Unraveling the neuroprotective and anti-seizure potential of Calendula officinalis L. extracts in PTZ-induced experimental epilepsy in rats.

To examine the potential neuroprotective and anti-seizure effects of Calendula officinalis L. extracts (COE) in PTZ-induced seizures in rats as well as its effects on hippocampal electrophysiological alterations and signaling pathways implicated in epileptogenesis. A recording electrode was stereotaxically inserted in the CA1 hippocampus area of 36 male rats. Rats were randomly allocated into 3 equal groups (i) sham group, (ii) PTZ group (50 mg/kg i.p in 0.2 mL on alternate days for 2 weeks) and (iii) COE group (200 mg/Kg COE orally in 1.0 ml saline daily for 2 weeks with PTZ injection). COE considerably reduced the Racine score and lengthened the latency to the first seizure. In comparison to the PTZ and sham groups, we observed a large increase in delta and theta waves and a significant decrease in gamma waves with high amplitude sharp spikes in the electrophysiological recordings of the COE group. Also, we found a significant decrease in MDA and HO-1 expression, an increase in GSH and catalase and Nrf2 expression in the COE group compared to the PTZ group (p < 0.01). In addition, the COE group showed a significant rise in BDNF and Hsp70 expression and decrease in caspase-3 expression compared to the PTZ group (p < 0.001). COE exhibited neuroprotective and anti-seizures actions in PTZ-induced kindled rats. Resetting the electrophysiological rhythm from hippocampal CA1 gamma waves, reducing oxidative stress, upregulating the antioxidant Nrf2/HO-1 pathway and neuroprotective proteins (Hsp70 and BDNF), and downregulating apoptotic proteins (caspase-3) could be potential mechanisms.