title: Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms.
abstract: Piperine, an alkaloid present in the Piper genus, was shown to have an anticonvulsant activity, evaluated by the pilocarpine-induced model, in mice. Pilocarpine (350mg/kg, i.p.) was administered 30min after piperine (2.5, 5, 10 and 20mg/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 2.5mg/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, 2mg/kg, p.o.) or nimodipine (a calcium channel blocker, 10mg/kg, p.o.), both associated with piperine (1 or 2.5mg/kg), as compared to the piperine plus pilocarpine group. Moreover, the pilocarpine group pretreated with diazepam (which binds to the GABAA receptor, 0.2 and 0.5mg/kg, i.p.) plus piperine (1 and 2.5mg/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 (2mg/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-α 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-α reduction. In addition, piperine effects on inhibitory amino acids and on the GABAergic system may certainly contribute to the drug anticonvulsant activity.
authors: Faculty of Medicine Estácio of Juazeiro do Norte, FMJ, Ceará, Brazil.
authors: Giovany Michely Pinto
authors: GM
authors: da Cruz
authors: Cícero Francisco Bezerra
authors: CF
authors: Felipe
authors: Fúlvio Alexandre
authors: FA
authors: Scorza
authors: Marta Aline Coelho
authors: MA
authors: da Costa
authors: Alinne Farias
authors: AF
authors: Tavares
authors: Maria Luiza Feitosa
authors: ML
authors: Menezes
authors: Geanne Matos
authors: GM
authors: de Andrade
authors: Luzia Kalyne A M
authors: LK
authors: Leal
authors: Gerly Anne C
authors: GA
authors: Brito
authors: Maria
authors: M
authors: da Graça Naffah-Mazzacoratti
authors: Esper Abrão
authors: EA
authors: Cavalheiro
authors: Glauce Socorro
authors: GS
authors: de Barros Viana
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology; D005442:Flumazenil / Q000494:pharmacology; D006801:Humans; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D009553:Nimodipine / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000470:Alkaloids; D000596:Amino Acids; D000927:Anticonvulsants; D000975:Antioxidants; D052117:Benzodioxoles; D015306:Biogenic Monoamines; D009573:Nitrites; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D010862:Pilocarpine; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D009553:Nimodipine; D001285:Atropine; D003975:Diazepam; C008922:piperine; D008559:Memantine