** Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410000, P.R. China.
†† Department of Healthy Management Center, The Third Xiangya Hospital, Central South University, Changsha 410013, P.R. China.
Am J Chin Med. 2017;45(3):557-573. doi: 10.1142/S0192415X17500331. Epub 2017 Apr 7.
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 5[Formula: see text]mg/kg and 10[Formula: see text]mg/kg, respectively) was administered through gavage for two weeks before lithium-pilocarpine injection. Rats were sacrificed at 4, 24 and 72[Formula: see text]h after SE induction. Pretreatment with both low-dose and high-dose aucubin significantly reduced the number of death neurons ([Formula: see text]) and increased the number of surviving neurons ([Formula: see text]) in DG, Hilus, CA1 and CA3 hippocampal regions post SE. Meanwhile, it significantly inhibited necroptosis proteins (MLKL and RIP-1) ([Formula: see text] or [Formula: see text]) and enhanced autophagy protein (Beclin-1 and LC3BII/LC3BI) prevalence in the hippocampus ([Formula: see text] or [Formula: see text]). 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.
杜仲是一种著名的中药，具有抗氧化应激和神经保护作用。桃叶珊瑚苷是杜仲的主要成分。本研究旨在通过建立体内锂-匹罗卡品诱导的癫痫持续状态（SE）大鼠模型，探讨桃叶珊瑚苷对海马神经元癫痫的潜在保护作用。桃叶珊瑚苷（低剂量和高剂量分别为 5[Formula: see text]mg/kg 和 10[Formula: see text]mg/kg）灌胃给药两周，然后锂-匹罗卡品注射。SE 诱导后 4、24 和 72[Formula: see text]h 处死大鼠。低剂量和高剂量桃叶珊瑚苷预处理均可显著减少 DG、Hilus、CA1 和 CA3 海马区死亡神经元的数量([Formula: see text])，增加存活神经元的数量([Formula: see text])。同时，它显著抑制坏死蛋白（MLKL 和 RIP-1）([Formula: see text]或[Formula: see text])，并增强海马自噬蛋白（Beclin-1 和 LC3BII/LC3BI）的表达([Formula: see text]或[Formula: see text])。总之，桃叶珊瑚苷通过诱导自噬和抑制坏死可能改善锂-匹罗卡品诱导的 SE 引起的海马损伤，减少凋亡神经元数量，增加存活神经元数量。这些发现可能为进一步研究桃叶珊瑚苷在治疗或预防癫痫相关神经元损伤中的治疗作用提供重要依据。
