基于“有效性”完整表达的白芍质量标志物研究
投稿时间:2024-01-31  修订日期:2024-02-26   点此下载全文
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韩彦琪 韩彦琪 天津药物研究院药物成药性评价与系统转化全国重点实验室 Tianjin Institute of Pharmaceutical Research hanyanqi619@163.com 
徐佳新 XU Jiaxin 天津药物研究院药物成药性评价与系统转化全国重点实验室 Tianjin Institute of Pharmaceutical Research xujiaxin112118@163.com 
许浚* XU Jun 天津药物研究院药物成药性评价与系统转化全国重点实验室 Tianjin Institute of Pharmaceutical Research xuj@tjipr.com 
张铁军 ZHANG Tiejun 天津药物研究院药物成药性评价与系统转化全国重点实验室 Tianjin Institute of Pharmaceutical Research zhangtj@tjipr.com 
基金项目:安徽省科技重大专项(202303a07020007)第一作者:韩彦琪,副研究员,主要从事中药药理研究,Email: hanyq@tjipr.com*通信作者:许浚,研究员,主要从事中药大品种二次开发研究,Email: xuj@tjipr.com张铁军,研究员,主要从事中药新药开发及二次开发研究,Email: zhangtj@tjipr.com
中文摘要:目的 基于中药质量标志物“有效性”原则,采用“性-效-物”三元论研究思路,从“药性(味)”和“药效”角度揭示白芍质量标志物。方法 采用LC-MS方法,解析白芍、炒白芍、赤芍化学物质组;在此基础上,通过分子对接方法,选择白芍中各结构类型代表化合物为配体小分子,通过与苦、酸味受体进行分子对接实验,预测白芍潜在药性(味)物质基础;采用网络药理学方法,通过Swiss Target Prediction、TCMSP等数据库预测化合物潜在作用靶点,并进行生物信息学分析,构建 “化合物-靶点-信号通路-药理作用-功效”网络,进一步以体外抗炎药效筛选模型,验证白芍及关键化合物的抗炎药效作用,明晰基于“药效”的白芍物质基础,进而基于“有效性”完整表达结果确定白芍质量标志物。结果 共解析出白芍中42个成分、炒白芍中41个成分、赤芍中34个成分。其中单萜及其苷类化合物可能为白芍药材最主要的苦味物质基础,带有没食子酰基的鞣质类化合物可能为白芍最主要的酸味物质基础。网络药理学结果发现,白芍中17个成分通过作用于191个潜在靶点干预了165条相关通路,可发挥促进骨髓造血功能、抑制子宫收缩、抗炎、镇痛、保肝、抗高血压和抑制汗腺分泌等作用;验证实验表明,白芍中8个主要成分可通过下调IL-6、TNF-α和NO等炎症因子的表达发挥抗炎作用。结论 初步确定芍药苷、芍药内酯苷、氧化芍药苷、没食子酰芍药苷、苯甲酰芍药苷、儿茶素、五没食子酰葡萄糖及没食子酸为基于有效性完整表达的白芍质量标志物。
中文关键词:“性-效-物”三元论  有效性完整表达  质量标志物  分子对接  网络药理学
 
Study on the quality markers of Paeoniae Radix Alba based on the complete expression of "effectiveness"
Abstract:Objective To reveal the quality markers (Q-markers) of Paeoniae Radix Alba from the perspectives of 'medicinal properties (five flavors)' and 'efficacy' by using the ternary theory of 'property-efficacy- component'. Methods LC-MS method was used to analyze the chemical components of Radix Paeoniae Alba, stir-fried Radix Paeoniae Alba and Radix Paeoniae Rubra. On this basis, through the molecular docking method, the representative compounds of each structural type in Paeoniae Radix Alba were selected as ligands, and the molecular docking experiments with bitter and sour receptors were carried out to predict the potential medicinal (five flavors) material basis of Paeoniae Radix Alba. The network pharmacology was used to predict the potential targets of the compounds through Swiss Target Prediction, TCMSP and other databases, and bioinformatics analysis was performed to construct a 'compound-target-signaling pathway-pharmacological effect-efficacy' network. The anti-inflammatory effects of Radix Paeoniae Alba and key compounds were further verified by the in vitro anti-inflammatory effect screening model, and the material basis of Radix Paeoniae Alba based on 'efficacy' was clarified, and then the Q-markers of Radix Paeoniae Alba were determined based on the complete expression results of 'efficacy'. Results A total of 42,34 and 35 components in Radix Paeoniae Alba, stir-fried Radix Paeoniae Alba and Radix Paeoniae Rubra were analyzed respectively. Among them, monoterpene glycosides may be the most important bitter material basis of Radix Paeoniae Alba, and tannin compounds with galloyl may be the material basis of sour taste. The results of network pharmacology showed that 17 components in Paeoniae Radix Alba interfered with 165 related pathways by acting on 191 potential targets, which could promote bone marrow hematopoietic function, inhibit uterine contraction, anti-inflammatory, analgesic, liver protection, anti-hypertension and inhibit sweat gland secretion. The results of verification experiments showed that the 8 main components in Paeoniae Radix Alba could exert anti-inflammatory effects by down-regulating the expression of inflammatory factors such as IL-6, TNF-α and NO. Conclusion Paeoniflorin, albiflorin, oxypaeoniflorin, galloylpaeoniflorin, benzoylpaeoniflorin, catechin, pentagalloylglucose and gallic acid were preliminarily identified as Q-markers of Radix Paeoniae Alba based on the complete expression of 'effectiveness'.
keywords:ternary theory of "property-efficacy- component"  complete expression of effectiveness  quality markers  molecular docking  network pharmacology
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