Coronary heart disease (CHD) is often accompanied with diabetes mellitus, which leads the limited effect of monotherapy. Drug combinations are deemed to a promising approach for treating CHD, and traditional Chinese medicine (TCM) formulas are important source of drug combinations discovery. In this study, to dissect the synergic bioactive compounds from TCM formula for CHD, Gualou Xiebai Decoction (GXD), is exemplified by employing a systems pharmacology strategy. 16 potential bioactive compounds are screened out by ADME evaluation. The Probability Ensemble Approach is used to predict potential drug combination pairs. Then, we exploit network analysis to dissect the synergistic mechanisms and find compound combinations act on multiple pathways. In vitro experiments confirm that the three compound combinations alleviate high-glucose induced myocardial injury. In summary, the integrated systems pharmacology method supplies accurate illustration of the molecular mechanisms of GXD to treat CHD and provides a new way for developing combination therapeutics.

冠心病（CHD）通常伴有糖尿病，这导致单一疗法的作用有限。药物组合被认为是治疗冠心病的一种有前途的方法，中药配方是发现药物组合的重要来源。在这项研究中，为了从CHD的中药配方中分离出协同生物活性化合物，可通过采用系统药理学方法来举例说明瓜X泻白汤（GXD）。通过ADME评估筛选出16种潜在的生物活性化合物。概率集合法用于预测潜在的药物组合对。然后，我们利用网络分析来剖析协同机制，并发现化合物组合作用于多种途径。体外实验证实这三种化合物的组合减轻了高糖诱导的心肌损伤。综上所述，综合系统药理学方法提供了GXD治疗冠心病的分子机制的准确例证，并为开发联合疗法提供了新途径。