基于网络药理学和分子对接探讨桂芍镇痫片治疗颞叶癫痫的作用机制

doi:10.3976/j.issn.1002-4026.2023.03.004

摘要/Abstract

摘要：

基于网络药理学研究桂芍镇痫片抗颞叶癫痫的作用机制。通过中药系统药理学数据库与分析平台检索桂芍镇痫片的有效成分和作用靶点,使用Uniprot 数据库进行标准基因名转化;通过OMIM,GeneCards和DrugBank数据库检索颞叶癫痫相关的疾病靶点,使用维恩图获得桂芍镇痫片治疗颞叶癫痫的交集靶点;运用Cytoscape 3.8.2软件构建药材-成分-靶标网络图,分析核心成分和关键分子靶点;使用基因本体富集和京都基因与基因组百科全书分析靶点的生物学过程和相关通路;使用前三个关键靶点与其对应的前两个核心化合物进行分子对接验证。通过筛选,共获得127个有效成分和46个相关靶点,其中,β-谷甾醇、槲皮素、山柰酚等14个成分发挥核心作用,涉及CALM1、SCN5A、GSK3B等11个关键靶点。抗癫痫作用主要涉及膜电位调节、药物响应等生物学过程,突触后膜和树突等细胞组成,离子通道和钙调蛋白等分子功能,神经活性配体-受体相互作用、尼古丁成瘾等相关通路。分子对接结果显示CALM1、SCN5A、GSK3B三个靶点分别和对应的核心化合物有较好的结合能力。桂芍镇痫片通过减轻氧化损伤和保护神经元,影响离子通道和受体、细胞内信号传导、细胞凋亡和突触结构等环节,多成分、多靶标、多通路地协同发挥抗癫痫作用。

关键词: 网络药理学, 分子对接, 桂芍镇痫片, 颞叶癫痫, 作用机制

Abstract:

To study the mechanism of Guishaozhenxian Tablet in the treatment of temporal lobe epilepsy (TLE) based on network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to retrieve the active ingredients and action targets of Guishaozhenxian Tablet, and the standard gene was transformed using the UniProt database. The OMIM, GeneCards, and DrugBank databases were searched for disease targets related to TLE, and the intersection targets of Guishaozhenxian Tablet in the treatment of TLE were obtained using a Venn diagram. The medicinal herb-component-target network diagram was constructed using the Cytoscape 3.8.2 software, and the core components and key molecular targets were analyzed.Gene Ontology enrichment and the Kyoto encyclopedia of genes and genomes were used to analyze the biological processes and related pathways. The first three key targets and their corresponding top two core compounds were validated using molecular docking. In total, 127 active ingredients and 46 related targets were identified, with 14 ingredients, including β-sitosterol, quercetin, and kaempferol, playing a central role in 11 key targets such as CALM1, SCN5A, and GSK3B. The anti-TLE effect was primarily due to biological processes (regulation of membrane potential, response to drug, etc.), cell components (postsynaptic membrane, dendrites, etc.), molecular functions (channel activity, calmodulin binding, etc.), neuroactive ligand-receptor interaction, nicotine addiction, and other related pathways. Molecular docking results showed that CALM1, SCN5A, and GSK3B had good binding abilities with core compounds. Guishaozhenxian Tablet can reduce oxidative damage; protect neurons; affect ion channels and receptors, intracellular signal transduction, apoptosis, and synaptic structure; and exert anti-TLE effects via multi-components, multi-targets, and multi-pathway coordination.

Key words: network pharmacology, molecular docking, Guishaozhenxian Tablet, temporal lobe epilepsy, mechanism of action

中图分类号:

R285.5

赵鑫, 黄碧云, 吴丹, 张梅. 基于网络药理学和分子对接探讨桂芍镇痫片治疗颞叶癫痫的作用机制[J]. 山东科学, 2023, 36(3): 27-37.

ZHAO Xin, HUANG Biyun, WU Dan, ZHANG Mei. The mechanism of Guishaozhenxian Tablet in the treatment of temporal lobe epilepsy based on network pharmacology and molecular docking[J]. Shandong Science, 2023, 36(3): 27-37.

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药材	成分数	成药性筛选后		药材-疾病靶点交集后
药材	成分数	有效成分数	药物靶点数	有效成分数	有效靶点数
桂枝	220	7	51	2	14
党参	134	21	107	7	20
柴胡	349	17	186	8	30
甘草	280	92	226	81	34
大枣	133	29	201	14	35
白芍	85	13	89	4	20
半夏	116	13	97	6	17
黄芩	143	36	121	21	18
生姜	265	5	55	3	15
合计(去重后)	—	206	285	127	46

类型	GO条目	描述	-lg P
BP	0060078	突触后膜电位的调节	14.8
	0042391	膜电位调节	13.7
	0098916	顺行跨突触信号	12.8
CC	0032590	树突膜	11.9
	1902711	GABA_A受体复合物	11.5
	1902710	GABA受体复合物	11.4
MF	0008503	苯二氮卓受体活性	12.9
	0022851	GABA门控氯离子通道活性	12.4
	0005237	抑制细胞外配体门控离子通道活性	12.1

通路名称	富集靶标
神经活性配体-受体相互作用	GABRA2, GABRA1, GRIA2, CHRNA2, GABRA6, GABRA5, CHRNA7, GABRA3, OPRM1, DRD2, ADRA2B
尼古丁成瘾	GABRA2, GABRA1, GRIA2, GABRA6, GABRA5, CHRNA7, GABRA3