Objective: To investigate the effects of Honokiol on cognitive function in mice with epilepsy.
Methods: Kainic acid (38 mg/kg) was intraperitoneally injected in 5 weeks old male ICR mice to induce epilepsy. Honokiol at dose of 3, 10, 30 mg/kg was given to epilepic mice by intraperitoneal injection for 10 days. Fluoro-Jade B staining was used to assess neuronal death; Morris water maze and Y maze tests were used to measure cognitive function such as learning and memory; Western blot was performed to detect the expression of acetylated superoxide dismutase (SOD), microtubule associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and P62 in hippocampus tissue; thiobarbituric acid and WST-1 methods were used to detect malondialdehyde (MDA) and SOD.
Results: Compared with control group, the levels of acetylated-SOD, MDA, LC3-Ⅱ, P62 and neuronal death increased, cognitive function and SOD decreased in model group (P<0.05 or P<0.01). Honokiol at the dose of 10 mg/kg and 30 mg/kg decreased SOD acetylation, MDA content, expression of LC3-Ⅱ and P62, as well as neuronal death, and the cognitive function was improved (P<0.05 or P<0.01), especially in 30 mg/kg Honokiol group.
Conclusions: Honokiol alleviates oxidative stress and autophagy degradation disorder, decreases neuronal death, and therefore improves cognitive function in epilepsy mice.
目的: 探索和厚朴酚对癫痫小鼠学习记忆能力的改善作用并探讨其机制。
方法: 5周龄雄性ICR小鼠采用腹腔注射红藻氨酸（38 mg/kg）的方式建立癫痫模型。治疗组小鼠腹腔注射和厚朴酚（3、10、30 mg/kg）10 d。Fluoro-Jade B染色法检测神经元活性；Morris水迷宫和Y迷宫实验观察小鼠学习记忆能力；蛋白质印迹法检测乙酰化超氧化物歧化酶（SOD）、微管相关蛋白1轻链3-Ⅱ（LC3-Ⅱ）和P62蛋白表达水平；硫代巴比妥酸法和WST-1法分别测定丙二醛和SOD等氧化应激产物的含量。
结果: 与对照组比较，模型组神经元凋亡数量增加，学习记忆能力下降，乙酰化SOD和丙二醛表达量增加，SOD活性下降，LC3-Ⅱ和P62蛋白表达量增加（ P < 0.05或 P < 0.01）；与模型组比较，和厚朴酚10 mg/kg和30 mg/kg均可减少神经元凋亡数量，改善学习记忆能力，并可逆转癫痫发作所致的丙二醛和SOD乙酰化水平，降低LC3-Ⅱ和P62的表达量（ P < 0.05或 P < 0.01），且药物剂量为30 mg/kg时效果更加显著。
结论: 和厚朴酚可缓解癫痫发作导致的氧化应激和自噬降解障碍，减少神经元凋亡，从而改善癫痫小鼠的学习记忆能力。