Disturbance of HDL apolipoprotein AI metabolism in severe hyperlipidemic and lipodystrophic HIV patients on a protease inhibitor treatment

International audiencen.

Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended-Release Nicotinic Acid: a Pilot Study

Background Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment. Methods Eight hypertriglyceridemic patients enrolled in a crossover randomized trial with ERN for 8 weeks and treated with 2 g/day of ERN or a placebo. Ultra-performance liquid chromatography (UPLC) coupled to high-resolution mass spectrometry (HRMS) was used in mass spectrometry energy mode (HRMSE) combined with ion mobility spectrometry to characterize the plasma and very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) lipidome. The accuracy and precision of the method were validated on plasma samples. Results Compared to placebo, among 155 plasma lipids characterized using UPLC-ESI-HRMS, a multivariate analysis revealed a significant increase of lysophosphatidylcholine (LPC 20:5), a significant decrease of phosphatidylethanolamine (PE 16:0/22:3) and sphingomyelin (SM d18:1/22:0) and a decrease of triacylglycerol (TG 16:0/16:1/18:2) after ERN treatment. Analysis of these lipids in lipoproteins showed an increase of LPC (20:5) in HDL, a decrease of PE (16:0/22: 3) in HDL and LDL, of SM (d18:1/22:0) in VLDL and LDL and of TG (16:0/16:1/18:2) in VLDL. Conclusion This lipidomic strategy characterized new specific lipid markers likely to be involved in the effect of ERN on cardiovascular risk opening a new strategy to analyze randomized controlled with this treatment

Correlation of Total Polyphenolic Content with Antioxidant Activity of Hydromethanolic Extract and Their Fractions of the Salvia officinalis Leaves from Different Regions of Morocco

The purpose of this study is to determine the total content of phenols, flavonoids, and condensed tannins, as well as on the antioxidant activity of the extract, and their fractions were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), phosphomolybdate reduction (or total antioxidant capacity), and cyclic voltammetry (CV). The hydromethanolic extract of Salvia officinalis showed the highest values of total phenolic (176 mgGAE/g of extract) and condensed tannins (162.53 mgEC/g of extract) from the Boulemane and Khenifra regions, respectively. The results showed that the best DPPH assay was found in the ethyl acetate fraction of Salvia officinalis leaves of the Boulemane region (IC50 = 0.002 mg/ml). For the ethyl acetate and butanolic fractions of Salvia officinalis leaves, those collected from different regions have a better reducing capacity (EC50 = 0.021 mg/ml, respectively). For the total antioxidant capacity, the best activity was found in the aqueous fraction of Salvia officinalis leaves of the Boulemane region (108 mgGAE/g of extract). By the cyclic voltammetry method, hydromethanolic extract of Salvia officinalis leaves from the Boulemane region showed an important result (288.8 mgGAE/g). There was a positive correlation between total phenol content (TPC), condensed tannin content (TCT), and total antioxidant capacity (TAC) (r = 0.932, r = 0.896, respectively). The main compounds that have been identified in the hydromethanolic extract of Salvia officinalis are ascorbic acid, gallic acid, 4-hydroxybenzoic acid, tannic acid, and rutin. Due to their antioxidant property, the leaf extracts from Salvia officinalis are used as natural preservative ingredients in food and/or pharmaceutical industries

HPLC-PDA/ESI-MS Analysis of Phenolic Compounds and Bioactivities of the Ethanolic Extract from Flowers of Moroccan <i>Anacyclus clavatus</i>

In this work, polyphenols were extracted from Anacylus clavatus flowers using a hydroethanolic solvent, and the obtained extract was studied for its total phenol and flavonoid contents and evaluated for its antioxidant and antibacterial capacities. The contents of total phenols and flavonoids were measured by employing gallic acid and quercetin as references, respectively, and the phenolic composition analysis was conducted using high-performance liquid chromatography combined with a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA/ESI-MS). The antioxidant capacity of the extracts was tested using a potassium ferric reducing antioxidant power (PFRAP) assay, and the antibacterial activity assay was carried out against Gram-negative bacteria (Escherichia coli and Salmonella typhimirium) and Gram-positive bacteria (Staphyloccocus aureus and Listeria monocytogenes) using the broth microdilution assay. The phenolic and flavonoid contents of the extracts equaled 9.53 ± 0.48 mg GAE/g dm and 1.31 ± 0.06 mg QE/g dm, respectively. The chromatographic analysis of the phenolic profile detected 26 phenolic compounds belonging to phenolic acids, flavones and flavonols, and with the caffeoylquinic acid derivatives being the major phenolic compounds present in 12 isomers. Only one organic compound, viz. citric acid, was found. The extracts exhibited interesting antioxidant activity. Bacteriostatic activity towards Escherichia coli and bactericidal activity against Salmonella typhimirium, Staphyloccocus aureus and Listeria monocytogenes were determined. This study revealed that Anacyclus clavatus flower extracts contain phenolic compounds with interesting bioactivities

Determination of the Phenolic Profile, and Evaluation of Biological Activities of Hydroethanolic Extract from Aerial Parts of Origanum compactum from Morocco

Origanum compactum belonging to the family Lamiaceae is widely used in food and pharmaceutical fields due to its biologically active substances. We aimed to investigate the total phenol and flavonoid contents and the phenolic composition, and to evaluate the antioxidant and antibacterial properties of hydroethanolic extract from of Origanum compactum. Total phenol and flavonoid contents were evaluated using gallic acid and quercetin as standards, respectively, and the phenolic profile was characterized using high-performance liquid chromatography coupled to a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). The antioxidant activity was determined by two methods: ferric reducing power (FRAP) assay and the phosphomolybdate method. The antibacterial effect was evaluated against four bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Listeria monocytogenes) using the broth microdilution method. The findings show that the total phenolic and flavonoid contents were 107.789 &plusmn; 5.39 mg GAE/g dm and 14,977 &plusmn; 0.79 mg QE/g dm, respectively. A total of sixteen phenolic compounds belonging to phenolic acids and flavonoids were detected. Furthermore, the extract showed strong antioxidant activity, and displayed a bacteriostatic effect against Escherichia coli and Salmonella typhimuriumn, and a bactericidal effect against Staphylococcus aureus and Listeria monocytogenes. Therefore, this study reveals that Origanum compactum extracts display potential as antibacterial and natural antioxidant agents for fighting against pathogenic bacteria and preventing oxidative stress

Phenolic Composition, Antioxidant and Antibacterial Activities of Extract from Flowers of <i>Rosa damascena</i> from Morocco

Rosa damascena is referred to as the queen of roses due to its ornamental, flavoring, and perfuming uses, along with its recognized use in therapy. This study aimed to investigate the total phenols and flavonoids contents, the phenolic compounds, and study the antioxidant and antibacterial properties of the hydroethanolic extract from Rosa damascena flowers, collected from the Middle Atlas of Morocco (Khenifra). The total phenols and flavonoids were assessed using gallic acid and quercetin as standards, and the phenolic compounds were characterized using HPLC-PDA-ESI/MS. The antioxidant activity was evaluated by two methods, namely ferric reducing assay power and total antioxidant capacity. The broth microdilution method was employed to evaluate the antibacterial activity of extract against four bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Listeria monocytogenes). Up to 16 phenolic compounds belonging to tannins and flavonoids were positively identified in the Rosa damascena extract. The latter displayed high antioxidant activity and exhibited a bacteriostatic effect against Escherichia coli and a bactericidal effect against Salmonella typhimuriumn, Staphylococcus aureus, and Listeria monocytogenes. As a result, the flowers of Rosa damascena might be employed as natural agents in the pharmaceutical field

Characterization of Autosomal Dominant Hypercholesterolemia Caused byPCSK9Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody

Background—Patients with PCSK9 gene gain of function (GOF) mutations have a rare form of autosomal dominant hypercholesterolemia. However, data examining their clinical characteristics and geographic distribution are lacking. Furthermore, no randomized treatment study in this population has been reported. Methods and Results—We compiled clinical characteristics of PCSK9 GOF mutation carriers in a multinational retrospective, cross-sectional, observational study. We then performed a randomized placebo-phase, double-blind study of alirocumab 150 mg administered subcutaneously every 2 weeks to 13 patients representing 4 different PCSK9 GOF mutations with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL on their current lipid-lowering therapies at baseline. Observational study: among 164 patients, 16 different PCSK9 GOF mutations distributed throughout the gene were associated with varying severity of untreated LDL-C levels. Coronary artery disease was common (33%; average age of onset, 49.4 years), and untreated LDL-C concentrations were higher compared with matched carriers of mutations in the LDLR (n=2126) or apolipoprotein B (n=470) genes. Intervention study: in PCSK9 GOF mutation patients randomly assigned to receive alirocumab, mean percent reduction in LDL-C at 2 weeks was 62.5% (P<0.0001) from baseline, 53.7% compared with placebo-treated PCSK9 GOF mutation patients (P=0.0009; primary end point). After all subjects received 8 weeks of alirocumab treatment, LDL-C was reduced by 73% from baseline (P<0.0001). Conclusions—PCSK9 GOF mutation carriers have elevated LDL-C levels and are at high risk of premature cardiovascular disease. Alirocumab, a PCSK9 antibody, markedly lowers LDL-C levels and seems to be well tolerated in these patients

A fourth locus for autosomal dominant hypercholesterolemia maps at 16q22.1

Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated increase in plasmatic low-density lipoprotein (LDL) cholesterol levels associated with high risk of premature cardiovascular disease. Mutations in LDLR, APOB, and PCSK9 genes have been shown to cause ADH. We now report further genetic heterogeneity of ADH through the study of a large French family in which the involvement of these three genes was excluded. A genome-wide scan mapped the disease-causing gene, named HCHOLA4, at 16q22.1 in a 7.89-Mb interval containing 154 genes with a maximum LOD score of 3.9. To reduce the linked region, we genotyped 18 smaller non-LDLR/non-APOB/non-PCSK9-ADH families at the HCHOLA4 locus. Six families did not exclude linkage to the locus, but none allowed reduction of the disease interval. The 154 regional genes were sorted according to the function of the encoded protein and tissue expression profiles, and 57 genes were analyzed through sequencing of their coding region and close flanking intronic parts. No disease-causing mutation was identified in these families, particularly in the LCAT gene. Finally, our results also show the existence of other ADH genes as nine families were neither linked to LDLR, APOB, and PCSK9 genes nor to the new HCHOLA4 locus