The Free Radical Scavenging Property of the Leaves, Branches, and Roots of Mansoa hirsuta DC: In Vitro Assessment, 3D Pharmacophore, and Molecular Docking Study.

In this work, a metabolic profile of Mansoa hirsuta was investigated, and in vitro assays and theoretical approaches were carried out to evaluate its antioxidant potential. The phytochemical screening detected saponins, organic acids, phenols, tannins, flavonoids, and alkaloids in extracts of leaves, branches, and roots. Through LC-MS analysis, the triterpenes oleanolic acid (m/z 455 [M-H]-) and ursolic acid (m/z 455 [M-H]-) were identified as the main bioactive components. The extracts of the leaves, branches, and roots revealed moderate antioxidant potential in the DPPH test and all extracts were more active in the ABTS test. The leaf extracts showed better antioxidant capacity, displaying IC50 values of 43.5 ± 0.14, 63.6 ± 0.54, and 56.1 ± 0.05 µg mL-1 for DPPH, ABTS, and kinetics assays, respectively. The leaf extract showed higher total flavonoid content (TFC) (5.12 ± 1.02 mg QR/g), followed by branches (3.16 ± 0.88 QR/g) and roots (2.04 ± 0.52 QR/g/g). The extract of the branches exhibited higher total phenolic content (TPC) (1.07 ± 0.77 GAE/g), followed by leaves (0.58 ± 0.30 GAE/g) and roots (0.19 ± 0.47 GAE/g). Pharmacophore and molecular docking analysis were performed in order to better understand the potential mechanism of the antioxidant activity of its major metabolites.

Anticonvulsant, Anxiolytic and Antidepressant Properties of the ß-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems.

BACKGROUND: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. METHODS: This study evaluated the neurobehavioral effects of ß-CBP using the open field test, rota- rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. RESULTS: The results demonstrated that the neuropharmacological activities of ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of ß-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500-750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.

Palmatine antioxidant and anti-acetylcholinesterase activities: A pre-clinical assessment.

There is evidence that palmatine (PA), an alkaloid isolated from the Guatteria friesiana plant, has some important biological activities, including anti-inflammatory and antidepressant effects. In this study, the antioxidant and anti-acetylcholinesterase (AChE) effects of PA were assessed. The antioxidant capacity was evaluated in vitro and in vivo through 7 distinct assays, and the anti-AChE activity was determined in vitro. The standards, trolox and ascorbic acid were used for the in vitro antioxidant test, while hydrogen peroxide was selected as a stressor for the Saccharomyces cerevisiae test. Additionally, PA was also combined with trolox and ascorbic acid to determine the likelihood of synergistic effects occurrence to what concerns to antioxidant potential. PA exhibited a potent and concentration-dependent antioxidant potential, although a stronger antioxidant activity was stated using the PA + trolox combination. PA was also found to inhibit AChE activity when compared to the negative control. Thus, PA may be viewed as a promissory phytotherapeutic agent to manage oxidative stress-mediated neurological diseases, especially the Alzheimer's and Parkinson's diseases.

Toxicity, cytotoxicity, mutagenicity and in vitro antioxidant models of 2-oleyl-1,3-dipalmitoyl-glycerol isolated from the hexane extract of Platonia insignis MART seeds.

2-oleyl-1,3-dipalmitoyl-glycerol (ODG) was obtained from Platonia insignis (bacurizeiro) seeds. There are no studies on its toxicity and protective activities against oxidative stress. This study was aimed to evaluate antioxidant effects in vitro, as well as to evaluate the toxicological and mutagenic effects of the ODG. ODG showed a median lethal dose (LD50) greater than 1200 µg mL-1 in A. salina. In the assay of A. cepa (0.2-0.002 mg mL-1) the ODG compound at the highest concentration was slightly cytotoxic with decrease in the size of roots and mitotic indexes, but did not induce chromosomal alterations. ODG (8.75-140.00 µg mL-1) was found to reduce nitric oxide production by 41.6 %, while the antioxidant standard ascorbic acid (AA) reduced 54.14 %. ODG (15.625-250.00 µg mL-1) promoted removal of the hydroxyl radical by 35.69 % at the highest concentration and was able to prevent lipid peroxidation induced by 2,2'-azobis-2-amidinopropane (AAPH), inhibiting the amount of TBARS formed, up to 35.69 %, a result close to that obtained with AA. Thus, ODG moderately reduced the levels of hydroxyl radicals, nitric oxide, and TBARS in vitro and was nontoxic at low concentrations.

Determination by chromatography and cytotoxotoxic and oxidative effects of pyriproxyfen and pyridalyl.

Pyriproxyfen (PPF) is a larvicide, used to combat the proliferation of Aedes aegypti larvae. The objective of this study was to analyze the compounds of pyriproxyfen and pyridalyl (PYL) in a commercial larvicide to analyze the cytotoxic and oxidative effects of PPF and PYL. The toxic potential of PPF and PYL were assessed based on lethal concentration (LC50) in Artemia salina, cytotoxicity based on the mitotic index and the chromosomal alterations in Allium cepa and the oxidative damage in Saccharomyces cerevisiae. The PPF and PYL compounds were identified by HPLC-PDA based on their retention times and spectral data. The wavelengths λmax (258 nm) and (271 nm) of the UV spectrum of PYL and PPF and the retention times (RT) (3.38 min) and (4.03 min), respectively. The toxicological potentials of PPF and PYL were significant at concentrations (1, 10, 100 and 1000 ppm), with an LC50 of 48 h (0.5 ppm). PPF and PYL pointed out a cytotoxic effect in A. cepa at all concentrations (0.0001, 0.001, 0.01, 0.1, 1.0, 100 and 1000 ppm), genotoxic effect at concentrations only (0.0001; 0.1; 1; 100 and 1000 ppm), and mutagenic for concentrations (0.1, 100 and 1000 ppm). In relation S. cerevisiae, PPF e PYL prompted oxidative damage at concentrations (100 and 1000 ppm) in all strains (SODWT, Sod1, Sod2, Sod1Sod2, Cat1 and Sod1Cat1). Therefore, the PPF and PYL identificated in commercial larvicide by HPLC-PDA produced cytotoxic and oxidative effects that could cause health and ecosystem risks.

Determination of Parameters of Oxidative Stress in vitro Models of Neurodegenerative Diseases-A Review.

Oxidative stress is a major mechanism underlying the development of various neurodegenerative diseases (Alzheimer, Parkinson, Huntington and amyotrophic lateral sclerosis). Excessive formation of reactive oxygen species (ROS) and nitrogen (RNSs) can overburden the ability of the enzymatic antioxidant defense mechanisms (superoxide dismutase, catalase and glutathione reductase) and non-enzymatic (uric acid, ascorbic acid, α-tocopherol and reduced glutathione), causing the development of oxidative stress, and consequently, impairing the neuronal system cells by means of oxidative damage to a variety of important biological molecules such as lipids, DNA and proteins. Considering the importance of oxidative stress in neurodegenerative diseases, the present review aims to address the main parameters evaluated in in vitro studies on oxidative stress in different models of neurodegenerative diseases.The literary review was conducted through Pubmed, Science Direct, LILACS, Scielo and Google using following keywords: oxidative stress, neurodegenerative diseases and parameters of oxidative stress. We selected articles published between 2002 and 2017.The in vitro evaluation of the oxidative stress related parameters has provided a preliminary view about the pathogenesis of many neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's and Amyotrophic lateral sclerosis). In this way, it has demonstrated the mechanism of action of ROS/RNSs in these diseases by direct or indirect detection through several experimental procedures in vitro.

A Brief Review on the Neuroprotective Mechanisms of Vitexin.

The neural dysfunction is triggered by cellular and molecular events that provoke neurotoxicity and neural death. Currently, neurodegenerative diseases are increasingly common, and available treatments are focused on relieving symptoms. Based on the above, in this review we describe the participation of vitexin in the main events involved in the neurotoxicity and cell death process, as well as the use of vitexin as a therapeutic approach to suppress or attenuate neurodegenerative progress. Vitexin contributes to increasing neuroprotective factors and pathways and counteract the targets that induce neurodegeneration, such as redox imbalance, neuroinflammation, abnormal protein aggregation, and reduction of cognitive and/or motor impairment. The results obtained provide substantial evidence to support the scientific exploration of vitexin in these pathologies, since their effects are still little explored for this direction.

Non-clinical toxicity of ß-caryophyllene, a dietary cannabinoid: Absence of adverse effects in female Swiss mice.

ß-caryophyllene is a food additive that is found in food plants and has broad pharmacological potential. However, little toxicological information has been reported and its use is based on the fact that this bicyclic sesquiterpene is daily consumed as a plant food in much larger quantities than as a food additive. Thus, this study evaluated acute (14-day) and repeated-dose (28 days) oral ß-caryophyllene toxicity in female Swiss mice analyzing changes in body weight, food intake, water intake, hematological and biochemical parameters, organ weight after necropsy, oxidative stress markers and histopathology of various tissues. Acute (300 and 2000 mg/kg) and repeated-dose (300 and 2000 mg/kg) toxicity studies were performed according to the Organization for Economic Cooperation and Development (OECD) guideline 423 and 407, respectively. There was absence of adverse clinical signs and mortality in any animal subjected to acute and repeated-dose toxicity study. In addition, no significant changes in body weight, food and water intake, oxidative stress biomarkers, hematological and biochemical parameters were observed when compared to control group from single-dose and repeated-dose toxicity study. Therefore, the results of this study provide an understanding of the toxicity profile of ß-caryophyllene which can be considered a compound with toxicity at doses higher than 2000 mg/kg body weight.

Evaluation of Antioxidant Activity of Phytol Using Non- and Pre-Clinical Models.

BACKGROUND: Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol; PHY), the alcoholic diterpenoid is particularly interesting due to its diverse activities found in literature. This study evaluated in vitro and in vivo antioxidant capacity of PHY. METHODS: We conducted DPPH• (2,2-diphenyl-1-picrylhydrazyl) and ABTS•+ (2,2'-azino-bis(3- ethylbenzthiazoline-6-sulphonic acid)) radical scavenging tests as in vitro, while Saccharomyces cerevisiae test as in vivo. For in vitro tests, trolox and for in vivo test hydrogen peroxide (H2O2) were taken as standard and stressor, respectively. Additionally, we measured the superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), lipid peroxidation (LP) and nitrite (NO2 -) contents in mouse hippocampus taking 0.05% Tween 80 dissolved in 0.9% saline (0.25 ml) and ascorbic acid (250 mg/kg; AA) as vehicle and standard, respectively. PHY was administered at doses 25, 50 and 75 mg/kg. In the latter case, all the treatments were administered via intraperitoneal (i.p.) route. RESULTS: PHY at 7.2 µg/ml exhibited 59.89 ± 0.73% and 62.79 ± 1.99% scavenging capacity of DPPH• and ABTS•+, respectively. In S. cerevisiae strains, PHY showed prominent protective effects. Moreover, in Swiss mouse hippocampus; PHY reduced the LP and NO2 - contents, while increased in GSH, SOD and CAT activities. CONCLUSION: PHY exerted antioxidant potential in our current non- and preclinical test systems and can be a good candidate for the development of treatments of oxidative stress mediated diseases.

Alkaloids Pharmacological Activities - Prospects for the Development of Phytopharmaceuticals for Neurodegenerative Diseases.

The study of natural substances has increased in recent years in the search for compounds with pharmacological properties that can be used for the development of new drugs. The alkaloids, substances extracted natural sources, show promising pharmacological activities, including pharmacological activities for the treatment of neurodegenerative diseases such as Alzheimer's disease, whose treatment is based on the use of various drugs. Thus, the article aims to a technological prospecting of alkaloids that presented important properties in the treatment of neurodegenerative diseases, namely, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties. A literature review was conducted in the databases PubMed, Science Direct, Scopus, Scielo and Google Academics using the following key words: alkaloids, pharmacology, neurodegenerative diseases, cholinesterase inhibitors, antidepressants, anti-inflammatories, antioxidant and anxiolytic. Articles, dissertations and theses published between 2003 and 2015 were selected. Several studies showed through in vitro of in vitro and/or in vivo methods that many alkaloids extracted from plants showed anticholinesterase, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties in the treatment of symptoms and progression of certain diseases such as Alzheimer's disease.

Ensaios pré-clínicos em ratos tratados com 1, 3-diestearil-2-oleilglicerol, constituinte isolado de Platonia insignis / Pre clinical trials in rats treated with 1, 3 -distearoyl-2-oleoylglycerol (TG1) constituent isolated from Platonia insignis

Introdução: Avaliou-se a toxicidade aguda de 1,3-diestearil-2-oleil-glicerol (TG1), composto obtido de Platonia insignis Mart. (bacurizeiro), após administração oral em ratos Wistar. Métodos: A toxicidade aguda foi analisada através dos parâmetros hematológicos e bioquímicos. A análise de citotoxicidade in vitro foi feita pelo método do sal 3-(4,5-dimetil-2-tiazol)-2,5-difenil-2-H-brometo de tetrazolium (MTT). Os tecidos cerebrais e hepáticos foram avaliados histopatologicamente. Resultados: O tratamento agudo com TG1(dose de 30 mg kg -1) não produziu alterações hematológicas e histopatológicas nas áreas cerebrais e hepáticas. A redução dos níveis das enzimas transaminase (AST) e fosfatase alcalina (ALKP) pode sugerir proteção hepática. As análises bioquímicas da aspartato aminotransferase, ALKP e do ácido úrico apresentaram seus níveis reduzidos, conferindo preservação dos rins e fígado dos animais (p<0,05). TG1 não revelou potencial citotóxico pelo método MTT. Conclusão: O tratamento com TG1 não produz alterações hematológicas, bioquímicas, histopatológicas cerebrais e hepáticas em ratos o que caracteriza uma baixa toxicidade.

Introduction: The aim of this study was to assess the acute toxicity of 1,3-distearoyl-2-oleoylglycerol (TG1), a compound isolated from Platonia insignis Mart. (bacurizeiro). Methods: The acute toxicity was analyzed by biochemical and hematological parameters. The cytotoxic study was conducted by the MTT method. The histopathological study was conducted in brain and liver tissues. Results: Acute treatment with TG1 (dose of 30 mg. kg -1) did not change the general behavior pattern of rats and not result in hematological and histological changes in the liver. The reduced levels of transaminase and alkaline phosphatase (ALKP) enzymes may suggest even certain liver protection. The biochemical analyzes demonstrated low levels of aspartate aminotransferase, ALKP and uric acid, providing preservation of kidneys and livers of animals (p<0.05). TG1 this study did not reveal cytotoxic potential by MTT method. Conclusion: These results indicate that treatment with TG1 not produce hematological, biochemical and histopathological alterations in rats suggesting low toxicity

Investigation of biological activities of dichloromethane and ethyl acetate fractions of Platonia insignis Mart. seed.

Platonia insignis Mart., a native species of the Brazilian Amazon more commonly known as bacuri, is a member of the Clusiaceae family. In this study, we evaluated the chemical composition and the antioxidant and toxicity activities of the dichloromethane and ethyl acetate fractions from P. insignis seed ethanolic extract using different experimental models. Our results demonstrate in vitro antioxidant effects, by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1,1-diphenyl-2-picryl-hydrazyl assays, as well as in vivo effects in antioxidant-defective Saccharomyces cerevisiae strains to both fractions. Toxicity was evaluated against the micro-crustaceous Artemia salina Leach. and promastigote Leishmania amazonensis. The dichloromethane fraction was the most active fraction evaluated on A. salina and promastigote L. amazonensis (IC(50)  = 24.89 µg/mL and 2.84 µg/mL, respectively). In addition, a slight cytotoxicity was observed in mammalian V79 cells using ethyl acetate and dichloromethane fractions with MTT assays. Both fractions displayed genotoxicity up to 25 µg/mL (dichloromethane) and 10 µg/mL (ethyl acetate) in V79 cells, as evaluated by the alkaline comet assay. Thus, in this study, we demonstrate for the first time that ethyl acetate and dichloromethane fractions from P. insignis seeds display antioxidant effects, a toxic effect against A. salina and L. amazonensis and induce genotoxicity in V79 mammalian cells. The observed activities can be attributed to the phenolic compounds present in these fractions and to the presence of xanthones (alpha- and gamma-mangostin).

Efeito do tratamento agudo do óleo essencial de Citrus sinensis (L) Osbeck na aquisição da memória espacial de ratos avaliada no labirinto aquático de Morris / Effect of oral treatment with essential oil of Citrus sinensis (L) Osbeck in the retention of spatial memory in rats evaluated in the Morris water maze

A Doença de Alzheimer está relacionada a prejuízos na aquisição e retenção da memória, processos que podem ser estudados no laboratório por meio de modelos animais, entre eles o labirinto aquático de Morris, que avalia a memória espacial em ratos. Estudos sobre as propriedades biológicas do gênero Citrus destacam atividades importantes como antioxidantes e anticolinesterásica. O objetivo desse trabalho é avaliar os efeitos do tratamento agudo com o óleo essencial de folhas (OEF) de Citrus sinensis (L.) Osbeck no processo de aquisição da memória espacial em ratos Wistar, utilizando o paradigma do labirinto aquático de Morris. O óleo essencial de Citrus sinensis possui em sua composição principalmente compostos da classe dos monoterpenos, como o limoneno (20,14%), citronelol (30,42%) e o geranial (31,42%). Os animais foram tratados previamente com doses do óleo essencial (OE) de C. sinensis (L.) Osbeck de 50, 100 e 200 mg/kg e realizados testes de campo aberto e do labirinto aquático de Morris. A aquisição da memória espacial é avaliada pelo tempo que o animal leva para localizar a plataforma depois de ter sido treinado. Nos resultados do campo aberto foi demonstrado que os animais não apresentam estímulo motor quando tratados com o óleo essencial de Citrus sinensis e os resultados do labirinto aquático foram significativamente menores na latência para encontrarem a plataforma submersa do que o grupo controle negativo [p<0,01] indicando uma capacidade de memória maior nos animais tratados, mas que devem ser reforçados por outros testes de memória preconizado na literatura.

Alzheimer?s disease is related to damage in memory acquisition and retention that can be studied in the laboratory through animal studies, including the Morris water maze, which assesses the spatial memory in rats. The Citrus has many studies on biological activities that are important for memory function as antioxidants and anticholinesterase. The objective of this study is to evaluate the effects of acute treatment with the essential oil of leaves (EOL) from Citrus sinensis (L.) Osbeck in the acquisition of spatial memory in rats, using the paradigm of the Morris water maze. The essential oil of Citrus sinensis has in composition mainly composed of the class of monoterpenes such as limonene (24.14%), citronellol (30.42%) and geranial (31,42%). The animals were previously untreated with doses of essential oil (EO) of Citrus sinensis 50, 100 e 200 mg/kg and the open test conducted and the Morris water maze task. The acquisition of memory space is evaluated by time the animal takes to locate the platform after having been trained. The results of the open was demonstrated that animals do not exhibit motor stimulus when treated with the essential oil of Citrus sinensis and the results of water maze were significantly lower in to find the submerged platform than the negative control group [p<0.01] indicating an increased memory capacity in the treated animals, but must be reinforced by other memory tests recommended by the literature.

Evaluation of effects of dichloromethane fraction from Platonia insignis on pilocarpine-induced seizures

The objective of present study was to evaluate the antioxidant and anticonvulsant activities of dichloromethane fraction (DMF) from Platonia insignis Mart., Clusiaceae. The DMF from P. insignis (2 mg/kg) was tested by intraperitoneal (i.p.) to evaluate effects on lipid peroxidation level, nitrite formation, as well as on locomotor and anticonvulsant activities. Wistar rats were treated with, (saline/Tween 80 0.5 percent, i.p., control group), DMF (2 mg/kg, i.p., DMF group), pilocarpine (400 mg/kg, i.p., P400 group), or the combination of DMF (2 mg/kg, i.p.) and pilocarpine (400 mg/kg, i.p., DMF plus P400). After the treatments all groups were observed for 24 h. In P400 group rats there was a decrease in the motor activity when compared with control group. In DMF plus P400 co-administered rats was observed an increase in motor activity when compared with P400 group. In P400 group rats there was a significant increase in lipid peroxidation and nitrite levels. In DMF plus P400 co-administered rats, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content after seizures. Previous findings strongly support the hypothesis that oxidative stress occurs in rat striatum during pilocarpine-induced seizures, and our results imply that strong neuprotective effect on this brain region could be achieved using DMF from P. insignis.

Evaluation of central nervous system effects of Citrus limon essential oil in mice

The central nervous system (CNS) depressant and anticonvulsant activities of Citrus limon (L.) Osbeck, Rutaceae, essential oil (EO) were investigated in animal models. The EO (50, 100 and 150 mg/kg) injected by oral route (p.o.) in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to thirty days after the administration and the dose of 150 mg/kg significantly reduced the remaining time of the animals on the Rota-rod apparatus. Additionally, C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). The administration of FLU (10 mg/kg, i.p.), GABA A-benzodiazepine (GABA-BZD) receptor antagonist, antagonized the effect of C. limon essential oil at higher dose. This C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at higher dose. In the same way, the anticonvulsant effect of the EO was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities in mice that needs further investigation.

Antioxidant activity of Citrus limon essential oil in mouse hippocampus.

CONTEXT: Citrus limon (L.) Burms (Rutaceae) has been shown in previous studies to have various biological functions (anti-inflammatory, antiallergic, antiviral, antimutagenic, and anticarcinogenic). However, traditional uses in folk medicine suggest that C. limon may have an effect on the central nervous system (CNS). OBJECTIVE: This study investigated the effects of C. limon essential oil (EO) on lipid peroxidation level, nitrite content, glutathione reduced (GSH) concentration, and antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx)] activities in mice hippocampus. MATERIALS AND METHODS: Swiss mice were treated with the suspension of 0.5% Tween 80, in distilled water used as vehicle (i.p., control group) and with EO in three different doses (0.05, 0.1, or 0.15 g/kg, i.p., EO 50, EO 100, and EO 150 groups, respectively). After the treatments, all groups were observed for 24 h. The enzyme activities as well as the lipid peroxidation, nitrite, and GSH concentrations in mice hippocampus were measured using spectrophotometric methods and the results were compared with values obtained from control group. RESULTS: EO of C. limon treatment significantly reduced the lipid peroxidation level and nitrite content but increased the GSH levels and the SOD, catalase, and GPx activities in mice hippocampus. DISCUSSION AND CONCLUSION: Our findings strongly support the hypothesis that oxidative stress in hippocampus can occur during neurodegenerative diseases, proving that hippocampal damage induced by the oxidative process plays a crucial role in brain disorders, and also imply that a strong protective effect could be achieved using EO of C. limon as an antioxidant.

Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures.

Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

Antioxidant and antinociceptive effects of Citrus limon essential oil in mice.

The antioxidant and antinociceptive activities of Citrus limon essential oil (EO) were assessed in mice or in vitro tests. EO possesses a strong antioxidant potential according to the scavenging assays. Moreover, it presented scavenger activity against all in vitro tests. Orally, EO (50, 100, and 150 mg/kg) significantly reduced the number of writhes, and, at highest doses, it reduced the number of paw licks. Whereas naloxone antagonized the antinociceptive action of EO (highest doses), this suggested, at least, the participation of the opioid system. Further studies currently in progress will enable us to understand the action mechanisms of EO.

Avaliação do potencial neuroprotetor do óleo essencial de Citrus limon em hipocampo e corpo estriado de camundongos após convulsões induzidas pela pilocarpina / Evaluation of neuroprotective potential of Citrus limon essential oil in hippocampus and striatum of mice after pilocarpine-induced seizures

The seizures can produce neuronal damage in several brain structures. The aim of this study was to investigate the potential neuroprotective effect of essential oil of Citrus limon (EOCL) on the histopathological changes observed in the hippocampus and striatum of mice after seizures induced by pilocarpine. Adult Swiss mice were 2 months old. The animals were divided into four groups. The first group was treated with 0.05 percent Tween 80 (control group) and the second with pilocarpine (400 mg/kg group P400). The third and fourth group were treated with EOCL (150 mg/kg) and 30 min after received P400 (P400 +/- EOCL group) or 0.05 percent Tween 80, respectively. After treatment, all groups were observed for 24 h, then sacrificed and their brains removed for histopathological analysis. The group P400, presented with seizures that progressed to status epilepticus in 75 percent of animals. Pretreatment with OECL produced a 25 percent reduction in this index. Groups P400 and P400 + EOCL showed 83.33 percent and 25 percent of animals with brain damage in the hippocampus, respectively. In the striatum of group P400 was a compromise of 75 percent. In turn, in the striatal region of group EOCL P400 + was seen a decrease of 58.34 percent in this neuronal damage. The seizures induced by pilocarpine are installed by the cholinergic system and produce brain damage. According to our results we suggest that the EOCL may modulate epileptogenesis and promote neuroprotective effects during the seizures in the model investigated.

As convulsões podem produzir danos neuronais em diversas estruturas cerebrais. O objetivo desse estudo foi investigar o potencial efeito neuroprotetor do óleo essencial de Citrus limon (OECL) nas alterações histopatológicas observadas no hipocampo e corpo estriado de camundongos após convulsão induzida por pilocarpina. Foram utilizados camundongos Swiss adultos com 2 meses de idade. Os animais foram divididos em 4 grupos. O primeiro grupo foi tratado com Tween 80 0,05 por cento (grupo controle) e o segundo com pilocarpina (400 mg/kg, grupo P400). Já o terceiro e quarto grupo foram tratados com OECL (150 mg/kg), e 30 min depois receberam P400 (grupo OECL + P400) ou Tween 80 0,05 por cento 0.9 por cento (grupo OECL), respectivamente. Após os tratamentos, todos os grupos foram observados durante 24 h e em seguida sacrificados e seus cérebros removidos para as análises histopatológicas. O grupo P400, apresentou convulsões que progrediram para o estado epiléptico em 75 por cento dos animais. O pré-tratamento com OECL produziu uma redução de 25 por cento nesse índice. Os grupos P400 e OECL + P400 apresentaram 83,33 por cento e 25 por cento de animais com lesão cerebral no hipocampo, respectivamente. No corpo estriado dos animais do grupo P400 houve um comprometimento de 75 por cento. Por sua vez, na região estriatal dos animais do grupo OECL + P400 foi visto uma redução de 58,34 por cento nesse comprometimento. As convulsões induzidas pela pilocarpina são instaladas pelo sistema colinérgico e produzem dano cerebral. De acordo com nossos resultados podemos sugerir que o OECL pode modular a epileptogênese e promover ação neuroprotetora durante as convulsões no modelo investigado.

Caffeic acid effects on oxidative stress in rat hippocampus after pilocarpine-induced seizures.

The objective of the study was to evaluate the caffeic acid (CA) effects against the oxidative stress (OS) observed during seizures. Wistar rats were intraperitoneally treated with either 0.9% saline (control), CA (4 mg/kg), pilocarpine (400 mg/kg, pilocarpine group), or the association of CA (4 mg/kg) plus pilocarpine (400 mg/kg). The thiobarbituric-acid-reacting substances and the hippocampal nitrite content were significantly increased (89 and 94%, respectively) in pilocarpine group when compared with control. There were marked decreases in lipid peroxidation level (43%) and nitrite content (45%) in CA group when compared with pilocarpine group. There were no marked alterations in superoxide dismutase (SOD) and catalase (CAT) activities in pilocarpine group; however, the SOD and CAT activities were significantly increased (35 and 51%, respectively) after CA pretreatment. Our findings strongly support the hypothesis that OS was indeed generated in hippocampus. CA pretreatment can reduces the OS produced by seizures.