A metabolic exposure-oriented network regulation strategy for the identification of effective combination in the extract of Ginkgo biloba L.

Nowadays, network pharmacology-based methods were increasing proposed to screen synergistic or combinatorial compounds from herbal medicines (HMs), while these researches mainly focused on structural prediction or experiment-based interaction between single compound and target protein. The proportion of each chemical in the nature and their metabolic process was ignored, which might decide an optimized composition for their synergistic effect. To exact the effective combination of HMs, a metabolic distribution-oriented network regulation strategy was developed for the identification of effective combination. Firstly, comprehensive chemical profiling and metabolic exposure of HMs in a pathological state were conducted. Then the effective combination for HMs was screened by combining network regulation and the metabolic exposure level of HMs. Finally, with the extract of Ginkgo biloba (EGB) as a case, a combination of 12 active compounds was found for treating ischemia stroke, showing bioactivity equivalence with original herb. The results also indicated that beside the well-known ginkgolides and flavonoids, trace compounds might also play an important role of the holistic effect of EGB. This method can be used as an alternative for effective combination screening.