, positive control given quail egg yolk, and negative control without treatment. The ANOVA test showed that there were significant results between the treatment groups, positive control and negative control (p<0.05). Next, the BNJ test showed that giving bay leaf extract (0.18 g/day, 0.36 g/day) had a significant effect on LDL cholesterol levels (p<0.05), while a dose of 0.72 g/day showed that not significant (p>0.05), so we can conclude that the dose of 0.72 g/day was the most effective in preventing an increase in LDL cholesterol levels.

Comparison of Policosanols via Incorporation into Reconstituted High-Density Lipoproteins: Cuban Policosanol (Raydel®) Exerts the Highest Antioxidant, Anti-Glycation, and Anti-Inflammatory Activity.

Reconstituted high-density lipoproteins (rHDL) containing each policosanol from Cuba (Raydel®), China (Shaanxi Pioneer), and the United States (Lesstanol®) were synthesized to compare the physiological properties of policosanol depending on sources and origin countries. After synthesis with apolipoproteinA-I (apoA-I) into rHDL, all policosanols bound well with phospholipid and apoA-I to form discoidal rHDL. An rHDL containing Cuban policosanol (rHDL-1) showed the largest rHDL particle size of around 83 ± 3 nm, while rHDL containing Chinese policosanol (rHDL-2) or American policosanol (rHDL-3) showed smaller particles around 63 ± 3 nm and 60 ± 2 nm in diameter, respectively. The rHDL-1 showed the strongest anti-glycation activity to protect the apoA-I degradation of HDL from fructose-mediated glycation: approximately 2.7-times higher ability to suppress glycation and 1.4-times higher protection ability of apoA-I than that of rHDL-2 and rHDL-3. The rHDL-1 showed the highest antioxidant ability to inhibit cupric ion-mediated LDL oxidation in electromobility and the quantification of oxidized species. A microinjection of each rHDL into a zebrafish embryo in the presence of carboxymethyllysine (CML) showed that rHDL-1 displayed the strongest anti-oxidant activity with the highest embryo survivability, whereas rHDL-2 and rHDL-3 showed much weaker protection ability, similar to rHDL alone (rHDL-0). An intraperitoneal injection of CML (250 μg) into adult zebrafish caused acute death and hyperinflammation with an elevation of infiltration of neutrophils and IL-6 production in the liver. On the other hand, a co-injection of rHDL-1 resulted in the highest survivability and the strongest anti-inflammatory ability to suppress IL-6 production with an improvement of the blood lipid profile, such as elevation of HDL-C and lowering of the total cholesterol, LDL-cholesterol, and triglyceride. In conclusion, Cuban policosanol exhibited the most desirable properties for the in vitro synthesis of rHDL with the stabilization of apoA-I, the largest particle size, anti-glycation against fructation, and antioxidant activities to prevent LDL oxidation. Cuban policosanol in rHDL also exhibited the strongest in vivo antioxidant and anti-inflammatory activities with the highest survivability in zebrafish embryos and adults via the prevention of hyperinflammation in the presence of CML.

The power of berries against cardiovascular diseases.

Cardiovascular diseases (CVDs) pose a serious threat to human health and incidence is increasing gradually. Nutrition has an important impact on the prophylaxis and progression of CVD. In this article, general attention is drawn to the possible positive effects of berries on CVD. Polyphenols have beneficial effects on the vascular system by inhibiting low-density lipoprotein oxidation and platelet aggregation, lowering blood pressure, improving endothelial dysfunction, and attenuating antioxidant defense and inflammatory responses. This review provides an overview of the effects of berries for the prevention and treatment of CVDs. Berries contain several cardioprotective antioxidants, vitamins, and numerous phytochemicals, such as phenolic compounds, that have antioxidant properties and antiplatelet activity. Phytochemical compounds in their structures can modulate dissimilar signaling pathways related to cell survival, differentiation, and growth. Important health benefits of berries include their antioxidant roles and anti-inflammatory impacts on vascular function. The effectiveness and potential of polyphenols primarily depend on the amount of bioavailability and intake. Although circulating berry metabolites can improve vascular function, their biological activities, mechanisms of action, and in vivo interactions are still unknown. Analyzing human studies or experimental studies to evaluate the bioactivity of metabolites individually and together is essential to understanding the mechanisms by which these metabolites affect vascular function.

The association between lipid profile, oxidized LDL and the components of metabolic syndrome with serum mineral status and kidney function in individuals with obesity

BackgroundMetabolic syndrome (MetS) is presented with a cluster of cardio-metabolic risk factors with widespread prevalence. In the present case-control study, we aimed to examine the relationship between several minerals and renal function tests with the components of MetS in individuals with obesity.MethodsThis study included 127 individuals with obesity of both gender with or without MetS as the case and control, respectively. MetS was characterized based on the Adult Treatment Panel III (ATP III) criteria. Anthropometric variables and blood pressure were recorded. Mineral status including serum magnesium, copper, calcium, phosphorous, and iron were measured using standard colorimetric methods. Also, the serum lipid levels, concentrations of oxidized low-density lipoprotein (Ox-LDL), and renal function tests, including total protein, albumin, urea, creatinine, and uric acid were evaluated using commercial enzyme-linked immunosorbent assay (ELISA) kits.ResultsAccording to our results, individuals with obesity and MetS had higher levels of waist circumference (WC) and diastolic blood pressure (P < 0.05) compared to individuals with obesity and without MetS. Moreover, individuals with obesity and MetS had higher levels of serum total cholesterol (TC), triglyceride (TG), insulin, and iron (P < 0.05). In individuals with obesity and MetS, iron and albumin showed a positive relationship with LDL cholesterol and TG concentrations, respectively (P < 0.05 for all of them). Also, there was a positive association between serum magnesium and Ox- LDL in individuals with obesity with MetS. While, in individuals with obesity and without MetS, only a positive association between urea and uric acid with WC was observed (P < 0.05).ConclusionOur results suggest that disturbed serum lipids in obesity-metabolic syndrome is associated with homeostatic changes in the level of minerals or proteins that are involved in their metabolism. Although, further studies are needed to better explain and clarify the underlying mechanism of observed relationships.

Phosphatidylethanolamine alleviates OX-LDL-induced macrophage inflammation by upregulating autophagy and inhibiting NLRP1 inflammasome activation

Oxidized low-density lipoprotein (OX-LDL)-induced inflammation and autophagy dysregulation are important events in the progression of atherosclerosis. Phosphatidylethanolamine (PE), a multifunctional phospholipid that is enriched in cells, has been proven to be directly involved in autophagy which is closely associated with inflammation. However, whether PE can influence OX-LDL-induced autophagy dysregulation and inflammation has not been reported. In the present study, we revealed that OX-LDL significantly induced macrophage inflammation through the CD36-NLRP1-caspase-1 signaling pathway in fish. Meanwhile, cellular PE levels were significantly decreased in response to OX-LDL induction. Based on the relationship between PE and autophagy, we then examined the effect of PE supplementation on OX-LDL-mediated autophagy impairment and inflammation induction in macrophages. As expected, exogenous PE restored impaired autophagy and alleviated inflammation in OX-LDL-stimulated cells. Notably, autophagy inhibitors reversed the inhibitory effect of PE on OX-LDL-induced maturation of IL-1β, indicating that the regulation of PE on OX-LDL-induced inflammation is dependent on autophagy. Furthermore, the positive effect of PE on OX-LDL-induced inflammation was relatively conserved in mouse and fish macrophages. In conclusion, we elucidated the role of the CD36-NLRP1-caspase-1 signaling pathway in OX-LDL-induced inflammation in fish and revealed for the first time that altering PE abundance in OX-LDL-treated cells could alleviate inflammasome-mediated inflammation by inducing autophagy. Given the relationship between OX-LDL-induced inflammation and atherosclerosis, this study prompts that the use of PE-rich foods promises to be a new strategy for atherosclerosis treatment in vertebrates.

Plant Polyphenols and Their Potential Benefits on Cardiovascular Health: A Review.

Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary phytochemicals exhibit chemopreventive and therapeutic effects against numerous diseases. Polyphenols are secondary metabolites found in vegetables, fruits, and grains. These compounds exhibit several health benefits such as immune modulators, vasodilators, and antioxidants. This review focuses on recent studies on using dietary polyphenols to treat cardiovascular disorders, atherosclerosis, and vascular endothelium deficits. We focus on exploring the safety of highly effective polyphenols to ensure their maximum impact on cardiac abnormalities and discuss recent epidemiological evidence and intervention trials related to these properties. Kaempferol, quercetin, and resveratrol prevent oxidative stress by regulating proteins that induce oxidation in heart tissues. In addition, polyphenols modulate the tone of the endothelium of vessels by releasing nitric oxide (NO) and reducing low-density lipoprotein (LDL) oxidation to prevent atherosclerosis. In cardiomyocytes, polyphenols suppress the expression of inflammatory markers and inhibit the production of inflammation markers to exert an anti-inflammatory response. Consequently, heart diseases such as strokes, hypertension, heart failure, and ischemic heart disease could be prevented by dietary polyphenols.

Mitochondrial dysfunction in the pathogenesis of endothelial dysfunction.

Cardiovascular diseases (CVDs) are a matter of concern worldwide, and mitochondrial dysfunction is one of the major contributing factors. Vascular endothelial dysfunction has a major role in the development of atherosclerosis because of the abnormal chemokine secretion, inflammatory mediators, enhancement of LDL oxidation, cytokine elevation, and smooth muscle cell proliferation. Endothelial cells transfer oxygen from the pulmonary circulatory system to the tissue surrounding the blood vessels, and a majority of oxygen is transferred to the myocardium by endothelial cells, which utilise a small amount of oxygen to generate ATP. Free radicals of oxide are produced by mitochondria, which are responsible for cellular oxygen uptake. Increased mitochondrial ROS generation and reduction in agonist-stimulated eNOS activation and nitric oxide bioavailability were directly linked to the observed change in mitochondrial dynamics, resulting in various CVDs and endothelial dysfunction. Presently, the manuscript mainly focuses on endothelial dysfunction, providing a deep understanding of the various features of mitochondrial mechanisms that are used to modulate endothelial dysfunction. We talk about recent findings and approaches that may make it possible to detect mitochondrial dysfunction as a potential biomarker for risk assessment and diagnosis of endothelial dysfunction. In the end, we cover several targets that may reduce mitochondrial dysfunction through both direct and indirect processes and assess the impact of several different classes of drugs in the context of endothelial dysfunction.