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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2018, Vol. 47 Issue (5): 450-456    DOI: 10.3785/j.issn.1008-9292.2018.10.02
    
Effects of Honokiol on cognitive function in mice with kainic acid-induced epilepsy
WANG Qingmei1(),SHU Min1,XU Qianzi1,XIE Yiyi1,RUAN Shengzhe1,WANG Jianda2,*(),ZENG Linghui1,*()
1. School of Medicine, Zhejiang University City College, Hangzhou 310015, China
2. Department of Pediatrics, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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Abstract  

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. Conclusion: Honokiol alleviates oxidative stress and autophagy degradation disorder, decreases neuronal death, and therefore improves cognitive function in epilepsy mice.

Key words： Honokiol/pharmacology      Epilepsy/drug therapy      Memory/drug effects      Learning/drug effects      Oxidative stress      Autophagy      Mice, inbred ICR     
Received: 12 September 2018      Published: 23 January 2019
CLC:  R742.1  
Corresponding Authors: WANG Jianda,ZENG Linghui     E-mail: 2747912115@qq.com;2515165@zju.edu.cn;zenglh@zucc.edu.cn
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WANG Qingmei
SHU Min
XU Qianzi
XIE Yiyi
RUAN Shengzhe
WANG Jianda
ZENG Linghui
Cite this article:

WANG Qingmei,SHU Min,XU Qianzi,XIE Yiyi,RUAN Shengzhe,WANG Jianda,ZENG Linghui. Effects of Honokiol on cognitive function in mice with kainic acid-induced epilepsy. J Zhejiang Univ (Med Sci), 2018, 47(5): 450-456.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2018.10.02     OR     http://www.zjujournals.com/med/Y2018/V47/I5/450


和厚朴酚对癫痫小鼠学习记忆能力的改善作用

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。


关键词： 和厚朴酚/药理学,  癫痫/药物疗法,  记忆/药物作用,  学习/药物作用,  氧化应激,  自噬,  小鼠, 近交ICR 
Fig 1 Fluoro-Jade B(FJB) staining of neuro in hippocampus
Fig 2 Results of morris water maze tests(n=10)
Fig 3 Results of Y maze tests (n=10)
Fig 4 Expression of acetylated SOD in hippocampus
Fig 5 Expression of oxidative stress products in hippocampus (n=6)
Fig 6 Protein expression of LC3-Ⅱ and P62 in hippocampus (n=10)
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