Nutraceutical potential of olive pomace: insights from cell-based and clinical studies.

Olive oil production yields a substantial volume of by-products, constituting up to 80% of the processed fruits. The olive pomace by-product represents a residue of significant interest due to the diverse bioactive compounds identified in it. However, a thorough characterization and elucidation of the biological activities of olive pomace are imperative to redirect its application for functional food, nutraceutical, and pharmaceutical purposes both for animals and humans. In this review, we examine data from experimental models, including immortalized human vascular endothelial cells, human corneal and conjunctival epithelial cells, human colorectal adenocarcinoma cells, non-tumorigenic human hepatoma cells, and murine macrophages alongside clinical trials. These studies aim to validate the safety, nutritional value, and pharmacological effects of olive pomace. In vitro studies suggest that biophenols extracted from olive pomace possess antioxidant, anti-inflammatory, and antiproliferative properties that could be beneficial in mitigating cardiovascular disorders, particularly atherosclerosis, hepatosteatosis, and dry-eye disease. Protective effects against dry-eye disease were confirmed in a mouse model assay. Olive pomace used in the feed for fish and poultry has demonstrated the ability to enhance animals' immunity and improve nutritional quality of meat and eggs. Human clinical trials are scarce and have revealed minimal biological changes following the consumption of olive pomace-enriched foods. However, alterations in certain biomarkers tentatively suggest cardioprotective properties. The review underscores the value of olive pomace while addressing potential drawbacks and future perspectives, with a specific focus on the need for further investigation into the animal feed and human nutritional properties of olive pomace. © 2024 Society of Chemical Industry.

Cellular and molecular mechanisms of aflatoxin B1-mediated neurotoxicity: The therapeutic role of natural bioactive compounds.

Aflatoxin B1 (AFB1), a dietary toxin from the mold Aspergillus species, is well acknowledged to elicit extra-hepatic toxicity in both animals and humans. The neurotoxicity of AFB1 has become a global public health concern. Contemporary research on how AFB1 enters the brain to elicit neuronal dysregulation leading to noxious neurological outcomes has increased greatly in recent years. The current review discusses several neurotoxic outcomes and susceptible targets of AFB1 toxicity at cellular, molecular and genetic levels. Specifically, neurotoxicity studies involving the use of brain homogenates, neuroblastoma cell line IMR-32, human brain microvascular endothelial cells, microglial cells, and astrocytes, as well as mammalian and non-mammalian models to unravel the mechanisms associated with AFB1 exposure are highlighted. Further, some naturally occurring bioactive compounds with compelling therapeutic effects on AFB1-induced neurotoxicity are reviewed. In conclusion, available data from literature highlight AFB1 as a neurotoxin and its possible pathological contribution to neurological disorders. Further mechanistic studies aimed at discovering and developing effective therapeutics for AFB1 neurotoxicity is warranted.

Vitamin E reduces the reactive oxygen species production in dominant follicle during the negative energy balance in cattle.

In the postpartum period, there is an increase in non-esterified fatty acids (NEFA) in both serum and follicular fluid (FF) of cattle. The increase in fatty acid concentration results in increased production of reactive oxygen species (ROS) that can compromise bovine fertility. The objectives of this study were to characterize the lipid profile found in the FF of cows experiencing induced negative energy balance (NEB) and to evaluate the effect of α-tocopherol in the prevention of oxidative stress in the serum and FF of cows. Twenty-nine beef cows were divided into groups: (1) control; (2) Fasting for 24 days; and (3) Fasting + VitE. Between D0 and D4 blood samples were taken to assess concentrations of NEFA, ROS production, total antioxidant capacity (FRAP), lipid peroxidation, and α-tocopherol (vitamin E). On D4, follicular aspiration was performed for analysis of FF from the dominant follicle. Our results demonstrate that fasting was effective in causing increased fat mobilization in animals. The increase in serum concentration of C18:1c9 was reflected in the FF of fasting cows. Serum α-tocopherol concentration was higher in the control and Fasting + VitE groups compared to the Fasting group. In FF, there was an increase of α-tocopherol in the Fasting + VitE group in comparison to Fasting cows. There was an increase in ROS production in the serum of fasting cows. ROS production in FF was higher in the Fasting compared to the Fasting + VitE group. Vitamin E has beneficial effects in reducing ROS production in the dominant follicle of cows in NEB.

Grain Germination Changes the Profile of Phenolic Compounds and Benzoxazinoids in Wheat: A Study on Hard and Soft Cultivars.

Pre-harvest sprouting is a frequent problem for wheat culture that can be simulated by laboratory-based germination. Despite reducing baking properties, wheat sprouting has been shown to increase the bioavailability of some nutrients. It was investigated whether wheat cultivars bearing distinct grain texture characteristics (BRS Guaraim, soft vs. BRS Marcante, hard texture) would have different behavior in terms of the changes in phytochemical compounds during germination. Using LC-Q-TOF-MS, higher contents of benzoxazinoids and flavonoids were found in the hard cultivar than in the soft one. Free phytochemicals, mainly benzoxazinoids, increased during germination in both cultivars. Before germination, soft and hard cultivars had a similar profile of matrix-bound phytochemicals, but during germination, these compounds have been shown to decrease only in the hard-texture cultivar, due to decreased levels of phenolic acids (trans-ferulic acid) and flavonoids (apigenin) that were bound to the cell wall through ester-type bonds. These findings confirm the hypothesis that hard and soft wheat cultivars have distinct behavior during germination concerning the changes in phytochemical compounds, namely the matrix-bound compounds. In addition, germination has been shown to remarkably increase the content of benzoxazinoids and the antioxidant capacity, which could bring a health-beneficial appeal for pre-harvested sprouted grains.

Gut Microbiota Modulation by Bioactive Compounds from Ilex paraguariensis: an In Vivo Study.

Yerba-mate (Ilex paraguariensis) is recognized for its biocompounds and bioactive properties. This study aimed to assess the potential of yerba-mate extract to modulate the intestinal microbiota in rats. After the ethical committee approval (CEUA - UPF, number 025/2018), the Wistar rats were given a daily dose of 3.29 mg of phenolic compounds per animal for 45 days. The antioxidant activity of the extract was assessed by ABTS and FRAP assays and the total phenolic compounds was measured at different pH levels. Identification and quantification of chlorogenic acid isomers were carried out using high-performance liquid chromatography (HPLC). Intestinal microbiota modulation was evaluated by administering the yerba-mate extract or water (control) to Wistar rats via intragastric gavage and its efficiency was measured through PCR. The antioxidant capacity of the yerba-mate extract was 64.53 ± 0.26 µmol Trolox/mL (ABTS) and 52.96 ± 0.86 µmol Trolox/mL (FRAP). The total phenolic compounds showed higher levels at pH 7.5 compared to pH 2.0. Chlorogenic acid isomers were found in greater abundance, with a concentration of 14.22 g/100 g. The administration of the extract resulted in positive modulation of the intestinal microbiota, specifically for the genera Lactobacillus sp. and Prevotella sp. The increase of these genera is related to the promotion of homeostasis of the gut microbiota. Therefore, these findings indicate that yerba-mate extract possesses significant antioxidant activity and can effectively modulate the intestinal microbiota in rats. These results support the potential use of yerba-mate as an alternative for controlling and preventing diseases associated with intestinal dysbiosis.

Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats.

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.

Moringa oleifera modulates cholinergic and purinergic enzymes activity in BV-2 microglial cells.

Microglia are immune cells that are resident in central nervous system. Activation of microglial cells are detrimental to the survival of neurons. Thus, prevention of microglia activation and/or protection against microglia activation could be potential therapeutic strategy towards the management of inflammation-mediated neurodegenerative diseases. Moringa oleifera is widely consumed as food and used in folklore medicine for treating several diseases. This study was convened to investigate the effect of aqueous extract of Moringa oleifera on cell viability, cholinergic and purinergic enzymes in BV-2 microglial cultured cell. Aqueous extract of Moringa oleifera was prepared, lyophilized and reconstituted in 0.5% dimethylsulphoxide (DMSO). Cells were treated with Moringa oleifera extracts (0.1-100 µg/mL) and assessed for cell viability and nitric oxide production. Furthermore, the effect of Moringa oleifera on enzymes of cholinergic (acetylcholinesterase) and purinergic (nucleoside triphosphate diphosphohydrolase; NTPDase, 5' nucleotidase and adenosine deaminase; ADA) systems in BV-2 microglial cells were determined. Incubation of BV-2 microglia cell with M. oleifera extract maintained cell viability, modulated cholinergic and purinergic enzymes activity. The phenolic compounds found in M. oleifera extracts, include chlorogenic acid, rutin; quercetin pentoside, kaempferol derivative and quercetin derivative. Thus, this study suggest that the potential therapeutic effect of the phenolic compounds found in M. oleifera may have been responsible for the maintenance of cell viability in BV-2 microglia cells and modulation of cholinergic as well as purinergic enzymes activity.

Estimation of total arsenic contamination and exposure in Brazilian rice and infant cereals.

Arsenic (As) causes health effects, especially cancer. Rice (Oryza sativa L.) can contain high As concentrations. Using ICP-MS, we quantified the total As (tAs) levels in the main brands of rice (n = 103) and infant cereals (n = 27) consumed by Brazilians. The levels were compared to the maximum limits prescribed by regulatory agencies. We estimated the daily intake (EDI) of As by Brazilians by combining the mean As concentration determined in the white rice samples with per capita daily consumption divided by the average body weight as reported by the Brazilian Institute of Geography and Statistics in 2010. The possible health risk for consumers was assessed by calculating the margin of exposure (MOE) as prescribed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Moreover, tAs was determined in 11 pesticides used by Brazilian farmers. The tAs levels in the rice ranged from 0.003 to 1.3 mg kg-1. Approximately 27% of the white rice contained tAs levels above the limit set by Mercosul (0.3 mg kg-1) and 45% were above the limit set by the European Commission (0.2 mg kg-1). In the infant cereals, tAs levels ranged from 0.003 to 0.243 mg kg-1. In the pesticides, tAs levels ranged from 0.005 to 0.315 mg L-1. The EDI showed that, on average, Brazilians consume 4.13 µg As kg-1 BW weekly. In addition, a low MOE was observed, demonstrating that high use of rice presents a risk of high inorganic (iAs) exposure, which represents a public health concern.

Antiproliferative Effect of Colonic Fermented Phenolic Compounds from Jaboticaba (Myrciaria trunciflora) Fruit Peel in a 3D Cell Model of Colorectal Cancer.

Jaboticaba is a Brazilian native berry described as a rich source of phenolic compounds (PC) with health promoting effects. PC from jaboticaba peel powder (JPP) have low intestinal bio-accessibility and are catabolized by gut microbiota. However, the biological implication of PC-derived metabolites produced during JPP digestion remains unclear. This study aimed to evaluate the antiproliferative effects of colonic fermented JPP (FJPP) in a 3D model of colorectal cancer (CRC) composed by HT29 spheroids. JPP samples fermented with human feces during 0, 2, 8, 24 or 48 h were incubated (10,000 µg mL-1) with spheroids, and cell viability was assessed after 72 h. Chemometric analyses (cluster and principal component analyses) were used to identify the main compounds responsible for the bioactive effect. The antiproliferative effect of FJPP in the CRC 3D model was increased between 8 h and 24 h of incubation, and this effect was associated with HHDP-digalloylglucose isomer and dihydroxyphenyl-γ-valerolactone. At 48 h of fermentation, the antiproliferative effect of FJPP was negligible, indicating that the presence of urolithins did not improve the bioactivity of JPP. These findings provide relevant knowledge on the role of colonic microbiota fermentation to generate active phenolic metabolites from JPP with positive impact on CRC.

Oleic acid-containing semisolid dosage forms exhibit in vivo anti-inflammatory effect via glucocorticoid receptor in a UVB radiation-induced skin inflammation model.

The treatment of cutaneous inflammation with topical corticosteroids may cause adverse effects reinforcing the need for therapeutic alternatives to treat inflammatory skin disorders. We investigated the anti-inflammatory effect of oleic acid (OA), a fatty acid of the omega-9 (ω-9) family, and we point out it as an alternative to treat inflammatory skin disorders. OA was incorporated into Lanette®- or Pemulen® TR2-based semisolid preparations and the pH, spreadability, rheological behavior and in vivo anti-inflammatory performance in a UVB radiation-induced skin inflammation model in mice were assessed. The anti-inflammatory activity was verified after single or repeated treatment of the mouse ear following the UVB. The OA action on glucocorticoid receptors was investigated. Both semisolids presented pH values compatible with the deeper skin layers, appropriate spreadability factors, and non-Newtonian pseudoplastic rheological behavior. Pemulen® 3% OA inhibited ear edema with superior efficacy than Lanette® 3% OA and dexamethasone after a single treatment. Pemulen® 3% OA and dexamethasone also reduced inflammatory cell infiltration. After repeated treatments, all formulations decreased the ear edema at 24 h, 48 h and 72 h after UVB. OA in semisolids, especially Pemulen® TR2-based ones, presented suitable characteristics for cutaneous administration and its anti-inflammatory activity seems to occur via glucocorticoid receptors. OA was also capable to reduce croton oil-induced skin inflammation. Besides, the ex vivo skin permeation study indicated that OA reaches the receptor medium, which correlates with a systemic absorption in vivo. The natural compound OA could represent a promising alternative to those available to treat inflammatory skin disorders.

Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on Oral Dyskinesia in Rats.

Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg-1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.

Effects of dietary microencapsulated Cymbopogon flexuosus essential oil on reproductive-related parameters in male Rhamdia quelen.

In aquaculture, nutrition and supplemented diets have been shown to affect broodstock reproductive performance. In this study, we investigated the effects of dietary supplementation with Cymbopogon flexuosus essential oil (CFEO) microcapsules on reproductive-related parameters in silver catfish (Rhamdia quelen) male broodfish. Adult male broodstocks were separated into three groups according to the concentrations of supplemented CFEO (0.0 = control; 1.0 or 3.0 mL per kg of diet). After 20 days under experimental conditions, the animals were euthanized and the gonads were harvested for gonadosomatic index, sperm analysis, oxidative stress, and histopathology; testosterone levels were measured in the plasma; gene expression of prl, smtl, pomca, and pomcb was assessed in the pituitary gland by real-time PCR. The results showed no alterations on reproductive parameters in R. quelen males treated with Cymbopogon flexuosus essential oil compared to the control-diet animals. In conclusion, CFEO microcapsules supplied for 20 days in the concentrations of 1.00 or 3.00 mL per kilogram of diet did not affect the reproduction criteria evaluated in this study in male silver catfish.

Chemical, microbiological, and sensory parameters during the refrigerated storage of silver catfish (Rhamdia quelen) exposed in vivo to the essential oil of Lippia alba.

This study evaluated whether the essential oil of Lippia alba (EO) used as a sedative for fish transport would increase the stability of silver catfish during ice storage. Fish were transported (6 h) with water alone (control), 30 or 40 µL/L of EO in water. After transport, fish were slaughtered and stored in ice. Data on mesophilic and psychrotrophic bacteria counts during storage did not support the evidence for the antimicrobial activity of EO. However, fish treated with EO (30 and 40 µL/L) had delayed onset of rigor mortis, delayed increase of pH after 34 days of storage, and delayed peak of hypoxanthine formation and its degradation. In addition, the demerit sensory score of EO-treated fish (30 and 40 µL/L) was lower than that of controls along the storage. Thus, the use of EO as a sedative in the water used to transport silver catfish can delay the loss of freshness and the deterioration of whole fish stored in ice.

Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death.

Activated hepatic stellate cells (HSC) are the major source of collagen I in liver fibrosis. Eugenia uniflora L. is a tree species that is widely distributed in South America. E. uniflora L. fruit-popularly known as pitanga-has been shown to exert beneficial properties. Autophagy contributes to the maintenance of cellular homeostasis and survival under stress situation, but it has also been suggested to be an alternative cell death pathway. Mitochondria play a pivotal role on signaling cell death. Mitophagy of damaged mitochondria is an important cell defense mechanism against organelle-mediated cell death signaling. We previously found that purple pitanga extract induced mitochondrial dysfunction, cell cycle arrest, and death by apoptosis and necrosis in GRX cells, a well-established activated HSC line. We evaluated the effects of 72-h treatment with crescent concentrations of purple pitanga extract (5 to 100 µg/mL) on triggering autophagy in GRX cells, as this is an important mechanism to cells under cytotoxic conditions. We found that all treated cells presented an increase in the mRNA expression of autophagy-related protein 7 (ATG7). Concomitantly, flow cytometry and ultrastructural analysis of treated cells revealed an increase of autophagosomes/autolysosomes that consequentially led to an increased mitophagy. As purple pitanga extract was previously found to be broadly cytotoxic to GRX cells, we postulated that autophagy contributes to this scenario, where cell death seems to be an inevitable fate. Altogether, the effectiveness on inducing activated HSC death can make purple pitanga extract a good candidate on treating liver fibrosis.

Eggshell fractions containing different particle sized affect mineral absorption but not bone mineral retention in growing rats.

The purpose of this study was to compare the calcium (Ca) bioavailability from eggshell fractions containing different particle size to purified CaCO3 in male growing rats. Mineral absorption, bone mineral concentration, and biomechanical properties were evaluated. Mean Ca absorption of rats fed with eggshell diets amounted to 56.2% of the ingested Ca, which is considered high. However, we observed lower Ca absorption in large-sized particle eggshell fraction (ES L) and small-sized particle eggshell fraction groups but similar Ca absorption in intermediate-sized particle eggshell fraction (ES M) compared with the CaCO3 group. Rats that received ES M and ES L had higher P and Mg absorption than the CaCO3 group. No changes were observed in the bone mineral deposition, weight or mechanical resistance. We conclude that eggshell Ca is well absorbed by the intestine and retained in bones of growing rats, being a low cost alternative to achieve adequate Ca ingestion.

Influence of Harvest Season and Cultivar on the Variation of Phenolic Compounds Composition and Antioxidant Properties in Vaccinium ashei Leaves.

The effect of variation of harvest season and cultivar on the total phenolic content (TPC), total flavonoid content (TFC), HPLC-UV/DAD profile and antioxidant properties in Vaccinium ashei (Rabbiteye blueberry) leaves grown in Brazil was evaluated. The cultivars collected in December and March were Aliceblue, Powderblue, Climax, Bluegem and FloridaM. It was observed that leaves from March had the highest TPC values (222 ± 1 mg gallic acid equivalents/g to Aliceblue cultivar) and highest TFC values (49.8 ± 0.8 and 48.7 ± 0.7 µg rutin/g to Clímax and Powderblue cultivars, respectively). The chromatographic profile was quantitatively similar, however, the proportions of each compound were influenced by cultivar and harvest season. Chlorogenic acid and rutin were the main identified phenolic compounds, but chlorogenic acid was the most abundant in both harvest seasons. Antioxidant capacities values ranged from 5.80 ± 0.04 to 105 ± 2 µg/mL (DPPH) and 178 ± 5 to 431 ± 8 mmol Trolox/100 g (ORAC). The cultivar Bluegem by March had the highest values in both assays. The results indicate that the blueberry leaves from different cultivars and harvest seasons have different phenolic compounds content and different antioxidant capacities. In addition, the antioxidant properties demonstrated a high correlation with rutin content.

Cross-generational trans fat intake modifies BDNF mRNA in the hippocampus: Impact on memory loss in a mania animal model.

Recently, we have described the influence of dietary fatty acids (FA) on mania-like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)-induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short- (1 h) and long- (24 h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF- mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA ratio. Interestingly, our data showed a positive correlation between brain-derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2) = 0.53; P = 0.000/r(2) = 0.32; P = 0.011, respectively), as well as a negative correlation between PC and DAT levels (r(2) = 0.23; P = 0.015). Our findings confirm that provision of n-3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania-like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions.

The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects.

Hypercholesterolemia and oxidative stress have been implicated in the pathophysiology of atherosclerosis and coronary artery disease. We investigated whether the carotenoid bixin (BIX) may reduce oxidative damage, inflammatory response, and the atherosclerotic lesion induced by hypercholesterolemia in rabbits. Rabbits received regular chow (control) or a hypercholesterolemic diet (0.5% cholesterol) alone or supplemented with BIX (10, 30 or 100 mg/kg body weight, b.w.) or simvastatin (15 mg/kg b.w.) for 60 days. Treatment with BIX or simvastatin reduced the atherosclerotic lesions in cholesterol-fed rabbits (up to 55 and 96% reduction, respectively). This protective effect of BIX was accompanied by decrease in the levels of tumor necrosis factor alpha by 15%, interleukin 6 by 19%, lipid peroxidation by 60%, non-high-density lipoprotein cholesterol (non-HDL-C) by 37%, and triglycerides by 41%. BIX increased by 160% the HDL-C levels and decreased by 67% the atherogenic index of hypercholesterolemic rabbits. In atherosclerotic rabbits, the non-protein thiol groups content and the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase were increased in the aortic tissue, whereas paraoxonase activity was reduced in the serum. All these changes were completely prevented by BIX or simvastatin treatment. These results demonstrate that BIX reduces the extent of atherosclerotic lesions and this effect was associated with the decrease in oxidative stress, inflammatory response, and improvement of dyslipidemia, which were most effectively controlled after treatment with 10-30 mg BIX/kg b.w. BIX consumption may, therefore, be an adjuvant to prevent atherosclerosis reducing risk factors for coronary diseases.

Hypolipidemic effects of Solidago chilensis hydroalcoholic extract and its major isolated constituent quercetrin in cholesterol-fed rats.

CONTEXT: Despite several studies on the effects of Solidago chilensis Meyen (Asteraceae), the phytochemical and hypolipidemic properties remain underappreciated. OBJECTIVE: This study evaluates the hypolipidemic and antioxidant effects of hydroalcoholic extract (HE) and quercetrin from S. chilensis aerial parts in cholesterol-fed rats. MATERIALS AND METHODS: The HE was analyzed by high-performance liquid chromatography, followed by quercetrin isolation. Hypercholesterolemic rats (1% cholesterol and 0.5% cholic acid for 15 d) were treated with HE (150, 300, and 600 mg/kg p.o.; n = 6), simvastatin (4 mg/kg p.o.; n = 6), or quercetrin (10 mg/kg p.o.; n = 6) once a day for 30 d. During this period, a high-cholesterol diet was maintained until the 30th day of treatment. RESULTS: Rats treated with HE (150, 300, and 600 mg/kg) and quercetrin showed decreased serum levels of total cholesterol (-19.9, -27.5, -31.0, and -39.4%), lipoprotein-cholesterol (-36.0, -37.5, -43.3, and -59.4%), and triacylglycerides (-15.6, -23.5, -29.8, and -27.2%) when compared with the control group similar to simvastatin. Moreover, treatment with HE and quercetrin decreased hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity (35.1% on average) and increased fecal cholesterol levels (38.2% on average). DISCUSSION AND CONCLUSIONS: Our results suggest that hypolipidemic effects of HE are associated with it modulating the activity of HMG-CoA reductase and its interference in the reabsorption and/or excretion of intestinal lipids. Solidago chilensis and its main constituent, quercetrin, may thus be effective as cholesterol-lowering agents and in preventing atherosclerosis.

Dietary omega-3 deficiency reduces BDNF content and activation NMDA receptor and Fyn in dorsal hippocampus: implications on persistence of long-term memory in rats.

Omega-3 (n-3) fatty acids are important for adequate brain function and cognition. The aim of the present study was to evaluate how n-3 fatty acids influence the persistence of long-term memory (LTM) in an aversive memory task and to explore the putative mechanism involved. Female rats received isocaloric diets that included n-3 (n-3 group) or not (D group). The adult litters were subjected to an inhibitory avoidance task (0.7 mA, 1.0 seconds foot shock) to elicit persistent LTM. Twelve hours after the training session, the fatty acid profile and the brain derived neurotrophic factor (BDNF) content of the dorsal hippocampus were assessed. In addition, we measured the activation of the NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor and the SRC family protein Fyn. Despite pronounced learning in both groups, the persistence of LTM was abolished in the D group 7 days after the training session. We also observed that the D group presented reductions in hippocampal DHA (22:6 n-3) and BDNF content. Twelve hours after the training session, the D group showed decreased NR2B and Fyn phosphorylation in the dorsal hippocampus, with no change in the total content of these proteins. Further, there was a decrease in the interaction of Fyn with NR2B in the D group, as observed by co-immunoprecipitation. Taken together, these data suggest that n-3 fatty acids influence the persistence of LTM by maintaining adequate levels of DHA and BDNF as well as by influencing the activation of NR2B and Fyn during the period of memory formation.