Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide.

OBJECTIVE: Major depressive disorder is a debilitating and recurrent psychiatric disorder. Blueberries have several biological properties, including neuroprotective effects, through antioxidant and anti-inflammatory actions. The aim of this study was to evaluate the effect of blueberry extract on depressive-like behavior and lipopolysaccharide (LPS)-induced neurochemical changes. METHODS: Mice were pretreated with vehicle, fluoxetine (20 mg/kg) or blueberry extract (100 or 200 mg/kg) intragastrically for seven days before intraperitoneal LPS (0.83 mg/kg) injection. Twenty-four hours after LPS administration, mice were submitted to behavioral tests. Oxidative stress and neuroinflammatory parameters were evaluated in the cerebral cortex, hippocampus, and striatum. RESULTS: Our data showed that blueberry extract or fluoxetine treatment protected against LPS-induced depressive-like behavior in tail suspension and splash tests (P < 0.05), without changes in locomotor activity (P > 0.05). LPS induced an increase in the levels of reactive oxygen species (P < 0.001), nitrite (P < 0.05) and thiobarbituric acid reactive substances (P < 0.01), as well as a reduction in total sulfhydryl content (P < 0.05) and catalase activity (P < 0.05) in brain structures; blueberry extract restored these alterations (P < 0.05). In addition, blueberry extract attenuated the increase in tumor necrosis factor-alpha (TNF-α) levels induced by LPS administration (P < 0.05). CONCLUSION: This study showed that blueberry extract exerted antidepressant-like effects, protected the brain against oxidative damage, and modulated TNF-α levels induced by LPS.

Hypolipidemic and anti-inflammatory properties of phenolic rich Butia odorata fruit extract: potential involvement of paraoxonase activity.

Aim: This study investigated the effects of polar Butia odorata fruit extract on metabolic, inflammatory, and oxidative stress parameters in rats submitted to a hyperlipidaemia condition induced by tyloxapol.Methods: Animals were divided into 3 groups: saline, saline plus tyloxapol, and B. odorata extract plus tyloxapol. Animals were treated for 15 days with a saline solution or B. odorata fruit extract and after hyperlipidaemia was induced by tyloxapol.Results: Treatment with B. odorata extract reduced serum triglyceride, total cholesterol, C-reactive protein, and adenosine deaminase and butyrylcholinesterase activities when compared to the tyloxapol group. HDL-cholesterol and paraoxonase 1 activity were higher in B. odorata extract treated animals when compared to tyloxapol-treated animals. No differences were observed in hepatic oxidative stress parameters. Phenolic compounds present in B. odorata fruit extract were identified and quantified by LC-MS/MS.Conclusion: These findings indicated that phenolic rich B. odorata extract has hypolipidemic and anti-inflammatory effects in hyperlipidemic rats.

High levels of methionine and methionine sulfoxide: Impact on adenine nucleotide hydrolysis and redox status in platelets and serum of young rats.

We investigated acute and chronic effects administration of methionine (Met) and/or methionine sulfoxide (MetO) on ectonucleotidases and oxidative stress in platelets and serum of young rats. Wistar rats were divided into four groups: control, Met, MetO, and Met + MetO. In acute treatment, the animals received a single subcutaneous injection of amino acid(s) and were euthanized after 1 and 3 hours. In chronic protocol, Met and/or MetO were administered twice a day with an 8-hour interval from the 6th to the 28th day of life. Nucleoside triphosphate phosphohydrolase and 5'-nucleotidase activities were reduced in platelets and serum by Met, MetO, and Met + MetO after 3 hours and 21 days. Adenosine deaminase activity reduced in platelets at 3 hours after MetO and Met + MetO administration and increased after 21 days in animals treated with Met + MetO. Superoxide dismutase and catalase activities decreased in platelets in MetO and Met + MetO groups after 3 hours, while reactive oxygen species (ROS) levels increased in same groups. Catalase activity in platelets decreased in all experimental groups after chronic treatment. Met, MetO, and Met + MetO administration increased plasmatic ROS levels in acute and chronic protocols; glutathione S-transferase activity increased by MetO and Met + MetO administration at 3 hours, and ascorbic acid decreased in all experimental groups in acute and chronic protocols. Thiobarbituric acid reactive substances increased, superoxide dismutase and catalase activities reduced in the Met and/or MetO groups at 3 hours and in chronic treatment. Our data demonstrated that Met and/or MetO induced changes in adenine nucleotide hydrolysis and redox status of platelets and serum, which can be associated with platelet dysfunction in hypermethioninemia.

Combined actions of blueberry extract and lithium on neurochemical changes observed in an experimental model of mania: exploiting possible synergistic effects.

Bipolar disorder is a psychiatric disease characterized by recurrent episodes of mania and depression. Blueberries contain bioactive compounds with important pharmacological effects such as neuroprotective and antioxidant actions. The aim of this study was to investigate the effects of blueberry extract and/or lithium on oxidative stress, and acetylcholinesterase (AChE) and Na+, K+-ATPase activity in an experimental ketamine-induced model of mania. Male Wistar rats were pretreated with vehicle, blueberry extract (200 mg/kg), and/or lithium (45 mg/kg or 22.5 mg/kg twice daily) for 14 days. Between the 8th and 14th days, the animals also received an injection of ketamine (25 mg/kg) or vehicle. On the 15th day the animals received a single injection of ketamine; after 30 min, the locomotor activity was evaluated in an open field test. Ketamine administration induced an increase in locomotor activity. In the cerebral cortex, hippocampus and striatum, ketamine also induced an increase in reactive oxygen species, lipid peroxidation and nitrite levels, as well a decrease in antioxidant enzyme activity. Pretreatment with blueberry extract or lithium was able to prevent this change. Ketamine increased the AChE and Na+, K+-ATPase activity in brain structures, while the blueberry extract partially prevented these alterations. In addition, our results showed that the neuroprotective effect was not potentiated when lithium and blueberry extract treatment were given together. In conclusion, our findings suggest that blueberry extract has a neuroprotective effect against an experimental model of mania. However, more studies should be performed to evaluate its effects as an adjuvant therapy.

Glioprotective Effects of Lingonberry Extract Against Altered Cellular Viability, Acetylcholinesterase Activity, and Oxidative Stress in Lipopolysaccharide-Treated Astrocytes.

Altered astrocytic function is a contributing factor to the development of neurological diseases and neurodegeneration. Berry fruits exert neuroprotective effects by modulating pathways involved in inflammation, neurotransmission, and oxidative stress. The aim of this study was to examine the effects of the lingonberry extract on cellular viability and oxidative stress in astrocytes exposed to lipopolysaccharide (LPS). In the reversal protocol, primary astrocytic cultures were first exposed to 1 µg/mL LPS for 3 h and subsequently treated with lingonberry extract (10, 30, 50, and 100 µg/mL) for 24 and 48 h. In the prevention protocol, exposure to the lingonberry extract was performed before treatment with LPS. In both reversal and prevention protocols, the lingonberry extracts, from 10 to 100 µg/mL, attenuated LPS-induced increase in reactive oxygen species (around 55 and 45%, respectively, P < 0.01), nitrite levels (around 50 and 45%, respectively, P < 0.05), and acetylcholinesterase activity (around 45 and 60%, respectively, P < 0.05) in astrocytic cultures at 24 and 48 h. Also, in both reversal and prevention protocols, the lingonberry extract also prevented and reversed the LPS-induced decreased cellular viability (around 45 and 90%, respectively, P < 0.05), thiol content (around 55 and 70%, respectively, P < 0.05), and superoxide dismutase activity (around 50 and 145%, respectively, P < 0.05), in astrocytes at both 24 and 48 h. Our findings suggested that the lingonberry extract exerted a glioprotective effect through an anti-oxidative mechanism against LPS-induced astrocytic damage.

Southern Brazilian native fruit shows neurochemical, metabolic and behavioral benefits in an animal model of metabolic syndrome.

In this work, we evaluated the effects of Psidium cattleianum (Red Type) (PcRT) fruit extract on metabolic, behavioral, and neurochemical parameters in rats fed with a highly palatable diet (HPD) consisted of sucrose (65% carbohydrates being 34% from condensed milk, 8% from sucrose and 23% from starch, 25% protein and 10% fat). Animals were divided into 4 groups: standard chow, standard chow + PcRT extract (200 mg/Kg/day by gavage), HPD, HPD + extract. The animals were treated for 150 days. Concerning chemical profiling, LC/PDA/MS/MS analysis revealed cyanidin-3-O-glucoside as the only anthocyanin in the PcRT extract. Our results showed that the animals exposed to HPD presented glucose intolerance, increased weight gain and visceral fat, as well as higher serum levels of glucose, triacylglycerol, total cholesterol, LDL-cholesterol and interleukin-6. These alterations were prevented by PcRT. In addition, HPD caused an increase in immobility time in a forced swimming test and the fruit extract prevented this alteration, indicating an antidepressant-like effect. PcRT treatment also prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD consumption. Moreover, PcRT extract was able to restore Ca2+-ATPase activity in the prefrontal cortex, hippocampus, and striatum, as well as Na+,K+-ATPase activity in the prefrontal cortex and hippocampus. PcRT treatment decreased thiobarbituric acid-reactive substances, nitrite, and reactive oxygen species levels and prevented the reduction of superoxide dismutase activity in all cerebral structures of the HPD group. Additionally, HPD decreased catalase in the hippocampus and striatum. However, the extract prevented this change in the hippocampus. Our results showed that this berry extract has antihyperglycemic and antihyperlipidemic effects, and neuroprotective properties, proving to be a potential therapeutic agent for individuals with metabolic syndrome.

Chronic administration of methionine and/or methionine sulfoxide alters oxidative stress parameters and ALA-D activity in liver and kidney of young rats.

High levels of methionine (Met) and methionine sulfoxide (MetO) are found in several genetic abnormalities. Oxidative stress is involved in the pathophysiology of many inborn errors of metabolism. However, little is known about the role of oxidative damage in hepatic and renal changes in hypermethioninemia. We investigated the effect of chronic treatment with Met and/or MetO on oxidative stress parameters in liver and kidney, as lipid peroxidation (TBARS), total sulfhydryl content (SH), reactive oxygen species (ROS) and enzymes activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and delta aminolevulinic dehydratase (ALA-D). Serum biochemical parameters were evaluated. Wistar rats were treated daily with two subcutaneous injections of saline (control), Met (0.2-0.4 g/kg), MetO (0.05-0.1 g/kg) and the association between these (Met plus MetO) from the 6th to the 28th day of life. Our data demonstrated an increase of glucose and urea levels in all experimental groups. Cholesterol (MetO and Met plus MetO) were decreased and triglycerides (MetO) were increased. SOD (MetO and Met plus MetO) and CAT (Met, MetO and Met plus MetO) activities were decreased, while GPx was enhanced by MetO and Met plus MetO treatment in liver. In kidney, we observed a reduction of SH levels, SOD and CAT activities and an increase of TBARS levels in all experimental groups. ROS levels in kidney were increased in MetO and Met plus MetO groups. ALA-D activity was enhanced in liver (MetO and Met plus MetO) and kidney (Met plus MetO). These findings help to understand the pathophysiology of hepatic and renal alterations present in hypermethioninemia.

Acute administration of methionine and/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex.

High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia can present neurological dysfunction; however, the neurotoxicity mechanisms induced by these amino acids remain unknown. The aim of the present work was to study the effects of Met and/or MetO on oxidative stress, genotoxicity, cytotoxicity and to evaluate whether the cell death mechanism is mediated by apoptosis in the cerebral cortex of young rats. Forty-eight Wistar rats were divided into groups: saline, Met 0.4 g/Kg, MetO 0.1 g/Kg and Met 0.4 g/Kg + MetO 0.1 g/Kg, and were euthanized 1 and 3 h after subcutaneous injection. Results showed that TBARS levels were enhanced by MetO and Met+MetO 1 h and 3 h after treatment. ROS was increased at 3 h by Met, MetO and Met+MetO. SOD activity was increased in the Met group, while CAT was reduced in all experimental groups 1 h and 3 h after treatment. GPx activity was enhanced 1 h after treatment by Met, MetO and Met+MetO, however it was reduced in the same experimental groups 3 h after administration of amino acids. Caspase-3, caspase-9 and DNA damage was increased and cell viability was reduced by Met, MetO and Met+MetO at 3 h. Also, Met, MetO and Met+MetO, after 3 h, enhanced early and late apoptosis cells. Mitochondrial electrochemical potential was decreased by MetO and Met+MetO 1 h and 3 h after treatment. These findings help understand the mechanisms involved in neurotoxicity induced by hypermethioninemia.

Preventive Effect of Cecropia pachystachya Against Ketamine-Induced Manic Behavior and Oxidative Stress in Rats.

Cecropia species are widely used in traditional medicine by its anti-diabetic, anti-hypertensive and anti-inflammatory properties. In the present study, we investigated the neuroprotective and antioxidant effects of the crude aqueous extract from Cecropia pachystachya leaves in a rat model of mania induced by ketamine. The results indicated that ketamine treatment (25 mg/kg i.p., for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex and hippocampus, evaluated by increased lipid peroxidation, carbonyl protein formation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in hippocampus. Pretreatment of rats with C. pachystachya aqueous extract (200 and 400 mg/kg p.o., for 14 days) or with lithium chloride (45 mg/kg p.o., for 14 days, used as a positive control) prevented both behavioral and pro-oxidant effects of ketamine. These findings suggest that C. pachystachya might be a useful tool for preventive intervention in bipolar disorder, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder .

Effect of Probiotic Supplementation on Gut Microbiota and Sport Performance in Athletes and Physically Active Individuals: A Systematic Review.

The present systematic review aimed to evaluate the effect of probiotic supplementation on gut microbiota and sport performance in athletes and physically active individuals. This review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (P RISMA). The search had no time limits and included the following databases: MEDLINE, LILACS, Scopus, Web of Science, Cochrane, and SP ORT Discus. The risk of bias was assessed through the updated version of the Cochrane tool for assessing the risk of bias in randomized trials (RoB 2). Nine randomized clinical trials (RCTs) were included, accounting for 216 participants. Of these, seven studies found positive results on sport performance. Additionally, some studies showed significant decrease in biochemical parameters linked to inflammation. It was also observed direct results in the microbiota composition of the participants, such as an increase in the abundance of probiotics and a decrease in certain pathogenic bacteria. Therefore, the use of probiotics showed improvement in inflammatory biomarkers and oxidative stress, which indirectly may contribute to the improvement of sport performance. However, the majority of the studies presented a high risk of bias, which impair the reproducibility of the results. While the field of probiotic supplementation and sport performance is emerging, the promising results from this systematic review suggest that further investigation through larger and more robust randomized clinical trials can provide valuable insights for athletes and their performance.

Brazilian native fruit extracts act as preventive agents modulating the purinergic and cholinergic signalling in blood cells and serum in a rat model of metabolic syndrome.

In this study, we evaluated the effects of native fruit extracts on inflammatory and thromboregulatory parameters in animal model of metabolic syndrome (MetS) induced by highly palatable diet (HPD). Rats were divided into 4 experimental groups: standard chow, HPD, HPD and Psidium cattleianum extract, and HPD and Eugenia uniflora extract. HPD increased serum interleukin-6 (IL-6) levels. On the other hand, this change was prevented by extracts. HPD decreased NTPDase activity in lymphocytes and platelets and 5'-nucleotidase in platelets. Treatment with extracts prevented these changes. An increase in adenosine deaminase (ADA) activity was prevented by E. uniflora in lymphocytes and serum of rats. Fruit extracts prevented the increase in the activity of acetylcholinesterase (AChE) in lymphocytes and butyrylcholinesterase (BuChE) in serum induced by the HPD. Brazilian native fruit extracts have anti-inflammatory and antithrombotic effects, demonstrating therapeutic potential in the prevention of complications associated with MetS.

Antioxidant, antihyperglycemic, and antidyslipidemic effects of Brazilian-native fruit extracts in an animal model of insulin resistance.

OBJECTIVE: Insulin resistance (IR) plays an important role in the development of many diseases, such as diabetes mellitus. Therefore, the aim of the present study was to evaluate the effects of the extracts from fruits native to Brazil on metabolic parameters and hepatic oxidative markers in an animal model of insulin resistance induced by dexamethasone (DEX). METHODS: Wistar rats received water or extracts of Eugenia uniflora or Psidium cattleianum, once a day for 21 days. For the last 5 days, the rats received an intraperitoneal injection of saline or DEX. RESULTS: DEX caused a reduction in body weight gain and relative pancreatic weight, as well as glucose intolerance, and an increase in serum glucose and triacylglycerol levels. The extracts were found to prevent hyperglycemia and hypertriglyceridemia. DEX caused an increase in the levels of thiobarbituric acid-reactive substances and reactive oxygen species production in the liver of rats, and both extracts prevented these changes. In addition, hepatic glutathione peroxidase activity was reduced by DEX. However, total thiol content and activities of catalase, superoxide dismutase, and delta-aminolevulinate dehydratase were not altered in any of the tested groups. CONCLUSION: Fruit extracts of E. uniflora and P. cattleianum exhibited considerable antihyperglycemic, antidyslipidemic, and antioxidant effects, and may be useful in the therapeutic management of alterations due to IR.

Vaccinium virgatum fruit extract as an important adjuvant in biochemical and behavioral alterations observed in animal model of metabolic syndrome.

The aim of this study was to investigate the effect of blueberry (Vaccinium virgatum) fruit extract on metabolic, behavioral and oxidative stress parameters in the hippocampus and cerebral cortex of mice submitted to an experimental model of metabolic syndrome induced by a highly palatable diet (HPD). Mice C57BL/6 were divided into 4 experimental groups: (1) received standard chow and saline orally, (2) received standard chow and blueberry hydroalcoholic extract, (3) received HPD and saline orally, (4) received HPD and blueberry hydroalcoholic extract. The animals were treated for 150days. Our results showed that the animals fed with HPD presented insulin resistance, increased body weight, visceral fat, glucose, triglycerides, and total cholesterol when compared to the control group. The blueberry extract prevented the increase of these metabolic parameters. Also, the extract was able to reduce the levels of thiobarbituric acid reactive substances in the cerebral cortex and hippocampus of animals submitted to HPD. In contrast, no differences were observed in the total thiol content, activity of the antioxidant enzymes catalase and superoxide dismutase. In addition, the HPD fed animals showed a significant increase in immobility time in the forced swimming test and blueberry prevented this alteration, although no changes were observed in the ambulatory behavior, as well as in the anxiolytic profile of these animals. Overall, our findings suggest that chronic consumption of blueberry extract exhibits hypoglycemic, hypolipidemic, antidepressant-like and antiperoxidative effects in an animal model of metabolic syndrome.

Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management.

The aim of this study was to investigate the effect of Eugenia uniflora fruit (red type) extract on metabolic status, as well as on neurochemical and behavioral parameters in an animal model of metabolic syndrome induced by a highly palatable diet (HPD). Rats were treated for 150days and divided into 4 experimental groups: standard chow (SC) and water orally, SC and E. uniflora extract (200mg/kg daily, p.o), HPD and water orally, HPD and extract. Our data showed that HPD caused glucose intolerance, increased visceral fat, weight gain, as well as serum glucose, triacylglycerol, total cholesterol and LDL cholesterol; however, E. uniflora prevented these alterations. The extract decreased lipid peroxidation and prevented the reduction of superoxide dismutase and catalase activities in the prefrontal cortex, hippocampus and striatum of animals submitted to HPD. We observed a HPD-induced reduction of thiol content in these cerebral structures. The extract prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD and the increase in immobility time observed in the forced swim test. Regarding chemical composition, LC/MS analysis showed the presence of nine anthocyanins as the major compounds. In conclusion, E. uniflora extract showed benefits against metabolic alterations caused by HPD, as well as exhibited antioxidant and antidepressant-like effects.

Eugenol derivatives as potential anti-oxidants: is phenolic hydroxyl necessary to obtain an effect?

OBJECTIVES: Eugenol, obtained from clove oil (Eugenia caryophyllata), possess several biological activities. It is anti-inflammatory, analgesic, anaesthesic, antipyretic, antiplatelet, anti-anaphylactic, anticonvulsant, anti-oxidant, antibacterial, antidepressant, antifungal and antiviral. The anti-oxidant activity of eugenol have already been proven. From this perspective testing, a series of planned structural derivatives of eugenol were screened to perform structural optimization and consequent increase of the potency of these biological activities. METHODS: In an attempt to increase structural variability, 16 compounds were synthesized by acylation and alkylation of the phenolic hydroxyl group. Anti-oxidant activity capacity was based on the capture of DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), ABTS radical 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), measure of TBARS (thiobarbituric acid-reactive species), total sulfhydryl and carbonyl content (eugenol derivatives final concentrations range from 50 to 200 µm). KEY FINDINGS: Four derivatives presented an efficient concentration to decrease 50% of the DPPH radical (EC50 ) < 100 µm, which has a good potential as a free-radical scavenger. Three of these compounds also showed reduction of ABTS radical. Eugenol derivatives presenting alkyl or aryl (alkylic or arylic) groups substituting hydroxyl 1 of eugenol were effective in reducing lipid peroxidation, protein oxidative damage by carbonyl formation and increase total thiol content in cerebral cortex homogenates. In liver, the eugenol derivatives evaluated had no effect. CONCLUSIONS: Our results suggest that these molecules are promising anti-oxidants agents.