Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A mistura triterpÃnica de α- e β-amirina (AMI) Ã obtida da planta Protium heptaphyllum Aubl March (FamÃlia
Burseraceae), comum em vÃrios estados brasileiros e conhecida popularmente como breu branco, tambÃm Ã
utilizada na prÃtica da medicina popular para tratar vÃrias enfermidades. O acetato de α- e β- amirina (AcAMI) Ã a
forma acetilada desta mistura triterpÃnica. VÃrios estudos experimentais jà foram feitos utilizando estes
triterpenos, mas estudos da aÃÃo destes no Sistema Nervoso Central (SNC) ainda sÃo escassos. O objetivo deste
trabalho foi avaliar o efeito da administraÃÃo destes compostos naturais em camundongos e verificar uma possÃvel
atividade sedativa, ansiolÃtica, antidepressiva e anticonvulsivante, procurando ainda esclarecer por que
mecanismos estes compostos agem. A metodologia utilizada foi utilizando testes farmacolÃgicos jà descritos na
literatura e estudos de doseamento de monoaminas e aminoÃcidos atravÃs de HPLC. Os resultados mostraram que
tanto a AMI como o AcAMI mostraram-se bastante ativos farmacologicamente. No teste do Campo Aberto ambas
misturas (AMI e AcAMI) administradas por via aguda e sub-crÃnica demonstraram efeitos sedativos, nas doses de
10, 25 e 50 mg/kg, apÃs a constataÃÃo da diminuiÃÃo do movimento exploratÃrio dos animais e do nÃmero de
grooming e de rearing, utilizando o diazepam como controle positivo. No Teste do Plus Maze tambÃm ambas as
misturas demonstraram atividade ansiolÃtica aumentando o nÃmero de entradas e o tempo de permanÃncia nos
braÃos abertos. No teste do nado forÃado, AMI nas doses de 2,5 e 5 mg/kg,, i.p., aumentou o tempo de
imobilidade dos animais comparado ao controle, e foi potencializado pela imipramina. No teste de induÃÃo de
sono por pentobarbital, AMI e AcAMI tiveram o tempo de sono aumentado de forma significante. As misturas
triterpÃnicas apresentaram atividade anticonvulsivante quando a induÃÃo da convulsÃo foi feita com
pentilenotetrazol (PTZ) efeito este nÃo aparecendo quando a induÃÃo foi com pilocarpina e estricnina. A atividade
sedativa e ansiolÃtica da AMI foram revertidas com a presenÃa de flumazenil, efeito similar ao diazepam. O efeito
anticonvulsivante da AMI foi aumentado por drogas que inibem a proteÃna quinase C, polimixina B e
estaurosporina. O doseamento de monoaminas de cÃrtex de camundongos tratados com AMI (1, 2,5 e 5 mg/kg)
mostrou diminuiÃÃo nas concentraÃÃes de noradrenalina e serotonina. No doseamento de aminoÃcidos, houve
aumento nas concentraÃÃes de taurina e tirosina e uma diminuiÃÃo de aspartato, glutamato e GABA nos grupos
tratados com AMI e AcAMI na dose de 25 mg/kg, por 7 dias. Conclui-se, portanto com este trabalho, que tanto a
AMI e o AcAMI possuem atividades sedativas, ansiolÃticas, antidepressivas e anticonvulsivante e provavelmente
estas aÃÃes possam estar ligadas a inibiÃÃo de proteÃna quinase C, envolvimento gabaÃrgico e diminuiÃÃo de
monoaminas e aminoÃcidos / The mixture of alpha- and beta-amyrin (AMY) triterpenes was isolated from Protium heptaphyllum Aubl March
(Burseraceae) which is a medicinal plant common to several Brazilian states and popularly known as âbreu
brancoâ. Although the literature presents several studies with these triterpenes, only a few of them emphasizes the
CNS, and almost none were performed with triterpene acetylated derivatives. Then, the objectives of the present
work were to evaluate, in mice, sedative, anxiolytic, antidepressant and anticonvulsant activities of these drugs, in
order to clarify their mechanisms of action. Besides, measurements of monoamines and amino acids by HPLC, in
the cortex of mice treated with these drugs, were also performed. The results showed that not only the mixture of
alpha- and beta-amyrin (AMY) but also its acetylated derivative (AcAMY) were pharmacologically active and, at
some instances, AcAMY was even more efficacious than AMY. In the open field test, AMY and AcAMY,
administered acutely or sub-chronically at the doses of 10, 25 and 50 mg/kg, showed a great sedative effect, as
indicated by the significant decrease of the exploratory activity (decrease in the number of crossings) as well as
the decrease in numbers of grooming and rearing, as compared to diazepam used as a positive control. In the plus
maze test, both drugs presented a potent anxiolytic activity indicated by the increase in the number of entrances as
well as in the time spent in the open arms. In the forced swimming test, AMY at the doses 2.5 and 5 mg/kg, i.p.,
increased the immobility time as compared to control and was potentiated by imipramine. In the barbiturateinduced
sleeping time, AMY and AcAMY showed a significant increase in parameter analysed, duration of sleep.
Furthermore, AMY and its acetylated derivative showed anticonvulsant activities, in the model of PTZ-induced
convulsions, but not in two other convulsion models (pilocarpine- and strychnine-induced convulsions). Sedative
and anxiolytic activities of AMY were reversed in the presence of flumazenil, a competitive benzodiazepine
action inhibitor, an effect similar to that observed with diazepam. In addition, the anticonvulsant effect of AMY
was potentiated by polymyxin B and staurosporine, drugs known to inhibit protein kinase C (PKC). Data from
cortical monoamine measurements showed significant decreases in noradrenaline and serotonin concentrations,
after mice treatments with AMY (1, 2,5 and 5 mg/kg). As far as the amino acid determination is concerned, results
showed an increase in taurine and tyrosine levels, and a decrease in glutamate, aspartate and GABA contents, with
AMY and AcAMY at the dose of 25mg/kg for seven days. In conclusion, the present study demonstrated
anxiolytic, sedative, antidepressant and anticonvulsant actions in AMY and AcAMY, probably involving PKC
inhibition and interaction with BDZ receptor. Decreases in monoamines levels, as noradrenaline and serotonin,
and amino acid alterations may also play a role
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:948 |
| Date | 11 January 2008 |
| Creators | Gislei Frota AragÃo |
| Contributors | Glauce Socorro de Barros Viana, AntÃnio Josà Lapa, Reinaldo Nobre de Almeida, Marta Maria de FranÃa Fonteles, Geanne Matos de Andrade |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em Farmacologia, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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