Overweight, Obesity, and Age Are the Main Determinants of Cardiovascular Risk Aggregation in the Current Mexican Population: The FRIMEX III Study.

Background: The Mexican population exhibits several cardiovascular risk factors (CVRF) including high blood pressure (HBP), dysglycemia, dyslipidemia, overweight, and obesity. This study is an extensive observation of the most important CVFRs in six of the most populated cities in Mexico. Methods: In a cohort of 297,370 participants (54% female, mean age 43 ± 12.6 years), anthropometric (body mass index (BMI)), metabolic (glycemia and total cholesterol (TC)), and blood pressure (BP) data were obtained. Results: From age 40, 40% and 30% of the cohort's participants were overweight or obese, respectively. HBP was found in 27% of participants. However, only 8% of all hypertensive patients were controlled. Fifty percent of the subjects 50 years and older were hypercholesterolemic. Glycemia had a constant linear relation with age. BMI had a linear correlation with SBP, glycemia, and TC, with elevated coefficients in all cases and genders. The ß1 coefficient for BMI was more significant in all equations than the other ß, indicating that it greatly influences the other CVRFs. Conclusions: TC, glycemia, and SBP, the most critical atherogenic factors, are directly related to BMI.

(-)-Epicatechin Inhibits Metastatic-Associated Proliferation, Migration, and Invasion of Murine Breast Cancer Cells In Vitro.

Breast cancer, due to its high incidence and mortality, is a public health problem worldwide. Current chemotherapy uses non-specific cytotoxic drugs, which inhibit tumor growth but cause significant adverse effects. (-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids. It is widely distributed in the plant kingdom; it can be found in green tea, grapes, and cocoa. Several studies in animals and humans have shown that EC induces beneficial effects in the skeletal muscle and the cardiovascular system, reducing risk factors such as arterial hypertension, endothelial dysfunction, damage to skeletal muscle structure, and mitochondrial malfunction by promoting mitochondrial biogenesis, with no adverse effects reported. Recently, we reported that EC had an antitumor effect in a murine triple-negative mammary gland tumor model, decreasing tumoral size and volume and increasing survival by 44%. This work aimed to characterize the effects of flavanol EC on proliferation, migration, and metastasis markers of triple-negative murine breast (4T1) cancer cells in culture. We found proliferation diminished and Bax/Bcl2 ratio increased. When the migration of culture cells was evaluated, we observed a significant reduction in migration. Also, the relative expression of the genes associated with metastasis, Cdh1, Mtss1, Pten, Bmrs, Fat1, and Smad4, was increased. In conclusion, these results contribute to understanding molecular mechanisms activated by EC that can inhibit metastatic-associated proliferation, migration, and invasion of murine breast cancer cells.

The TG/HDL-c Lipid Ratio as a Cardiovascular Risk Marker in a Mexican Urban Middle-Class Population: Do We Need a Risk Score Tailored for Mexicans?

INTRODUCTION: Risk scores are essential in primary prevention to detect high-risk patients. The most common scores exclude hypertriglyceridemia and abdominal obesity in their risk assessment. We examined the triglyceride/HDL-cholesterol (TG/HDL-c) ratio as a cardiovascular (CV) risk marker in a middle-class urban Mexican population sample. AIM: Our aim was to test the concept of a scoring system reflecting Mexican population characteristics. METHODS: A total of 2602 healthy adults from the Lindavista primary prevention program were considered, evaluating gender, age, blood pressure, smoking, body mass index, waist circumference, lipid profile, and fasting glucose. According to the abnormality, a score from -3 to +3 was assigned. RESULTS: The summation of eleven variables yielded the Lindavista score (LS), which was calibrated versus the TG/HDL ratio and ACC ASCVD Risk Estimator Plus score to determine its correlation with risk categories. The TG/HDL-c ratio had a linear correlation with LS and high-risk ACC ASCVD categories. CONCLUSIONS: Compared with LS and TG/HDL-c, the ACC ASCVD system underestimates the high-risk category. The high prevalence of obesity and lipid triad in the Mexican population requires a scale that considers those traits. The TG/HDL-c ratio is a practical, easy, and economical instrument to categorize risk in Mexicans.

Improving Cardiovascular Risk in Postmenopausal Women with an (-)-Epicatechin-Based Nutraceutical: A Randomly Assigned, Double-Blind vs. Placebo, Proof-of-Concept Trial.

BACKGROUND: Age-adjusted rates of cardiovascular disease (CVD) are higher in men than in women. CVD risk-factor outcomes are underrecognized, underestimated, and undertreated in women because the clinical expressions in women differ from those of men. There are no universally accepted recommendations on what to do in women when the values of fasting glucose, blood pressure, and lipids are only slightly altered or at borderline values. We reported the positive effects on CVD risk markers using cacao by-products, showing that alternative approaches can be used to prevent cardiovascular disease in women. The objective was to evaluate the changes in lipoprotein subfractions induced by three months of treatment with an epicatechin-enriched cacao supplement. METHODS: A double-blind, placebo-controlled proof-of-concept study was developed to evaluate the effects of 3 months of treatment with an (-)-epicatechin-enriched cacao supplement on lipoprotein subfractions. RESULTS: The usual screening workshop for postmenopausal women could be insufficient and misleading. Assessing the effect of a (-)-epicatechin-enriched cacao supplement employing a lipoprotein subfractionation profile analysis suggests a decrease in cardiovascular risk. CONCLUSIONS: A simple, low-cost, safe (-)-epicatechin-enriched cacao supplement product can improve the cardiovascular risk in postmenopausal women.

Correlation of Biomarkers of Endothelial Injury and Inflammation to Outcome in Hospitalized COVID-19 Patients.

COVID-19 can trigger an intense systemic inflammation and prothrombotic state, leading to a rapid and disproportionate deterioration of lung function. An effective screening tool is essential to identify the patients at risk for severe disease. This observational study was conducted on hospitalized patients with moderate and severe COVID-19 pneumonia in a general hospital in Mexico City between 1 March 2021 and 15 March 2021. Serum samples were analyzed to explore the role of biomarkers of inflammation, coagulation, oxidative stress, and endothelial damage with the severity of the disease. Our results demonstrated that Syndecan-1 and nitrites/nitrates showed a high correlation in severely ill patients. In conclusion, COVID-19 patients with elevated levels of SDC-1 were associated with severe disease. This molecule can potentially be used as a marker for the progression or severity of COVID-19. Preservation of glycocalyx integrity may be a potential treatment for COVID-19.

In silico evaluation of flavonoids as potential inhibitors of SARS-CoV-2 main nonstructural proteins (Nsps)-amentoflavone as a multitarget candidate.

Despite the development of vaccines against COVID-19 disease and the multiple efforts to find efficient drugs as treatment for this virus, there are too many social, political, economic, and health inconveniences to incorporate a fully accessible plan of prevention and therapy against SARS-CoV-2. In this sense, it is necessary to find nutraceutical/pharmaceutical drugs as possible COVID-19 preventives/treatments. Based on their beneficial effects, flavonoids are one of the most promising compounds. Therefore, using virtual screening, 478 flavonoids obtained from the KEGG database were evaluated against non-structural proteins Nsp1, Nsp3, Nsp5, Nsp12, and Nsp15, which are essential for the virus-host cell infection, searching for possible multitarget flavonoids. Amentoflavone, a biflavonoid found mainly in Ginkgo biloba, Lobelia chinensis, and Byrsonima intermedia, can interact and bind with the five proteins, suggesting its potential as a multitarget inhibitor. Molecular docking calculations and structural analysis (RMSD, number of H bonds, and clustering) performed from molecular dynamics simulations of the amentoflavone-protein complex support this potential. The results shown here are theoretical evidence of the probable multitarget inhibition of non-structural proteins of SARS-CoV-2 by amentoflavone, which has wide availability, low cost, no side effects, and long history of use. These results are solid evidence for future in vitro and in vivo experiments aiming to validate amentoflavone as an inhibitor of the Nsp1, 3, 5, 12, and 15 of SARS-CoV-2.

(-)-Epicatechin Is a Biased Ligand of Apelin Receptor.

(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the ß-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. ß-arrestin gained interest in selective pharmacology and mediators of the so-called "biased agonism". With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the ß-arrestin in the active conformation of the APLN receptor acting as a biased agonist.

Markers of oxidative stress in postmenopausal women with metabolic syndrome.

During the postmenopausal period, there are metabolic alterations that predispose individuals to metabolic syndrome (MS), oxidative stress (OS), and the risk of developing cardiovascular diseases. We aimed to compare the concentrations of OS markers in postmenopausal women with and without MS. Malondialdehyde, carbonyl groups, and total antioxidant capacity (TAC) were quantified. We conducted a cross-sectional study: Group 1 (n = 42) included women without MS, and Group 2 (n = 58) comprised women with MS. Participants' age was similar between groups. Glucose, insulin, the homeostasis model assessment of insulin resistance, triglycerides, uric acid, and body mass index were significantly lower in postmenopausal women without MS. OS markers were significantly lower in Group 1 vs. Group 2: malondialdehyde, 31.32 ± 14.93 vs. 40.27 ± 17.62 pmol MDA/mg dry weight (p = .01); protein carbonylation, 6325 ± 1551 vs. 7163 ± 1029 pmol PC/mg protein (p = .0003); and TAC, 1497 ± 297.3 vs. 1619 ± 278.8 pmol Trolox equivalent/mg protein (p = .041). OS markers were significantly higher in postmenopausal women with MS. Impact statementWhat is already known on this subject? Oxidative stress has been implicated in numerous disease processes; however, information on the relationship between oxidative stress and metabolic syndrome among postmenopausal women remains limited.What do the results of this study add? Our results indicate that in postmenopausal Mexican women, oxidative stress markers were significantly lower in those without metabolic syndrome, whereas total antioxidant capacity was higher in those with metabolic syndrome, which could be explained as an antioxidant defense mechanism capable of neutralising excess oxidative damage markers.What are the implications of these findings for clinical practice and/or further research? This study is of interest to a broad audience because it compares the concentrations of oxidative stress markers in postmenopausal women with and without metabolic syndrome. Our study could support intervention with supplements or foods rich in antioxidants as lifestyle modifications in postmenopausal women with metabolic syndrome.

Beneficial Effects of Flavonoids on Skeletal Muscle Health: A Systematic Review and Meta-Analysis.

Skeletal muscle (SkM) is a highly dynamic tissue that responds to physiological adaptations or pathological conditions, and SkM mitochondria play a major role in bioenergetics, regulation of intracellular calcium homeostasis, pro-oxidant/antioxidant balance, and apoptosis. Flavonoids are polyphenolic compounds with the ability to modulate molecular pathways implicated in the development of mitochondrial myopathy. Therefore, it is pertinent to explore its potential application in conditions such as aging, disuse, denervation, diabetes, obesity, and cancer. To evaluate preclinical and clinical effects of flavonoids on SkM structure and function. We performed a systematic review of published studies, with no date restrictions applied, using PubMed and Scopus. The following search terms were used: "flavonoids" OR "flavanols" OR "flavones" OR "anthocyanidins" OR "flavanones" OR "flavan-3-ols" OR "catechins" OR "epicatechin" OR "(-)-epicatechin" AND "skeletal muscle." The studies included in this review were preclinical studies, clinical trials, controlled clinical trials, and randomized-controlled trials that investigated the influence of flavonoids on SkM health. Three authors, independently, assessed trials for the review. Any disagreement was resolved by consensus. The use of flavonoids could be a potential tool for the prevention of muscle loss. Their effects on metabolism and on mitochondria function suggest their use as muscle regulators.

Is it possible to treat nonalcoholic liver disease using a flavanol-based nutraceutical approach? Basic and clinical data.

Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of diseases, ranging from simple steatosis to hepatocellular carcinoma. The main factors for NAFLD are closely related to obesity, insulin resistance, intestinal microbiota alterations, hyperinsulinism, low-grade systemic inflammation, nitroxidative stress, lipid peroxidation, and mitochondrial dysfunction. Currently, the treatment of NAFLD is based on diet and exercise because, to date, there is no specific pharmacological agent, already approved, that raises the need for new therapeutic strategies. Nutraceuticals, such as polyphenols, have potential beneficial effects for health. In this article, the beneficial effects of epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC) are discussed. EGCG is the main catechin in green tea, which has shown in various studies its potential effect preventing and treating NAFLD since it has shown antihyperlipidemic, anti-inflammatory, antifibrotic, antioxidant, and improvement of liver lipid metabolism. However, it has been found that excessive consumption may cause hepatotoxicity. EC is widely distributed in nature (fruits and vegetables). This flavanol has shown many beneficial effects, including antihypertensive, anti-inflammatory, anti-hyperglycemic, antithrombotic, and antifibrotic properties. It increases mitochondrial biogenesis, and it also has effects on the regulation of synthesis and metabolism of lipids. This flavanol is a nontoxic substance; it has been classified by the United States Food and Drug Administration as harmless. The EC-induced effects can be useful for the prevention and/or treatment of NAFLD.

Anticancer potential of (-)-epicatechin in a triple-negative mammary gland model.

OBJECTIVES: The main aim of this work was to analyse the potential tumour growth inhibition effects of (-)-epicatechin (EC). Triple-negative breast cancer (TNBC) is an invasive form of cancer characterized by the absence of progesterone receptor, estrogen receptor and human epidermal growth factor receptor 2. Doxorubicin (DOX) is widely used for its anti-tumour activity. EC belongs to the flavanol subfamily and is a candidate molecule for the adjuvant treatment of cancer due to its antiproliferative activities. METHODS: Evaluation of EC effects and pathways involved in a model of TNBC. KEY FINDINGS: EC inhibited tumour growth as efficiently as DOX (inhibition rates of 74% and 79% for EC and DOX, respectively). The evaluation of adenosine monophosphate-activated protein kinase (AMPK) and Akt phosphorylation and mTOR expression indicates that EC modulates these pathways, resulting in the inhibition of cell proliferation. Additionally, we found an increase in the survival of EC-treated animals compared with control-treated animals. This effect was similar to the effects induced by DOX (survival rates of 44% and 30% for EC and DOX, respectively). CONCLUSION: EC has antiproliferative properties and increases survival in a model of TNBC. These effects may occur through the modulation of deregulated AMPK and Akt/mTOR signalling pathways.

[Breast cancer, the risk attributable to type 2 diabetes]. / Cáncer de mama, el riesgo atribuible a diabetes tipo 2.

BACKGROUND: Several studies have evaluated the association between a history of type 2 diabetes (T2D) and risk of breast cancer (BC), with controversial results. However, information regarding the population-attributable risk percent (PAR%) remains scarce. Objective: To estimate the association and the PAR% for BC and T2D, lifestyle and gynecologic factors in women in Mexico City. METHODS: This case-control study was performed from May-December 2020. Women >40 years of age, from Mexico City, with a confirmed diagnosis for BC were included as cases. Controls were women with a BIRADS 1 or 2 mammography or an ultrasound clear of any BC suggestive findings. RESULTS: A total of 134 cases and 134 controls were included. A higher risk for BC was identified among women who did not perform routine physical activity and those who had a history of hormonal contraceptive use > 5 years. The use of hormone replacement therapy (HRT) was associated with an odds ratio (OR) of 5.0 (p = 0.22) in the first model. After adjustment, HRT was associated with an OR of 2.92 (p=0.492) in the second and an OR of 3.6 (p = 0.753) in the third model. T2D was associated with an OR of 1.04 (p = 0.96) in the first model; an OR of 0.65 (p = 0.65) in the second model and an OR of RMa 0.75(p = 0.79) for the third model. CONCLUSION: In this case-control study, there was no significant association identified between a T2D diagnosis and BC.

INTRODUCCIÓN: diversas investigaciones han evaluado el riesgo de cáncer de mama (CaMa) asociado a diabetes tipo 2 (DT2) con resultados inconsistentes. Pocas investigaciones han evaluado el porcentaje de riesgo atribuible a la población (PAR%). OBJETIVO: estimar la asociación y el PAR% para CaMa por DT2, así como los factores del estilo de vida y ginecológicos en mujeres de la Ciudad de México. MÉTODOS: estudio de casos y controles, realizado de mayo a diciembre de 2020. Se incluyeron mujeres > 40 años, de la Ciudad de México, con diagnóstico confirmado de CaMa. Los controles fueron mujeres con una mastografía BIRADS 1 o 2, o ultrasonido mamario sin datos sugestivos de CaMa. RESULTADOS: se incluyeron en total 134 casos y 134 controles. Se identificó un mayor riesgo de CaMa en aquellas mujeres que no realizan actividad física y con el uso de anticonceptivos > 5 años. El uso de terapia de reemplazo hormonal (TRH) se asoció con una razón de momios ajustada (RMa) de 5.0, p = 0.22 en el modelo 1. Conforme se ajustan los modelos, la TRH para el modelo 2 tuvo una RMa de 2.92, p = 0.492 y en el modelo 3 una RMa de 3.6 p = 0.753. La presencia de diabetes se asoció a una RMa de 1.04, p = 0.96 en el modelo 1; RMa de 0.65, p = 0.65 en el modelo 2 y una RMa de 0.75, p = 0.79 en el modelo 3. CONCLUSIONES: en este estudio de casos y controles no se encontró asociación entre el diagnóstico de DT2 y CaMa.

Restricted Water Intake and Hydration with Fructose-Containing Beverages during Infancy Predispose to Aggravate an Acute Renal Ischemic Insult in Adolescent Rats.

We aimed to investigate the effects of chronic fluid restriction and hydration with a sweetened beverage (SB) in rats from weaning until adolescence, in a posterior acute kidney injury (AKI) event induced by ischemia-reperfusion (I/R). We followed 5 groups of weaning rats: control group (C); two groups with 22 h/day fluid restriction, a group hydrated for two hours with water (-W) and a group hydrated with SB; one group receiving SB ad libitum all day (+SB); and one group in which water consumption was increased using a gel diet. The rats that reached adolescence were submitted to I/R. Fluid restriction and/or SB hydration induced mild renal alterations that were significantly accentuated in the -SB group and resulted in worse outcomes after I/R-induced AKI that resulted in a catastrophic fall in creatinine clearance and diffuse acute tubular necrosis. In summary, low tap water intakes, as well as SB intake in infancy, prompt kidney worse outcomes in a later event of AKI during adolescence and both insults magnify kidney damage. Studies on hydration habits in children are recommended to disclose the potentially harmful effects that those behavioral patterns might carry to future renal health.

PXR is a target of (-)-epicatechin in skeletal muscle.

(-)-Epicatechin (EC) is a flavanol that has shown numerous biological effects such as: decrease risk of cardiovascular dysfunction, metabolism regulation, skeletal muscle (SkM) performance improvement and SkM cells differentiation induction, among others. The described EC acceptor/receptor molecules do not explain the EC's effect on SkM. We hypothesize that the pregnane X receptor (PXR) can fulfill those characteristics, based on structural similitude between EC and steroidal backbone and that PXR activation leads to similar effects as those induced by EC. In order to demonstrate our hypothesis, we: 1) analyzed the possible EC and mouse PXR interaction through in silico strategies, 2) developed an EC's affinity column to isolate PXR, 3) evaluated, in mouse myoblast (C2C12 cells) the inhibition of EC-induced PXR's nucleus translocation by ketoconazole, a specific blocker of PXR and 4) analyzed the effect of EC as an activator of mouse PXR, evaluating the expression modulation of cytochrome 3a11 (Cyp3a11) gen and myogenin protein. (-)-Epicatechin interacts and activates PXR, promoting this protein translocation to the nucleus, increasing the expression of Cyp3a11, and promoting C2C12 cell differentiation through increasing myogenin expression. These results can be the base of further studies to analyze the possible participation of PXR in the skeletal muscle effects shown by EC.

(-)-Epicatechin reduces muscle waste after complete spinal cord transection in a murine model: role of ubiquitin-proteasome system.

The skeletal muscle mass reduces 30-60% after spinal cord injury, this is mostly due to protein degradation through ubiquitin-proteasome system. In this work, we propose that the flavanol (-)-epicatechin, due its widespread biological effects on muscle health, can prevent muscle mass decrease after spinal cord injury. Thirty-six female Long Evans rats were randomized into 5 groups: (1) Spinal cord injury 7 days, (2) Spinal cord injury + (-)-epicatechin 7 days, (3) Spinal cord injury 30 days, (4) Spinal cord injury + (-)-epicatechin 30 days and (5) Sham (Only laminectomy). Hind limb perimeter, muscle cross section area, fiber cross section area and ubiquitin-proteasome system protein expression together with total protein ubiquitination were assessed. At 30 days Spinal cord injury group lost 49.52 ± 2.023% of muscle cross section area (-)-epicatechin treated group lost only 24.28 ± 15.45% being a significant difference. Ubiquitin-proteasome markers showed significant changes. FOXO1a increased in spinal cord injury group vs Sham (-)-epicatechin reduced this increase. In spinal cord injury group MAFbx increased significantly vs Sham but decrease in (-)-epicatechin treatment group at 30 days. At 7 and 30 days MuRF1 increased in the spinal cord injury and decreased in the (-)-epicatechin group. The global protein ubiquitination increases after spinal cord injury, epicatechin treatment induce a significant decrease in protein ubiquitination. These results suggest that (-)-epicatechin reduces the muscle waste after spinal cord injury through down regulation of the ubiquitin-proteasome system.

Flavonoids from dark chocolate and (-)-epicatechin ameliorate high-fat diet-induced decreases in mobility and muscle damage in aging mice.

Age-related muscle decline, when associated with obesity, leads to adverse outcomes with increased risks for falling, loss of independence, disability and risk of premature mortality. The aim of this study was to assess the potential beneficial effects of flavonoids in improving the age-/high-fat-diet-induced decrease in physical activity/capacity related to the onset of skeletal muscle decline. The effects of the administration of a cocoa beverage enriched with flavanols or pure (-)-epicatechin for 5 wk in a model of physical activity decline induced by the ingestion of a high-fat diet (60% fat) in middle-age mice were evaluated. The results showed that both products, the cocoa beverage enriched with flavanols and pure (-)-epicatechin, improved physical performance evaluated with the hang-wire, inverted-screen, and weight-lifting tests and dynamometry compared with the performance of the controls. The beverage and (-)-epicatechin increased the follistatin/myostatin ratio and increased the expression of myocyte enhancer factor 2A (MEF2A), suggesting an effect on molecular modulators of growth differentiation. Furthermore, the beverage and (-)-epicatechin decreased the expression of O-type fork-head transcription factor (FOXO1A) and muscle ring finger 1 (MURF1) markers of the skeletal muscle ubiquitin-proteasome degradation pathway.

Arginase inhibition by (-)-Epicatechin reverses endothelial cell aging.

Endothelial dysfunction (EnD) occurs with aging and endothelial nitric oxide (NO) production by NO synthase (NOS) can be impaired. Low NO levels have been linked to increased arginase (Ar) activity as Ar competes with NOS for L-arginine. The inhibition of Ar activity can reverse EnD and (-)-epicatechin (Epi) inhibits myocardial Ar activity. In this study, through in silico modeling we demonstrate that Epi interacts with Ar similarly to its inhibitor Norvaline (Norv). Using in vitro and in vivo models of aging, we examined Epi and Norv-inhibition of Ar activity and its endothelium-protective effects. Bovine coronary artery endothelial cells (BCAEC) were treated with Norv (10 µM), Epi (1 µM) or the combination (Epi + Norv) for 48 h. Ar activity increased in aged BCAEC, with decreased NO generation. Treatment decreased Ar activity to levels seen in young cells. Epi and Epi + Norv decreased nitrosylated Ar levels by ~25% in aged cells with lower oxidative stress (~25%) (dihydroethidium) levels. In aged cells, Epi and Epi + Norv restored the eNOS monomer/dimer ratio, protein expression levels and NO production to those of young cells. Furthermore, using 18 month old rats 15 days of treatment with either Epi (1 mg/kg), Norv (10 mg/kg) or combo, decreased hypertension and improved aorta vasorelaxation to acetylcholine, blood NO levels and tetra/dihydribiopterin ratios in cultured rat aortic endothelial cells. In conclusion, results provide evidence that inhibiting Ar with Epi reverses aged-related loss of eNOS function and improves vascular function through the modulation of Ar and eNOS protein levels and activity.

Effects of Cacao By-Products and a Modest Weight Loss Intervention on the Concentration of Serum Triglycerides in Overweight Subjects: Proof of Concept.

Therapeutic approaches to decrease serum triglyceride (TG) concentrations are not successful mainly due to poor adherence or adverse effects of therapies. In consequence, the search for new low-cost and safer therapeutic alternatives is mandatory. Dark chocolate and cacao have shown promising results improving lipid profiles. Recently, using cacao by-products to reduce elevated cardiometabolic risk markers in an animal model of obesity induced by a high-fat diet and fructose, we showed that TGs, low-density lipoprotein cholesterol, and the TG/high-density lipoprotein (HDL) ratio decreased, suggesting that cacao by-products improved the metabolic function of obese animals. Based on these results, as a proof of concept, a blinded placebo-controlled study was implemented to explore the effects of cacao by-products on anthropometric and biochemical variables in a group of overweight subjects participating in a program composed of reduced-calorie-diet counseling plus a simple aerobic exercise plan. The results showed that counseling induced weight and abdominal circumference reductions in both groups. TGs did not change in the control group; however, TG decreased significantly by 54.9 mg/dL (27.9%) in the experimental group. The TG/HDL cholesterol ratio changed markedly (1.5) in the experimental group. The results reported suggest the use of cacao by-products as an alternative for the treatment of hypertriglyceridemia.

Effects of (-)-epicatechin on the time course of the expression of perilipins in a diet-induced model of nonalcoholic steatohepatitis.

The existing treatments for nonalcoholic steatohepatitis (NASH) are not completely effective. The need for new alternatives without adverse effects and low cost, such as the flavonoid (-)-epicatechin (EC), which has beneficial effects on lipid metabolism and cardiovascular diseases, arises. The objective of this work was to analyze EC effects in the NASH induced by a Paigen-type diet (PD). Mice were administered with (1) normal chow and water, (2) PD + fructose 30% and (3) PD + fructose 30% + EC (1 mg/kg) per gavage during 9 weeks. At the end of each treatment, serum was collected for analysis of the biochemical profile and liver enzymes. The liver was collected for microscopic analysis and for the evaluation of the relative expression of Plin2, Plin3, CD36, adiponectin and UCP2. Results showed that EC reduced weight gain and decreased triglyceride (TG), low-density lipoprotein cholesterol, TG/high-density lipoprotein and the activity of liver enzymes (alanine aminotransferase and alkaline phosphatase), suggesting lower liver damage. The microscopic analysis showed less "balloonization" of the hepatocyte, small drops of lipids, less accumulation of collagen and infiltration of inflammatory cells as compared to nontreated group. Finally, a decrease in the expression of Plin 2 was observed. While CD36 decreased, adiponectin and UCP2 increased. In conclusion, EC improves the biochemical profile, the microscopic characteristics and protein expression. Therefore, it may be a possible therapeutic approach for NASH since it prevents the progression of the hepatic and metabolic damage induced by high-fat diets.