基于有效性完整表达的白芍质量标志物研究OACSTPCD
Study on the Quality Markers of Paeoniae Radix Alba Based on the Complete Expression of Effectiveness
目的:基于中药质量标志物(Q-marker)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Q-marker.方法:采用液相色谱-质谱联用法(LC-MS),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SwissTargetPrediction、中药系统药理学数据库与分析平台(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Q-marker.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白细胞介素-6、肿瘤坏死因子-α和一氧化氮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Q-marker.
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:Liquid chromatography-mass spectrometry(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,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 using the in vitro anti-inflammatory drug screening model,and the material basis of Radix Paeoniae Alba was clarified based on efficacy.Then the Q-markers of Radix Paeoniae Alba were determined based on the complete expression of effectiveness.Results:A total of 42 components in Radix Paeoniae Alba,42 components in stir-fried Radix Paeoniae Alba and 34 components,in Radix Paeoniae Rubra were identified,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 have the effects of promoting bone marrow hematopoietic function,inhibiting uterine contraction,anti-inflammatory,analgesic,liver protection,anti-hypertension and inhibiting 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 interleukin-6,tumor necrosis factor α and nitric oxide.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.
韩彦琪;徐佳新;许浚;张立娜;张铁军
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,天津 300462||天津药物研究院 天津市中药质量标志物重点实验室,天津 300462||天津药物研究院 中药现代制剂与质量控制技术国家地方联合工程实验室,天津 300462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,天津 300462||天津药物研究院 天津市中药质量标志物重点实验室,天津 300462||天津药物研究院 中药现代制剂与质量控制技术国家地方联合工程实验室,天津 300462||天津中医药大学,天津 301617河北医科大学第三医院,河北 石家庄 050051
中医学
"性-效-物"三元论有效性完整表达质量标志物液相质谱联用法分子对接网络药理学
ternary theory of"property-efficacy-component"complete expression of effectivenessquality markerLC-MSmolecular dockingnetwork pharmacology
《中国现代中药》 2024 (002)
252-264 / 13
安徽省科技重大专项(202303a07020007);河北省中医药管理局科研计划项目(2019125)
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