Abstract
Drug combinations have gained increasing interest due to their potential for optimal efficacy and for overcoming drug resistance. Herbal medicine is a complex system with multiple ingredients and has illustrated apparent therapeutic effects through thousands of years of clinical experience, offering a rich resource for combinational therapies. However, the underlying mechanisms of their synergistic therapeutic effects in disease treatment remain obscure for most herbal medicines. To fill this gap, we developed an integrated database, HerbComb (https://herbcomb.com/), to discover combinatorial therapies in herbal medicine, featuring three unique functions: drug prepositioning, customized combinatorial analysis, and biological and pharmacological features. Additionally, transcriptional gene signatures and ADMET properties were also interrogated as interactive functionalities to facilitate combinational analysis. Using Tongxinluo for Stroke as a case study, we identified and validated Oleanolic acid and Ferulic acid as synergistic ingredients. In summary, HerbComb is a versatile data exploration platform designed to characterize synergistic interactions among herbal medicines, enhance understanding of synergistic mechanisms, and facilitate the discovery of effective drug combinations.