Deciphering the multicomponent synergy mechanism from a systems pharmacology perspective: Application to Gualou Xiebai Decoction for coronary heart disease

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.