Amomum tsaoko fruit extract exerts anticonvulsant effects through suppression of oxidative stress and neuroinflammation in a pentylenetetrazol kindling model of epilepsy in mice

Saudi J Biol Sci. 2021 Aug;28(8):4247-4254. doi: 10.1016/j.sjbs.2021.06.007. Epub 2021 Jun 9.

Abstract

Background: Chronic epilepsy is a multifaceted common brain disorder with manifold underlying factors. Epilepsy affects around 70 million peoples worldwide. Amomum tsaoko is a perennial herbaceous plant that is extensively cultivated in many provinces of China reported to exert immense biological activities.

Objective: This research work was aimed to reveal the therapeutic actions of ethanolic extract of A.tsaoko fruits (EE-ATF) against the pentylenetetrazol (PTZ)-provoked convulsive seizures in the mice.

Methodology: The convulsive seizures were provoked to the animals via administering 70 mg/kg of PTZ through intraperitoneally to trigger the convulsive seizures then treated with the EE-ATF at 50, 75, and 100 mg/kg orally 30 min prior to PTZ challenge. After the 30 min of PTZ challenge, animals closely monitored for signs of convulsion, generalized clonic and tonic convulsion durations, and mortality. A sub-convulsive dose 35 mg/kg of PTZ was used to provoke the kindling and seizure stages were examined using standard method. The levels of dopamine, GABA, glutamate, and Na + K + ATPase and Ca + ATPase activities in the brain tissues were studied using marker specific assay kits. The oxidative stress and antioxidant markers studied using standard methods. The mRNA expressions of COX-2, TNF-α, NF-κB, TLR-4, and IL-1β in the brain tissues were studied using RT-PCR analysis. The brain tissues were examined histologically.

Results: EE-ATF treatment remarkably decreased the onset and duration of convulsion and suppressed the seizure severity and mortality in the PTZ animals. EE-ATF treatment appreciably ameliorated the PTZ triggered modifications in the GABA, glutamate, dopamine levels and Ca + 2ATPase and Na + K + ATPase activities in the brain tissues. EE-ATF suppressed the mRNA expressions of NF-κB, IL-1β, TLR-4, TNF-α, and COX-2. The status of antioxidants were elevated by the EE-ATF. Histological findings also demonstrated the curative actions of EE-ATF.

Conclusion: Our findings evidenced that the EE-ATF substantially ameliorated the PTZ-provoked convulsive seizures in the mice.

Keywords: Amomum tsaoko; Epilepsy; Na+K+ATPase; Pentylenetetrazol; Seizure.