Effects of an Optimized Aged Garlic Extract on Cardiovascular Disease Risk Factors in Moderate Hypercholesterolemic Subjects: A Randomized, Crossover, Double-Blind, Sustainedand Controlled Study.

The consumption of aged black garlic (ABG) has been related to improvements in several cardiovascular disease (CVD) risk factors. However, the extent of the beneficial effects depends on the garlic aging process and the amount and type of chemical compounds accumulated. The main objective of this study was to assess the effect of daily intake of a well-characterized ABG extract with a standardized S-allyl-L-cysteine (SAC) yield in combination with dietary recommendations regarding CVD risk factors in individuals with moderate hypercholesterolemia. Sixty-seven hypercholesterolemic individuals with low-density lipoprotein cholesterol levels ≥115 mg/dL were randomized in a crossover, double-blind, sustained, and controlled intervention study. The participants consumed 250 mg (1.25 mg SAC)/tablet/day ABG or a placebo for 6 weeks, with 3 weeks of washout. Blood and pulse pressure and other CVD risk biomarkers were determined at the beginning and end of each intervention. At 6 weeks, ABG extract reduced diastolic blood pressure (DBP) (mean (95% CI) −5.85 (−10.5; −1.3) mm Hg) compared to the placebo, particularly in men with a DBP > 75 mm Hg. The consumption of an improved ABG extract with 1.25 mg of SAC decreased DBP, particularly in men with moderate hypercholesterolemia. The potential beneficial effects of ABG may contribute to obtaining an optimal DBP.

Anti-influenza virus activity of the elenolic acid rich olive leaf (Olea europaea L.) extract Isenolic®.

Seasonal flu is caused by influenza infection, a virus that spreads easily in human population with periodical epidemic outbreaks. The high mutational rate of influenza viruses leads to the emergence of strains resistant to the current treatments. Due to that, scientific research is focusing on the development of new anti-influenza agents as alternative or complementary treatments. Olive tree (Olea europaea L.) has been a source of ancestral remedies due to its antimicrobial activity. Thus, the aim of this study was to test the anti-influenza activity of a standardized olive leaf extract rich in elenolic acid (EA), Isenolic®, compared with oseltamivir. Isenolic® extract was characterized by High Performance Liquid Chromatography (HPLC)-Mass Spectrometry and its content in EA was determined by HPLC. Cytotoxicity, viral neuraminidase inhibitor activity and cell viability protection against influenza infection of Isenolic® were tested in vitro using sialic acid overexpressing Madin-Darby Canine Kidney cells. Isenolic® formulations showed a 4% and 8% dry basis. Oseltamivir and Isenolic® extracts showed anti-influenza activity. The 8% Isenolic® formulation showed a dose-dependent neuraminidase inhibitor activity higher than the 4% formulation, and preserved cell viability under viral infection. Thus, Isenolic® become a promising natural alternative to existing influenza treatments.

Aging Induces Hepatic Oxidative Stress and Nuclear Proteomic Remodeling in Liver from Wistar Rats.

Aging is a continuous, universal, and irreversible process that determines progressive loss of adaptability. The liver is a critical organ that supports digestion, metabolism, immunity, detoxification, vitamin storage, and hormone signaling. Nevertheless, the relationship between aging and the development of liver diseases remains elusive. In fact, although prolonged fasting in adult rodents and humans delays the onset of the disease and increases longevity, whether prolonged fasting could exert adverse effects in old organisms remains incompletely understood. In this work, we aimed to characterize the oxidative stress and nuclear proteome in the liver of 3-month- and 24-month-old male Wistar rats upon 36 h of fasting and its adaptation in response to 30 min of refeeding. To this end, we analyzed the hepatic lipid peroxidation levels (TBARS) and the expression levels of genes associated with fat metabolism and oxidative stress during aging. In addition, to gain a better insight into the molecular and cellular processes that characterize the liver of old rats, the hepatic nuclear proteome was also evaluated by isobaric tag quantitation (iTRAQ) mass spectrometry-based proteomics. In old rats, aging combined with prolonged fasting had great impact on lipid peroxidation in the liver that was associated with a marked downregulation of antioxidant genes (Sod2, Fmo3, and Cyp2C11) compared to young rats. Besides, our proteomic study revealed that RNA splicing is the hepatic nuclear biological process markedly affected by aging and this modification persists upon refeeding. Our results suggest that aged-induced changes in the nuclear proteome could affect processes associated with the adaptative response to refeeding after prolonged fasting, such as those involved in the defense against oxidative stress.

Central leptin regulates heart lipid content by selectively increasing PPAR ß/δ expression.

The role of central leptin in regulating the heart from lipid accumulation in lean leptin-sensitive animals has not been fully elucidated. Herein, we investigated the effects of central leptin infusion on the expression of genes involved in cardiac metabolism and its role in the control of myocardial triacylglyceride (TAG) accumulation in adult Wistar rats. Intracerebroventricular (icv) leptin infusion (0.2 µg/day) for 7 days markedly decreased TAG levels in cardiac tissue. Remarkably, the cardiac anti-steatotic effects of central leptin were associated with the selective upregulation of gene and protein expression of peroxisome proliferator-activated receptor ß/δ (PPARß/δ, encoded by Pparb/d) and their target genes, adipose triglyceride lipase (encoded by Pnpla2, herefater referred to as Atgl), hormone sensitive lipase (encoded by Lipe, herefater referred to as Hsl), pyruvate dehydrogenase kinase 4 (Pdk4) and acyl CoA oxidase 1 (Acox1), involved in myocardial intracellular lipolysis and mitochondrial/peroxisomal fatty acid utilization. Besides, central leptin decreased the expression of stearoyl-CoA deaturase 1 (Scd1) and diacylglycerol acyltransferase 1 (Dgat1) involved in TAG synthesis and increased the CPT-1 independent palmitate oxidation, as an index of peroxisomal ß-oxidation. Finally, the pharmacological inhibition of PPARß/δ decreased the effects on gene expression and cardiac TAG content induced by leptin. These results indicate that leptin, acting at central level, regulates selectively the cardiac expression of PPARß/δ, contributing in this way to regulate the cardiac TAG accumulation in rats, independently of its effects on body weight.

Aging impairs the hepatic subcellular distribution of ChREBP in response to fasting/feeding in rats: Implications on hepatic steatosis.

Aging is associated with alterations of lipid metabolism and increased prevalence of non alcoholic hepatic steatosis. Nevertheless, the mechanisms by which fat is accumulated in the liver during aging remain incompletely understood. In the present study, we investigated potential alterations that might contribute to the development of hepatic steatosis with aging. To this end, we analyzed the expression and the subcellular localization of key transcriptional factors involved in lipid metabolism such as ChREBP, Foxo1, Foxa2 and SREBP-1c in the liver of 3- and 24-month old Wistar rats. In addition, we studied the intracellular redistribution of ChREBP in response to fasting/refeeding transition. Old rats were characterized by hepatic steatosis, low serum ketone body levels and postprandial hyperinsulinemia. These observations were paralleled by the cytoplasmic localization and decreased expression of Foxa2, while ChREBP expression was markedly up-regulated and mainly localized in the nucleus. Consequently, the expression of lipogenic and ß-oxidation genes was up-regulated or down-regulated, respectively. Besides, the intracellular redistribution of ChREBP in response to fasting/refeeding transition was also impaired in old animals. Additionally, a negative correlation between serum ketone body levels and the nuclear localization of ChREBP was observed only in adult but not in old rats. Taken together, these data suggest that an age-related dysfunctional adaptation of ChREBP, in response to changes in the nutritional state, might contribute to the development of liver steatosis with aging.