[关键词]
[摘要]
目的 挖掘含枳实-厚朴药对的方剂,统计分析组方用药规律,并探究其治疗食积的潜在作用机制。方法 检索整理《中医方剂大辞典》中含枳实-厚朴药对的方剂,录入Excel建立数据库,分析其来源出处、剂型、中药配伍频数、性味归经与主治病症,运用R语言(4.3.3)软件与OriginPro软件进行共现次数、关联规则、相关性聚类分析及可视化。继而对枳实-厚朴药对与其主治病症食积进行“枳实-厚朴药对-活性成分-食积靶点”网络构建、蛋白质相互作用(Protein-protein interaction network,PPI)分析、基因本体(Gene ontology,GO)功能与基因组百科全书(Kyoto encyclopedia of genes and genome,KEGG)通路富集分析,并通过分子对接评估核心活性成分与关键靶点蛋白之间的结合情况。结果 纳入含枳实-厚朴药对的方剂349 首,包含268 味中药,其中高频配伍药物包括陈皮、甘草、白术、大黄与木香5 味。性味以性温,味辛、苦、甘为主,大多归脾、肝、胃经。涉及主治病症141 种,以食积、痢疾、胀满等脾胃系病症居多。相关性聚类分析表明枳实-厚朴药对常与具有行气健脾、清热祛湿功效的药物合用。通过网络药理学分析,发现枳实-厚朴药对的核心活性成分为木犀草素、(R,R)-2,3-丁二醇、柚皮素、和厚朴酚及川陈皮素,食积关键靶点为BDNF、AKT1、ESR1、TNF和IL-6,分子对接结果显示木犀草素与AKT1结合最为紧密。结论 常与枳实-厚朴药对配伍的中药有陈皮、白术、木香等,含有枳实-厚朴药对方剂的优势主治病症为食积,其关键活性成分可通过AKT1、TNF等多靶点发挥治疗作用。本研究揭示了枳实-厚朴药对的组方配伍规律,初步阐释了其治疗食积的作用机制,可为研究枳实-厚朴配伍机制与临床合理用药提供参考与依据。
[Key word]
[Abstract]
Objective Excavate the prescriptions containing the drug pair of Aurantii Fructus Immaturus-Magnoliae Officinalis Cortex(AFI-MOC), and statistically analyze the rules of prescription medication, and explore its potential mechanism of action in the treatment of food retention disorder. Methods The prescriptions containing the pair of AFI-MOC in the Great Dictionary of Traditional Chinese Medicine Prescriptions were retrieved and typed into Excel to establish a database. The source, dosage form, frequency of compatibility of traditional Chinese medicine, nature, taste and meridian attribution and indications were analyzed. Using R language (4.3.3) software with OriginPro to analysis co-occurrence frequency, association rule, correlation clustering analysis, and visualization. Then, the network construction, Protein-Protein Interaction Network (PPI) analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis of the "AFI-MOC-active ingredient-food retention disorder target" network were performed for the AFI-MOC drug pair and its indications food retention disorder. The binding between the core active ingredients and key target proteins was evaluated by molecular docking. Results A total of 349 prescriptions containing the pair of AFI-MOC were included, involving 268 Chinese herbs. Among them, the high-frequency compatibility drugs included Citri Reticulatae Pericarpium, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Rhei Radix et Rhizoma and Aucklandiae Radix.They are mainly warm in nature, spicy, bitter and sweet in taste, spleen, liver and stomach in meridian. There were 141 kinds of indications, most of which were diseases of the spleen and stomach system such as food retention disorder, dysentery and fullness. Correlation cluster analysis shows that the AFI-MOC drug pair is frequently combined with drugs that have the efficacy of promoting qi circulation, strengthening the spleen, clearing heat, and eliminating dampness. Found through the analysis of network pharmacology AFI-MOC drug pair on the core of the active ingredient of Luteolin, BU3, Naringenin, Honokiol and Nobiletin. Key targets for food retention disorder are BDNF, AKT1, ESR1, TNF and IL-6. Molecular docking results show Luteolin, combined with AKT1 is most closely. Conclusion AFI-MOC drug pair often compatible with Citri Reticulatae Pericarpium, Atractylodis Macrocephalae Rhizoma, Aucklandiae Radix. The advantages of the prescription containing AFI-MOC drug pair is food retention disorder. Its key active components can exert therapeutic effects through multiple targets such as AKT1 and TNF. This study reveals the AFI-MOC drug pair on compatibility laws, preliminary interpretation of the mechanism for the treatment of food retention disorder. It can provide references and a basis for studying the compatibility mechanism of AFI-MOC and guiding rational clinical medication.
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[基金项目]
(1)北京市自然科学基金资助项目(NO.7232281):Lnc517368调控胃癌前病变线粒体自噬介导凋亡机制及化浊解毒方的干预研究,负责人:王彦刚;(2)河北省中医药管理局科研计划项目(2020105):苍术炮制过程中颜色与物质基础变化相关性研究,负责人:陈炯;(3)河北省高等学校科学技术研究-青年拔尖人才项目(BJK2024183):香连化浊方调控线粒体稳态抑制泛凋亡治疗CAG机制研究,负责人:孙建慧。