In Vitro and In Vivo Insights into a Broccoli Byproduct as a Healthy Ingredient for the Management of Alzheimer's Disease and Aging through Redox Biology.

Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer's disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-ß- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.

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.

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.

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.

Unravelling potential biomedical applications of the edible flower Tulbaghia violacea.

Traditionally, edible flowers have been used as foods and for therapeutic purposes, today they have gained importance due to their bioactive compounds such as flavonols, anthocyanins or other phenolic compounds, which give them potential for biomedical applications. This work evaluated a methanolic extract of Tulbaghia violacea. Eleven individual phenolic compounds were found and quantified by mass spectrometry in the extract. Antioxidant activity tests (TEAC, FRAP and DPPH) and other characterization parameters were assayed (total phenolic content and total flavonoid content). In vitro studies showed antitumoral activity against ovarian tumoral cells mediated by the induction of non-dependent caspase cell death and by the activation of reactive oxygen species. The effect of the extract against features of Alzheimer disease was in vivo assayed in Caenorhabditis elegans. Tulbaghia extract led to a reduction in the 1-42 beta amyloid peptide formation and prevented oxidative stress. These results suggested that Tulbaghia violacea could be a new source of phenolic compounds for nutraceuticals and functional food development.

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.

Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats.

Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar white adipose tissues (IWAT and SWAT, respectively). Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues (p > 0.05), with the exception of Zn in liver. In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p < 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model.

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.

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.

In vitro and in situ experiments to evaluate the biodistribution and cellular toxicity of ultrasmall iron oxide nanoparticles potentially used as oral iron supplements.

Well-absorbed iron-based nanoparticulated materials are a promise for the oral management of iron deficient anemia. In this work, a battery of in vitro and in situ experiments are combined for the evaluation of the uptake, distribution and toxicity of new synthesized ultrasmall (4 nm core) Fe2O3 nanoparticles coated with tartaric/adipic acid with potential to be used as oral Fe supplements. First, the in vitro simulated gastric acid solubility studies by TEM and HPLC-ICP-MS reveal a partial reduction of the core size of about 40% after 90 min at pH 3. Such scenario confirms the arrival of the nanoparticulate material in the small intestine. In the next step, the in vivo absorption through the small intestine by intestinal perfusion experiments is conducted using the sought nanoparticles in Wistar rats. The quantification of Fe in the NPs suspension before and after perfusion shows Fe absorption levels above 79%, never reported for other Fe treatments. Such high absorption levels do not seem to compromise cell viability, evaluated in enterocytes-like models (Caco-2 and HT-29) using cytotoxicity, ROS production, genotoxicity and lipid peroxidation tests. Moreover, regional differences in terms of Fe concentration are obtained among different parts of the small intestine as duodenum > jejunum > ileum. Complementary transmission electron microscopy (TEM) images show the presence of the intact particles around the intestinal microvilli without significant tissue damage. These studies show the high potential of these NP preparations for their use as oral management of anemia.

Spent coffee grounds improve the nutritional value in elements of lettuce (Lactuca sativa L.) and are an ecological alternative to inorganic fertilizers.

The element concentration in lettuces grouped in 5 categories (baby variety, cultivated in agricultural soils with low or high percentages of spent coffee grounds-SCG, without SCG and with NPK) were measured. Lettuces cultivated in agricultural soils amended with SCG had significantly higher levels of several essential (V, Fe, Co, V, and probably Mn and Zn) and toxic elements (Al and probably As), without reaching their toxicological limits. Additionally, blocking of N uptake and therefore plant biomass, and probably Cd absorption from agricultural soil was observed. Organic farming with SCG ameliorates element concentrations in lettuces vs. NPK fertilization. The linear correlations among element uptake and the amendment of SCG could be related with their chelation by some SCG components, such as melanoidins and with the decrease in the soil pH. In conclusion, the addition of SCG produces lettuces with higher element content.

Whey versus soy protein diets and renal status in rats.

Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.

Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats.

Vanadium is an element whose role as a micronutrient for humans is not yet completely established, but which has been shown to possess hypoglycaemic properties in diabetes. In an earlier study, we showed that in STZ-diabetic rats, exposure to 1 mg V per day has no effect on glycaemia or on antioxidant status. When the exposure was raised to 3 mg V per day there was a hypoglycaemic effect, together with reduced Se in the tissues, which reduced antioxidant defences. The aim of the present study was to examine whether exposure to 1 mg V per day modifies Se nutritional status and/or antioxidant defences in healthy rats. Two groups of rats were examined: control and vanadium-treated. Vanadium, as bis(maltolato)oxovanadium(iv), was supplied in the drinking water. The experiment had a duration of five weeks. Selenium was measured in excreta, serum, skeletal muscle, kidneys, liver, heart, femur and adipose tissue. Number of red (RBC) and white (WBC) blood cells and haemoglobin (Hb) were determined in samples of whole blood. Glutathione peroxidase (GPx), glutathione transferase (GST), catalase (CAT) and NAD(P)H:quinine-oxidoreductase1 (NQO1) activity, and malondialdehyde (MDA) in the liver were evaluated. Treatment significantly reduced food intake, produced an anaemic state, and decreased Se absorption and Se content in serum, kidneys and the liver. GPx, GST and NQO1 activity were decreased in the liver, while MDA levels rose. We conclude that healthy rats are more sensitive than diabetic ones to the effects of V. This should be taken into account for populations that are particularly exposed to V for environmental reasons, and/or that consume V as a nutritional supplement.

Effect of bis(maltolato)oxovanadium (IV) (BMOV) on selenium nutritional status in diabetic streptozotocin rats.

The role of V as a micronutrient, and its hypoglycaemic and toxicological activity, have yet to be completely established. The present study focuses on changes in the bioavailability and tissue distribution of Se in diabetic streptozotocin rats following treatment with V. The following four study groups were examined: control; diabetic (DM); diabetic treated with 1 mg V/d (DMV); diabetic treated with 3 mg V/d (DMVH). V was supplied in the drinking water as bis(maltolato)oxovanadium (IV). The experiment had a duration of 5 weeks. Se was measured in food, faeces, urine, serum, muscle, kidney, liver and spleen. Glucose and insulin serum were studied, together with glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione transferase (GST) activity and malondialdehyde (MDA) levels in the liver. In the DM group, we recorded higher levels of food intake, Se absorbed, Se retained, Se content in the kidney, liver and spleen, GSH-Px and GST activity, in comparison with the control rats. In the DMV group, there was a significant decrease in food intake, Se absorbed, Se retained and Se content in the liver and spleen, and in GSH-Px and GST activity, while fasting glycaemia and MDA remained unchanged, in comparison with the DM group. In the DMVH group, there was a significant decrease in food intake, glycaemia, Se absorbed, Se retained, Se content in the kidney, liver and spleen, and in GSH-Px and GST activity, and increased MDA, in comparison with the DM and DMV groups. We conclude that under the experimental conditions described, the treatment with 3 mg V/d caused a tissue depletion of Se that compromised Se nutritional status and antioxidant defences in the tissues.