基于系统药理学的白芍-甘草药对作用机制分析

Herb pair Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma: Mechanism analysis by systemic pharmacology approach

目的基于系统药理学方法,借助中药系统药理学分析平台(TCMSP),整合中医药大数据,探讨白芍-甘草药对的功效物质基础并分析其作用机制。方法在TCMSP检索"白芍"和"甘草"2味中药获得其化学成分,采用双侧曼-惠特尼U检验法对所有化学成分的分子描述符进行比较,以口服生物利用度(OB)和类药性(DL)为指标筛选药对的活性成分、靶点和相关疾病,进而构建成分-靶点-疾病网络模型和蛋白互作(PPI)网络模型,对靶蛋白进行基因本体(GO)生物过程和KEGG代谢通路富集分析,探讨药对物质基础和作用机制。结果通过OB、DL参数筛选得到49个药物活性成分、100个作用靶点和230种相关疾病。其中度(degree)值较高的药物活性成分有芒柄花黄素(formononetin)、柚皮素(naringenin)和维斯体素(vestitol);度值较高的靶点有前列腺素g/H合酶2(PTGS2)、雌激素受体(ESR1)和钙调蛋白(CALM);度值较高的相关疾病是非特异性癌症(cancer,unspecific)、炎症(inflammation)、非特异性心血管疾病(cardiovasculardisease,unspecific)、阿尔茨海默病(Alzheimer’s disease)和帕金森病(Parkinson’s disease),主要涉及肿瘤、神经系统疾病、内分泌、营养和代谢疾病及某些传染病和寄生虫病等16类疾病。靶蛋白参与信号传导、药物反应、细胞增殖、RNA聚合酶II启动子调控、细胞外信号调节激酶1(ERK1)和ERK2级联的正调节等生物过程,调控磷脂酰肌醇-3-激酶(PI3K)-蛋白激酶B(Akt)、5-羟色胺能突触等代谢通路。结论初步探索了白芍-甘草药对的基本药理作用及其机制,为该药对及其中药方剂的研究提供新的思路。

Objective To study the functional material basis of herb pair Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma and analyze their mechanism of action by the systematic pharmacological method based on the platform of traditional Chinese medicine systematic pharmacological analysis(TCMSP) and the big data of traditional Chinese medicine. Methods TCMSP was used to search for the chemical constituents of the two Chinese herbal medicines,"Baishao" and "Gancao". The molecular descriptors of the components were compared by the two tailed Mann-Whitney U test method, and the oral bioavailability(OB) and drug-likeness(DL) were used as indicators to screen the active components, targets and related diseases of the herb pair. The"component-target-disease" and PPI network models were constructed, and bioprocess and metabolic pathway were analyzed to explore the drug-based material basis and mechanism of action. Results Through the OB and DL parameters screening, 49 active pharmaceutical ingredients, 100 targets and 230 related diseases were obtained. The active ingredients with higher degree were formononetin, naringenin, and vestitol;The higher degree of targets were prostaglandin g/H synthase 2(PTGS2), estrogen receptor(ESR1), and calmodulin(CALM);The higher-grade related diseases were unspecific cancer, inflammation, cardiovascular disease,unspecified, Alzheimer’s disease, and Parkinson’s disease, mainly involving 16 categories of diseases such as cancer, nervous system diseases, endocrine, nutritional and metabolic diseases and certain infectious diseases and parasitic diseases. Target proteins are involved in bioprocess including signal transduction, drug response, cell proliferation, RNA polymerase II promoter regulation, positive regulation of ERK1 and ERK2 cascades, regulating metabolic pathways such as PI3 K-Akt and 5-hydroxytryptamine synapses. Conclusion This study preliminarily verified the basic pharmacological effects and mechanisms of the Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma herb pair, and explored new ideas for the study of the herb pair and related traditional Chinese medicine prescriptions.