Deciphering the combination principles of Traditional Chinese Medicine from a systems pharmacology perspective based on Ma-huang Decoction

The main therapeutic concept in Traditional Chinese Medicine (TCM) is herb formula, which treats various diseases via potential herb interactions to maximize the efficacy and minimize the adverse effects. However, the combination principle of herb formula still remains a mystery due to the lack of appropriate methods. A systems pharmacology method integrating the pharmacokinetic analysis, drug targeting, and drug–target–disease network is developed to dissect this rule embedded in the herbal formula. All these are exemplified by a representative TCM formula, Ma-huang decoction, made up of four botanic herbs. Based on the deep investigation of the function and compatibility of each herb, in a molecular/systems level, we demonstrate the different pharmacological roles that each herb might play in the prescription. By the way of enhancing the bioavailability and/or making the pharmacological synergy among different herbs, the four herbs effectively combine together to be suitable for treating diseases. The present work lays foundations for a more comprehensive understanding of the combination rule of TCM, which might also be beneficial to drug development and applications.