RESUMO
BACKGROUND: Plant lectins have shown promising neuropharmacological activities in animal models. OBJECTIVE: This study evaluated the effect of Dioclea altissima seed lectin (DAL) on adult zebrafish behavior. METHOD: Zebrafish (n=6/group) were treated (i.p.; 20 µL) with DAL (0.025; 0.05 or 0.1 mg/mL), vehicle or diazepam (DZP) and submitted to several tests (open field, light/dark preference or novel tank). Flumazenil, pizotifen or granisetron were administered 15 min before DAL (0.05 mg/mL), and the animals were evaluated on light/dark preference test. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. RESULTS: DAL decreased the locomotor activity of adult zebrafish (0.025; 0.05 or 0.1 mg/mL), increased the time spent in the upper region of the aquarium (0.025 mg/mL), and decreased the latency time of adult zebrafish to enter the upper region on the novel tank test. DAL (0.05 mg/mL) also increased their permanence in the light zone of the light/dark preference test. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and was prevented by pizotifen, granizetron and flumazenil. CONCLUSION: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors.
Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Dioclea/metabolismo , Lectinas/metabolismo , Peixe-Zebra/metabolismo , Animais , Ansiolíticos/uso terapêutico , Modelos Animais de Doenças , Locomoção/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Receptores de GABA-A/metabolismo , SementesRESUMO
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.
Assuntos
Ansiolíticos/química , Anticonvulsivantes/química , Antidepressivos/química , Antagonistas de Receptores de GABA-A/química , Sesquiterpenos Policíclicos/química , Animais , Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Arginina , Comportamento Animal , Benzodiazepinas/metabolismo , Bicuculina/química , Bicuculina/farmacologia , Feminino , Flumazenil/química , Flumazenil/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Humanos , Aprendizagem em Labirinto , Camundongos , Óxido Nítrico/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Transdução de SinaisRESUMO
BACKGROUND: Plant lectins have shown promising biological activities in the central nervous system (CNS). OBJECTIVE: This study evaluated the effect of DAL, a lectin isolated from the seeds of the Dioclea altissima species, having binding affinity to D-glucose or D-mannose residues, on mice behavior. METHODS: Mice (n=6/group) were treated (i.p.) with DAL (0.25, 0.5 or 1 mg/kg) or vehicle and subjected to several tests (open field/OFT, marble-burying/MBT, hole-board/HBT, elevated plus maze/PMT, tail suspension/ TST, forced swimming/FST or rotarod/RRT). Pizotifen, cyproheptadine, flumazenil, L-NAME, 7-NI, Larginine or yohimbine were administered 15 min before DAL (0.5 mg/kg) and the animals were evaluated on PMT. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. RESULTS: The results showed there were no neurobehavioral changes in the mice at the RRT, FST and locomotion in the OFT. DAL (0.25, 0.5 or 1 mg/kg) increased the behavior of grooming and rearing in the OFT, head dips in the HBT, pedalling in the TST and decreased the number of marbles hidden in the MBT. In the PMT, DAL (0.25, 0.5 and 1 mg/kg) and Diazepam increased the frequency of entries in the open arms and the time of permanence in the open arms without affecting the locomotor activity. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and it prevented by pizotifen, cyproheptadine, flumazenil, L-NAME and 7-NI, but not by L-arginine or yohimbine. CONCLUSION: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors and NO pathway.
Assuntos
Ansiolíticos , Dioclea , Animais , Ansiolíticos/farmacologia , Antidepressivos , Comportamento Animal , Lectinas , Camundongos , Extratos Vegetais , SementesRESUMO
The aim of the present study was to show the most relevant aspects of the flavonoids such as their origin, sources, chemical structures, and metabolism in the body human. We offer a brief review about their antiallergic, anti-cancer, anti-inflammatory, and analgesic properties. This review shows their effects on CNS and evidences their pharmacologic potential in the therapeutics of the mental disorders. Flavonoids may have existed in nature for over 1 billion years and thus have interacted with evolving organisms. These compounds are molecules of low molecular mass, abundant in all berries and citric fruits, chocolate, nuts, red wine, and several medicinal plants. Flavonoids interact with several enzymes responsible for the transport of xenobiotics to the brain, which are considering modifiers of the biological response. Perhaps the most studied have been their anti-oxidant properties, which have met reflected in his capacity to protect to the cells of the oxidative stress, implicated several pathologies associated with aging, such as Alzheimer's and Parkinson's diseases. In the last 30 years, a intensive research about the effects of the flavonoids on CNS has been carried out; in this regard, flavonoids have showed effective effects as anxiolytic, antidepressants, and anticonvulsive drugs, and although their actions in the CNS occur through a variety of interactions with different receptors and signaling pathways, it has been demonstrated that these effects are mediated principally by GABA, in particular GABA A receptors, which these has led them to being postulates as a new benzodiazepines family, but without the side effects of these.
El propósito de esta revisión fue describir los aspectos más relevantes de los flavonoides como su origen, sus fuentes y metabolismo, sus propiedades farmacológicas como antialérgicos, anticancerosos, anti-inflamatorios, analgésicos. También revisamos sus efectos sobre el SNC poniendo en evidencia su potencial farmacológico en la terapéutica de los trastornos mentales. Los flavonoides son sustancias de bajo peso molecular que han estado presentes en la naturaleza durante millones de años. El hombre los consume en la dieta ya que están presentes de forma abundante en los vegetales, las frutas rojas como las fresas, zarzamoras, frutas cítricas, el chocolate, las nueces, el vino tinto y en varias plantas medicinales. Estos compuestos poseen una amplia gama de actividades farmacológicas entre las que destacan sus propiedades anti-oxidantes, las cuales les confieren capacidad de proteger a las células del estrés oxidativo relacionado con patologías asociadas al envejecimiento, como las enfermedades de Alzheimer y Parkinson. En los últimos 30 años se ha realizado una intensa investigación sobre sus acciones en el SNC, entre las que sobresalen sus propiedades como ansiolíticos, sedantes, antidepresivos y anticonvulsivos. Se ha demostrado que estos efectos son mediados principalmente por los receptores GABA, en particular los receptores GABA A, por lo que los flavonoides han sido reconocidos como una nueva familia de benzodiazepinas, con la ventaja de no presentar los efectos colaterales que éstas producen.
RESUMO
A ativação de receptores GABAA e GABAB no núcleo parabraquial lateral (NPBL) com muscimol e baclofen, respectivamente, induz a ingestão de água e NaCl hipertônico em ratos. No presente estudo, investigamos os efeitos da injeção no NPBL bilateral de trans-4-aminocrotónic acid (TACA), um agonista não seletivo dos receptores GABAA e GABAC na ingestão de água e NaCl 1,8% induzida por depleção aguda de água e sódio. Foram utilizados ratos Wistar com cânulas de aço inoxidável implantadas bilateralmente no NPBL. Estes animais foram depletados de água e sódio com injeções do diurético furosemida (FURO 10 mg/kg de peso corporal) combinado com baixa dose do inibidor da enzima conversora de angiotensina captopril (CAP 5 mg/kg de peso corporal). Injeções bilaterais de um agonista seletivo do receptor GABAA, muscimol (0,5 nmol/0.2 μl) no NPBL aumentou a ingestão de NaCl 1,8% e água (34.6±6.9 e 29.2±2.8 vs. salina: 4.4±2.4 e 9.4±2.5 ml/210 min, respectivamente) em ratos tratados com FURO+CAP. Injeções bilaterais de TACA (0,5 e 2,0 nmol/0.2 μl) no NPBL não alterou a ingestão de NaCl 1,8% induzida pela depleção de sódio (6.1±2.2 e 5.2±1.4 ml/210 min vs salina: 3.8±1.0 e 4.6±1.3 ml/210 min, respectivamente). A combinação de um antagonista GABAC, Zapa sulphate (10 nmol/0.2 μl) e TACA (160 nmol/0.2 μl) injetados no NPBL não produziu nenhuma mudança na ingestão de NaCl 1,8% (6,8±1.7 ml/180 min). Injeções bilaterais isoladas de ZAPA sulphate no NPBL não mudou a ingestão de NaCl 1,8% e água. A Pressão Arterial e a Freqüência Cardíaca não foram alteradas por injeções de TACA no NPBL. O resultados do presente estudo mostram que injeções bilaterais de TACA não inibiram ou facilitaram a ingestão de água e o apetite ao sódio durante a depleção aguda de água e sódio promovida por FURO+CAP
Activation of GABAA and GABAB receptors in the lateral parabrachial nucleus (LPBN), with muscimol and baclofen, respectively, induces water and hypertonic NaCl intake in rats. In the present study we investigated the effects of bilateral injection of trans-4-aminocrotonic acid (TACA), an agonist of GABAA and GABAC receptors into the LPBN on water and 1.8% NaCl intake induced by acute fluid depletion. Male Wistar rats with stainless steel cannulas implanted bilaterally in the LPBN were used. They were acutely depleted of water and sodium by injections of the diuretic furosemide (FURO 10 mg/kg, bw) combined with low dose of the angiotensin converting enzyme inhibitor captopril (CAP 5 mg/kg, bw). Bilateral injections of a selective GABAA receptor agonist, muscimol (0.5 nmol/0.2 μl) into the LPBN strongly increased NaCl 1.8% and water intake (34.6±6.9 e 29.2±2.8 vs saline: 4.4±2.4 e 9.4±2.5 ml/210 min) in FURO+CAP treated rats. Bilateral injections of TACA (0.5 and 2.0 nmol/0.2 μl) into the LPBN did not change sodium depletion-induced 1.8% NaCl intake (6.1±2.2 and 5.2±1.4 ml/210 min, respectively, vs saline: 3.8±1.0 and 4.6±1.3 ml/210 min). The combination of a GABAC antagonist, ZAPA sulphate (10 nmol/0.2 μl) and TACA (160 nmol/0.2 μl) injected into the LPBN produced no change of 1.8% NaCl intake (6.8±1.7 ml/180 min). Bilateral injections of ZAPA sulphate alone into the LPBN did not change water and 1.8% NaCl intake. Arterial blood pressure and heart rate were not altered by TACA injected into the LPBN. We concluded that bilateral injection of TACA not inhibit or facilitate sodium appetite during acute fluid depletion