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ABSTRACTThis study evaluated the effects of Rubus sp. extract on behavioral and neurochemical parameters in female mice submitted to experimental model of depression induced by lipopolysaccharide (LPS). The results indicated that Rubus sp. extract protected against depressive-like behavior induced by LPS. Moreover, the administration of Rubus sp. extract was effective in preventing the increase in reactive species and nitrites levels, as well as the decrease in catalase activity induced by LPS in the cerebral cortex. In the serum, the Rubus sp. extract was effective in preventing the decrease in catalase activity induced by LPS. Treatment with Rubus sp. extract attenuated the increase in acetylcholinesterase activity induced by LPS in the cerebral cortex. Finally, blackberry extract also downregulated IL-1ß levels in cerebral cortex. In conclusion, our findings demonstrated that treatment with Rubus sp. exerted antidepressant, antioxidant, anticholinesterase and anti-inflammatory effects in a model of depressive - like behavior induced by LPS in female mice. This highlights Rubus sp. as a potential therapeutic agent for individuals with major depressive disorder.
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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.
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Antioxidantes , Astrocitos , Lipopolisacáridos , Polifenoles , Taninos , Zeína , Taninos/química , Taninos/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Zeína/química , Antioxidantes/farmacología , Antioxidantes/química , Lipopolisacáridos/farmacología , Animales , Escherichia coli/efectos de los fármacos , Ratas , Células Cultivadas , CápsulasRESUMEN
PURPOSE: Considering that the combination of dasatinib and quercetin (D + Q) demonstrated a neuroprotective action, as well as that females experience a decline in hormonal levels during aging and this is linked to increased susceptibility to Alzheimer's disease, in this study we evaluated the effect of D + Q on inflammatory and oxidative stress markers and on acetylcholinesterase and Na+, K+-ATPase activities in brain of female mice. METHODS: Female C57BL/6 mice were divided in Control and D (5 mg/kg) + Q (50 mg/kg) treated. Treatment was administered via gavage for three consecutive days every two weeks starting at 30 days of age. The animals were euthanized at 6 months of age and at 14 months of age. RESULTS: Results indicate an increase in reactive species (RS), thiol content and lipid peroxidation followed by a reduction in nitrite levels and superoxide dismutase, catalase and glutathione S-transferase activity in the brain of control animals with age. D+Q protected against age-associated increase in RS and catalase activity reduction. Acetylcholinesterase activity was increased, while Na+, K+-ATPase activity was reduced at 14 months of age and D+Q prevented this reduction. CONCLUSION: These data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.
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Acetilcolinesterasa , Senoterapéuticos , Ratas , Femenino , Ratones , Animales , Catalasa/metabolismo , Acetilcolinesterasa/metabolismo , Ratas Wistar , Ratones Endogámicos C57BL , Antioxidantes/farmacología , Estrés Oxidativo , Quercetina/farmacología , Encéfalo/metabolismo , Superóxido Dismutasa/metabolismo , Adenosina TrifosfatasasRESUMEN
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.
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Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I - Control; II - STZ; III - STZ + blackberry extract (100 mg/kg); IV - STZ + blackberry extract (200 mg/kg) and V - STZ + metformin (150 mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21 days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3ß and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3ß, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease.
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Transcranial direct current stimulation (tDCS) can modulate cortical excitability and relieve neuropathic pain (NP), but the role of several biomarkers in this process is not well understood. This study aimed to analyze the effects of tDCS on biochemical parameters in rats with neuropathic pain (NP) induced by chronic constriction injury (CCI) of the right sciatic nerve. Eighty-eight male 60-day-old Wistar rats were divided into nine groups: control (C), control-electrode off (CEoff), control-tDCS (C-tDCS), sham-lesion (SL), sham-lesion electrode off (SLEoff), sham-lesion (SL-tDCS), lesion (L), lesion electrode off (LEoff), and lesion-tDCS (L-tDCS). After NP establishment, 20-minute bimodal tDCS for 8 consecutive days was applied to the rats. Fourteen days after the induction of NP, rats developed mechanical hyperalgesia with a decreased threshold, and at the end of treatment, an increase in the pain threshold was observed in NP rats. In addition, NP rats had increased levels of reactive species (RS) in the prefrontal cortex, while superoxide dismutase (SOD) activity was decreased in NP rats. In the spinal cord, nitrite levels and glutathione-S-transferase (GST) activity decreased in the L-tDCS group, and it was observed that increased levels in total sulfhydryl content for neuropathic pain rats were reversed by tDCS. In serum analyses, the neuropathic pain model increased the levels of RS and thiobarbituric acid-reactive substances (TBARS) and decreased the activity of butyrylcholinesterase (BuChE). In conclusion, bimodal tDCS increased total sulfhydryl content in the spinal cord of rats with neuropathic pain, positively modulating this parameter.
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Neuralgia , Estimulación Transcraneal de Corriente Directa , Ratas , Masculino , Animales , Umbral del Dolor , Ratas Wistar , Butirilcolinesterasa , Neuralgia/terapia , Hiperalgesia/terapia , Estrés OxidativoRESUMEN
The blackberry (Rubus sp.) is a popular fruit that has a high concentration of phenolic compounds. Pharmacological investigations have demonstrated the important biological activities of the blackberry extract, such as neuroprotective actions. This study aimed to evaluate the effects of blackberry extract on memory and neurochemical parameters in rats subjected to scopolamine (SCO)-induced amnesia. Male rats were divided into five groups: I, control (saline); II, SCO; III, SCO + Rubus sp. (100 mg/kg); IV, SCO + Rubus sp. (200 mg/kg); and V, SCO + donepezil (5 mg/kg). Blackberry extract and donepezil were orally administered for 10 days. On day 11, group I received saline, and groups II, III, IV, and V received SCO (1 mg/kg) intraperitoneally after object recognition behavioral training. Twenty-four hours after the training session, animals were subjected to an object recognition test. Finally, the animals were euthanized, and the cerebral cortex, hippocampus, and cerebellum were collected to evaluate the oxidative stress and acetylcholinesterase (AChE) activity. Rubus sp. extract prevented memory impairment induced by SCO in a manner similar to that of donepezil. Additionally, Rubus sp. extract and donepezil prevented the increase in AChE activity induced by SCO in all the evaluated brain structures. SCO induced oxidative damage in the cerebral cortex, hippocampus, and cerebellum, which was prevented by Rubus sp. and donepezil. Our results suggest that the antioxidant and anticholinesterase activities of Rubus sp. are associated with memory improvement; hence, it can potentially be used for the treatment of neurodegenerative diseases.
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Rubus , Ratas , Masculino , Animales , Rubus/metabolismo , Acetilcolinesterasa/metabolismo , Donepezilo/farmacología , Donepezilo/uso terapéutico , Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Amnesia/prevención & control , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/inducido químicamente , Escopolamina/farmacología , Hipocampo/metabolismo , Corteza Cerebral/metabolismo , Estrés Oxidativo , Antioxidantes/farmacología , Cerebelo/metabolismo , Aprendizaje por LaberintoRESUMEN
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 ââof 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.
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Achyrocline , Antineoplásicos , Melanoma , Humanos , Achyrocline/química , Extractos Vegetales/química , Antineoplásicos/farmacología , Línea Celular , Melanoma/tratamiento farmacológico , HongosRESUMEN
Objective: In this study, we aimed to determine the role of Psidium cattleianum extract (PCE) and compare its effects with those of metformin (Met) in an animal model with type 2 diabetes mellitus (T2DM).Methods: T2DM was induced in rats using a high-fat diet (HFD), followed by a single dose of streptozotocin (STZ). Met and PCE were administered intragastrically once a day throughout the experiment, and their effects on biochemical, inflammatory, oxidative, and histological parameters were evaluated.Results: Met and PCE prevented the increase in serum levels of glucose, total cholesterol (TC), triacylglycerol (TG), very low-density lipoprotein (VLDL) and interleukin-6 (IL-6) induced by T2DM, and restored redox homeostasis in the liver and brain. Met increased the serum levels of anti-inflammatory cytokine and interleukin-10 (IL-10). Furthermore, both treatments restored the liver and pancreas from marked cellular disorganisation, vacuolisation, and necrosis, with PCE being more effective than Met in recovering histological changes.Conclusion: PCE is a promising agent for the prevention of T2DM complications.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metformina , Psidium , Animales , Ratas , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Frutas , Hipoglucemiantes/farmacología , Metformina/farmacología , Metformina/uso terapéutico , Modelos AnimalesRESUMEN
Alzheimer's disease (AD) is characterized mostly by memory decline. The current therapeutic arsenal for treating AD is limited, and the available drugs only produce symptomatic benefits, but do not stop disease progression. The search for effective therapeutic alternatives with multitarget actions is therefore imperative. One such a potential alternative is thiazolidin-4-one, a compound that exhibits anti-amnesic, anticholinesterase, and antioxidant activities. The aim of this study was evaluated the effects of 2-(4-(methylthio)phenyl)- 3-(3-(piperidin-1-yl)propyl) thiazolidin-4-one (DS12) on memory and neurochemical parameters in a model of AD induced by an intracerebroventricular injection of streptozotocin (STZ). Adult male rats were divided into five groups: I, control (saline); II, DS12 (10 mg/kg); III, STZ; IV, STZ + DS12 (10 mg/kg); V, STZ + donepezil (5 mg/kg). The rats were orally treated with DS12 and donepezil for a period of 20 days. Memory, acetylcholinesterase (AChE) activity, phosphorylated tau protein levels and oxidative stress were analyzed in the cerebral cortex, hippocampus, and cerebellum. Biochemical and hematological parameters were evaluated in the blood and serum. Memory impairment and the increase in AChE activity and phosphorylated tau protein level induced by STZ were prevented by DS12 and donepezil treatment. Streptozotocin induces an increase in reactive oxygen species levels and a decrease in catalase activity in the hippocampus, cerebral cortex, and cerebellum. DS12 treatment conferred protection from oxidative alterations in all brain structures. No changes were observed in serum biochemical parameters (glucose, triglycerides, cholesterol, uric acid, and urea) or hematological parameters, such as platelets, lymphocytes, hemoglobin, hematocrit, and total plasma protein. DS12 improved memory and neurochemical changes in an AD model and did not show toxic effects, suggesting the promising therapeutic potential of this compound.
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Enfermedad de Alzheimer , Ratas , Masculino , Animales , Enfermedad de Alzheimer/metabolismo , Donepezilo/farmacología , Donepezilo/uso terapéutico , Proteínas tau/metabolismo , Estreptozocina/toxicidad , Acetilcolinesterasa/metabolismo , Estrés Oxidativo , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/prevención & control , Trastornos de la Memoria/inducido químicamente , Antioxidantes/farmacología , Inhibidores de la Colinesterasa/farmacología , Modelos Animales de Enfermedad , Aprendizaje por LaberintoRESUMEN
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.
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Antioxidantes , Estrés Oxidativo , Ratas , Ratones , Masculino , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratas Wistar , Catalasa/metabolismo , Hígado/metabolismo , Superóxido Dismutasa/metabolismo , Riñón/metabolismo , Encéfalo/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacología , Peso CorporalRESUMEN
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.
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Trastorno Depresivo Mayor , Lipopolisacáridos , Masculino , Animales , Ratones , Lipopolisacáridos/toxicidad , Antocianinas/metabolismo , Fluoxetina/farmacología , Enfermedades Neuroinflamatorias , Trastorno Depresivo Mayor/metabolismo , Acetilcolinesterasa/metabolismo , Simulación del Acoplamiento Molecular , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Depresión/metabolismo , Hipocampo/metabolismo , Encéfalo/metabolismo , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/farmacología , Monoaminooxidasa/metabolismo , Conducta AnimalRESUMEN
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.
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Astrocitos , Lipopolisacáridos , Ratas , Animales , Astrocitos/metabolismo , Lipopolisacáridos/farmacología , Acetilcolinesterasa/metabolismo , Nucleótidos de Adenina/efectos adversos , Interleucina-6 , Enfermedades Neuroinflamatorias , Hidrólisis , Estrés Oxidativo , Inflamación/tratamiento farmacológico , Células CultivadasRESUMEN
Glioblastoma (GBM) is the deadliest primary brain tumor in adults due to the high rate of relapse with current treatment. Therefore, the search for therapeutic alternatives is urgent. Gallic acid (GA), a potent natural antioxidant, has antitumor and modulatory actions on purinergic signaling. In this study, we investigated the cytotoxic effects of GA on the rat GBM (C6) cell line and on astrocyte culture and analyzed its role in regulating oxidative stress and purinergic enzymes involved in GBM proliferation. Cells were exposed to GA from 50 to 400 µM for 24 and/or 48 h. Next, the effect of GA was evaluated in the preclinical model of GBM. Wistar rats were treated with 50 or 100 mg/kg of GA for 15 days, and cerebral and systemic redox status and degradation of adenine nucleotides and nucleosides in circulating platelets, lymphocytes, and serum were evaluated. Our results demonstrated that GA has selective anti-glioma activity in vitro, without inducing cytotoxicity in astrocyte. Furthermore, GA prevented oxidative stress and changes in the hydrolysis of nucleotides in GBM cells. The anti-glioma effect was also observed in vivo, as GA reduced tumor volume by 90%. Interestingly, GA decreased the oxidative damage induced by a tumor in the brain, serum, and platelets, and, also prevented changes in the degradation of nucleotides and nucleosides in lymphocytes, platelets, and serum. These results indicate, for the first time, the therapeutic potential of GA in a preclinical model of GBM, whose effects may be related to its role in redox and purinergic modulation.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Animales , Ratas , Glioblastoma/metabolismo , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Ratas Wistar , Glioma/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Oxidación-Reducción , Homeostasis , Nucleótidos/metabolismo , Línea Celular TumoralRESUMEN
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.
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Acetilcolinesterasa , Trastorno Depresivo Mayor , Acetilcolinesterasa/metabolismo , Animales , Hipocampo/metabolismo , Lipopolisacáridos/farmacología , Ratones , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Taninos/farmacología , Taninos/uso terapéuticoRESUMEN
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.
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Glioblastoma , Tiazolidinedionas , Animales , Glioblastoma/tratamiento farmacológico , Masculino , Ratas , Ratas Wistar , TiazolidinasRESUMEN
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.
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Glioblastoma , Adenosina/farmacología , Adenosina Difosfato/metabolismo , Adenosina Monofosfato/farmacología , Adenosina Trifosfato/metabolismo , Animales , Antioxidantes/farmacología , Encéfalo/metabolismo , Glioblastoma/tratamiento farmacológico , Nitritos , Estrés Oxidativo , Ratas , Especies Reactivas de Oxígeno , Superóxido Dismutasa , Taninos/farmacología , Taninos/uso terapéutico , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
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.
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Arándanos Azules (Planta) , Ketamina , Adenosina Trifosfatasas/metabolismo , Animales , Conducta Animal , Arándanos Azules (Planta)/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ketamina/farmacología , Manía , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
Alzheimer's disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.
Asunto(s)
Enfermedad de Alzheimer , Inosina , Receptores Purinérgicos , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inosina/farmacología , Inosina/uso terapéutico , Masculino , Aprendizaje por Laberinto , Trastornos de la Memoria/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Ratas , Ratas Wistar , Receptores Purinérgicos/metabolismo , EstreptozocinaRESUMEN
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.