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石菖蒲与郁金联用治疗癫痫的网络药理学研究

[Research on network pharmacology of Acori Tatarinowii Rhizoma combined with Curcumae Radix in treating epilepsy].

作者信息

Wang Qian, Yuan Li-Li, Zhang Yong-Ling, Fan Wen-Tao

机构信息

Shaanxi University of Chinese medicine Xianyang 712046,China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2019 Jul;44(13):2701-2708. doi: 10.19540/j.cnki.cjcmm.20190416.403.

Abstract

The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.

摘要

采用网络药理学方法筛选石菖蒲和郁金的化学成分及作用靶点,分析石菖蒲与郁金配伍治疗癫痫的作用机制。通过中药系统药理学数据库与分析平台(TCMSP)检索石菖蒲和郁金的所有化学成分,并筛选其作用靶点,构建成分-靶点蛋白质-蛋白质相互作用(PPI)网络。从药物基因组知识库(PharmGkb)数据库检索癫痫相关基因,并用Cytoscape软件绘制疾病靶点PPI网络。利用Cytoscape软件合并网络、筛选核心网络,并进一步分析基因的基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集情况,通过实验研究进行验证。检索到石菖蒲的105个化学成分和郁金的222个化学成分,根据口服生物利用度(OB)和药物相似性(DL)值筛选出19个化合物作为候选化合物,其中发现石菖蒲的4个化学成分和郁金的15个化学成分。通过检索TCMSP数据共获得88个靶蛋白,构建PPI网络。通过PharmGkb数据库检索到29个癫痫相关基因,建立疾病靶点网络。利用Cytoscape软件及插件进行网络合并和核心网络筛选,筛选出69个基因。通过GO功能分析和KEGG通路分析,发现抗癫痫作用机制与催乳素信号通路、人类嗜T淋巴细胞病毒Ⅰ型(HTLV-Ⅰ)感染信号通路、丝裂原活化蛋白激酶(MAPK)信号通路和单纯疱疹感染信号通路有关。进一步实验验证表明,癫痫大鼠血清催乳素水平显著升高。癫痫发作24小时后,海马CA1区神经元发生变性、坏死、丢失,部分神经元间质水肿。石菖蒲与郁金配伍的可能作用机制与血清催乳素水平、MAPK信号通路、HTLV-Ⅰ感染及单纯疱疹感染有关。分析可能与HTLV-Ⅰ病毒及单纯疱疹感染引起的病毒性脑炎损伤神经细胞导致癫痫发作有关。

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