Piperine, A Highly Purified Chemical from Peppers, Reduces the Incidence of Seizure-Induced Mortality in DBA/1 Mice
Abstract number :
1.209
Submission category :
2. Translational Research / 2E. Other
Year :
2025
Submission ID :
131
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Emory Farrell, BS – Massachusetts General Hospital
Yupeng Zhou, BS – Massachusetts General Hospital
Presenting Author: Hua-Jun Feng, PhD – Massachusetts General Hospital and Harvard Medical School
Rationale: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, particularly in patients with drug-resistant epilepsy. It has been shown that enhancing serotonergic neurotransmission prevents seizure-induced apnea, a primary event leading to death after generalized seizures, and exerts an antiseizure effect in animal models of SUDEP, including DBA/1 mice. Piperine, a piperidine alkaloid extracted from peppers, enhances serotonin (5-HT) levels in the brain. We hypothesized that piperine prevents seizure-induced mortality in animal models of SUDEP. This study aimed to investigate the effects of piperine on seizure-induced mortality, apnea and seizures in DBA/1 mice.
Methods: DBA/1 mice of both sexes were acoustically primed using an electrical bell (96 dB SPL) once daily for 3-4 days. Primed DBA/1 mice display consistent susceptibility to seizure-induced apnea following generalized audiogenic seizures characterized by wild running and tonic-clonic seizures. Seizure-induced apnea was always confirmed 24 hr prior to the experiment. Piperine or vehicle (10% DMSO in corn oil) was administered intraperitoneally (i.p.) 30 min before acoustic stimulation, and the effects of piperine/vehicle on seizure-induced mortality, apnea and seizures were examined and digitally recorded for offline analysis. Statistical comparison of seizure-induced mortality between the piperine treatment group and the control group was performed using the Chi-square test.
Results: Compared with the vehicle control (n = 14), the incidence of seizure-induced mortality was significantly reduced by i.p. injection of piperine at 30 mg/kg (n = 15; p < 0.01), 20 mg/kg (n = 13; p < 0.001) or 10 mg/kg (n = 14; p < 0.05) in DBA/1 mice. Seizure-induced mortality was not significantly altered by piperine at 5 mg/kg (n = 10) as compared with vehicle control. The suppressing effect of piperine on seizure-induced mortality was achieved by dual actions; piperine selectively prevented seizure-induced apnea (with audiogenic seizures intact) in 10% of mice tested at 5 mg/kg, 21.4% at 10 mg/kg, 7.7% at 20 mg/kg and 13.3% at 30 mg/kg. It blocked tonic seizures in 10% of mice tested at 5 mg/kg, 28.6% at 10 mg/kg, 61.5% at 20 mg/kg and 53.3% at 30 mg/kg.
Translational Research