Multi-species synbiotic supplementation increased fecal short chain fatty acids and anti-inflammatory cytokine interleukin-10 in adult men with dyslipidemia; A randomized, double-blind, clinical trial.

BACKGROUND: Mounting evidence revealed that an imbalance of Gut Microbiota (GM) leads to metabolic disorders. Synbiotics through regulation of GM composition can be an effective intervention in the management of metabolic diseases. This study aimed to investigate the effects of multi-species synbiotic supplementation on serum interleukin10 (IL-10) and fecal Short Chain Fatty Acids (SCFAs) in patients with dyslipidemia. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, fifty-six adult men with dyslipidemia were randomly allocated to intervention and control groups and received either synbiotic or placebo powder twice a day for 12 weeks. Each synbiotic sachet contained 6 species of probiotic microorganisms with a total dose of 3 × 1010 Colony Forming Unit (CFU) and 5 gr inulin and Fructooligosaccharide (FOS) as prebiotics. Blood and stool samples were collected at the baseline and end of the study. Dietary intake, physical activity, anthropometric measurements, serum IL-10, and fecal SCFAs were assessed before and after the intervention. RESULT: There were no significant differences between the baseline characteristics of patients in the two groups. Serum IL-10 was increased in the synbiotic group (p < 0.0001). Moreover, synbiotic supplementation increased fecal concentration of acetate (p < 0.0001), butyrate (p = 0.043), propionate (p < 0.0001), and valerate (p < 0.026). A significant positive correlation was observed between the changes in fecal butyrate level and serum IL-10 concentration in the control group (r = 0.48, p = 0.01). CONCLUSIONS: A Twelve-week synbiotic supplementation increased fecal SCFAs and improved inflammation in adult men with dyslipidemia.

Folic acid and plasma lipids: Interactions and effect of folate supplementation.

Dyslipidaemia and hyperhomocysteinemia are known risk factors for cardiovascular disease. While it is evident that optimization of plasma lipid is associated with low risk of cardiovascular disease in the general population, it is not yet fully clear whether reduction of homocysteinemia is associated with an improvement in risk in all subjects. The aim of our narrative review is to highlight eventual effects of folate supplementation on LDL-C levels, LDL-C oxidation and atherosclerosis-related complications. A comprehensive literature search was done in electronic database, including PubMed, Web of Science, Cochrane, and Scopus from inception up to January 2024. Based on the available evidence, epidemiological data, pathophysiological observations and meta-analyses of randomized clinical trials suggest that folic acid supplementation may modestly but significantly improve plasma lipid levels, lipid atherogenicity, and atherosclerosis-related early vascular damage, and that folic acid supplementation may significantly reduce the risk of cerebrovascular disease. Considering the low-cost and high safety profile of folic acid, its long-term supplementation could be considered for dyslypidaemic patients in secondary prevention for cardiovascular disease.

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30-40 years, who were randomly assigned to two groups-a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

Nutraceuticals for the Control of Dyslipidaemias in Clinical Practice.

Dyslipidaemias result in the deposition of cholesterol and lipids in the walls of blood vessels, chronic inflammation and the formation of atherosclerotic plaques, which impede blood flow and (when they rupture) result in acute ischaemic episodes. Whilst recent years have seen enormous success in the reduction of cardiovascular risk using conventional pharmaceuticals, there is increasing interest amongst patients and practitioners in the use of nutraceuticals to combat dyslipidaemias and inflammation in cardiovascular disease. Nutraceutical is a portmanteau term: 'ceutical' indicate pharmaceutical-grade preparations, and 'nutra' indicates that the products contain nutrients from food. Until relatively recently, little high-quality evidence relating to the safety and efficacy of nutraceuticals has been available to prescribers and policymakers. However, as a result of recent randomised-controlled trials, cohort studies and meta-analyses, this situation is changing, and nutraceuticals are now recommended in several mainstream guidelines relating to dyslipidaemias and atherosclerosis. This article will summarise recent clinical-practice guidance relating to the use of nutraceuticals in this context and the evidence which underlies them. Particular attention is given to position papers and recommendations from the International Lipid Expert Panel (ILEP), which has produced several practical and helpful recommendations in this field.

Reversal of Insulin Resistance in Overweight and Obese Subjects by trans-Resveratrol and Hesperetin Combination-Link to Dysglycemia, Blood Pressure, Dyslipidemia, and Low-Grade Inflammation.

The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = -0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = -0.68, p < 0.05)-a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = -0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = -0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.

Hypocholesterolemic Effect of Blackcurrant (Ribes nigrum) Extract in Healthy Female Subjects: A Pilot Study.

Blackcurrant extract (BCE) ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can prevent lipid abnormalities in healthy individuals. Lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined the effects of BCE administered for 29 days on serum lipids in young healthy women. Blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in the serum were separated using a gel-permeation high-performance liquid chromatography method to measure the triacylglycerol and cholesterol levels in lipoproteins. There were no effects on lipids on day 4 of BCE intake, but the total cholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL) cholesterol, small VLDL cholesterol, and large low-density lipoprotein cholesterol were significantly decreased. These results suggest that the daily intake of BCE has a hypocholesterolemic effect in healthy women, and that it is effective in preventing atherosclerosis.

Therapeutic potential of targeting intestinal bitter taste receptors in diabetes associated with dyslipidemia.

Intestinal release of incretin hormones after food intake promotes glucose-dependent insulin secretion and regulates glucose homeostasis. The impaired incretin effects observed in the pathophysiologic abnormality of type 2 diabetes have triggered the pharmacological development of incretin-based therapy through the activation of glucagon-like peptide-1 (GLP-1) receptor, including GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP4) inhibitors. In the light of the mechanisms involved in the stimulation of GLP-1 secretion, it is a fundamental question to explore whether glucose and lipid homeostasis can be manipulated by the digestive system in response to nutrient ingestion and taste perception along the gastrointestinal tract. While glucose is a potent stimulant of GLP-1 secretion, emerging evidence highlights the importance of bitter tastants in the enteroendocrine secretion of gut hormones through activation of bitter taste receptors. This review summarizes bitter chemosensation in the intestines for GLP-1 secretion and metabolic regulation based on recent advances in biological research of bitter taste receptors and preclinical and clinical investigation of bitter medicinal plants, including bitter melon, hops strobile, and berberine-containing herbs (e.g. coptis rhizome and barberry root). Multiple mechanisms of action of relevant bitter phytochemicals are discussed with the consideration of pharmacokinetic studies. Current evidence suggests that specific agonists targeting bitter taste receptors, such as human TAS2R1 and TAS2R38, may provide both metabolic benefits and anti-inflammatory effects with the modulation of the enteroendocrine hormone secretion and bile acid turnover in metabolic syndrome individuals or diabetic patients with dyslipidemia-related comorbidities.

Lipid Profile and Vascular Remodelling in Young Dyslipidemic Subjects Treated with Nutraceuticals Derived from Red Yeast Rice.

BACKGROUND AND AIMS: A relevant role is emerging for functional foods in cardiovascular prevention. The aim of this study was to assess the effect of a nutraceutical multitargeted approach on lipid profile and inflammatory markers along with vascular remodelling in a cohort of dyslipidemic subjects without history of cardiovascular (CV) disease. METHODS AND RESULTS: We enrolled 25 subjects (mean age 48.2 years) with low to moderate CV risk profile and total cholesterol (TC) levels between 150 and 250 mg/dl. The patients were assigned to receive for one year a tablet/die of a nutraceutical combination containing red yeast rice (RYR) extract (Monacolin 3 mg/tablet) and coenzyme Q10 (30 mg/tablet). Treatment with the nutraceutical compounds led to a significant reduction of TC (from 227 to 201 mg/dl, p < 0.001), LDL-c (from 150 to 130 mg/dl, p = 0.001), triglycerides (from 121 to 109 mg/dl, p = 0.013), non-HDL-cholesterol (from 168 to 141 mg/dl, p < 0.001), hs-CRP (from 1.74 to 1.20 mg/l, p = 0.015), and osteoprotegerin (from 1488 to 1328 pg/ml, p = 0.045). Levels of HDL-c, Lp(a), glucose, liver enzyme, CPK, or creatinine did not change over time. An ultrasound study was performed to assess changes in mean carotid intima-media thickness (IMT) and maximum IMT (M-MAX) as well as modification in local carotid stiffness by means of determining the carotid compliance coefficient (CC) and distensibility coefficient (DC). At the end of the treatment, we observed small but significant reductions in both mean-IMT (from 0.62 to 0.57 mm, p = 0.022) and M-MAX (from 0.79 to 0.73 mm, p = 0.002), and an improvement in carotid elasticity (DC from 22.4 to 24.3 × 10-3/kPa, p = 0.006 and CC from 0.77 to 0.85 mm2/kPa, p = 0.019). CONCLUSIONS: A long-term treatment with a combination of RYR and coenzyme Q10 showed lipid-lowering activity along with a reduction of inflammatory mediators and an improvement of vascular properties in young subjects with a low-to-moderate CV risk profile.

The relationship of coffee consumption and CVD risk factors in elderly patients with T2DM.

OBJECTIVE: Clinical studies suggest increasing prevalence of cardiovascular disease (CVD) risk factors and diabetes among the elderly. Meanwhile, some food compounds, such as coffee, can also have beneficial effects on CVD risk factors. The aim of the present study was to examine the relationship between coffee consumption and CVD risk factors in the elderly with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study was performed during 2017 on 300 elderly people above 60 years of age with T2DM in Isfahan, Iran. Dietary assessment was performed using a food frequency questionnaire. Coffee consumption was classified into three groups including < 1, 1-3, and > 3 cups/day. Partial correlation test was used to investigate the relationship between CVD risk factors and usual coffee consumption. RESULTS: The mean age and body mass index of participants were 70.04 ± 4.87 years and 24.74 ± 3.34 kg/m2 respectively. Coffee consumption had a significant inverse relationship with fasting plasma glucose (FPG) and diastolic blood pressure (DBP) in the elderly with T2DM (r: - 0.117, 0.134; p: 0.046, 0.022). Triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) had a significant positive relationship with coffee consumption levels (r: 0.636, 0.128; p: 0.028, 0.029). These results were obtained after controlling for potential confounders. CONCLUSION: Increasing coffee consumption was linked to improved status of some CVD risk factors including FPG, HDL-C, and DBP in the elderly with T2DM. Nevertheless, increasing coffee consumption was also associated with higher TG level and had no significant effect on other risk factors. Further studies are required to confirm these results.

Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review.

Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease. In this review, we explored the associations of Mg (dietary intake, Mg concentrations in the body) and the lipid profile, as well as the impact of Mg supplementation on serum lipids. A systematic search was computed in PubMed/MEDLINE and the Cochrane Library and 3649 potentially relevant papers were detected and screened (n = 3364 following the removal of duplicates). After the removal of irrelevant manuscripts based on the screening of their titles and abstracts (n = 3037), we examined the full-texts of 327 original papers. Finally, after we applied the exclusion and inclusion criteria, a number of 124 original articles were included in this review. Overall, the data analyzed in this review point out an association of Mg concentrations in the body with serum lipids in dyslipidemia and related disorders. However, further research is warranted to clarify whether a higher intake of Mg from the diet or via supplements can influence the lipid profile and exert lipid-lowering actions.

The efficacy of niacin supplementation in type 2 diabetes patients: Study protocol of a randomized controlled trial.

BACKGROUND: Dyslipidemia is a main risk factor of cardiovascular disease in the diabetic patients. Niacin was found acutely to decrease the plasma concentration of free fatty acids by inhibiting their mobilization from adipose tissue. This present study is a double blinded, randomized, and prospective trial to determine the effect of niacin during dyslipidemia in type 2 diabetic patients. METHODS: This randomized controlled, double-blinded, single center trial is carried out according to the principles of Declaration of Helsinki. This present study was approved in institutional review committee of the Second Affiliated Hospital of Dalian Medical University. All the patients received the informed consent. Diabetic patients were randomized (1:1) to receive 3-month treatment with extended-release niacin or matching placebo. The major outcome of our present study was the change in the level of HbA1c from the baseline to week 12. Secondary outcome measures contained the levels of fasting blood glucose, the concentrations of serum transaminase, the other laboratory variables, and self-reported adverse events. The P < .05 was regarded as statistically significant. RESULTS: We assumed that adding the niacin to the medication in patients with type 2 diabetes would reduce dyslipidemia and achieve target lipid levels. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5925).

Analysis of Serum Fatty Acids Profile in Kidney Transplant Recipients.

Patients with end-stage kidney disease, treated with renal transplantation, are at increased risk of cardio-vascular disease (CVD) and cardio-vascular mortality. They are also characterized by an atherogenic dyslipidemia. Alterations of the fatty acids (FA) profile contribute to increased cardio-vascular risk in the general population. In the current study, we test the hypothesis that kidney transplantation is associated with ab-normalities in FA profile. The FA profile was analyzed by gas chromatography-mass spectrometry in 198 renal transplant recipients, and 48 control subjects. The most profound differences between renal transplant patients and controls were related to the content of branched chain FA, monounsaturated FA, and n-6 polyunsaturated FA, respectively. The FA profile significantly separated the patients from the controls in the principal component analysis (PCA). The abnormalities of FA profile showed a tendency for normalization in long-term kidney recipients, as compared to patients with recent transplants. The n-3 PUFA content demonstrated a strong inverse association with the presence of inflammation. Most profound alterations of the FA profile were observed in patients with impaired graft function (glomerular filtration rate < 45 mL/min). The study demonstrated significant disorders of the FA profile in kidney transplant recipients, which might contribute to cardio-vascular risk in this vulnerable patient population.

In vivo, Lipid Profile Efficacy of Ethanol Extracts of Stevia rebaudiana Bertoni in Rabbits.

BACKGROUND AND OBJECTIVE: Contraceptive pills are chemical substances used as a means to prevent pregnancy, but they have several effects, including high lipid profile and in many cases, patients with heart and blood diseases cannot use it as a contraceptive helps in increasing the risk of cardiovascular diseases (CVD). A Stevia extract with high sweetening capacity due to its content of glycosides is used to reduce lipid profile and this study aimed to decrease lipid profile levels and lowering the risk factor in women using contraceptive drugs by stevia extracts. MATERIALS AND METHODS: Sixteen rabbits have been used as a case-control study design due to their anatomical and physiological similarity to humans. The stevia leaves are extracted using Soxhlet apparatus of ethanol solvent. Statistical package (SPSS), were used for data analysis and management using independent sample t-test, test, comparison of means for lipid profile of Triglyceride (TG), Cholesterol, High-density lipoprotein (HDL-C), Low-density lipoprotein (LDL-C) between (di-contraceptive, mono-contraceptive and control groups). RESULTS: The results showed increasing cholesterol and LDL-C during the combined oral contraceptive (COCP) and progesterone-only pills with decreased HDL-C level. A comparison of means before and after stevia used explains the elevated HDL-C and decreased LDL-C. CONCLUSION: The lipid profile levels should continuously be monitored during oral contraceptive intake and Stevia leaf powder extraction is suggested to reduce the risk of CVD.

Effect of DLT-SML on Chronic Stable Angina Through Ameliorating Inflammation, Correcting Dyslipidemia, and Regulating Gut Microbiota.

ABSTRACT: Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1ß, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.

Revealing hypoglycemic and hypolipidemic mechanism of Xiaokeyinshui extract combination on streptozotocin-induced diabetic mice in high sucrose/high fat diet by metabolomics and lipidomics.

Type 2 diabetic mellitus (T2DM), often accompanied by disorders of glucose and lipid metabolism, has troubled hundreds of millions of people. Xiaokeyinshui extract combination (XEC), derived from traditional Chinese medicines formula, has exerted hypoglycemic effects against T2DM. However, its mechanism of metabolic level is still unclear. In this study, a T2DM mice model, induced by a high sucrose/high fat diet combined with low-dose streptozotocin (STZ) injections, was adopted. The biochemical index was determined and a combination of metabolomics and lipidomics analyses of plasma were performed. The results showed that XEC increased secretion of insulin and level of HDL-C, decreased levels of FBG, HbA1c, TC, TG, LDL-C and repaired islet structure in diabetic mice. In addition, the metabolic profiles of plasma were analyzed and 54 potential biomarkers were screened out, mainly including carbohydrates, lipids and amino acids. These potential biomarkers were found to be correlated with the following pathways: galactose metabolism, fructose and mannose metabolism, TCA cycle, arachidonic acid metabolism, glycerolipid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and amino acid metabolism. In conclusion, we speculated that carbohydrate metabolism, lipid metabolism and amino acid metabolism played roles in the therapeutic mechanisms of XEC on T2DM.

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results.

AIMS: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. METHODS AND RESULTS: EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. CONCLUSION: EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. CLINICALTRIALS. GOVIDENTIFIER: NCT029226027.

TMT-based proteomics analysis reveals the efficacy of jiangzhuo formula in improving the lipid profiles of dyslipidemia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiangzhuo Formula (JZF) is a traditional Chinese herbal prescription that is clinically applied to treat dyslipidemia. However, the mechanism underlying its efficacy remains unexplored. AIM OF THE STUDY: This study aims to elucidate the underlying mechanisms, explore potential pathways, and identify the key proteins of JZF for the treatment of dyslipidemia. METHODS: In this work, Q-Orbitrap high-resolution liquid chromatography mass spectrometry was used to identify the natural ingredients in JZF, rats with dyslipidemia were established via a high-fat diet for four weeks, then the dyslipidemia rats were treated with high-dose JZF (9 g/d) and low-dose JZF (4.5 g/d) for four weeks. After treatment, serum lipid detection and Oil-red-O staining were conducted to assess the efficacy of JZF in ameliorating dyslipidemia. Tandem mass tag (TMT) -based quantitative proteomics technology was then used to evaluate the roles and importance of proteins from the extracted hepatic tissue. The differentially expressed proteins were assessed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO), and protein-protein interaction (PPI) networks. Western blot and PCR analysis were used to validate the potential targets regulated by JZF. RESULTS: JZF could significantly improve the blood lipid profiles of serum and fat deposits of the liver. A total of 123 differentially expressed proteins were detected after JZF intervention, comprising 65 up-regulated proteins and 58 down-regulated proteins. The KEGG pathway analysis revealed that cholesterol metabolism, the PPAR signaling pathway, and bile secretion were the principal pathways involved in the disordered lipid metabolism, while GO analysis suggested that proteins that are located in the cell, regulate cellular processes, and show binding activity contribute to reductions in lipids. The combination of proteomics, Western blot, and PCR suggested that Apolipoprotein B (APOB), Apolipoprotein E (APOE), cholesterol 7 alpha-hydroxylase A1 (CYP7A1), and Hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) might play critical roles in JZF's lipid-lowering network. CONCLUSION: JZF can effectively improve lipid profiles via multiple pathways involved in cholesterol metabolism, the PPAR signaling pathway, and bile secretion. Generally, the proteomics techniques used in this research show that JZF could be a promising drug for the treatment of dyslipidemia.

Antidyslipidemic and Antioxidant Activities of Matricaria pubescens (Desf.) Shultz. in Streptozotocin-Induced Diabetic Rats.

AIMS: The study aimed to evaluate the antihyperlipidemic and antioxidant activities of Matricaria pubescens. BACKGROUND: Matricaria pubescens (Desf.) Shultz belongs to Asteraceae family and it is commonly used traditionally for handling diabetes mellitus. OBJECTIVE: The objective of this study was to assess the antioxidant activity of Matricaria pubescens (Desf.) Shultz and its effect on lipid and lipoprotein profile in normal and streptozotocin-induced diabetic rats. METHODS: The effect of repeated (7 days of treatment) oral administration of the aqueous extracts of aerial part of Matricaria pubescens (MPAE) at a dose of 40 mg/kg on lipid and lipoprotein profile was examined in normal and streptozotocin-induced diabetic rats. Furthermore, a preliminary phytochemical screening and the quantification of phenolic, flavonoid and tannin contents as well as the antioxidant activity using two methods (FRAP and ABTS) were carried out. RESULTS: MPAE demonstrated a potent antidyslipidemic effect in diabetic rats by reducing serum levels of triglycerides, total cholesterol and Low-Density Lipoprotein (LDL). In addition, the results showed that the extract is rich in several phytochemical compounds and revealed an important antioxidant activity. CONCLUSION: In summary, this study proved that Matricaria pubescens (Desf.) Shultz. has a favorable effect on diabetic dyslipidemia.

Dose-dependent reductions in plasma ceramides after anthocyanin supplementation are associated with improvements in plasma lipids and cholesterol efflux capacity in dyslipidemia: A randomized controlled trial.

BACKGROUND & AIMS: Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. METHODS: In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. RESULTS: A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values < 0.05). Specifically, 320 mg/day anthocyanins effectively lowered plasma N-palmitoylsphingosine (Cer 16:0, mean change: -28.3 ± 41.2 versus 2.9 ± 38.2, nmol/L, P = 0.018) and N-tetracosanoylsphingosine (Cer 24:0, mean change: -157.1 ± 493.9 versus 10.7 ± 439.9, nmol/L, P = 0.002) compared with the placebo. The declines in plasma Cer 16:0 and Cer 24:0 were significantly correlated with the decreases in plasma non-high-density lipoprotein cholesterol (nonHDL-C, Spearman's r = 0.32, P = 0.040 for Cer 16:0; Spearman's r = 0.35, P = 0.026 for Cer 24:0), apolipoprotein B (Spearman's r = 0.33, P = 0.031 for Cer 16:0; Spearman's r = 0.48, P = 0.002 for Cer 24:0), and total cholesterol (Spearman's r = 0.34, P = 0.026 for Cer 16:0; Spearman's r = 0.31, P = 0.042 for Cer 24:0) after 12-week 320 mg/day anthocyanin administration. Besides, we found that anthocyanins at 320 mg/day also markedly enhanced cholesterol efflux capacity in the dyslipidemia, the changes of which were positively associated with the reductions in Cer 16:0 (Spearman's r = 0.42, P = 0.006) independent of HDL-C and apolipoprotein A-I. CONCLUSIONS: Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.