背景:如何筛选和识别复杂物质系统中的有效成分是实现中药(TCM)配方现代化的核心问题之一。然而,从TCM配方的成百上千个成分中系统地筛选出有效成分仍然具有挑战性。
目的:一种创新的五层漏斗过滤模式,逐步整合化学剖面,定量分析,异源生物概况,成功地提出了网络药理学和生物活性评估,以发现有效成分并以止食-泻白-桂枝汤(ZXG)为例进行了研究,冠心病(CHD)的著名中医配方。
方法:最初,系统表征了ZXG的化学特征。随后,对代表性成分进行了定量分析。第三步,系统地描绘了ZXG的多组分异源生物特征,并且吸收到血液中的原型被鉴定并指定为主要的生物可利用成分。接下来,构建了“生物可利用成分-CHD靶标-途径-治疗效果”的综合网络,筛选出ZXG抗冠心病的关键生物可利用成分。最后,进一步评估了关键生物可利用成分的生物活性,以确定有效成分。
结果:首先,通过检测201种成分,对ZXG的化学特征进行了系统表征。其次,对37个代表性成分进行了定量,以全面描述其含量分布特征。第三,在量化的组成部分中,基于多组分异源生物谱鉴定了ZXG的24种生物可利用组分。第四,一个集成的网络导致了11种针对CHD的关键生物可利用成分的鉴定。最终,9组分(和厚朴酚、厚朴酚,柚皮苷,Magnoflorine,橙皮苷,Hesperetin,柚皮苷,首次将具有体外心肌保护作用的新橙皮苷和沙鲁丁)鉴定为ZXG的有效成分。
结论:总体而言,这一创新战略首次成功确定了ZXG的有效成分。不仅有助于阐明ZXG治疗冠心病的治疗机制,同时也为中药方剂质量评价系统发现有效成分和理想的质量标志提供了有益的参考。
BACKGROUND: How to screen and identify the effective components in the complex substance system is one of the core issues in achieving the modernization of traditional Chinese medicine (TCM) formulas. However, it is still challenging to systematically screen out the effective components from the hundreds or thousands of components in a TCM formula.
OBJECTIVE: An innovative five-layer-funnel filtering mode stepwise integrating chemical profile, quantitative analysis, xenobiotic profile, network pharmacology and bioactivity evaluation was successfully presented to discover the effective components and implemented on a case study of Zhishi-Xiebai-Guizhi decoction (ZXG), a well-known TCM formula for coronary heart disease (CHD).
METHODS: Initially, the chemical profile of ZXG was systemically characterized. Subsequently, the representative constituents were quantitatively analyzed. In the third step, the multi-component xenobiotics profile of ZXG was systemically delineated, and the prototypes absorbed into the blood were identified and designated as the primary bioavailable components. Next, an integrated network of \"bioavailable components-CHD targets-pathways-therapeutic effects\" was constructed, and the crucial bioavailable components of ZXG against CHD were screened out. Lastly, the bioactivities of crucial bioavailable components were further evaluated to pinpoint effective components.
RESULTS: First of all, the chemical profile of ZXG was systemically characterized with the detection of 201 components. Secondly, 37 representative components were quantified to comprehensively describe its content distribution characteristics. Thirdly, among the quantified components, 24 bioavailable components of ZXG were identified based on the multi-component xenobiotic profile. Fourthly, an integrated network led to the identification of 11 crucial bioavailable components against CHD. Ultimately, 9 components (honokiol, magnolol, naringenin, magnoflorine, hesperidin, hesperetin, naringin, neohesperidin and narirutin) exhibiting myocardial protection in vitro were identified as effective components of ZXG for the first time.
CONCLUSIONS: Overall, this innovative strategy successfully identified the effective components of ZXG for the first time. It could not only significantly contribute to elucidating the therapeutic mechanism of ZXG in the treatment of CHD, but also serve as a helpful reference for the systematic discovery of effective components as well as ideal quality markers in the quality assessment of TCM formulas.