title: Piperine exerts anti-seizure effects via the TRPV1 receptor in mice.
abstract: The mechanisms involved in the anti-seizure property of piperine (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]-(E,E)-piperidine, C17H19NO3) are still unclear. Piperine could activate transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, and the rapid activation of whole-cell currents is antagonized by the competitive TRPV1 antagonist capsazepine. Interestingly, recent studies have reported that TRPV1 may be a novel anti-epileptogenic target which led us to hypothesize that the anti-seizure property of piperine involves the TRPV1 receptor. To test this hypothesis, we examined the effect of piperine on seizures induced in mice and identified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) models. Piperine, administered at doses of 40 and 80 mg/kg, significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with the vehicle-treated animals. Piperine also significantly reduced the incidence of MES-induced tonic hindlimb extension (THE) and PTZ-induced Fos immunoreactivity in the dentate gyrus. The anti-seizure effects of piperine were blocked by a TRPV1-selective antagonist capsazepine. Taken together, these data support the further investigation of piperine as a TRPV1 agonist for anti-seizure therapy.
authors.affiliation: Department of Cardiovascular Diseases, First Hospital, Lanzhou University, Lanzhou 730043, Gansu, PR China.
authors.forename: Chang-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Qu
authors.forename: Chang-Rui
authors.initials: CR
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D052117:Benzodioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D004597:Electroshock / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000009:adverse effects; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000494:pharmacology* / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D000927:Anticonvulsants; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D016760:Proto-Oncogene Proteins c-fos; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C008922:piperine; D010433:Pentylenetetrazole
keywords: Capsazepine; Pentylenetetrazol; Piperine; Seizure; TRPV1 receptor