The Protective Effect of Aucubin from Eucommia ulmoides Against Status Epilepticus by Inducing Autophagy and Inhibiting Necroptosis.

Abstract: Eucommia ulmoides Oliv. is a famous traditional Chinese medicine which exhibits anti-oxidative stress ability and neuro-protective effects. Aucubin is the predominant component of Eucommia ulmoides Oliv. Our present study is intended to investigate aucubin’s potential protective effects on neurons against epilepsy in the hippocampus by establishing the lithium-pilocarpine induced status epilepticus (SE) rat model in vivo. Aucubin (at a low dose and a high dose of 5mg/kg and 10mg/kg, respectively) was administered through gavage for two weeks before lithium-pilocarpine injection. Rats were sacrificed at 4, 24 and 72h after SE induction. Pretreatment with both low-dose and high-dose aucubin significantly reduced the number of death neurons (p<0.05) and increased the number of surviving neurons (p<0.05) in DG, Hilus, CA1 and CA3 hippocampal regions post SE. Meanwhile, it significantly inhibited necroptosis proteins (MLKL and RIP-1) (p<0.05 or p<0.01) and enhanced autophagy protein (Beclin-1 and LC3BII/LC3BI) prevalence in the hippocampus (p<0.05 or p<0.01). In conclusion, aucubin appeared to ameliorate damages in lithium-pilocarpine induced SE in hippocampus, reduce the number of apoptotic neurons, and increased the number of survival neurons by inducing autophagy and inhibiting necroptosis. These original findings might provide an important basis for the further investigation of the therapeutic role of aucubin in treatment or prevention of epilepsy-related neuronal damages.