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.

Valorization of Olea europaea and olive oil processing by-products/wastes.

Olive (Olea europaea) is a native species from the Mediterranean region and widely cultivated for its edible fruit, known as olives. Olives are a rich source of monounsaturated fatty acids, vitamin E, and polyphenols, and have been shown to have various health benefits. They are commonly used for cooking and are also employed in cosmetics and the pharmaceutical industry. The extract obtained from olive fruits and several subproducts of the olive industry has demonstrated several biological activities mainly associated with their antioxidant and inflammatory properties. Thus, olives, olive-derived products, and subproducts of the olive industry have gained popularity in recent years due to their potential health benefits and their use in traditional medicine. The present chapter summarizes the main applications of Olea europaea and olive oil processing by-products as therapeutic agents against cancer, cardiovascular diseases, and antimicrobial agents.

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.

Molecular Mechanisms of the Protective Effects of Olive Leaf Polyphenols against Alzheimer's Disease.

Alzheimer's Disease (AD) is the cause of around 60-70% of global cases of dementia and approximately 50 million people have been reported to suffer this disease worldwide. The leaves of olive trees (Olea europaea) are the most abundant by-products of the olive grove industry. These by-products have been highlighted due to the wide variety of bioactive compounds such as oleuropein (OLE) and hydroxytyrosol (HT) with demonstrated medicinal properties to fight AD. In particular, the olive leaf (OL), OLE, and HT reduced not only amyloid-ß formation but also neurofibrillary tangles formation through amyloid protein precursor processing modulation. Although the isolated olive phytochemicals exerted lower cholinesterase inhibitory activity, OL demonstrated high inhibitory activity in the cholinergic tests evaluated. The mechanisms underlying these protective effects may be associated with decreased neuroinflammation and oxidative stress via NF-κB and Nrf2 modulation, respectively. Despite the limited research, evidence indicates that OL consumption promotes autophagy and restores loss of proteostasis, which was reflected in lower toxic protein aggregation in AD models. Therefore, olive phytochemicals may be a promising tool as an adjuvant in the treatment of AD.

In Vivo Anti-Alzheimer and Antioxidant Properties of Avocado (Persea americana Mill.) Honey from Southern Spain.

There is growing evidence that Alzheimer's disease (AD) can be prevented by reducing risk factors involved in its pathophysiology. Food-derived bioactive molecules can help in the prevention and reduction of the progression of AD. Honey, a good source of antioxidants and bioactive molecules, has been tied to many health benefits, including those from neurological origin. Monofloral avocado honey (AH) has recently been characterized but its biomedical properties are still unknown. The aim of this study is to further its characterization, focusing on the phenolic profile. Moreover, its antioxidant capacity was assayed both in vitro and in vivo. Finally, a deep analysis on the pathophysiological features of AD such as oxidative stress, amyloid-ß aggregation, and protein-tau-induced neurotoxicity were evaluated by using the experimental model C. elegans. AH exerted a high antioxidant capacity in vitro and in vivo. No toxicity was found in C. elegans at the dosages used. AH prevented ROS accumulation under AAPH-induced oxidative stress. Additionally, AH exerted a great anti-amyloidogenic capacity, which is relevant from the point of view of AD prevention. AH exacerbated the locomotive impairment in a C. elegans model of tauopathy, although the real contribution of AH remains unclear. The mechanisms under the observed effects might be attributed to an upregulation of daf-16 as well as to a strong ROS scavenging activity. These results increase the interest to study the biomedical applications of AH; however, more research is needed to deepen the mechanisms under the observed effects.

Bioactive Properties of Tagetes erecta Edible Flowers: Polyphenol and Antioxidant Characterization and Therapeutic Activity against Ovarian Tumoral Cells and Caenorhabditis elegans Tauopathy.

Tagetes erecta is an edible flower deeply rooted in traditional Mexican culture. It holds a central role in the most popular and iconic Mexican celebration, "the Day of the Dead". Furthermore, it is currently receiving interest as a potential therapeutic agent, motivated mainly by its polyphenol content. The present study aims to evaluate the biological activity of an extract synthesized from the petals of the edible flower T. erecta. This extract showed significant antioxidant scores measured by the most common in vitro methodologies (FRAP, ABTS, and DPPH), with values of 1475.3 µM trolox/g extr, 1950.3 µM trolox/g extr, and 977.7 µM trolox/g extr, respectively. In addition, up to 36 individual polyphenols were identified by chromatography. Regarding the biomedical aspects of the petal extract, it exhibited antitumoral activity against ovarian carcinoma cells evaluated by the MTS assay, revealing a lower value of IC50 compared to other flower extracts. For example, the extract from T. erecta reported an IC50 value half as low as an extract from Rosa × hybrida and six times lower than another extract from Tulbaghia violacea. This antitumoral effect of T. erecta arises from the induction of the apoptotic process; thus, incubating ovarian carcinoma cells with the petal extract increased the rate of apoptotic cells measured by flow cytometry. Moreover, the extract also demonstrated efficacy as a therapeutic agent against tauopathy, a feature of Alzheimer's disease (AD) in the Caenorhabditis elegans experimental model. Treating worms with the experimental extract prevented disfunction in several motility parameters such as wavelength and swimming speed. Furthermore, the T. erecta petal extract prevented the release of Reactive Oxygen Species (ROS), which are associated with the progression of AD. Thus, treatment with the extract resulted in an approximate 20% reduction in ROS production. These findings suggest that these petals could serve as a suitable source of polyphenols for biomedical applications.

Molecular bases for the use of functional foods in the management of healthy aging: Berries, curcumin, virgin olive oil and honey; three realities and a promise.

As the number of older people has grown in recent decades, the search for new approaches to manage or delay aging is also growing. Among the modifiable factors, diet plays a crucial role in healthy aging and in the prevention of age-related diseases. Thus, the interest in the use of foods, which are rich in bioactive compounds such as functional foods with anti-aging effects is a growing market. This review summarizes the current knowledge about the molecular mechanisms of action of foods considered as functional foods in aging, namely berries, curcumin, and virgin olive oil. Moreover, honey is also analyzed as a food with well-known healthy benefits, but which has not been deeply evaluated from the point of view of aging. The effects of these foods on aging are analyzed from the point of view of molecular mechanisms including oxidative stress, mitochondrial dysfunction, inflammation, genomic stability, telomere attrition, cellular senescence, and deregulated nutrient-sensing. A comprehensive study of the scientific literature shows that the aforementioned foods have demonstrated positive effects on certain aspects of aging, which might justify their use as functional foods in elderly. However, more research is needed, especially in humans, designed to understand in depth the mechanisms of action through which they act.

An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents ß-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans.

Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like Aß- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred µg/mL of extract treatment revealed prevention of oxidative stress and a delay in Aß-induced paralysis related with a lower presence of Aß aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects.

Strawberry (Fragaria × ananassa cv. Romina) methanolic extract attenuates Alzheimer's beta amyloid production and oxidative stress by SKN-1/NRF and DAF-16/FOXO mediated mechanisms in C. elegans.

Bioactive compounds from strawberries have been associated with multiple healthy benefits. The present study aimed to assess chemical characterization of a methanolic extract of the Romina strawberry variety in terms of antioxidant capacity, polyphenols profile and chemical elements content. Additionally, potential toxicity, the effect on amyloid-ß production and oxidative stress of the extract was in vivo evaluated in the experimental model Caenorhabditis elegans. Results revealed an important content in phenolic compounds (mainly ellagic acid and pelargonidin-3-glucoside) and minerals (K, Mg, P and Ca). The treatment with 100, 500 or 1000 µg/mL of strawberry extract did not show toxicity. On the contrary, the extract was able to delay amyloid ß-protein induced paralysis, reduced amyloid-ß aggregation and prevented oxidative stress. The potential molecular mechanisms present behind the observed results explored by RNAi technology revealed that DAF-16/FOXO and SKN-1/NRF2 signaling pathways were, at least partially, involved.

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.

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.

Longevity and Cause of Death in Male Wistar Rats Fed Lifelong Diets Based on Virgin Olive Oil, Sunflower Oil, or Fish Oil.

Extending life by delaying the aging process has been proven to be the most effective way to fight multiple chronic diseases in elderly adults. Evidence suggests that longevity is inversely related to unsaturation of membrane phospholipids. This study investigated how different unsaturated dietary fats affect life span and cause of death in male Wistar rats fed diets based on virgin olive oil (V), sunflower oil (S), or fish oil (F), which were supplemented or not with Coenzyme Q10 (CoQ10). Previous results suggest that individual longevity and survival probability at different ages may be modulated by an appropriate dietary fat treatment. Lifelong feeding with V or F diets would reduce death probability compared to feeding with S diet at certain ages, although the effects of V diet would be maintained for most of life. Furthermore, the addition of lower amounts of CoQ10 reduced mortality associated with S diet, but CoQ10 had no effect on survival when combined with virgin olive oil or fish oil. Supplementation with low doses of CoQ10 failed to increase the maximum life span potential of rats fed a V or F diet. No clear evidence showing that monounsaturated fatty acids, n-3 polyunsaturated fatty acids, or CoQ10 exerted the observed effects by modulating the rate of aging has been found.

An update on the mechanisms related to cell death and toxicity of doxorubicin and the protective role of nutrients.

Doxorubicin (DOX), is a very effective chemotherapeutic agent against cancer whose clinical use is limited by toxicity. Different strategies have been proposed to attenuate toxicity, including combined therapy with bioactive compounds. This review update mechanisms of action and toxicity of doxorubicin and the role of nutrients like vitamins (A, C, E), minerals (selenium) and n-3 polyunsaturated fatty acids. Protective activities against DOX toxicity in liver, kidney, skin, bone marrow, testicles or brain have been reported, but these have not been evaluated for all of the reviewed nutrients. In most cases oxidation-related effects were present either, by reducing ROS levels and/or increasing antioxidant defenses. Antiapoptotic and anti-inflammatory mechanisms are also commonly reported. In some cases, interferences with autophagy and calcium homeostasis also have shown to be affected. Notwithstanding, there is a wide variety in duration and doses of treatment tested for both, compounds and DOX, which make difficult to compare the results of the studies. In spite of the reduction of DOX cardiotoxicity in health models, DOX anti-cancer activity in cancer cell lines or xenograft models usually did not result compromised when this has been evaluated. Importantly, clinical studies are needed to confirm all the observed effects.

Heart Histopathology and Mitochondrial Ultrastructure in Aged Rats Fed for 24 Months on Different Unsaturated Fats (Virgin Olive Oil, Sunflower Oil or Fish Oil) and Affected by Different Longevity.

Diet plays a decisive role in heart physiology, with lipids having especial importance in pathology prevention and development. This study aimed to investigate how dietary lipids varying in lipid profile (virgin olive oil, sunflower oil or fish oil) affected the heart of rats during aging. Heart histopathology, mitochondrial morphometry, and oxidative status were assessed. Typical histopathological features associated with aging, such as valvular lesions, endomyocardical hyperplasia, or papillary muscle calcification, were found at a low extent in all the experimental groups. The most relevant finding was that inflammation registered by fish oil group was lower compared to the other treatments. At the ultrastructural level, heart mitochondrial area, perimeter, and aspect ratio were higher in fish oil-fed rats than in those fed on sunflower oil. Concerning oxidative stress markers, there were differences only in coenzyme Q levels and catalase activity, lower in sunflower oil-fed animals compared with those fed on fish oil. In summary, dietary intake for a long period on dietary fats with different fatty acids profile led to differences in some aspects associated with the aging process at the heart. Fish oil seems to be the fat most protective of heart during aging.

Industrial-Scale Decontamination Procedure Effects on the Content of Acaricides, Heavy Metals and Antioxidant Capacity of Beeswax.

Beeswax is useful for the beekeeping sector but also for the agro-food, pharmaceutical or cosmetics sectors. Frequently, this bee product is contaminated with pesticides reducing its utility and causing the decline in its market. This study aimed to prove the effectiveness of an industrial-scale decontamination method in removing acaricides from beeswax. Chlorfenvinphos and coumaphos decrease was higher than 90%, whereas tau fluvalinate decrease was only 30%. No changes were observed in the beeswax content of hydrocarbons and monoesters, whereas a decrease in the concentrations of Ca, Fe, Zn, Hg, Mn and P, and an increase in the concentrations of As and Si were found after the decontamination. Filtration reduced total phenolics, flavonoids and the antioxidant capacity of the lipophilic extract. These results demonstrate that the industrial method used was as effective as the method previously tested on a laboratory scale. The study also contributes to a better knowledge and characterization of beeswax, specially related to trace and ultra-trace elements and antioxidant capacity. Moreover, it offers the chance to further develop a method to effectively detect wax adulterations based on the chemical elements profile.

Nutraceuticals in Periodontal Health: A Systematic Review on the Role of Vitamins in Periodontal Health Maintenance.

Periodontal disease, a relevant public health problem worldwide, is generally considered a common pathology of elderly people. In this respect, there is agreement about that nutritional status may be a modifying factor in the progression and healing of the periodontal tissues. Vitamins have been recommended as nutraceuticals for prevention and treatment of some pathological conditions, such as cardiovascular diseases, obesity or cancer. Thus, a systematic approach to determining how the different vitamin type could ameliorate periodontal risks or improve periodontal health is necessary to further the understanding of the potential benefits and risks of vitamins supplementation use. For this, a systematic review of English-written literature in PubMed until February 2018, which included both human and animal research on the relationship of each vitamin with periodontal disease, was conducted. Among all the analyzed vitamins those with antioxidant capacity and effects on immune system seem to be useful for prevention or improvement of periodontal disease, as well as those implicated in bone metabolism. In the first case, there are quite information in favor of various vitamins, mainly vitamin C, that is the most studied. In the second case, vitamin D seems to have the most relevant role.