Pharmacological properties of bergapten: mechanistic and therapeutic aspects

Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.info:eu-repo/semantics/publishedVersio

Efectes d'una prova d'esforç sobre marcadors d'inflamació i d'estrès oxidatiu en pacients amb síndrome metabòlica

[cat] La síndrome metabòlica és un conjunt de condicions: hipertensió, hiperglucèmia, excés de greix visceral i nivells alterats de colesterol i/o triglicèrids que es produeixen conjuntament, augmentant el risc cardiovascular i de diabetis. Aquesta patologia, a més, es caracteritza per un augment del grau d’estrès oxidatiu associat a un desequilibri d’adipocitoquines produïdes pel teixit adipós que a l’hora promou un estat inflamatori crònic i una disfunció endotelial vascular. Aquesta situació es veu agreujada per l’elevat grau de sedentarisme de la població en general. L’objectiu d’aquest estudi és avaluar els efectes que provoca la realització d’una prova d’esforç en cinta de córrer al 60-70% de la capacitat màxima sobre la resposta inflamatòria i antioxidant en persones majors que pateixen síndrome metabòlica. Als subjectes se’ls va agafar mostres de sang abans i després d’haver realitzar una prova d’esforç on es controlava el temps i la intensitat de la mateixa. Es van mesurar en plasma i a les cèl·lules immunitàries mononucleades (PBMCs) paràmetres antioxidants i inflamatoris. Els resultats evidenciaren augments estadísticament significatius dels nivells plasmàtics de la molècula d’adhesió intercel·lular 1 (ICAM-1), de la interleuquina 6 (IL-6), del malondialdehid (MDA) i l’expressió dels enzims antioxidants en PBMCs catalasa (CAT) i glutatió peroxidasa (GPx) una vegada realitzada la prova d’esforç respecte als nivells inicials. Per altra banda, l’augment de la concentració del factor de necrosi tumoral (TNFa) no va ser estadísticament significatiu. En conclusió, s’ha evidenciat com la prova d’esforç indueix una situació d’estrès oxidatiu que promou l’activació d’una cascada de citoquines proinflamatòries diferent a la que s’activa quan la lesió es deu a una infecció. És per això, que es recomana la pràctica regular d’activitat física per prevenir malalties cròniques i envellir de manera saludable.[eng] The metabolic syndrome is a cluster of common factors: hypertension, hyperglycemia, excess of visceral fat, altered cholesterol and/or triglyceride levels that occur together, increasing cardiovascular risk and diabetes. This pathology is characterized by an increase in the degree of oxidative stress and is associated with an imbalance in adipocytokine production by adipose tissue promoting chronic inflammatory status and vascular endothelial dysfunction. This situation is exacerbated by the high degree of sedentary lifestyle of the population in general. The aim of this study is to evaluate the maximum effects of 60-70% exercise test on inflammatory and antioxidant response in elderly people suffering from metabolic syndrome. Blood samples from the subjects were taken before and after having performed an exercise test on a treadmill controlling the time and intensity of the same. Antioxidant and inflammatory parameters were measured in plasma and mononuclear immune cells (PBMCs). The results demonstrated statistically significant increases in plasma levels of the intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), malondialdehyde (MDA) and expression in PBMCs, the antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPx) once the stress test has been performed in respect of the initial levels. While the increase in the tumour necrosis factor (TNFa) concentration was not statistically significant. In conclusion, it has been shown that the exercise test induces a situation of oxidative stress that promotes the activation of a proinflammatory cytokine cascade. This cytokine cascade is different from that triggered when the lesion is due to an infection. That is why the regular practice of physical activity is recommended to prevent chronic illnesses and to age in a healthy way

Oxidative Stress and Inflammatory Biomarkers Are Related to High Intake of Ultra-Processed Food in Old Adults with Metabolic Syndrome

In the last few decades the consumption of ultra-processed foods (UPFs) worldwide has substantially augmented. Increasing evidence suggests that high UPF consumption is associated with an increase in non-communicable diseases, being overweight, and obesity. The aim of this study was to assess how UPF consumption affects oxidative and inflammatory status in the plasma, neutrophils, and urine of old adults with metabolic syndrome. Participants (n = 92) were classified into two groups according to UPF consumption. Dietary intakes were measured by a validated semi-quantitative 143-item food frequency questionnaire and UPF consumption was determined according to the NOVA classification system. Low UPF consumers showed higher adherence to the Mediterranean diet than high UPF consumers. A high intake of fiber and a high concentration of polyphenols in urine were also observed in subjects with low UPF consumption. Despite the absence of differences in biochemical profile, oxidative and inflammatory biomarkers showed some significant changes. Catalase and superoxide dismutase activities were lower in high UPF consumers, whereas myeloperoxidase activity was higher. ROS production in neutrophils stimulated with zymosan was higher in high UPF consumers than in low UPF consumers. Biomarkers such as xanthine oxidase, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-15, and leptin levels were higher in participants with high intake of UPF. No differences were found in malondialdehyde and other inflammatory cytokines. The current study evidenced that MetS participants with high UPF consumption have a more pro-oxidant and inflammatory profile than those with low UPF consumption, despite showing similar blood biochemical profiles

Inflammatory and Oxidative Stress Markers Related to Adherence to the Mediterranean Diet in Patients with Metabolic Syndrome

Metabolic syndrome (MetS) is characterized by increased pro-oxidative stress and a pro-inflammatory state. Several studies emphasized the protective effect of the Mediterranean dietary pattern (MDP). To assess the oxidative and inflammatory state according to the adherence to MDP using biomarkers in patients with MetS. Antioxidant and pro-inflammatory biomarkers were determined in plasma, peripheral blood mononuclear cells (PBMCs), and neutrophils of adults (aged 55–75 years old; 60% women) with MetS living in Mallorca (Spain). Anthropometrics, dietary intake by a validated semi-quantitative 143-item food frequency questionnaire, and a Dietary Inflammatory Index were measured. Patients with low adherence to MDP showed higher levels of glycated haemoglobin A1c and triglycerides, and lower levels of HDL cholesterol. Plasma levels of interleukin-1β, IL-6, IL-15, tumour necrosis factor α, xanthine oxidase, and ghrelin, and activities of superoxide dismutase, and myeloperoxidase were higher in subjects with low adherence to the MDP. Reactive oxygen species production in PBMCs and neutrophils stimulated with lipopolysaccharide was higher in participants with low adherence to the MDP. Patients with MetS and higher adherence to the MDP showed less altered anthropometric parameters, blood biochemical profile, and better oxidative and inflammatory status

Effects of Regular Exercise on the Biochemical, Oxidative, and Inflammatory Profiles and Quality of Life in Older Spaniards with Metabolic Syndrome

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55–70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome

Plasma Fatty Acid Composition, Oxidative and Inflammatory Status, and Adherence to the Mediterranean Diet of Patients with Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a complex and increasingly prevalent cardiometabolic disorder worldwide. As of today, NAFLD is a pathology without specific pharmacological treatment, with the Mediterranean diet (MedDiet) being the most widely used approach for its management. The objective of this study is to assess the effects of adherence to the Mediterranean diet on fatty acid plasma levels, as well as on the oxidative and inflammatory status of NAFLD patients. A total of 100 adult patients (40–60 years old) diagnosed with NAFLD and from the Balearic Islands, Spain, were classified into three groups according to their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Food items (g/day) were categorised according to their processing using the NOVA system. Anthropometrics, blood pressure, aminotransferases, Dietary Inflammatory Index (DII), inflammatory biomarkers, and fatty acid levels were measured in the plasma of NAFLD patients. High adherence to the MedDiet is associated to a highly plant-based diet, low ultra-processed food (UPF) consumption, low intake of dietary lipids, low intake of animal fats, high intake of monounsaturated fatty acid (MUFA; mainly palmitoleic acid), low intake of saturated fatty acids (SFAs; practically all dietary SFAs), low intake of trans-fatty acids, high intake of omega-3 fatty acids (mainly eicosapentaenoic acid), a higher n-6:n-3 in ratio, low intake of omega-6 fatty acids, and a low level of interleukin-6 (IL-6). High adherence to the MedDiet is related to a better fatty acid profile in the plasma, fewer SFAs and more MUFA and polyunsaturated fatty acids (PUFAs), a plasma biochemical profile, better proinflammatory status, and decreased ultra-processed food consumption of NAFLD patients

Impact of Adherence to the Mediterranean Diet on Antioxidant Status and Metabolic Parameters in NAFLD Patients: A 24-Month Lifestyle Intervention Study

Background: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. Objectives: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40–60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. Results: After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. Conclusions: Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes

Effects of a Two-Year Lifestyle Intervention on Intrahepatic Fat Reduction and Renal Health: Mitigation of Inflammation and Oxidative Stress, a Randomized Trial

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease observed in clinical practice worldwide. This disorder has been independently associated with an increased risk of developing chronic kidney disease (CKD). The aim of this study was to evaluate whether a 2-year intervention based on a Mediterranean diet (MedDiet) and physical activity focussed on reducing intrahepatic fat contents (IFC) was associated with a decreased risk of CKD. Forty adults (50% women) residing in Mallorca, aged 48 to 60 years, diagnosed with MAFLD were recruited. Participants were divided into two groups based on whether they improved IFC measured by nuclear magnetic resonance. Anthropometric and clinical parameters improved in responders, including reduced weight, body mass index (BMI), and waist circumference. Only responders showed improvements in lipid profile and liver enzymes. Haematological parameters showed favourable changes in both groups. Oxidative stress and inflammatory biomarkers differed between groups. Responders had lower plasma interleukine-18 (IL-18) levels, but higher erythrocyte malonaldehyde (MDA) levels. Non-responders showed increased erythrocyte catalase and superoxide dismutase activity. After 2 years, non-responders had higher serum creatinine, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) levels, while responders showed reductions in these parameters together with uric acid and urine albumin-to-creatinine ratio (UACR). Positive correlations were found between changes in IFC and kidney injury biomarkers, including MDRD and serum creatinine levels. In conclusion, a healthy diet based on the Mediterranean dietary pattern and lifestyle promotes significant improvements in parameters related to cardiovascular, hepatic, and renal health

Mediterranean Diet Improves Plasma Biomarkers Related to Oxidative Stress and Inflammatory Process in Patients with Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) shows liver fat depots without alcohol consumption. NAFLD does not have specific drug therapies, with a healthy lifestyle and weight loss being the main approaches to prevent and treat NAFLD. The aim was to assess the antioxidant and pro-inflammatory state in patients with NAFLD after 12-month-lifestyle intervention depending on the change in adherence to a Mediterranean diet (AMD). Antioxidant and inflammatory biomarkers were measured in 67 adults (aged 40–60 years old) diagnosed with NAFLD. Anthropometric parameters and dietary intake were measured by a validated semi-quantitative 143-item food frequency questionnaire. The nutritional intervention improved anthropometric and biochemical parameters after a 12-month follow-up. However, decreases in alanine aminotransferase (ALT) and C reactive protein (CRP) were higher in participants with high AMD, which also showed higher improvement in physical fitness (Chester step test) and intrahepatic fat contents. The intervention reduced plasma levels of malondialdehyde, myeloperoxidase, zonulin, and omentin, and increased resolvin D1 (RvD1), whereas the decrease in leptin, ectodysplasin-A (EDA), cytokeratin-18 (CK-18), interleukin-1ra (IL-1ra) and endotoxin was only significant in participants with higher AMD. The current study showed that a one-year nutritional intervention improved main NAFLD features such as body mass index, IFC, liver enzymes, and prooxidant and proinflammatory status. There was also a decrease in the concentration of plasmatic endotoxin, suggesting an improvement in intestinal permeability. These health benefits were more evident in participants that improved AMD to a greater extent. The trial was registered at ClinicalTrials.gov with registry number NCT04442620

Ex Vivo Study on the Antioxidant Activity of a Winemaking By-Product Polyphenolic Extract (Taurisolo) on Human Neutrophils

[eng] Oxidative stress (OxS) has been linked to several chronic diseases and is recognized to have both major causes and consequences. The use of antioxidant-based nutraceuticals has been licensed as an optimal tool for management of OxS-related diseases. Currently, great interest is focused on the valorization of agri-food by-products as a source of bioactive compounds, including polyphenols. In this sense, we evaluated the efficacy of a novel nutraceutical formulation based on polyphenolic extract from Aglianico cultivar grape pomace (registered as Taurisolo ). In particular, we tested both native and in vitro gastrointestinal digested forms. The two extracts have been used to treat ex vivo neutrophils from subjects with metabolic syndrome, reporting a marked antioxidant activity of Taurisolo, as shown by its ability to significantly reduce both the levels of reactive oxygen species (ROS) and the activities of catalase and myeloperoxidase in the cell medium after stimulation of neutrophils with phorbol 12-myristate 13-acetate (PMA). Interestingly, we observed an increase in intracellular enzymatic activities in PMA-treated cells, suggesting that Taurisolo polyphenols might be able to activate nuclear factors, up-regulating the expression of this target antioxidant gene. In addition, Taurisolo  reversed the increase in malondialdehyde induced by PMA; reduced the expression of pro-inflammatory genes such as cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNFα) and myeloperoxidase (MPO); and induced the expression of the antiinflammatory cytokine IL-10. Overall, these results suggest the efficacy of Taurisolo  in contrasting the OxS at blood level, providing evidence for its therapeutic potential in the management of OxSrelated pathological conditions in humans