基于特征图谱和网络药理学的经典名方黄连汤质量标志物(Q-Marker)预测分析

Q-Marker prediction analysis of classical prescription Huanglian Decotion based on characteristic spectrums and network pharmacology

目的建立经典名方黄连汤HPLC特征图谱,结合网络药理学,分析预测黄连汤潜在的质量标志物(Q-Marker)。方法建立黄连汤基准样品特征图谱的检测方法,匹配共有峰并进行色谱峰归属;基于文献及特征图谱研究筛选黄连汤活性成分,通过网络药理学建立“成分-靶点-通路”网络,预测黄连汤潜在的Q-Marker。结果黄连汤HPLC特征图谱标定了17个共有峰,经对照品指认出黄连碱、巴马汀、小檗碱、甘草苷、甘草酸、桂皮醛、6-姜辣素7个色谱峰,18批黄连汤基准样品与其参照图谱(R)的相似度均大于0.95,且17个共有峰均能明确归属到黄连、甘草、干姜、桂枝4味饮片;经网络药理学分析,筛选出黄连碱、巴马汀、小檗碱、甘草苷、甘草酸、桂皮醛、6-姜辣素7个活性成分,PIK3CA、MAPK3、SRC等30个核心靶点,AGE-RAGE信号通路、T细胞受体信号通路等139条关键通路,表明黄连汤主要通过这些成分、靶点、通路治疗胃肠道相关疾病,初步预测黄连碱、巴马汀、小檗碱、甘草苷、甘草酸、桂皮醛、6-姜辣素为黄连汤潜在的Q-Marker。结论通过特征图谱和网络药理学分析预测黄连汤中的Q-Marker,所建立的方法操作便捷,结果准确,重复性好,可用于黄连汤的质量控制和评价,为全面控制黄连汤的质量提供依据,为进一步研究黄连汤的作用机制提供参考。

Objective To establish the HPLC characteristic spectrums of classical prescription Huanglian Decotion(HLD,黄连汤),and analyze and predict the potential quality markers(Q-Marker)combined with network pharmacology.Methods A method for characteristic spectrum of HLD was developed,then the common peaks were matched and the chromatographic peaks were assigned.Based on literature and characteristic spectrum,the active ingredients of HLD were screened,and a network of“component-targetpathway”was established through network pharmacology to predict the potential Q-Marker.Results The HPLC characteristic map of HLD was calibrated with 17 common peaks,and seven chromatographic peaks of coptisine,palmatine,berberine,liquiritin,glycyrrhizic acid,6-gingerol,cinnamaldehyde were identified by the reference substance.The similarity between the 18 batches of substance reference and the reference map R was all greater than 0.95,and the 17 common peaks could be clearly assigned to four pieces of Huanglian(Coptidis Rhizoma),Gancao(Glycyrrhizae Radix et Rhizoma),Ganjiang(Zingiberis Rhizoma),and Guizhi(Cinnamomi Ramulus).Through network pharmacology analysis,seven active ingredients of coptisine,palmatine,berberine,liquiritin,glycyrrhizic acid,6-gingerol,cinnamaldehyde,30 core targets such as PIK3CA,MAPK3 and SRC,139 key pathways including Age-rage signaling pathway and T cell receptor signaling pathway were screened out.It showed that HLD mainly treated gastrointestinal diseases through these components,targets and pathways,and coptisine,palmatine,berberine,liquiritin,glycyrrhizic acid,6-gingerol,cinnamaldehyde were preliminary predicted as potential Q-marker of HLD.Conclusion Q-marker in HLD was predicted by characteristic spectrum and network pharmacology,and the established method was convenient to operate,accurate and reproducibility,which could be used for quality control and evaluation of HLD,and provide basis for comprehensive quality control of HLD and reference for further study on the mechanism of HLD.