Avaliação neurofarmacológica das atividades tipo ansiolítica e/ou antidepressiva da fração diclorometano, ácido oleanólico e (E)-metilisoeugenol das folhas de pimenta pseudocaryophyllus (Gomes) L. R. Landrum (Myrtaceae) quimiotipo (E)-metilisoeugenol
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2015-10-16
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Universidade Federal de Goiás
Resumo
Depression and anxiety are widely acclaimed as psychiatric disorders of global concern.
These disorders are among the leading causes of disability worldwide. Unsatisfactory
responses of patients to the available pharmacotherapy make the search for new drugs a
necessity. Medicinal plants remain important source of new drugs and new chemical
entities. The ethnopharmacological knowledge and previous data have revealed calming
and anxiolytic like effects of the organic leaf extract of Pimenta pseudocaryophyllus
(Gomes) L.R. Landrum. The present study sought to investigate antidepressive like effect
of dichloromethane fraction (DF) of the ethanolic leaf extract of Pimenta
pseudocaryophyllus as well as anxiolytic and antidepressive like effects of oleanolic acid
(OA), (E) methyl isoeugenol (MIE) and possible mechanisms of action that are involved.
Animal models like barbiturate-induced sleep, light dark box test (LDB), elevated plusmaze
(EPM), open field (OF), wire hanging test, pentylenetetrazol-induced convulsion test,
forced swimming test (FST), tail suspension test (TST) were conducted to evaluate
behavioural alterations that were elicited by the administrations of vehicle, DF, OA, MIE or
reference drugs. Bioassays (ex vivo and in vitro) of monoamine oxidase (MAO) and
quantification of hippocampal level of brain derived neurotrophic factor (BDNF) were
conducted in an attempt to elucidate possible mechanisms of action. Oral administration of
DF 125, 250 or 500 mg/kg (potentiated the hypnotic effect of sodium pentobarbital). In the
TST and FST, DF 125 or 250 mg/kg induced antidepressant-like response. The data
obtained in the OF suggest sedative effect of DF at 500 mg/kg. Pretreatment (i.p) with pchlorophenylalanine
methyl ester (PCPA) 100 mg/kg (serotonin depletor) or 𝛼-methyl-ptyrosine
(AMPT) 100 mg/kg (catecholamine depletor) blocked anti-immobility effect of DF
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in the FST. The enzymatic activity of MAO remained unaltered by DF. Oral administration
of OA (5-20 mg/kg) increased the duration of barbiturate - induced sleep and
demonstrated anxiolytic like effect in both LDB and EPM. In the FST and TST, OA 5-20
mg/kg elicited antidepressant like effect without altering locomotion activity of the animals.
The antidepressant like effect of OA was attenuated by NAN-190 (non-selective antagonist
of 5-HT1A), AMPT, PCPA, WAY and PRAZ. Chronic administration of OA increased
hippocampal level of BDNF. Oral administration of MIE 250 or 500 mg/kg potentiated
hypnotic effect of sodium pentobarbital without protecting mice against PTZ - induced
convulsion. The parameters evaluated in the LDB, EPM and OF demonstrated anxiolytic
like property of MIE. This effect was blocked by WAY (selective antagonist of 5-HT1A)
pretreatment. MIE 125 or 250 mg/kg showed antidepressant like effect in the FST.
Locomotion activity of the animal in the OF remained unaltered by MIE administration at
125 or 250 mg/kg. Pretreatment of mice with PCPA attenuated antidepressant like
property of MIE. In conclusion, our findings demonstrated anxiolytic and/or antidepressant
like effects of dichloromethane fraction, oleanolic acid and (E) methyl isoeugenol, thereby
suggesting the involvement of monoaminergic pathway.
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FAJEMIROYE, J. O. Avaliação neurofarmacológica das atividades tipo ansiolítica e/ou antidepressiva da fração diclorometano, ácido oleanólico e (E)-metilisoeugenol das folhas de pimenta pseudocaryophyllus (Gomes) L. R. Landrum (Myrtaceae) quimiotipo (E)-metilisoeugenol. 2015. 145 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2015.