天麻活性成分巴利森苷B对匹鲁卡品致痫小鼠痫性行为的干预作用及网络药理学作用机制分析  

Intervention and network pharmacology mechanism of parishin B form Gastrodia elata on epileptic mice induced by intraperitoneal injection of pilocarpine

作　　者：王信[1] 李莉[2] 杨宝慧[1] 辛义周[1] 马传江[1] 杨培民[1] WANG Xin;LI Li;YANG Bao-hui;XIN Yi-zhou;MA Chuan-jiang;YANG Pei-min(Department of Pharmacy,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Shandong Jinan 250011,China;Department of Pediatrics,Affiliated Hospital of Shandong University of Chinese Medicine,Shandong Jinan 250011,China)

机构地区：[1]山东中医药大学附属医院药学部,山东济南250011 [2]山东中医药大学附属医院儿科,山东济南250011

出　　处：《中国医院药学杂志》2022年第6期595-600,630,共7页Chinese Journal of Hospital Pharmacy

基　　金：山东省中医药科技发展计划项目(编号:2017-084)。

摘　　要：目的:研究天麻活性成分巴利森苷B(parishin B,PB)对癫痫小鼠痫性行为的干预作用及其潜在的作用机制。方法:采用匹鲁卡品腹腔注射方法建立小鼠癫痫模型;通过观察小鼠的癫痫潜伏期、持续状态时间、痫性发作等级变化评价PB对癫痫小鼠的干预作用;采用网络药理学技术分析PB抗癫痫作用机制;使用Auto Dock vina软件对PB成分与抗癫痫关键靶点进行分子对接验证。结果:PB给药组(100,200 mg·kg^(-1))可显著延长癫痫小鼠的癫痫潜伏期(P<0.05)、缩短癫痫持续时间(P<0.05),降低癫痫小鼠痫性发作等级;通过网络药理学技术共筛选获得34个PB抗癫痫核心靶点。GO分析得到64个相关过程,KEGG分析共映射出23条信号通路。分子对接结果显示,PB与7个关键核心靶点具有较好的结合活性。结论:PB具有潜在的抗癫痫活性,其效果呈现一定的剂量依赖性,可能通过与NRAS、HRAS、FGFR3等靶点相互作用,调控PI3K-Akt、Rap1、VEGF等信号通路,发挥抗癫痫的作用,本研究为PB抗癫痫创新药物研究提供参考。OBJECTIVE To study the intervention and network pharmacology mechanism of Parishin B(PB)formGastrodia elataon epileptic mice.METHODS The intervention of PB was evaluated by observing the changes of epileptic latency,duration and the states of epileptic seizure on epileptic mice induced by intraperitoneal injection of pilocarpine.Network pharmacology strategy was used to analyze the mechanism of anti-epileptic action of PB.The key targets were verified in molecular docking technology by using Auto Dock vina software.RESULTS The epileptic latency was significantly prolonged(P<0.05),the duration was shortened(P<0.05)and the states of epileptic seizure was reduced in the PB administration group(100,200 mg·kg^(-1))compared with the model group.34 major antiepileptic targets of PB were obtained after network pharmacology analysis.GO analysis determined 64 items and KEGG analysis mapped 23 signal pathways according to P<0.05.Molecular docking results showed that the seven key targets had a good affinity with PB.CONCLUSION PB has potential antiepileptic activity and its effect is dose-dependent.PB can improves epilepsy through the interaction with targets such as NRAS,HRAS and FGFR3 to regulate PI3K-Akt,Rap1,VEGF and other signal pathways.The results can provide a reference for further research on the antiepileptic innovative drugs of PB.

关 键 词：天麻 巴利森苷B 癫痫 痫性行为 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]