Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms

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Date
2013-03-01Author
Cruz, Giovany Michely Pinto da [UNIFESP]
Felipe, Cícero Francisco Bezerra
Scorza, Fulvio Alexandre [UNIFESP]
Costa, Marta Aline Coelho da
Tavares, Alinne Farias
Menezes, Maria Luiza Feitosa
Andrade, Geanne Matos de
Leal, Luzia Kalyne Almeida Moreira
Brito, Gerly Anne de Castro
Naffah-Mazzacoratti, Maria da Graca [UNIFESP]
Cavalheiro, Esper Abrão [UNIFESP]
Viana, Glauce Socorro de Barros
Type
ArtigoISSN
0091-3057Is part of
Pharmacology Biochemistry and BehaviorDOI
10.1016/j.pbb.2013.01.002Metadata
Show full item recordAbstract
Piperine, an alkaloid present in the Piper genus, was shown to have an anticonvulsant activity, evaluated by the pilocarpine-induced model, in mice. Pilocarpine (350 mg/kg, i.p.) was administered 30 min after piperine (2.5, 5, 10 and 20 mg/kg, i.p.) which significantly increased latencies to 1st convulsion and to death, and percentage of survivals. These parameters were also increased in the pilocarpine groups pretreated with atropine plus piperine (10 and 2.5 mg/kg, respectively), as related to the pilocarpine group. However, they were not altered in the pilocarpine groups pretreated with memantine (a NMDA-type glutamate receptors blocker, 2 mg/kg, p.o.) or nimodipine (a calcium channel blocker, 10 mg/kg, p.o.), both associated with piperine (1 or 2.5 mg/kg), as compared to the piperine plus pilocarpine group. Moreover, the pilocarpine group pretreated with diazepam (which binds to the GABA(A) receptor, 0.2 and 0.5 mg/kg, i.p.) plus piperine (1 and 2.5 mg/kg) significantly increased latency to the 1st convulsion, as related to the pilocarpine group, suggesting that the GABAergic system is involved with the piperine action. Furthermore, the piperine effect was blocked by flumazenil (2 mg/kg, i.p.), a benzodiazepine antagonist. Untreated P350 animals showed decreased striatal DA and increased DOPAC and HVA levels that were not affected in the piperine plus pilocarpine groups. Piperine increased striatal levels of GABA, glycine and taurine, and reversed pilocarpine-induced increases in nitrite contents in sera and brain. Hippocampi from the untreated pilocarpine group showed an increased number of TNF-alpha immunostained cells in all areas, as opposed to the pilocarpine group pretreated with piperine. Taken together, piperine anticonvulsant effects are the result of its anti-inflammatory and antioxidant actions, as well as TNF-alpha reduction. in addition, piperine effects on inhibitory amino acids and on the GABAergic system may certainly contribute to the drug anticonvulsant activity. (C) 2013 Elsevier Inc. All rights reserved.
Citation
Pharmacology Biochemistry and Behavior. Oxford: Pergamon-Elsevier B.V., v. 104, p. 144-153, 2013.Keywords
PiperinePilocarpine-induced convulsions
Antioxidant and anti-inflammatory effects
Monoamines
Amino acids
Sponsorship
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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