Neuroprotective Effect of Celastrus Paniculatus Seed Extract in Epilepsy and Epilepsy-Associated Cognitive Deficits

Purpose: Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus (C- paniculatus) seed extract on seizure severity and cognitive deficit following Pentylenetetrazole (PTZ) -induced chemical kindling model. Methods: PTZ kindling model was developed by daily administration of sub-convulsive dose of PTZ 30 mg/kg for 4 weeks. After 4 weeks of induction, the following treatment namely Sodium valproic acid (SVA) 200 mg/kg, C- paniculatus 500 mgkg, Pergolide 2 mg/kg alone and combination groups C- paniculatus 250 mgkg+ Pergolide 1 mg/kg and C- paniculatus 250 mgkg+ SVA 100 mg/kg were administered 30 minute prior to PTZ 30 mg/kg injection for a period of next 14 days. Neurobehavioral parameters Morris water maze test (MWM), Grip strength test (GPS) brain superoxide dismutase (SOD), Catalase, reduced glutathione (GSH) and dopamine level. Hematoxylin & Eosin (H&E) staining of hippocampus pyramidal layers Cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex were assessed. Results: C- paniculatus 500 mg/kg alone and combination groups C- paniculatus 250 mgkg+ Pergolide 1 mg/kg and Celastrus  paniculatus 250 mgkg+ SVA 100 mg/kg  significantly (p<0.05) reduced the seizure score, mean latency time, and distance traveled in MWM. However, no significant effect was seen in grip strength test. Biochemical analysis showed elevated antioxidant markers namely GSH, catalase, and SOD & elevated dopamine levels.  C- paniculatus and its combination were also found significantly (p<0.05) protected against neuronal loss in hippocampus and frontal cortex as evidenced by H&E staining.  Conclusion: C- paniculatus alone and its combination may have the potential to treat epilepsy and associated cognitive deficits