Polysaccharide-rich extract of Genipa americana leaves protects seizures and oxidative stress in the mice model of pentylenetetrazole-induced epilepsy.

Plant polysaccharides have biological activities in the brain and those obtained from Genipa americana leaves present antioxidant and anticonvulsant effects in the mice model of pentylenetetrazole (PTZ)-induced acute seizures. This study aimed to evaluate the polysaccharide-rich extract of Genipa americana leaves (PRE-Ga) in the models of acute seizures and chronic epilepsy (kindling) induced by PTZ. In the acute seizure model, male Swiss mice (25-35 g) received PRE-Ga (1 or 9 mg/kg; intraperitoneal- IP), alone or associated with diazepam (0.01 mg/kg), 30 min before induction of seizures with PTZ (70 mg/kg; IP). In the chronic epilepsy model, seizures were induced by PTZ (40 mg/kg) 30 min after treatment and in alternated days up to 30 days and evaluated by video. Brain areas (prefrontal cortex, hippocampus, striatum) were assessed for inflammatory and oxidative stress markers. Diazepam associated to PRE-Ga (9 mg/kg; i.p.) increased the latency of seizures in acute (222.4 ± 47.57 vs. saline: 62.00 ± 4.709 s) and chronic models (6.267 ± 0.502 vs. saline: 4.067 ± 0.407 s). In hippocampus, PRE-Ga (9 mg/kg) inhibited TNF-α (105.9 ± 5.38 vs. PTZ: 133.5 ± 7.62 pmol/g) and malondialdehyde (MDA) (473.6 ± 60.51) in the chronic model. PTZ increased glial fibrillar acid proteins (GFAP) and Iba-1 in hippocampus, which was reversed by PRE-Ga (GFAP: 1.9 ± 0.23 vs PTZ: 3.1 ± 1.3 and Iba-1: 2.2 ± 0.8 vs PTZ: 3.2 ± 1.4). PRE-Ga presents neuroprotector effect in the mice model of epilepsy induced by pentylenetetrazole reducing seizures, gliosis, inflammatory cytokines and oxidative stress.

Ethanolic Extract of the Red Algae Meristiella echinocarpa (Areschoug) Confers Neuroprotection in Mice / Extrato Etanólico da Alga Vermelha Meristiella echinocarpa (Areschoug) Confere Neuroproteção em Camundongos

Objectives: This study aimed to investigate the neuroprotective effects of the ethanolic extract obtained from red algae marine Meristiella echinocarpa (Areschougiaceae) ­ EEMe. Methods: EEMe was used in doses ranging from 10 to 40 mg/kg, administered intraperitoneally in mice. Behavioral tests were performed to assess locomotor activity (open field), anxiety (elevated plus maze), depression (tail suspension), and motor coordination (rota-rod). The anticonvulsant effect of the algae extract was evaluated in two models of seizures induced by strychnine and pentylenetetrazol. The level of oxidative stress was also evaluated in the following brain areas: the prefrontal cortex, hippocampus, and striatum. Statistical analysis was performed applying ANOVA followed by the Bonferroni test. Results: EEMe reduced significantly the number of crossing (36%) and rearing (54%) in the open field test and increased 1.3x the immobility time in the tail suspension test. In brain areas EEMe also reduced significantly malondialdehyde levels (striatum: 45%, hippocampus: 38%, prefrontal cortex: 37%) and nitrite levels (striatum: 72%, hippocampus: 79%, prefrontal cortex: 63%), and increased the reduced-glutathione levels (striatum: 72%, hippocampus: 73%, prefrontal cortex: 42%). In addition, the extract significantly prolonged the latency of seizures induced by strychnine (38%) or pentylenetetrazol (57%), and the latency of death induced by pentylenetetrazol (6.1x). Conclusion: EEMe exhibits antioxidant and anticonvulsant effects, probably involving GABAergic and glycinergic pathways.

Objetivos: este estudo teve como objetivo investigar os efeitos neuroprotetores do extrato etanólico da alga marinha vermelha Meristiella echinocarpa (Areschougiaceae) - EEMe. Métodos: EEMe foi utilizado em doses que variaram de 10 a 40 mg/kg, administrados via intraperitoneal em camundongos. Foram realizados testes comportamentais que avaliaram a atividade locomotora (campo aberto), a ansiedade (labirinto em cruz elevado), a depressão (suspensão em cauda) e a coordenação motora (rota-rod). O efeito anticonvulsivante do extrato da alga foi avaliado em dois modelos de convulsões por estricnina e pentilenotetrazol. Foi também realizada a avaliação do nível de estresse oxidativo nas seguintes áreas cerebrais: córtex pré-frontal, hipocampo e corpo estriado. A análise estatística foi realizada, aplicando a ANOVA seguida do teste de Bonferroni. Resultados: o EEMe reduziu, significativamente, o número de cruzamentos (36%) e o número de rearing (54%) no teste de campo aberto e aumentou, em 1,3x, o tempo de imobilidade no teste de suspensão pela cauda. Nas áreas cerebrais, o EEMe também reduziu, significativamente, os níveis de malondialdeído (estriado: 45%, hipocampo: 38%, córtex pré-frontal: 37%) e os níveis de nitrito (estriado: 72%, hipocampo: 79%, córtex pré-frontal: 63%) e aumentou a glutationa reduzida (estriado: 72%, hipocampo: 73%, córtex pré-frontal: 42%). Além disso, o EEMe prolongou, significativamente, a latência das convulsões induzidas por estricnina (38%) ou pentilenotetrazol (57%), e a latência da morte induzida por pentilenetetrazol (6,1x). Conclusão: o EEMe apresenta efeitos antioxidantes e anticonvulsivantes, provavelmente envolvendo as vias GABAérgica e glicinérgica.

The anticonvulsant effect of a polysaccharide-rich extract from Genipa americana leaves is mediated by GABA receptor.

BACKGROUND: This study aimed to chemically characterize a polysaccharide-rich extract (PRE) obtained from Genipa americana leaves and evaluate its neuroprotective effect in the brain morphology and oxidative markers using mice behavioral models. METHODS: Dry powder (5 g) of G. americana leaves were submitted to depigmentation in methanol. PRE was obtained by extraction in NaOH and precipitation with absolute ethanol and characterized by infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H and 13C NMR). Swiss mice (25-35 g) received saline (0.9% NaCl) or PRE (1-27 mg/kg) by intraperitoneal (i.p.) route, 30 min before evaluation in behavioral models (open field, elevated plus maze, sleeping time, tail suspension, forced swimming, seizures induced by pentylenetetrazole-PTZ). Animal's brain were dissected and analyzed for histological alterations and oxidative stress. RESULTS: FTIR spectrum showed bands around 3417 cm-1 and 2928 cm-1, relative to the vibrational stretching of OH and CH, respectively. 1H NMR spectrum revealed signals at δ 3.85 (methoxyl groups) and δ 2.4 (acetyl) ppm. 13C NMR spectrum revealed signals at δ 108.0 and δ 61.5 ppm, corresponding to C1 and C5 of α-L-arabinofuranosyl residues. PRE presented central inhibitory effect, increasing the latency for PTZ-induced seizures by 63% (9 mg/kg) and 55% (27 mg/kg), and the latency to death by 73% (9 mg/kg) and 72% (27 mg/kg). Both effects were reversed by the association with flumazenil. CONCLUSIONS: PRE, containing a heteropolysaccharide, presents antioxidant and anticonvulsant effect in the model of PTZ-induced seizures via gamma-aminobutyric acid (GABA), decreasing the number of hippocampal black neurons.

The anxiolytic-like effect of 6-styryl-2-pyrone in mice involves GABAergic mechanism of action.

The present work aims to investigate the anxiolytic activity of 6-styryl-2-pyrone (STY), obtained from Aniba panurensis, in behavioral tests and amino acids dosage on male Swiss mice. The animals were treated with STY (1, 10 or 20 mg), diazepam (DZP 1 or 2 mg/kg) or imipramine (IMI 30 mg/kg). Some groups were administered with flumazenil, 30 min before administration of the STYor DZP. The behavioral tests performed were open field, rota rod, elevated plus maze (EPM), hole-board (HB) and tail suspension test (TST). After behavioral tests, these animals were sacrificed and had their prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) dissected for assaying amino acids (aspartate- ASP, glutamate- GLU, glycine- GLY, taurine- TAU and Gamma-aminobutyric acid- GABA). In EPM test, STY or DZP increased the number of entries and the time of permanence in the open arms, but these effects were reverted by flumazenil. In the HB test, STY increased the number of head dips however this effect was blocked by flumazenil. The effects of the STY on amino acid concentration in PFC showed increased GLU, GABA and TAU concentrations. In hippocampus, STY increased the concentrations of all amino acids studied. In striatum, STY administration at lowest dose reduced GLU concentrations, while the highest dosage caused the opposite effect. GLI, TAU and GABA concentrations increased with STY administration at highest doses. In conclusion, this study showed that STY presents an anxiolytic-like effect in behavioral tests that probably is related to GABAergic mechanism of action.

Protective effects of ethanolic extract from the red algae Amansia multifida on experimental inflammation, nociception and seizure experimental models / Efeito protetor do extrato etanólico da alga marinha vermelha Amansia multifida em modelos experimentais de inflamação, nocicepção e convulsão

This study aimed to investigate the EEAm effect in mice models of nociception, inflammation and in behavioral tests evaluating the central nervous system. EEAm had inhibitory effects in the following tests: acetic acid-induced writhing (78%); formalin (62% - inflammatory phase); open field (46%). EEAm increased the nociceptive latency (56%) in tail flick test and increased the death-latency by 36% in the pentylenetetrazole-induced seizure model. Moreover, EEAm inhibited paw edema (82%) and peritonitis (45%) induced by carrageenan. In conclusion, EEAm presents antinociceptive, anti-inflammatory and anticonvulsant effects involving peripheral and central-acting mechanisms in mice.

Neste estudo objetivou-se investigar o efeito do EEAm em modelos de nocicepção e inflamação, e em testes comportamentais que avaliam o sistema nervoso central em camundongos. EEAm exibiu efeitos inibitórios nos testes comportamentais de contorções abdominais induzidas por ácido acético (78%); formalina (62% - fase inflamatória) e campo aberto (46%). EEAm aumentou a latência de nocicepção no teste de retirada da cauda (56%) e a latência de morte 36% no modelo de convulsões induzidas por pentilenetetrazol. Além disso, EEAm inibiu o edema de pata (82%) e a peritonite (45%) induzidos por carragenana. Como conclusão, EEAm apresenta efeitos antinociceptivo, anti-inflamatório e anticonvulsivante em camundongos por mecanismos periféricos e centrais.

Novel Pharmacological Properties of Dinoponera quadriceps Giant Ant Venom.

The South American giant ant, Dinoponera quadriceps (Hymenoptera, Formicidae, Ponerinae), produces proteinaceous venom that has antinociceptive, neuroprotective and antimicrobial effects, thereby supporting the popular use of these ants to treat asthma, rheumatism, earache and back pain. Anticoagulant activity is another biological property that has been shown for the venom of other hymenopteran species, like wasps. The aim of this study was to assess the anti-inflammatory, anticoagulant and antiplatelet properties of D. quadriceps venom (DqV). DqV anti-inflammatory activity was assessed by intravenous administration in Swiss mice in the models of paw edema and peritonitis. In vitro, DqV was assessed in coagulation (activated partial thromboplastin time) and platelet aggregation tests. DqV inhibited (27-33%) the edema elicited by carrageenan and the leucocyte migration (43%) elicited by zymosan. DqV decreased by 57% and 42%, respectively, the content of malondialdehyde and nitrite in the peritoneal fluid. DqV prolonged (1.8x) the clotting time and decreased (27%) the platelet aggregation induced by adenosine diphosphate. The crude venom of D. quadriceps presents an anti-inflammatory effect in mice and in vitro anticoagulant and antiplatelet effects.

Efeito do ultrassom terapêutico sobre as propriedades mecânicas do gastrocnêmio em ratos / Effect of therapeutic ultrasound on mecnanical properties of gastrocnemius in rats / Efecto del ultrasounido terapéutico sobre las propiedades mecánicas del gastrocnemio en ratones

INTRODUÇÃO: Apesar de algumas controvérsias quanto à sua utilização, o ultrassom terapêutico (UST) é um recurso comumente aplicado na reabilitação desportiva para aceleração do reparo tecidual de lesões musculares. Sabe-se que lesões musculares influenciam negativamente as propriedades mecânicas da musculatura estriada esquelética e algumas evidências demonstram que o UST poderia ter efeitos benéficos sobre o reparo muscular e, consequentemente, sobre suas propriedades mecânicas. OBJETIVO: Analisar o efeito do UST no reparo tecidual por meio das propriedades mecânicas musculares de ratos após trauma por criolesão. MÉTODOS: Foram utilizados no estudo 30 ratos da linhagem Wistar, os quais foram divididos em três grupos: grupo controle intacto (GC), grupo lesionado sem tratamento (GL), e grupo lesionado e estimulado com UST (frequência de 1 MHz; intensidade de 0,5 W/cm2; ciclo de trabalho de 50%; por quatro minutos diários), durante sete dias consecutivos (GLUST). As propriedades mecânicas obtidas através de ensaio mecânico de tração foram avaliadas em uma máquina universal de ensaios. RESULTADOS: Foram analisados estatisticamente, com nível de significância de 95% (P<0,05). Após sete sessões de tratamento, houve melhora estatisticamente significativa nas propriedades mecânicas de carga no limite de proporcionalidade, carga no limite máximo e resiliência para o GLUST em relação ao GL (p<0,05). CONCLUSÃO: O UST foi eficaz no processo de reparo tecidual, conferindo ao tecido muscular maior resistência à tração e absorção de energia. .

INTRODUCTION: Despite controversial, ultrasonic therapy (UST) is commonly applied in sports rehabilitation practice to accelerate tissue repair after muscle damage. Muscle injuries have a negative influence on the mechanical properties of skeletal striated muscles and some scientific evidence shows that UST could have a positive effects on tissue repair and, therefore, on its mechanical properties. OBJECTIVE: To analyze the effect of UST on muscle repair by evaluation of the mechanical properties of rat muscles after cryolesion. METHODS: We used 30 adult Wistar rats which were divided into three groups: CG (control group), IG (injured group) and IGUST (injured plus UST) - (frequency of 1 MHz; intensity of 0.5 W/cm2; pulsed to 50%; four minutes daily) for seven consecutive days. The mechanical properties obtained through mechanical tests were evaluated in a universal testing machine. RESULTS: Data were statistically analyzed with a significance level of 95% (p<0.05). After seven treatment sessions, we found significant improvement in the mechanical properties of load at the proportionality limit, load at maximum limit and resilience in IGUST compared to IG (p<0.05). CONCLUSION: The UST was effective in the tissue repair process, giving higher tensile strength and energy absorption to the muscle tissue. .

INTRODUCCIÓN: A pesar de algunas controversias cuanto a su utilización, el ultrasonido terapéutico (UST) es un recurso aplicado comúnmente en la rehabilitación deportiva para aceleración de la reparación tecidual de lesiones musculares. Se sabe que las lesiones musculares influyen negativamente en las propiedades mecánicas de la musculatura estriada esquelética y algunas evidencias demuestran que el UST podría tener efectos sobre la reparación muscular y, en consecuencia, con respecto a sus propiedades mecánicas. OBJETIVO: Analizar el efecto del UST en la reparación tecidual por medio de las propiedades mecánicas musculares de ratones después de traumatismo por criolesión. MÉTODOS: Se utilizaron, en el estudio, 30 ratones de la raza Wistar, los cuales fueron divididos en tres grupos: grupo de control intacto (GC), grupo lesionado sin tratamiento (GL) y grupo lesionado y estimulado con UST (frecuencia de 1 MHz; intensidad de 0,5 W/cm2; ciclo de trabajo de 50%, durante cuatro minutos diarios) a lo largo de siete días consecutivos (GLUST). Las propiedades mecánicas obtenidas, mediante el ensayo mecánico de tracción, fueron evaluadas en una máquina universal de ensayos. RESULTADOS: Se analizaron estadísticamente, con nivel de significancia de 95% (P<0,05). Después de siete sesiones de entrenamiento, hubo mejora estadísticamente significativa en las propiedades mecánicas de carga en el límite de proporcionalidad, carga en el límite máximo y resiliencia para el GLUST en relación con el GL (p<0,05). CONCLUSIÓN: El UST fue eficaz en el proceso de reparación tecidual, dando al tejido muscular más resistencia cuanto a la tracción y la absorción de energía. .