Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 104, Issue -, Pages 144-153Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2013.01.002
Keywords
Piperine; Pilocarpine-induced convulsions; Antioxidant and anti-inflammatory effects; Monoamines; Amino acids
Funding
- Brazilian National Research Council (CNPq)
- CAPES
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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.
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