Neuroprotective Efficacy of Curcumin and Berberine With Gabapentin Pretreatment Against Chemically Induced Intractable Epilepsy in Albino Mice

Background- Epilepsy is a chronic neurological disease characterized by recurrent seizure and a significant number of patients suffering from drug resistant (intractable) epilepsy against conventional antiepileptic drugs. The present study was designed to evaluate the neuroprotective potential of curcumin and berberine, alone and in combination, along with gabapentin pre-treatment on the pentylenetetrazole (PTZ)-induced intractable epilepsy in albino mice. Methods- Intractable epilepsy was induced by repeated administrations of PTZ (40 mg/kg) on alternate days after a single administration of gabapentin (20 mg/kg) with one or more other treatment regimens. Assessment of behavioral activities including seizure severity, behavioural response, locomotor activity, anxiety-like behavior and cognitive performance was carried out using standard behavioral models. Biochemically determined oxidative stress markers viz.; malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured. Other parameters assessed included nitric oxide (NO), acetylcholinesterase (AChE) and total protein. Brain was removed for histopathological assessment of neuronal integrity. Results- The repeated administration of PTZ induced frequent seizures, oxidative stress, impairment of learning and memory as well as substantial neuronal degeneration when compared to normal control. PTZ + gabapentin pre-treatments significantly increased the intensity of seizures whereas the concurrent administration of VPA ameliorated the PTZ induced seizure effects and enhanced anticonvulsant activity. Curcumin and berberine provided a dose-dependent protection, improved behavioural parameters, attenuated oxidative damage and reduced lipid peroxidation with significant preservation of neuronal integrity. In combination, curcumin and berberine (100 mg/kg each) with gabapentin and VPA showed excellent neuroprotection against PTZ induced intractable epilepsy as evident from superior seizure protection and normalization of various parameters examined. Conclusion- Curcumin and berberine can be employed as promising adjunctive neuroprotective agents along with gabapentin in the treatment of chemically induced intractable epilepsy. These study suggest that curcumin and berberine can be used as effective adjunctive neuroprotective agents in combination with gabapentin in the treatment of chemically induced intractable epilepsy.