Conessine alleviates PTZ-induced epilepsy in rat model via attenuating neuroinflammation and oxidative stress

Abstract

Epilepsy is a complex neurological disorder which affects the quality life of individual and also hinders the economic status of both the individuals and the country since it requires prolonged medications. The etiology of epilepsy is varied and the neuroinflammation has been considered to be the prime initiator and the stimulator of the disease progression. Therefore anti-inflammatory drugs are suggested to treat seizure and also to prevent epilepsy. The currently available antiepileptic drugs cause’s adverse effects which obstructs the usage of these drugs and also these drugs are not cost effective. Phytochemicals are effective alternative to these drugs and it is prescribed in the traditional medicine. Conessine, a steroidal alkaloid present in bark extracts of Holarrhena sps possess antibiotic, anti-diarrheal, antimalarial and anti-inflammatory properties. We evaluated the antiepileptic potency of conessine in PTZ challenged animal model treated with 10 and 20 mg/kg of conessine respectively. The seizure induction, severity and the behavioral changes were observed in the rats. The impact of conessine on neurochemical signaling in PTZ challenged rats were assessed via quantifying the neurotransmitter and ATPase levels in the brain tissue. Antioxidants and MDA levels were measured to evaluate the antioxidant potency of conessine in epilepsy induced rats. iNOS and nNOS which are inducers of NO during epileptic conditions were analyzed in the test rats. The stimulators and inflammatory cytokines levels were quantified in the brain to analyze the anti-neuroinflammatory efficacy of the conessine in PTZ challenged rats. AKT/mTOR prime signaling proteins in initiation and progression of epilepsy was quantified in the brain tissue of experimental animals. Neurodegeneration inducers cytochrome c, NF-κB, COX-2 and Caspase 3 were quantified to evaluate the ameliorative potency of conessine against PTZ induced neuronal damage. The neuroprotective and antiepileptic potency of conessine was confirmed with the histopathological scoring of brain tissue in PTZ challenged rats. Conessine treatment effectively inhibited the seizure induction and regulated the neurochemical signaling in epileptic induced rats. It also attenuated the neuroinflammation and oxidative stress induction induced by PTZ treatment. The prime signaling proteins nitric oxide synthatase and AKT/mTOR signaling proteins were effectively inhibited by the conessine treatment which eventually prevented the neurodegeneration inducers. Conessine treatment significantly enhanced the levels of Caspase 3. The histopathological analysis confirms the neuroprotective, anti-inflammatory and antiepileptic potency of conessine. Conessine treatment also doesn’t caused any behavioral alterations in the rats hence it is safe and potent alternative for currently available antiepileptic drugs.