The Impact of Polyphenols-Based Diet on the Inflammatory Profile in COVID-19 Elderly and Obese Patients

The World Health Organization declared the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated disease (coronavirus disease 2019 - COVID-19) as a pandemic in March 2020. COVID-19 is characterized by cytokine storm, acute respiratory distress syndrome (ARDS), and systemic inflammation-related pathology and already kills more than 1.5 million of people worldwide. Since aged and obese COVID-19 patients exhibit an enhanced inflammatory status, they represent a high-risk cluster for rapidly progressive clinical deterioration. These individuals present comorbid disorders and immunosenescence that may promote viral-induced cytokine storm and expression of molecules acting as virus receptor as angiotensin I converting enzyme 2 (ACE2) and CD26 (dipeptidyl-peptidase 4), resulting in respiratory failure and increased morbidity and mortality. A better knowledge of SARS-CoV-2 infection in inflammatory-associated high-risk population is essential in order to develop the therapies needed to combat or prevent severe COVID-19. Here, we review the pathogenesis and clinical implications of inflammatory disorders and disease markers associated to senescence in COVID-19 patients and the emerging evidence to argue that a high intake of polyphenols may have a protective effect on SARS-CoV-2 illness severity

The Positive Effects of Yerba Maté (Ilex paraguariensis) in Obesity

The prevalence of obesity has increased worldwide over the past three decades. Global anti-obesity strategies focus on dietary and lifestyle modifications to slow the development of obesity. Research in the nutrition field has recently aroused considerable interest based on the potential of natural products to counteract obesity. Several studies have identified yerba maté (Ilex paraguariensis) as an excellent candidate. In this review, we evaluated the impact of yerba maté on obesity and obesity-related inflammation. Cellular studies demonstrate that yerba maté suppresses adipocyte differentiation and triglyceride accumulation and reduces inflammation. Animal studies show that yerba maté modulates signaling pathways that regulate adipogenesis, antioxidant, anti-inflammatory and insulin signaling responses. In summary, the data presented here showed that the use of yerba maté might be useful against obesity, improving the lipid parameters in humans and animal models. In addition, yerba maté modulates the expression of genes that are changed in the obese state and restores them to more normal levels of expression. In doing so, it addresses several of the abnormal and disease-causing factors associated with obesity. Protective and ameliorative effects on insulin resistance were also observed. Thus, as a general conclusion, it seems that yerba maté beverages and supplements might be helpful in the battle against obesity

Iron chelators in obesity therapy - Old drugs from a new perspective?

Alterations in iron homeostasis are well described in obese patients. The effects of iron chelators on adipose tissue and other organs affected by obesity have been the interest of experimental studies, both in vivo and in vitro. The aim of this review was to update the available information indicating the potential of iron chelators as adjuvant drugs in the management of obesity and its comorbidities. The pharmacological actions of iron chelators, mainly deferoxamine, deferasirox, and deferiprone, on adipose tissue and liver alterations associated with obesity, were reviewed. Renal and other organ modifications observed in experimental obesity models (endotoxemia, beta-cell function, and systemic inflammation) were included, as well as data from clinical studies that were relevant to this review. The experimental results obtained with iron chelators showed their potential in the control of obesity-induced alterations in the adipose tissue and liver. However, knowledge about the possible systemic effects on endotoxemia and low-grade inflammation in obesity models is still lacking. In endotoxemia in humans, data obtained did not corroborate the anti-inflammatory effect described in experimental models. Clinical and experimental data reveal renal, beta-cell protection and inhibition of advanced glycation end products, which have long-term benefits in obesity. Experimental models of obesity demonstrated the beneficial effects of iron chelators on the adipose tissue, liver, kidneys, and beta-cells. Hence, clinical studies could be designed to evaluate the potential of iron chelators as a therapeutic option in the management of obesity861CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informação2018/03665-

Pharmacological antagonism of Anchietia salutaris extracts on the contraction induced by prostaglandin D2 and U46619 in guinea-pig lung parenchymal strips

Anchietia salutaris tea is traditionally used in Brazil to treat allergies, suggesting it contains compounds with antagonistic activity on the allergic mediators. We have evaluated extracts and semi-purified fractions of Anchietia salutaris as a source of compounds having this type of antagonism on the contraction induced in guinea-pig lung parenchymal strips and on platelet aggregation and shape change. After 10 min pre-incubation dichloromethane extracts containing 30 or 100 μg mL-1 inhibited the contraction induced by prostaglandin D2 (PGD2) in guinea-pig lung parenchymal strips with dose ratios (DR) of 0.76 ± 0.14 and 0.93 ± 0.19, respectively; the amount of inhibition depended both on the concentration and on the time of preincubation (DR after 30 min pre-incubation was 1.21 ± 0.51). The dichloromethane extract and its semi-purified fractions also inhibited the contractions induced by U46619, a more potent, stable, synthetic agonist of thromboxane A2 (TxA2) prostanoid (TP) receptors, the receptors acted upon by PGD2 to produce lung contractions. The dichloromethane extract did not inhibit the lung parenchymal contractions induced by histamine, leukotriene D4 (LTD4) or platelet-activating factor (PAF). Platelet aggregation induced by U46619, adenosine 5'-diphosphate (ADP) or PAF was not inhibited by the dichloromethane extract. Indeed, the extract potentiated platelet aggregation induced by low concentrations of these agonists and also potentiated the shape change induced by U46619. These results imply that the dichloromethane extract of Anchietia salutaris and its semipurified fractions contain an active principle that competitively inhibits TxA2 TP receptors, the stimulation of which causes lung parenchymal contraction. The inhibition seems to be selective for this receptor subtype, because the extract fails to inhibit platelet aggregation or shape change. This provides additional support of earlier reports suggesting the occurrence of TP receptor subtypes

Guarana (Paullinia cupana) Stimulates Mitochondrial Biogenesis in Mice Fed High-Fat Diet

The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD)-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA). Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight). Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO2 and energy expenditure (EE) were determined by indirect calorimetry. Gene expression was evaluated by real-time PCR and protein content by western blotting. The HFD-GUA group presented lower body weight, subcutaneous, retroperitoneal, visceral, and epididyimal adipose tissue depots, and glycemic and triglyceride levels, with no change in food intake and cholesterol levels. Furthermore, the HFD-GUA group presented an increase in VO2 and basal energy expenditure (EE), as well as Pgc1α, Creb1, Ampka1, Nrf1, Nrf2, and Sirt1 expression in the muscle and brown adipose tissue. In addition, the HFD-GUA group presented an increase in mtDNA (mitochondrial deoxyribonucleic acid) content in the muscle when compared to the HFD group. Thus, our data showed that guarana leads to an increase in energetic metabolism and stimulates mitochondrial biogenesis, contributing to control of weight gain, even when associated with high-fat diet

Evaluation of structured lipids with behenic acid in the prevention of obesity

Obesity affects all social classes, making it necessary to develop effective products that aid weight loss or help prevent weight gain. The objective of this work was to study the anti-obesity effects of structured lipids (SL) obtained by enzymatic interesterification, based on olive oil, soy oil and fully hydrogenated crambe oil. Twenty-four C57Bl/6 mice were distributed into four experimental groups according to the diet consumed: Control Diet (CD), Structured Lipids Diet (SLD), High-fat Control Diet (HCD), High-fat Structured Lipids Diet (HSLD). The animals that were fed SLs presented a smaller weight gain, despite a larger intake of the diet. The lowest weight gain was reflected in reduced amounts of adipose tissue and lower liver weight. A significant increase in lipids excreted by the animals in the feces was observed, despite there being no sign of toxicity or presence of diarrhea. The animals that consumed the HSLD presented lower total and LDL-cholesterol, increased HDL-cholesterol and increased hepatic arachidonic acid and docosahexaenoic acid levels. In addition, they did not develop hepatic steatosis. The study therefore showed that SLs could play a major role in combating or preventing obesity and other resultant diseases, without producing side effects95525

Effects of Yerba maté, a Plant Extract Formulation (“YGD”) and Resveratrol in 3T3-L1 Adipogenesis

We aimed to evaluate the in vitro effects of yerba maté, YGD (a herbal preparation containing yerba maté, guarana and damiana), and resveratrol on adipogenesis. The anti-adipogenic effects of yerba mate, YGD, resveratrol and YGD + resveratrol and yerba mate + resveratrol combinations were evaluated in 3T3-L1 cells by Oil Red staining, cellular triglyceride content, and PCR quantitative array. The results demonstrated that all of the tested compounds inhibited adipogenesis. Yerba maté extract significantly down-regulated the expression of genes that play an important role in regulating adipogenesis, such as Adig, Axin, Cebpa, Fgf10, Lep, Lpl, and Pparγ2. In addition, these genes, YGD also repressed Bmp2, Ccnd1, Fasn, and Srebf1. Resveratrol also modulated the expression of Adig, Bmp2, Ccnd1, C/EBPα, Fasn, Fgf10, Lep, Lpl, and Pparγ2. Moreover, resveratrol repressed Cebpb, Cdk4, Fgf2, and Klf15. The yerba maté extract and YGD up-regulated the expression of genes involved in inhibiting adipogenesis, such as Dlk-1, Klf2, and Ucp1. Resveratrol also induced the expression of Klf2 and Ucp1. In addition resveratrol modulated the Ddit3, Foxo1, Sirt1, and Sirt2. The combined effects of these compounds on gene expression showed similar results observed from individual treatments. Our data indicates that the synergy between the compounds favors the inhibition of adipogenesis

Nitric Oxide Has A Role In Regulating Vla-4-integrin Expression On The Human Neutrophil Cell Surface.

Recent research demonstrates that the beta1 integrins may be involved in neutrophil migration. Here, we investigate the role of nitric oxide in the expression and function of the very late antigen-4 (VLA-4) and Mac-1 integrins on human neutrophils. Human blood neutrophils were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) and their adhesion to fibronectin (FN) and serum observed. Adhesion of neutrophils to FN and serum increased significantly following incubation with 0.1mM L-NAME by 65.5 and 44.6%, respectively. Increased adhesions to FN and serum were abolished by a VLA-4-specific monoclonal antibody, HP2/1, and a Mac-1-specific monoclonal antibody, ICRF 44, respectively. The microfilament- and microtubule-depolymerizing agents, dihydrochalasin B and nocodazole, were also able to reverse L-NAME-induced adhesion to both FN and serum. L-NAME induced a discrete increase in the expression of CD49d (VLA-4, 25.3+/-4.8%), but not CD11b, on the neutrophil cell surface, as detected by flow cytometry. Results indicate that NO has a role in regulating VLA-4 and Mac-1 function on the human neutrophil cell surface and that this modulation in integrin function is accompanied by cytoskeletal rearrangements and changes in the ability of the neutrophil to adhere to the extracellular matrix.6643-5

Signalling Pathways Regulating Human Neutrophil Migration Induced By Secretory Phospholipases A2.

This study was designed to elucidate the signalling pathways by which secretory phospholipases A2 (sPLA2s) induce in vitro neutrophil migration. The cell migration assays were performed with Naja mocambique venom PLA2 (sPLA2 with high catalytic activity), bothropstoxin-I (sPLA2 devoid of catalytic activity) and platelet-activating factor (PAF), using a 48-well microchemotaxis chamber. Both the non-selective protein kinase inhibitor staurosporine (30-300 nM) and the selective protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpyperazine (H7; 50-200 microM) as well as the Gi inactivator pertussis toxin (30-300 nM) caused a concentration-dependent inhibition of the neutrophil migration induced by either N. mocambique venom PLA2 (100 microg/ml) or bothropstoxin-I (100 microg/ml). Pertussis toxin nearly abolished PAF-induced migration, while staurosporine and H7 partly (but significantly) inhibited the chemotactic responses to PAF. The dual inhibitor of cytosolic PLA2 and Ca2+ -independent PLA2 (iPLA2), arachidonil-trifluoromethyl-ketone (ATK; 0.2-20 microM), or the specific iPLA2 inhibitor bromoenol lactone (1-30 microM) caused a concentration-dependent inhibition of the migration induced by either sPLA2s. At the maximal concentration used for each compound, the migration was almost suppressed. In contrast, both of these compounds caused only slight inhibitions of PAF-induced migration. No rise in intracellular Ca2+ was observed in neutrophil-stimulated sPLA2, as determined in cells preloaded with fura 2-AM. In the experimental condition used, pertussis toxin, staurosporine, H7, ATK or bromoenol lactone did not induce cytotoxic effects, according to MTT assay. Our results suggest that activation of an endogenous PLA2 through activation of GTP-binding protein and PKC is the main mechanism by which exogenous sPLA2s cause neutrophil migration.44473-8