成分-靶点-代谢模式分析丹参的质量标志物及初步验证

Analysis on Q-markers of Salvia miltiorrhiza and relevant preliminary verification based on the strategy of component-target-metabolism

目的 基于“成分-靶点-代谢”分析模式,筛选并验证丹参中潜在的质量标志物(Q-marker)。方法 基于文献整合及数据分析对丹参Q-marker的来源范围进行筛选,构建“成分-靶点-通路”的网络药理学模型;采用HPLC进行丹参饮片指纹图谱指认和定量分析,结合网络药理学结果,初步确定丹参Q-marker,再通过UPLC-MS法鉴别丹参入血成分并进行体内验证。结果 丹参酚酸类和酮类成分为丹参Q-marker的主要来源范围;丹参酮ⅡA、隐丹参酮、咖啡酸在“成分-靶点-通路”网络中具有高连接度,是其主要活性成分;15批丹参饮片的HPLC指纹图谱中指认了6个色谱峰,分别为丹酚酸B、迷迭香酸、紫草酸、丹参酮Ⅰ、隐丹参酮和丹参酮ⅡA;丹酚酸B、隐丹参酮、丹参酮ⅡA可作为丹参的Q-marker,进一步确认这3个入血成分为潜在的药效活性成分。结论 确定了丹酚酸B、隐丹参酮及丹参酮ⅡA作为丹参潜在Q-marker具有较高的合理性,为完善丹参的质量控制和评价方法提供了依据。

OBJECTIVE To explore potential Q-markers of Salvia miltiorrhiza(Danshen) based on the strategy of components-targets-metabolism.METHODS On the basis of literature integration and data analysis, source range of Q-marker of Danshen was screened, and by means of network pharmacology a "component-target-pathway" network was constructed.Then, Q-markers of Danshen was predicted based on HPLC-UV fingerprint and quantitative analysis of Danshen and relevant network pharmacological results.Finally, the prototypes in plasma were identified by UPLC-MS after intragastrically administering the water extract of Danshen to rats, which justified that the screened Q-markers were the relevant bioactive components.RESULTS It was demonstrated that salvianolic acids and tanshinones were the main source of Q-markers for Danshen.TanshinoneⅡA,cryptotanshinone and caffeic acid showed high connectivity in the component-target-pathway network and these were main active components.In the HPLC fingerprints of 15 Danshen samples, six chromatographic peaks were identified, namely, rosmarinic acid, lithospermic acid, salvianolic acid B,cryptotanshinone, tanshinone I and tanshinoneⅡA.Salvianolic acid B,cryptotanshinone and tanshinoneⅡA could be regarded as the Q-markers of Danshen, and it was further justified that the three components in plasma are potential bioactive components.CONCLUSION This study reveals that salvianolic acid B,cryptotanshinone and tanshinoneⅡA as the potential Q-marker of Danshen are scientific and reasonable.The present study is expected to provide scientific reference both to strengthening the quality control and evaluation of Danshen.