基于数据挖掘和网络药理学探讨名老中医用清热凉血药治疗银屑病的组方规律和作用机制

Exploration of Formulation Regularity and Mechanism of Action of Renowned Traditional Chinese Medicine Physicians in Treating Psoriasis with Clearing Heat and Cooling Blood Drugs Based on Data Mining and Network Pharmacology

目的 探讨清热凉血药在名老中医治疗银屑病中的组方规律,分析其潜在作用机制,为银屑病的临床遣方用药和新药开发提供依据。方法 筛选出若干本中医著作中名老中医用清热凉血药治疗银屑病的方剂,运用Microsoft Excel 2010计算中药用药频数,SPSS Clementine 12.0软件的Apriori版块和R软件的arules、arulesViz插件进行关联规则分析。选取核心药物在TCMSP数据库获取有效活性成分,在SwissADME平台进行药动学参数筛选,并将活性成分导入至SWisstargetprediction中预测药物靶点。在Gene Card、TTD、DrugBank、Dis Ge NET、OMIM等疾病数据库中获取银屑病疾病靶点,利用Cytoscape3.8.2中的BisoGent插件和CytoNCA插件进行核心作用靶点筛选,所得核心靶点利用R软件进行基因功能注释(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。结果 共纳入181个方剂,涉及215种中药,用药频次≥17的高频中药有35种,频次最高的药物是生地黄。关联规则分析显示最常用的药对配伍是生地黄-牡丹皮,提升度最高的药物配伍是金银花-连翘。核心药物配伍是生地黄、牡丹皮、赤芍、紫草。它们共有62个有效成分,关键成分可能是异戊酰紫草素、乙酰紫草根素、黄芩素、木犀草素、山柰酚,其中筛选出376个核心靶点。GO分析和KEGG富集分析显示核心药物可能通过神经营养因子信号通路、磷酸化磷脂酰肌醇3激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinase B,PI3K-Akt)信号通路和缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等发挥作用。结论 治疗银屑病方剂使用清热凉血药为主,同时辅以活血化瘀、养血解毒、祛风止痒、破血祛瘀之法,且注重祛邪不忘扶正。核心药物作用机制可能是通过异戊酰紫草素、乙酰紫草根素、黄芩素、木犀草素、山柰酚等活性成分作用于神经营养因子信号通路、PI3K-Akt信号通路和HIF-1信号通路等发挥抗炎、调节免疫反应、调控转录水平、血管损伤修复的作用。本研究可为银屑病的临床遣方用药和新药开发提供一定参考。

Objective To explore the medication rules of clearing heat and cooling blood drugs in treating psoriasis among the famous traditional Chinese medicine practitioners,analyze their potential mechanisms,and provide the basis for the clinical prescription medication and new drug development for psoriasis.Methods After selecting formulas those related to the application of heat clearing and blood cooling drugs by renowned traditional Chinese medicine practitioners to treat psoriasis from several traditional Chinese medicine books,the traditional Chinese medicine medication frequency was calculated by Microsoft Excel 2010.The Apriori section of SPSS Clementine 12.0 software and the arules and arulesViz plug-ins of R software were performed for association rule analysis.Obtain the active ingredients of core drugs in the TCMSP database.Screening pharmacokinetic parameters on the SwissADME and importing the screened active ingredients into SWisstargetprediction to predict drug targets.Subsequently,psoriasis targets were obtained from disease databases such as GeneCard,TTD,DrugBank,DisGeNET,and OMIM.The BisoGent plug-in and CytoNCA plug-in in Cytoscape 3.8.2 was used for core role target screening,and R software was used for GO and KEGG analysis.Results A total of 181 prescriptions were included,with 215 traditional Chinese medicine drugs involved.There were 35 high-frequency types of traditional Chinese medicine with a medication frequency greater than or equal to 17.The most frequent drug was Rehmannia glutinosa.Association rule analysis showed that the most common drug pairing was raw Rehmannia glutinosa-Moutan Cortex,and the highest promotion of drug compatibility was Lonicera japonica Thunb-Forsythia suspensa.The core drug compatibilities were raw Rehmannia glutinosa,Moutan Cortex,Paeoniae Radix Rubra,and Lithospermum.They had a total of 62 active components,and the key components may be[(1R)-1-(5,8-dihydroxy-1,4-dioxo-2-naphthyl)-4-methyl-pent-3-enyl]propanoate,Acetylshikonin,Baicalein,luteolin,Kaempferol.And they had 376 core targets.GO analysis and KEGG pathway enrichment analysis showed that core drugs may function through neurotrophin signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway.Conclusion The prescriptions for treating psoriasis mainly used heat clearing and blood cooling drugs,supplemented by promoting blood circulation and resolving stasis,nourishing blood and detoxifying,dispelling wind and itching,breaking blood and removing stasis.The mechanism of action of core drugs may be that the active components such as isovalerylshikonin,acetylshikonin,baicalein,luteolin,kaempferol act on neurotrophin signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway to play the role of anti-inflammatory,regulating immune response,regulating transcription level,and repairing vascular damage.This study can provide a reference for the clinical prescription and new drug development of psoriasis.