The Protective Action of Rubus sp. Fruit Extract Against Oxidative Damage in Mice Exposed to Lipopolysaccharide.

Neuroinflammation is an event that occurs in several pathologies of brain. Rubus sp. (blackberry) is a powerful antioxidant fruit, and its extract has neuroprotective activity. The aim of this study was to investigate the blackberry extract properties on lipopolysaccharide (LPS)-induced neuroinflammation, in relation to oxidative parameters and acetylcholinesterase activity in the brain structures of mice. We also investigated interleukin-10 levels in serum. Mice were submitted to Rubus sp. extract treatment once daily for 14 days. On the fifteenth day, LPS was injected in a single dose. LPS induced oxidative brain damage and the blackberry extract demonstrated preventive effects in LPS-challenged mice. LPS administration increased reactive oxygen species levels in the cerebral cortex and striatum, as well as lipid peroxidation in the cerebral cortex. However, the blackberry extract prevented all these parameters. Furthermore, LPS decreased thiol content in the striatum and hippocampus, while a neuroprotective effect of blackberry extract treatment was observed in relation to this parameter. The blackberry extract also prevented a decrease in catalase activity in all the brain structures and of superoxide dismutase in the striatum. An increase in acetylcholinesterase activity was detected in the cerebral cortex in the LPS group, but this activity was decreased in the Rubus sp. extract group. Serum IL-10 levels were reduced by LPS, and the extract was not able to prevent this change. Finally, we observed an antioxidant effect of blackberry extract in LPS-challenged mice suggesting that this anthocyanin-rich extract could be considered as a potential nutritional therapeutic agent for preventive damage associated with neuroinflammation.

Effects of Bidens gardneri Baker leaves aqueous extract in glucose homeostasis of rats.

Bidens gardneri Baker, popularly known as "picão-vermelho", has been used, traditionally, as a medicinal plant for the treatment of Diabetes mellitus. This study aimed to evaluate antidiabetic effect of leaves from B. gardneri aqueous extract (BGAE). We also evaluated in vitro anti-glycation potential. Chemical composition was analyzed based on a colorimetrics and HPLC methods. The oral glucose tolerance test (OGTT), was performed in rats with different doses (30, 100 and 300 mg/kg). Alloxan-induced diabetic and hypercaloric diet-fed rats were treated with 300 mg/kg of BGAE, orally, for 10 days and then 10 weeks, respectively. The activity of intestinal disaccharidases (maltase, sucrase and lactase) and quantification of muscle and liver glycogen content were also evaluated. On chemical analysis, the extract showed high phenolics content and the chromatogram showed 4-O-caffeoylquinic acid as the major component. The extract presented inhibition in the formation of advanced glycation end products (AGEs) and disaccharidases activity. In OGTT the dose of 300 mg/kg significantly decreased the blood glucose. In diabetic animals, BGAE significantly decreased blood glucose levels, preventing weight loss. In addition, in hypercaloric diet-fed rats, the extract prevented hyperglycemia. Our results suggest that, aqueous extract of B. gardneri has a potential for therapeutic intervention of diabetes.

Antigenotoxic and antimutagenic effects of Myrciaria dubia juice in mice submitted to ethanol 28-day treatment.

Myrciaria dubia is a native plant from the Amazon region which produces red-purplish fruit rich in antioxidant compounds such as ascorbic acid, carotenoids, and phenolic. M. dubia fruit is used to prepare juices considered to possess high nutritional content providing health benefits. The aim of this study was to examine the ability of M. dubia juice to protect DNA against genomic instability induced by sub-acute ethanol consumption attributed to oxidative stress. Mice were treated for 28 days with juice at 25% and 50% diluted in distilled water or with the diluted combination juice plus ethanol (5 g/kg). The genotoxic/antigenotoxic and mutagenic/antimutagenic effects were assessed using comet assay in blood, liver, and kidney and micronucleus (MN) test with bone marrow. In addition, the mutagenicity was also evaluated using Salmonella/microsome assay. Phytochemical compounds were determined using HPLC/PDA/MS/MS. The juice did not induce genotoxic effects in blood, kidney, and liver cells at both doses. In combination with ethanol, the juice reduced the alcohol-mediated DNA damage in all tissues analyzed. Further, the juice did not produce mutagenic effects and decreased mutagenicity induced by ethanol in the bone marrow. The anthocyanins were major compounds detected by HPLC/PDA/MS/MS, which modulated genotoxic and mutagenic effects initiated by ethanol and at least in part appeared responsible for the observed antigenotoxic and antimutagenic effects of M. dubia juice.

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.

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.

Enhancement of antioxidant activity and physicochemical properties of yogurt enriched with concentrated strawberry pulp obtained by block freeze concentration.

Strawberry juice was concentrated using block freeze concentration process. The concentrate was used to produce two yogurts with different concentrations of cryoconcentrated strawberry pulp (15% and 30%). Total lactic acid bacteria count, physicochemical and rheological properties was evaluated during storage (7days) for all yogurts. Also, the beverages produced were compared with two commercial trademarks. It was observed that the total lactic acid bacteria count remained higher than 108CFU·mL-1 during the storage time for all beverages studied. The viscosity of the yogurts decreased when the ratio of strawberry cryoconcentrate was increased. The Power Law model was successfully applied to describe the flow of the yogurts, which had a thixotropic behaviour. The incorporation of the cryoconcentrated strawberry pulp in the yogurt resulted in a product with 3-fold more anthocyanins content and antioxidant activity. The enrichment of natural yogurt with strawberry cryoconcentrated pulp proved to be effective in the production of a beverage with higher nutritional characteristics.

Molecular mechanism of action of Pelargonidin-3-O-glucoside, the main anthocyanin responsible for the anti-inflammatory effect of strawberry fruits.

Fragaria x ananassa Duch., popularly called strawberry, is known for its worldwide consumption and important biological activities, and these effects are related to its high concentration of anthocyanins. Pelargonidin-3-O-glucoside (P3G) is a major anthocyanin found in strawberry, and was evaluated for its anti-inflammatory action in experimental models. The effect of strawberry extract and P3G, on leukocyte migration, exudation levels and many inflammatory mediators, was therefore evaluated in an in vivo model. An in vitro study was also carried out to characterize the effect of P3G on mitogen-activated protein kinases, and on nuclear transcript factors NF-κB and AP-1. The results revealed that the strawberry and P3G have important anti-inflammatory proprieties, and the anti-inflammatory mechanism of P3G involves the arrest of IkB-α activation and reduction in JNKMAPK phosphorylation. The results reinforce that strawberry fruits are functional foods that can act as an adjuvant in the treatment of inflammatory conditions.

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.

LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant-like activity.

There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by the forced swimming test, splash test and open field test. EFF-Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya. Quantitatively, EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosyl flavonoids. In addition, EFF-Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF-Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF-Cp exerts antidepressant-like effects with its antioxidant properties.

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.

Preventive effects of blueberry extract on behavioral and biochemical dysfunctions in rats submitted to a model of manic behavior induced by ketamine.

The aim of the present study was to evaluate the protective effects of blueberry extract on oxidative stress and inflammatory parameters in a model of mania induced by ketamine administration in rats. Male rats were pretreated with blueberry extract (200mg/kg, once a day for 14days), lithium chloride (45mg/kg, mood stabilizer used as a positive control, twice a day for 14days), or vehicle. Between the 8th and 14th days, rats also received an injection of ketamine (25mg/kg) or vehicle. In the 15th day, thirty minutes after ketamine administration the hyperlocomotion of the animals was assessed in the open - field apparatus. Immediately after the behavioral analysis brain and blood were collected for biochemical determinations. ketamine treatment induced hyperlocomotion and oxidative damage in cerebral cortex, hippocampus and striatum such as an increase in lipid peroxidation and a decrease in the antioxidant enzymes activities (superoxide dismutase, catalase e glutatione peroxidase). Ketamine administration also increased the IL-6 levels in serum in rats. Pretreatment of rats with blueberry extract or lithium prevented the hyperlocomotion, pro - oxidant effects and inflammation induced by ketamine. Our findings suggest that blueberry consumption has a neuroprotective potential against behavioral and biochemical dysfunctions induced in a preclinical model that mimic some aspects of the manic behavior.