Tannic acid: A possible therapeutic agent for hypermethioninemia-induced neurochemical changes in young rats.

This study explores the therapeutic benefits of tannic acid (TnA) in an experimental protocol of chronic hypermethioninemia in rats. Rats were categorized into four groups: Group I - control, Group II - TnA 30 mg/kg, Group III - methionine (Met) 0.2-0.4 g/kg + methionine sulfoxide (MS) 0.05-0.1 g/kg, Group IV - TnA/Met + MS. Saline was administered by subcutaneous pathway into groups I and II twice daily from postnatal day 6 (P6) to P28, whereas those in groups III and IV received Met + MS. From P28 to P35, groups II and IV received TnA orally. Animals from group III presented cognitive and memory impairment assessed through object recognition and Y-maze tests (p < 0.05). Elevated levels of reactive species, lipid peroxidation, and nitrites followed by a decline in sulfhydryl content, catalase activity, and superoxide dismutase activity were observed in animals treated with Met + MS (p < 0.05). However, TnA treatment reversed all these effects (p < 0.05). In group III, there was an increase in acetylcholinesterase activity and IL-6 levels, coupled with a reduction in Na+/K+-ATPase activity (p < 0.05). TnA was able to protect against these effects (p < 0.05). The gene expression of catalase, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor 2 was decreased in the hippocampus and striatum from group III (p < 0.05). TnA reversed almost all of these alterations (p < 0.05). These findings suggest that TnA is a therapeutic target for patients with hypermethioninemia.

Effect of Thiazolidin-4-one Against Lipopolysaccharide-Induced Oxidative Damage, and Alterations in Adenine Nucleotide Hydrolysis and Acetylcholinesterase Activity in Cultured Astrocytes.

Astrocytes play multiple important roles in brain physiology. However, depending on the stimuli, astrocytes may exacerbate inflammatory reactions, contributing to the development and progression of neurological diseases. Therefore, therapies targeting astrocytes represent a promising area for the development of new brain drugs. Thiazolidinones are heterocyclic compounds that have a sulfur and nitrogen atom and a carbonyl group in the ring and represent a class of compounds of great scientific interest due to their pharmacological properties. The aim of this study was to investigate the effect of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) on cell proliferation and morphology, oxidative stress parameters, activity of the enzymes ectonucleotidases and acetylcholinesterase (AChE) and interleukin 6 (IL-6) levels in primary astrocyte cultures treated with lipopolysaccharide (LPS), to model neuroinflammation. The astrocyte culture was exposed to LPS (10 µg/ml) for 3 h and subsequently treated with compound DS27 for 24 and 48 h (concentrations ranging to 10-100 µM). LPS induced an increase in astrocyte proliferation, AChE activity, IL-6 levels, oxidative damage, ATP and ADP and a reduction in AMP hydrolysis in rat primary astrocyte cultures. DS27 treatment was effective in reversing these alterations induced by LPS. Our findings demonstrated that DS27 is able to modulate cholinergic and purinergic signaling, redox status, and the levels of pro-inflammatory cytokines in LPS-induced astrocyte damage. These glioprotective effects of DS27 may be very important for improving neuroinflammation, which is associated with many brain diseases.

Blueberry Extract Modulates Brain Enzymes Activities and Reduces Neuroinflammation: Promising Effect on Lipopolysaccharide-Induced Depressive-Like Behavior.

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders with high rates of prevalence and mortality. MDD is pathophysiologically complex, and treatment options are limited. Blueberries are rich in polyphenols and have neuroprotective potential. The aim of this study was to investigate the effects of blueberry extract on neuroinflammatory and neuroplasticity parameters, as well as Na+/K+-ATPase, monoamine oxidase-A (MAO-A), and acetylcholinesterase (AChE) activities in the cerebral cortex and hippocampus of mice subject to lipopolysaccharide (LPS)-induced depressive-like behavior. We also analyzed the interaction between anthocyanins and indoleamine 2 3-dioxygenase (IDO). Male Swiss mice (60-day-old) received vehicle, fluoxetine (20 mg/kg), or blueberry extract (100 or 200 mg/kg) intragastrically for 7 days before intraperitoneal LPS (0.83 mg/kg) injection. Twenty-four hours after LPS administration, the mice were subjected to behavioral tests. Both fluoxetine and blueberry extract (200 mg/kg) decreased the immobility time in the forced swim test, without affecting locomotor activity. Fluoxetine attenuated the decrease of Na+/K+-ATPase in the cerebral cortex, while blueberry extract promoted this same effect in the hippocampus. Additionally, fluoxetine and blueberry extract attenuated the decrease in the activity of MAO-A in the hippocampus. Blueberry extract (200 mg/kg) also prevented LPS-induced increase in AChE activity in the hippocampus as well as LPS upregulation of relative mRNA expression of tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-10 in the cerebral cortex. Molecular docking analysis revealed binding sites for malvidin 3-galactoside (- 7.8 kcal/mol) and malvidin 3-glucoside (- 7.9 kcal/mol) residues with IDO. Taken together, these results indicate that blueberry extract improved depression-like behavior and attenuated the neurochemical and molecular changes in the brains of mice challenged with LPS.

Chemical hypermethioninemia in young mice: oxidative damage and reduction of antioxidant enzyme activity in brain, kidney, and liver.

High levels of methionine (Met) and its metabolites, such as methionine sulfoxide (MetO), found in hypermethioninemia, can be detrimental to the body; however, the underlying mechanisms are still uncertain. Using a recently standardized protocol, the aim of this study was to investigate the effects of chronic administration of Met and/or MetO on parameters of oxidative damage in the total brain, liver, and kidney of young mice. Swiss male mice were subcutaneously injected with Met and MetO at concentrations of 0.35-1.2 g/kg body weight and 0.09-0.3 g/kg body weight, respectively, from the 10th-38th day post-birth, while the control group was treated with saline solution. Results showed that Met and/or MetO caused an increase in reactive oxygen species (ROS) and lipoperoxidation, along with a reduction of superoxide dismutase (SOD) and catalase (CAT) activities in the brain. In the liver, Met and/or MetO enhanced ROS and nitrite levels, and reduced SOD, CAT, and delta aminolevulinic dehydratase activities. The effects on the kidney were an increase in ROS production and SOD activity, and a reduction in thiol content and CAT activity. These data demonstrated the contribution of redox imbalance to the systemic changes found in patients with hypermethioninemia. In conclusion, our findings may help future studies to better understand the pathophysiological mechanisms of hypermethioninemia as well as contribute to the search for new therapeutic agents for this pathology.

Tannic Acid Attenuates Peripheral and Brain Changes in a Preclinical Rat Model of Glioblastoma by Modulating Oxidative Stress and Purinergic Signaling.

Glioblastoma (GB) is a highly aggressive and invasive brain tumor; its treatment remains palliative. Tannic acid (TA) is a polyphenol widely found in foods and possesses antitumor and neuroprotective activities. This study aimed to investigate the effect of TA on oxidative stress parameters and the activity of ectonucleotidases in the serum, platelets, and lymphocytes and/or in the brain of rats with preclinical GB. Rats with GB were treated intragastrically with TA (50 mg/kg/day) for 15 days or with a vehicle. In the platelets of the animals with glioma, the adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and the catalase (CAT) activity decreased. Besides, the adenosine diphosphate (ADP) hydrolysis, adenosine (Ado) deamination, and the reactive oxygen species (ROS) and nitrite levels were increased in glioma animals; however, TA reversed ROS and nitrite levels and AMP hydrolysis alterations. In lymphocytes from animals with glioma, the ATP and ADP hydrolysis, as well as Ado deamination were increased; TA treatment countered this increase. In the brain of the animals with glioma, the ROS, nitrite, and thiobarbituric acid reactive substance (TBARS) levels increased and the thiol (SH) levels and CAT and superoxide dismutase (SOD) activities were decreased; TA treatment decreased the ROS and TBARS levels and restored the SOD activity. In the serum of the animals with glioma, the ATP hydrolysis decreased; TA treatment restored this parameter. Additionally, the ROS levels increased and the SH and SOD activity decreased by glioma implant; TA treatment enhanced nitrite levels and reversed SOD activity. Altogether, our results suggest that TA is an important target in the treatment of GB, as it modulates purinergic and redox systems.

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.

Effect of blueberry extract on energetic metabolism, levels of brain-derived neurotrophic factor, and Ca2+-ATPase activity in the hippocampus and cerebral cortex of rats submitted to ketamine-induced mania-like behavior.

Bipolar disorder (BD) is a psychiatric disease characterized by mood episodes. Blueberry is rich in bioactive compounds and shows excellent therapeutic potential against chronic diseases. The aim of this study was to evaluate the effects of blueberry extract on behavior, energetic metabolism, Ca2+-ATPase activity, and levels of brain-derived neurotrophic factor (BDNF) in the cerebral cortex and hippocampus of rats submitted to an animal model of mania induced by ketamine. Vehicle, lithium (45 mg/kg, twice a day), or blueberry extract (200 mg/kg), was orally administered to Wistar rats for 14 days. Ketamine (25 mg/kg) or vehicle was administered intraperitoneally, once a day, between the 8th and 14th day. On the 15th day, animals received ketamine or vehicle and were subjected to the open field test. Our results demonstrated that the administration of lithium and blueberry extract prevented ketamine-induced hyperlocomotion (P < 0.01). Blueberry extract attenuated the ketamine-induced reduction in the activity of complex I in the cerebral cortex (P < 0.05). Additionally, the administration of ketamine reduced the activities of complexes I and IV (P < 0.05) and citrate synthase in the hippocampus (P < 0.01). However, blueberry extract attenuated the inhibition in the activity of complex IV (P < 0.01). Furthermore, ketamine reduced the Ca2+-ATPase activity in the cerebral cortex and hippocampus (P < 0.05); however, blueberry extract prevented the change in the cerebral cortex (P < 0.05). There were no significant alterations in the levels of BDNF (P > 0.05). In conclusion, this suggested that the blueberry extract can serve as a potential therapeutic strategy for studies searching for novel therapeutic alternatives for BD patients.

LPS-induced impairment of Na+/K+-ATPase activity: ameliorative effect of tannic acid in mice.

Acetylcholine is an excitatory neurotransmitter that modulates synaptic plasticity and communication, and it is essential for learning and memory processes. This neurotransmitter is hydrolyzed by acetylcholinesterase (AChE), which plays other cellular roles in processes such as inflammation and oxidative stress. Ion pumps, such as Na+/K+-ATPase and Ca2+-ATPase, are highly expressed channels that derive energy for their functions from ATP hydrolysis. Impairment of the cholinergic system and ion pumps is associated with neuropsychiatric diseases. Major depressive disorder (MDD) is an example of a complex disease with high morbidity and a heterogenous etiology. Polyphenols have been investigated for their therapeutic effects, and tannic acid (TA) has been reported to show neuroprotective and antidepressant-like activities. Animal models of depression-like behavior, such as lipopolysaccharide (LPS)-induced models of depression, are useful for investigating the pathophysiology of MDD. In this context, effects of TA were evaluated in an LPS-induced mouse model of depression-like behavior. Animals received TA for 7 days, and on the last day of treatment, LPS (830 µg/kg) was administered intraperitoneally. In vitro exposure of healthy brain to TA decreased the AChE activity. Additionally, this enzyme activity was decreased in cerebral cortex of LPS-treated mice. LPS injection increased the activity of Ca2+-ATPase in the cerebral cortex but decreased the enzyme activity in the hippocampus. LPS administration decreased Na+/K+-ATPase activity in the cerebral cortex, hippocampus, and striatum; however, TA administration prevented these changes. In conclusion, tannins may affect Na+/K+-ATPase and Ca2+-ATPase activities, which is interesting in the context of MDD.

Thiazolidine-2,4-dione derivative exhibits antitumoral effect and reverts behavioral and metabolic changes in a model of glioblastoma.

The aim of the present study was to evaluate the anti-glioma activity of 3-(4-fluorobenzyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (AV23) in a preclinical model of glioblastoma, as well as behavioral parameters and toxicological profile. The implantation of C6 cells in the left striatum of male Wistar rats was performed by stereotaxic surgery. After recovery, animals were treated with vehicle (canola oil) or AV23 (10 mg/kg/day) intragastrically for 15 days. It was found that AV23 reduced tumor volume by 90%. Serum biochemical parameters such as triglycerides, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin, aspartate aminotransferase, urea, creatinine and total proteins were not changed; however, there was a slight increase in alanine aminotransferase. The compound AV23 reverted the hypoglycemia and the reduction in body weight caused by glioblastoma. Additionally, AV23 was able to revert the reduction of locomotion caused by the tumor implantation. Therefore, the compound AV23 can be considered a promising candidate in the treatment of glioblastoma.

Selective in vitro anticancer effect of blueberry extract (Vaccinium virgatum) against C6 rat glioma: exploring their redox status.

The aim of this study was to investigate the anticancer potential of blueberry extract (Vaccinium virgatum) against a C6 rat glioma lineage. Cultures of the C6 cells were exposed to blueberry extract at concentrations of 50 to 600 µg/mL for 12, 24, 48, or 72 h and then evaluated for cell viability, proliferation, migration, colony formation and oxidative stress. We also evaluated the effects of blueberry extract on primary rat cortical astrocytes. Our results show that treatment with blueberry extract did not alter the viability or proliferation of normal primary astrocytes but it did significantly reduce the viability in 21.54 % after 48 h and proliferation in 8.59 % after 24 h of C6 cells at 200 µg/mL. We also observed a reduction in the size of the colonies of 29.99 % at 100 µg/mL when compared to the control cells and cell migration was also reduced at 50 µg/mL. After 72 h, there was a reduction in the reactive oxygen species levels ranging from 46.26 to 34.73 %, in addition to a 380.2 % increase in total thiol content. Superoxide dismutase, catalase, and glutathione S-transferase activities were also enhanced when compared to the control. Taken together this data suggests that blueberry extract exerts some selective anticancer activity in C6 glioma cells.

Ameliorative effect of tannic acid on hypermethioninemia-induced oxidative and nitrosative damage in rats: biochemical-based evidences in liver, kidney, brain, and serum.

We investigated the ability of tannic acid (TA) to prevent oxidative and nitrosative damage in the brain, liver, kidney, and serum of a rat model of acute hypermethioninemia. Young Wistar rats were divided into four groups: I (control), II (TA 30 mg/kg), III (methionine (Met) 0.4 g/kg + methionine sulfoxide (MetO) 0.1 g/kg), and IV (TA/Met + MetO). Rats in groups II and IV received TA orally for seven days, and rats of groups I and III received an equal volume of water. After pretreatment with TA, rats from groups II and IV received a single subcutaneous injection of Met + MetO, and were euthanized 3 h afterwards. In specific brain structures and the kidneys, we observed that Met + MetO led to increased reactive oxygen species (ROS), nitrite, and lipid peroxidation levels, followed by a reduction in thiol content and antioxidant enzyme activity. On the other hand, pretreatment with TA prevented both oxidative and nitrosative damage. In the serum, Met + MetO caused a decrease in the activity of antioxidant enzymes, which was again prevented by TA pretreatment. In contrast, in the liver, there was a reduction in ROS levels and an increase in total thiol content, which was accompanied by a reduction in catalase and superoxide dismutase activities in the Met + MetO group, and pretreatment with TA was able to prevent only the reduction in catalase activity. Conclusively, pretreatment with TA has proven effective in preventing oxidative and nitrosative changes caused by the administration of Met + MetO, and may thus represent an adjunctive therapeutic approach for treatment of hypermethioninemia.

Antidepressant Effect and Modulation of the Redox System Mediated by Tannic Acid on Lipopolysaccharide-Induced Depressive and Inflammatory Changes in Mice.

Depression is an emotional disorder that causes mental and physical changes, and has limited pharmacotherapy. Tannic acid (TA) is a polyphenol with previously described antioxidant and neuroprotective properties. The aim of this study was to evaluate the effects of TA on lipopolysaccharide (LPS)-induced depressive-like behavior, as well as oxidative stress parameters and TNF-α levels in the brains of mice. Animals were pretreated once daily, with TA (30 or 60 mg/kg), fluoxetine (20 mg/kg) or vehicle for 7 days. On the 7th day, the animals received a single injection of LPS (830 µg/kg). After 24 h, open field, forced swimming, tail suspension, and splash tests were conducted. The endotoxin induced depressive-like behavior in these mice and this was attenuated by TA. In the cerebral cortex, hippocampus, and striatum, LPS increased lipid peroxidation and reactive oxygen species production, and this was also prevented by TA administration. TA treatment also prevented a decrease in catalase activity within the striatum. Further, LPS administration caused increased levels of TNF-α in all brain structures, and this was prevented in the cortex by TA treatment. In conclusion, TA shows many neuroprotective properties, with demonstrated antioxidant, anti-inflammatory and antidepressant effects in this animal model of acute depressive-like behavior. Therefore, this compound could provide an alternative therapeutic approach for the treatment of depression.

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.

2-(2-Methoxyphenyl)-3-((Piperidin-1-yl)ethyl)thiazolidin-4-One-Loaded Polymeric Nanocapsules: In Vitro Antiglioma Activity and In Vivo Toxicity Evaluation.

Among gliomas types, glioblastoma is considered the most malignant and the worst form of primary brain tumor. It is characterized by high infiltration rate and great angiogenic capacity. The presence of an inflammatory microenvironment contributes to chemo/radioresistance, resulting in poor prognosis for patients. Recent data show that thiazolidinones have a wide range of pharmacological properties, including anti-inflammatory and antiglioma activities. Nanocapsules of biodegradable polymers become an alternative to cancer treatment since they provide targeted drug delivery and could overcome blood-brain barrier. Therefore, here we investigated the in vitro antiglioma activity and the potential in vivo toxicity of 2- (2-methoxyphenyl) -3- ((piperidin-1-yl) ethyl) thiazolidin-4-one-loaded polymeric nanocapsules (4L-N). Nanocapsules were prepared and characterized in terms of particle size, polydispersity index, zeta potential, pH, molecule content and encapsulation efficiency. Treatment with 4L-N selectively decreased human U138MG and rat C6 cell lines viability and proliferation, being even more efficient than the free-form molecule (4L). In addition, 4L-N did not promote toxicity to primary astrocytes. We further demonstrated that the treatment with sub-therapeutic dose of 4L-N did not alter weight, neither resulted in mortality, toxicity or peripheral damage to Wistar rats. Finally, 4L as well as 4L-N did not alter makers of oxidative damage, such as TBARS levels and total sulfhydryl content, and did not change antioxidant enzymes SOD and CAT activity in liver and brain of treated rats. Taken together, these data indicate that the nanoencapsulation of 4L has potentiated its antiglioma effect and does not cause in vivo toxicity.

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.

Electrospraying and electrospinning of tannic acid-loaded zein: Characterization and antioxidant effects in astrocyte culture exposed to E. coli lipopolysaccharide.

Tannic acid (TA) exhibits low bioavailability in the gastrointestinal tract, limiting its benefits due to small amounts reaching the CNS. Thus, the objective of this study was to develop zein capsules and fibers by electrospraying/electrospinning for encapsulation of TA. Polymeric solutions were evaluated by electrical conductivity, density, and viscosity. In zein capsules, up to 2 % TA was added, and in fibers, up to 1 % TA was added. Zein capsule and fiber with TA were evaluated by morphology, size distribution, encapsulation efficiency, thermal and thermogravimetric properties, and functional groups. Zein capsule with 1.5 % TA was evaluated in astrocyte culture for cytotoxicity and antioxidant activity. TA zein capsules and fibers exhibited high encapsulation efficiency and homogeneous morphology. TA encapsulated in zein presented higher thermal stability than free TA. TA zein capsule did not present toxicity and elicited antioxidant action in lipopolysaccharide-induced astrocyte culture. Capsules and fibers were successfully produced by electrospraying/electrospinning techniques.

Antitumoral Activity of Cecropia Pachystachya Leaves Extract in Vitro and in Vivo Model of Rat Glioma: Brain and Blood Effects.

The aim of this study was to investigate the antiglioma effect of Cecropia pachystachya Trécul (CEC) leaves extract against C6 and U87 glioblastoma (GB) cells and in a rat preclinical GB model. The CEC extract reduced in vitro cell viability and biomass. In vivo, the extract decreased the tumor volume approximately 62%, without inducing systemic toxicity. The deficit in locomotion and memory and an anxiolytic-like behaviors induced in the GB model were minimized by CEC. The extract decreased the levels of reactive oxygen species, nitrites and thiobarbituric acid reactive substances and increased the activity of antioxidant enzymes in platelets, sera and brains of GB animals. The activity of NTPDases, 5'-nucleotidase and adenosine deaminase (ADA) was evaluated in lymphocytes, platelets and serum. In platelets, ATP and AMP hydrolysis was reduced and hydrolysis of ADP and the activity of ADA were increased in the control, while in CEC-treated animals no alteration in the hydrolysis of ADP was detected. In serum, the reduction in ATP hydrolysis was reversed by CEC. In lymphocytes, the increase in the hydrolysis of ATP, ADP and in the activity of ADA observed in GB model was altered by CEC administration. The observed increase in IL-6 and decrease in IL-10 levels in the serum of GB animals was reversed by CEC. These results demonstrate that CEC extract is a potential complementary treatment to GB, decreasing the tumor size, while modulating aspects of redox and purinergic systems.

Endophytic Fungus of Achyrocline satureioides: Molecular Identification, Chemical Characterization, and Cytotoxic Evaluation of its Metabolites in Human Melanoma cell line.

Endophytic fungi are important sources of anticancer compounds. An endophytic fungus was isolated from the medicinal plant Achyrocline satureioides, and molecularly identified as Biscogniauxia sp. (family Xylariaceae) based on partial nucleotide sequences of the internal transcribed spacer genomic region (GenBank Accession No. ON257911). The chemical characterization and cytotoxic properties of secondary metabolites produced by Biscogniauxia sp. were evaluated in a human melanoma cell line (A375). The fungus was grown in potato-dextrose liquid medium for 25 days, and the extracted compounds were subjected to solid-phase fractionation to obtain the purified FDCM fraction, for which the metabolites were elucidated via ultra-performance chromatography coupled to a mass spectrometer. In the present study, 17 secondary metabolites of Biscogniauxia sp., including nine polyketide derivatives, five terpenoids, and three isocoumarins, were putatively identified. This is the first study to report of the ability of Biscogniauxia sp. in the production of isocoumarin orthosporin; the terpenoids nigriterpene A and 10-xylariterpenoid; the polyketide derivatives daldinin C, 7'dechloro-5'-hydroxygriseofulvin, daldinone D, Sch-642305, curtachalasin A, cytochalasin E, epoxycytochalasins Z8, Z8 isomer, and Z17. Furthermore, this study has reported the biosynthesis of Sch-642305 by a Xylariaceae fungus for the first time. FDCM significantly reduced the viability and proliferation of human melanoma cells at half-maximal inhibitory concentrations ​​of 10.34 and 6.89 µg/mL, respectively, and induced late apoptosis/necrosis and cell cycle arrest in G2/M phase after 72 h of treatment. Given its ability to produce unique metabolites with promising cytotoxic effects, Biscogniauxia sp. of A. satureioides may be a reservoir of compounds with important therapeutic applications.