Effect of olive leaf phytochemicals on the anti-acetylcholinesterase, anti-cyclooxygenase-2 and ferric reducing antioxidant capacity.

In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their anti-cholinergic, anti-inflammatory, and antioxidant activities were evaluated. Luteolin-7-O-glucoside, isoharmnentin, and apigenin were involved in the acetylcholinesterase (AChE) inhibitory activity, while oleuropein and hydroxytyrosol showed noteworthy potential. Secoiridoids contributed to the cyclooxygenase-2 inhibitory activity and antioxidant capacity. Compounds such as oleuropein, ligstroside and luteolin-7-O-glucoside, may exert an important role in the ferric reducing antioxidant capacity. It should be also highlighted the role of hydroxytyrosol, hydroxycoumarins, and verbascoside concerning the antioxidant activity. This research provides valuable insights and confirms that specific compounds within OL extracts contribute to distinct anti-cholinergic, anti-inflammatory, and anti-oxidative effects.

Exploring the Antioxidant, Neuroprotective, and Anti-Inflammatory Potential of Olive Leaf Extracts from Spain, Portugal, Greece, and Italy.

The leaves of the olive tree (Olea europaea L.) are one of the major solid wastes from the olive industry. Globally, the European Union is the largest producer of olive by-products, with Spain, Italy, Greece, and Portugal accounting for almost the entire production. Many questions remain to be solved concerning olive leaves (OL), including those related to possible differences in composition and/or biological activities depending on their geographical origin. In the present work, OL from Spain, Italy, Greece, and Portugal have been characterized according to their phytochemical profile, antioxidant capacity, neuroprotective activity, and anti-inflammatory effects. The Spanish and Italian OL samples presented the highest antioxidant and neuroprotective activities, while the Greek OL showed the lowest. These results were strongly associated with the content of oleoside methyl ester and p-hydroxybenzoic acid for the Spanish and Italian samples, respectively, whereas the content of decarboxymethyl elenolic acid dialdehyde form (hydrated) was negatively associated with the mentioned biological activities of the Greek samples. No country-related effect was observed in the anti-inflammatory activity of OL. Comprehensively, this work could provide a useful tool for manufacturers and R&D departments in making environmentally friendly decisions on how OL can be used to generate nutraceutical products based on the composition and origin of this by-product.

Influence of a concurrent exercise training program during pregnancy on the placenta mitochondrial DNA integrity and content of minerals with enzymatic relevance. The GESTAFIT project.

INTRODUCTION: We aimed i) to investigate the effects of a concurrent (aerobic plus strength) exercise intervention during pregnancy on placental mtDNA copy number, proportion of deleted mtDNA, and on the content of some trace and ultra-trace minerals with coenzymatic relevance; ii) to explore the association of such mitochondrial markers with the concentration of these minerals. METHODS: For the present study specific aims, 47 placentas were randomly selected from women that participated in the GESTAFIT project into exercise (n = 24) or control (n = 23) groups. The exercise group followed a concurrent aerobic and strength training program, three 60-min sessions/week, from the 17th gestational week until birth. Placenta tissue was collected and processed for minerals determination by the inductively coupled plasma mass spectrometry technique. RT-PCR was used to determine placentas mtDNA copy number and ND1/ND4 deletion. RESULTS: After adjusting for potential confounders, the mothers who participated in the exercise program had placentas with greater mtDNA copy number (p = 0.04) and lower mtDNA deletion (p = 0.003). Placentas from mothers in the exercise group presented higher manganese content than those from the controls (0.26 ± 0.03 mg/dL vs. 0.13 ± 0.03 mg/dL, p = 0.003). Placenta manganese content was significantly associated with lower mtDNA deletions (r = -0.382) and greater mtDNA copy number (r = 0.513). Iron content was associated with higher mtDNA copy number (r = 0.393). Selenium content was associated with lower mtDNA deletion (r = -0.377) and greater mtDNA copy number (r = 0.442). Finally, zinc and magnesium content were associated with higher mtDNA copy number (r = 0.447 and r = 0.453, respectively). DISCUSSION: This concurrent exercise training program induced a better placental status, which might be mediated through an improvement of mitochondrial bioenergetics and antioxidative capacity.

Dietary antioxidants and lifespan: Relevance of environmental conditions, diet, and genotype of experimental models.

The rise of life expectancy in current societies is not accompanied, to date, by a similar increase in healthspan, which represents a great socio-economic problem. It has been suggested that aging can be manipulated and then, the onset of all age-associated chronic disorders can be delayed because these pathologies share age as primary underlying risk factor. One of the most extended ideas is that aging is consequence of the accumulation of molecular damage. According to the oxidative damage theory, antioxidants should slow down aging, extending lifespan and healthspan. The present review analyzes studies evaluating the effect of dietary antioxidants on lifespan of different aging models and discusses the evidence on favor of their antioxidant activity as anti-aging mechanisms. Moreover, possible causes for differences between the reported results are evaluated.

Influence of an exercise intervention plus an optimal Mediterranean diet adherence during pregnancy on the telomere length of the placenta. The GESTAFIT project.

We aimed to investigate whether the effects of exercise on placental relative telomere length (RTL) after delivery are modulated by the Mediterranean diet [MD] adherence in 65 pregnant women (control n = 34, exercise n = 31). No differences were found in placental RTL between the exercise and the control groups (p = 0.557). The interaction-term between exercise and MD adherence with placental RTL was significant (p = 0.001). Specifically, women in the exercise group showed longer placental RTL after birth compared to controls (referent group), only for those women with a high MD adherence (mean difference = 0.467, p=0.010). A concurrent-exercise training plus an optimal MD adherence during pregnancy might prevent the placental RTL shortening.

Involvement of redox signalling in tumour cell dormancy and metastasis.

Decades of research on oncogene-driven carcinogenesis and gene-expression regulatory networks only started to unveil the complexity of tumour cellular and molecular biology. This knowledge has been successfully implemented in the clinical practice to treat primary tumours. In contrast, much less progress has been made in the development of new therapies against metastasis, which are the main cause of cancer-related deaths. More recently, the role of epigenetic and microenviromental factors has been shown to play a key role in tumour progression. Free radicals are known to communicate the intracellular and extracellular compartments, acting as second messengers and exerting a decisive modulatory effect on tumour cell signalling. Depending on the cellular and molecular context, as well as the intracellular concentration of free radicals and the activation status of the antioxidant system of the cell, the signalling equilibrium can be tilted either towards tumour cell survival and progression or cell death. In this regard, recent advances in tumour cell biology and metastasis indicate that redox signalling is at the base of many cell-intrinsic and microenvironmental mechanisms that control disseminated tumour cell fate and metastasis. In this manuscript, we will review the current knowledge about redox signalling along the different phases of the metastatic cascade, including tumour cell dormancy, making emphasis on metabolism and the establishment of supportive microenvironmental connections, from a redox perspective.

Oxidative Stress Amelioration of Novel Peptides Extracted from Enzymatic Hydrolysates of Chinese Pecan Cake.

Pecan (Carya cathayensis) is an important economic crop, and its hydrolyzed peptides have been evidenced to reduce the effect of oxidative stress due to their antioxidant capacity. Hence, the protocols of ultrafiltration and gel filtration chromatography were established to obtain bioactive peptides from by-products of C. cathayensis (pecan cake). As measured by DPPH/ABTS radical scavenging, the peptides with less molecular weight (MW) possess higher antioxidant capacity. PCPH-III (MW < 3 kDa) presented higher radical scavenging capacity than PCPH-II (3 kDa < MW < 10 kDa) and PCPH-I (MW > 10 kDa) measured by DPPH (IC50: 111.0 µg/ mL) and measured by ABTs (IC50: 402.9 µg/mL). The secondary structure and amino acid composition varied by their MW, in which PCPH-II contained more α-helices (26.71%) and ß-sheets (36.96%), PCPH-III contained higher ratios of ß-turns (36.87%), while the composition of different secondary of PCPH-I was even 25 ± 5.76%. The variation trend of α-helix and random experienced slightly varied from PCPH-I to PCPH-II, while significantly decreased from PCPH-II to PCPH-III. The increasing antioxidant capacity is followed by the content of proline, and PCPH-III had the highest composition (8.03%). With regard to the six peptides identified by LC-MS/MS, two of them (VYGYADK and VLFSNY) showed stronger antioxidant capacity than others. In silico molecular docking demonstrated their combining abilities with a transcription factor Kelch-like ECH-associated protein 1 (Keap1) and speculated that they inhibit oxidative stress through activating the Keap1-Nrf2-ARE pathway. Meanwhile, increased activity of SOD and CAT­antioxidant markers­were found in H2O2-induced cells. The residue of tyrosine was demonstrated to contribute the most antioxidant capacity of VYGYADK and its position affected less. This study provided a novel peptide screening and by-product utilization process that can be applied in natural product developments.

Differences reported in the lifespan and aging of male Wistar rats maintained on diets containing fat with different fatty acid profiles (virgin olive, sunflower or fish oils) are not reflected by histopathological lesions found at death in central nervous and endocrine systems.

The present study was designed to examine if dietary fat sources that have shown differences in lifespan and if some aging-related aspects can modulate the range of histopathologic changes in central nervous and endocrine systems that occur during the lifespan of Wistar rats. Moreover, it was attempted to gain insight into the relationship between longevity and the development of the different pathological changes, as well as possible interaction with diet. In order to achieve this, male Wistar rats were randomly assigned to three experimental groups fed semisynthetic and isoenergetic diets from weaning until death with different dietary fat sources, namely virgin olive, sunflower, or fish oil. An individual follow-up until death of each animal was performed. Incidence, severity, and burden of specific or group (i.e., neoplastic or non-neoplastic proliferative and non-proliferative) of lesions was calculated along with individual's disease and individual organ lesion burden. Most of the histopathological lesions found have been described in previous studies. Neoplasms, and in particular pituitary adenomas followed by brain tumors, were the most prevalent lesions found in the rats and the main cause of death involving both systems. Incidence of brain lesions was associated with age-at-death. Assayed dietary fats did not present differential effects on pathological changes occurring in endocrine and central nervous systems throughout rat lifespan.

Differences in maternal and neonatal cardiometabolic markers and placenta status by foetal sex. The GESTAFIT project.

AIMS: To explore the differences in some maternal-neonatal metabolic markers and placenta status by foetal sex. METHODS: One hundred thirty-nine Caucasian pregnant women from the GESTAFIT project and their new-borns were included in the present cross-sectional study. Serum cardiometabolic markers (i.e. lipid and glycaemic profile and uric acid) were analysed at late pregnancy and at birth. In placenta, telomeres length, proportion of deleted mitochondrial-DNA and mitochondrial-DNA density, some minerals and interleukin 8, epidermal growth factor, fibroblast growth factor-2 and vascular endothelial growth factor were measured. The study was run between November 2015 and April 2018. RESULTS: Mothers carrying a male showed higher serum triglycerides than mothers carrying a female at late pregnancy (p < .05). Serum total and low-density lipoprotein cholesterol were greater in males' umbilical cord blood artery compared to females' new-borns (both, p < .05). Mothers of males and male new-borns presented higher uric acid than mothers of females and female new-borns at birth (p < .05). Female's placentas presented greater placental-newborn weight ratio, manganese content and fibroblast growth factor-2 (all, p ⩽ .05), and evidence of statistical significance in telomeres length, which were 17% longer (p = .076). CONCLUSION: Our findings show weak differences in some cardiometabolic and placental status markers by foetal sex. Notwithstanding, we observed a slightly more proatherogenic profile in both, mothers carrying males' foetuses and male new-borns. We also found lower serum uric acid and better placenta status in mothers carrying a female. These findings indicate that foetal sex might need to be considered for a more personalized follow-up of pregnancies.

Natural Bioactive Products and Alzheimer's Disease Pathology: Lessons from Caenorhabditis elegans Transgenic Models.

Alzheimer's disease (AD) is an age-dependent, progressive disorder affecting millions of people. Currently, the therapeutics for AD only treat the symptoms. Although they have been used to discover new products of interest for this disease, mammalian models used to investigate the molecular determinants of this disease are often prohibitively expensive, time-consuming and very complex. On the other hand, cell cultures lack the organism complexity involved in AD. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of human AD. Numerous models of both Tau- and Aß-induced toxicity, the two prime components observed to correlate with AD pathology and the ease of performing RNA interference for any gene in the C. elegans genome, allow for the identification of multiple therapeutic targets. The effects of many natural products in main AD hallmarks using these models suggest promising health-promoting effects. However, the way in which they exert such effects is not entirely clear. One of the reasons is that various possible therapeutic targets have not been evaluated in many studies. The present review aims to explore shared therapeutical targets and the potential of each of them for AD treatment or prevention.

Molecular Interactions between Dietary Lipids and Bone Tissue during Aging.

Age-related bone disorders such as osteoporosis or osteoarthritis are a major public health problem due to the functional disability for millions of people worldwide. Furthermore, fractures are associated with a higher degree of morbidity and mortality in the long term, which generates greater financial and health costs. As the world population becomes older, the incidence of this type of disease increases and this effect seems notably greater in those countries that present a more westernized lifestyle. Thus, increased efforts are directed toward reducing risks that need to focus not only on the prevention of bone diseases, but also on the treatment of persons already afflicted. Evidence is accumulating that dietary lipids play an important role in bone health which results relevant to develop effective interventions for prevent bone diseases or alterations, especially in the elderly segment of the population. This review focuses on evidence about the effects of dietary lipids on bone health and describes possible mechanisms to explain how lipids act on bone metabolism during aging. Little work, however, has been accomplished in humans, so this is a challenge for future research.

Evaluation of the Analgesic Efficacy of a Bioelectronic Device in Non-Specific Chronic Low Back Pain with Neuropathic Component. A Randomized Trial.

Low energy pulsed electromagnetic signals (PEMS) therapy, in the field of bioelectronics, has been suggested as a promising analgesic therapy with special interest in treating conditions with poor response to pharmacotherapy. This study evaluated the effectiveness of PEMS therapy on the treatment of chronic low back pain patients with a neuropathic component. A group of 64 individuals with such condition was allocated to a 2-week treatment period (10 twenty-minute sessions on consecutive days) with an active PEMS therapy device or an inactive device in random order. The pain was assessed on a visual analog scale, and the functional status was assessed using the SF-12 questionnaire. The visual analog scale scores were lower after treatment than at baseline but only in the group treated with the active device. According to the DN4 score, neuropathic pain decreased in both experimental groups with respect to baseline, but this was only significant for the group treated with the active device. Similarly, an improvement in the SF-12 and Medical Outcomes Study (MOS) sleep scale components was reported. The study demonstrated that low-energy PEMS therapy was efficient in reducing pain and improving function in chronic low back pain patients with a neuropathic component.

Rosa x hybrida extracts with dual actions: Antiproliferative effects against tumour cells and inhibitor of Alzheimer disease.

Edible flowers are being used as a new ingredient in modern gastronomy. Recently, these products have also gained interest as an important source of phenolic compounds with potential for biomedical applications. The present work studied a methanolic extract of Rosa x hybrida in which 35 individual phenolic compounds were identified. The extract has been evaluated for its antiproliferative properties in ovarian carcinoma cells. Results showed that the antiproliferative effect was associated with the induction of autophagy and apoptosis with the concomitant ROS increase probably related to mitochondria dysfunction. These antiproliferative effects might be associated with some components of the extract such as quercetin. The extract did not induce damage in healthy cells and that it was able to improve the wound healing activity. The present study also evaluated the properties of the mentioned extract in vivo in C. elegans. Tests demonstrated a lack of toxicity in the worm model. Promising results have been obtained in transgenic strains of C. elegans that produce human beta amyloid peptide, suggesting the possible utility of the extract from the point of view of Alzheimer disease. Altogether, results suggest that Rosa x hybrida extracts could be a new tool for the development of functional foods.

Ultra-Small Iron Nanoparticles Target Mitochondria Inducing Autophagy, Acting on Mitochondrial DNA and Reducing Respiration.

The application of metallic nanoparticles (materials with size at least in one dimension ranging from 1 to 100 nm) as a new therapeutic tool will improve the diagnosis and treatment of diseases. The mitochondria could be a therapeutic target to treat pathologies whose origin lies in mitochondrial dysfunctions or whose progression is dependent on mitochondrial function. We aimed to study the subcellular distribution of 2-4 nm iron nanoparticles and its effect on mitochondrial DNA (mtDNA), mitochondrial function, and autophagy in colorectal cell lines (HT-29). Results showed that when cells were exposed to ultra-small iron nanoparticles, their subcellular fate was mainly mitochondria, affecting its respiratory and glycolytic parameters, inducing the migration of the cellular state towards quiescence, and promoting and triggering the autophagic process. These effects support the potential use of nanoparticles as therapeutic agents using mitochondria as a target for cancer and other treatments for mitochondria-dependent pathologies.

The central role of mitochondria in the relationship between dietary lipids and cancer progression.

Evidence demonstrates the importance of lipid metabolism and signaling in cancer cell biology. De novo lipogenesis is an important source of lipids for cancer cells, but exogenous lipid uptake remains essential for many cancer cells. Dietary lipids can modify lipids present in tumor microenvironment affecting cancer cell metabolism. Clinical trials have shown that diets rich in polyunsaturated fatty acids (PUFA) can negatively affect tumor growth. However, certain n-6 PUFAs can also contribute to cancer progression. Identifying the molecular mechanisms through which lipids affect cancer progression will provide an opportunity for focused dietary interventions that could translate into the development of personalized diets for cancer control. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. Mitochondria controls ATP generation, redox homeostasis, metabolic signaling, apoptotic pathways and many aspects of autophagy, and it has been recognized to play a key role in cancer. The purpose of this review is to summarize the current evidence linking dietary lipids effects on mitochondrial aspects with consequences for cancer progression and the molecular mechanisms that underlie this association.

Role of flavonoids against adriamycin toxicity.

Doxorubicin (DOX), or adriamycin, is an anthracycline antineoplastic drug widely used in the chemotherapy of a large variety of cancers due to its potency and action spectrum. However, its use is limited by the toxicity on healthy cells and its acute and chronic side effects. One of the developed strategies to attenuate DOX toxicity is the combined therapy with bioactive compounds such as flavonoids. This review embraces the role of flavonoids on DOX treatment side effects. Protective properties of some flavonoidss against DOX toxicity have been investigated and observed mainly in heart but also in liver, kidney, brain, testis or bone marrow. Protective mechanisms involve reduction of oxidative stress by decrease of ROS levels and/or increase antioxidant defenses and interferences with autophagy, apoptosis and inflammation. Studies in cancer cells have reported that the anticancer activity of DOX was not compromised by the flavonoids. Moreover, some of them increased DOX efficiency as anti-cancer drug even in multidrug resistant cells.

Do nutrients and other bioactive molecules from foods have anything to say in the treatment against COVID-19?

The repositioning of therapeutic agents already approved by the regulatory agencies for the use of drugs is very interesting due to the immediacy of their use; similarly, the possibility of using molecules derived from foods, whether nutrients or not, is of great importance, also because of their immediate therapeutic applicability. Candidates for these natural therapies against COVID-19 should show certain effects, such as restoring mitochondrial function and cellular redox balance. This would allow reducing the susceptibility of risk groups and the cascade of events after SARS-CoV-2 infection, responsible for the clinical picture, triggered by the imbalance towards oxidation, inflammation, and cytokine storm. Possible strategies to follow through the use of substances of food origin would include: a) the promotion of mitophagy to remove dysfunctional mitochondria originating from free radicals, proton imbalance and virus evasion of the immune system; b) the administration of transition metals whose redox activity would lead to their own oxidation and the consequent generation of a reduced environment, which would normalize the oxidative state and the intracellular pH; c) the administration of molecules with demonstrated antioxidant capacity; d) the administration of compounds with anti-inflammatory and vasodilatory activity; e) the administration of immunomodulatory compounds.

A Diet Rich in Saturated Fat and Cholesterol Aggravates the Effect of Bacterial Lipopolysaccharide on Alveolar Bone Loss in a Rabbit Model of Periodontal Disease.

Increasing evidence connects periodontitis with a variety of systemic diseases, including metabolic syndrome, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). The proposal of this study was to evaluate the role of diets rich in saturated fat and cholesterol in some aspects of periodontal diseases in a lipopolysaccharide (LPS)-induced model of periodontal disease in rabbits and to assess the influence of a periodontal intervention on hyperlipidemia, atherosclerosis, and NAFLD progression to non-alcoholic steatohepatitis. Male rabbits were maintained on a commercial standard diet or a diet rich in saturated fat (3% lard w/w) and cholesterol (1.3% w/w) (HFD) for 40 days. Half of the rabbits on each diet were treated 2 days per week with intragingival injections of LPS from Porphyromonas gingivalis. Morphometric analyses revealed that LPS induced higher alveolar bone loss (ABL) around the first premolar in animals receiving standard diets, which was exacerbated by the HFD diet. A higher score of acinar inflammation in the liver and higher blood levels of triglycerides and phospholipids were found in HFD-fed rabbits receiving LPS. These results suggest that certain dietary habits can exacerbate some aspects of periodontitis and that bad periodontal health can contribute to dyslipidemia and promote NAFLD progression, but only under certain conditions.

Reductive Stress, Bioactive Compounds, Redox-Active Metals, and Dormant Tumor Cell Biology to Develop Redox-Based Tools for the Treatment of Cancer.

Significance: Cancer is related to redox biology from many points of view, such as initiation and promotion, metabolism and growth, invasion and metastasis, vascularization, or through the interaction with the immune system. In addition, this extremely complex relationship depends on the redox homeostasis of each cellular compartment, which might be used to fight cancer. Recent Advances: New ways of modulating specific and little explored aspects of redox biology have been revealed, as well as new delivery methods or uses of previously known treatments against cancer. Here, we review the latest experimental evidence regarding redox biology in cancer treatment and analyze its potential impact in the development of improved and more effective antineoplastic therapies. Critical Issues: A critical issue that deserves particular attention is the understanding that both extremes of redox biology (i.e., oxidative stress [OS] and reductive stress) might be useful or harmful in relation to cancer prevention and treatment. Future Directions: Additional research is needed to understand how to selectively induce reductive or OS adequately to avoid cancer proliferation or to induce cancer cell death.

Molecular inflammation and oxidative stress are shared mechanisms involved in both myocardial infarction and periodontitis.

BACKGROUND AND OBJECTIVE: Our aims were to improve the understanding of the pathogenic relationship between cardiovascular diseases and periodontitis and to generate new perspectives in the prevention and treatment of acute myocardial infarction (AMI) and periodontitis. The present study evaluates possible differences in inflammation, oxidative stress, and autophagy markers among subject suffering AMI, periodontitis, or both, to explore possible common pathogenic mechanisms. MATERIAL AND METHODS: A total of 260 subjects were enrolled in the study: 106 subjects that survived to a first AMI (AMI group) and 154 subjects had no cardiac events in their clinical record (control group). A questionnaire was used to assess age, height, weight, blood pressure, and heart rate. The clinical probing depth, clinical attachment loss, number of remaining teeth, and average number of sites with bleeding on probing were assessed. Lipid peroxidation and protein levels of phosphorylated AMP-activated protein kinase (p-AMPK) and microtubule-associated proteins 1A/1B-light chain 3-II (LC3-II) were determined in isolated peripheral blood mononuclear cells by thiobarbituric acid reactive substances (TBARS) assay and Western blot, respectively. Plasma levels of interleukin-1ß were determined using a commercial ELISA kit. All the obtained variables were compared between subjects suffering an AMI with or without periodontitis and control subject periodontal healthy or with periodontitis. RESULTS: A higher proportion of subjects suffering AMI + periodontitis than only AMI (without periodontitis) was found. Higher levels of TBARS were found in subjects with periodontitis than in subjects without periodontitis in both AMI and control subjects. Positive correlations between IL-1ß levels and TBARS and between IL-1ß levels and LC3-II were found only in control subjects. CONCLUSION: Results from the present study are consistent with the suggestion of periodontitis as a potential risk factor for AMI. Periodontitis association with circulating lipid peroxides in both AMI and control subjects were found. The absence of differences in IL-1ß levels between AMI subjects (only AMI vs AMI + periodontitis) suggests that oxidative stress could be the main pathogenic link between AMI and periodontitis.