Discovery and verification of the potential targets from bioactive molecules by network pharmacology-based target prediction combined with high-throughput metabolomics

Abstract

Natural products are an invaluable source for drug candidates. Currently, plasma metabolome has suggested that compounds present in herbs may exert bioactivity. The present investigation employed global metabolome analysis technology to explore the key target and action mechanism of scoparone, a representative ingredient of Yinchenhao (Artemisia capillaris Thunb.). First, we applied different databases for target prediction and focused on the potential targets of scoparone by network pharmacology, which also theoretically characterizes the effectiveness of scoparone on molecular docking. Among them, we selected the top predictions as the potential and crucial target. Then, non-targeted metabolomics technology based on an advanced UPLC-MS instrument coupled with a robust data processing platform was employed to characterize the metabolic profiling of alcoholic liver disease (ALD) rats. Furthermore, the ingenuity pathway analysis platform was used for metabolic network analysis, which mainly involved multiple-pathways, including tyrosine metabolism, glutathione metabolism, and primary bile acid biosynthesis. Interestingly, as a core biomarker, dopaquinone is directly related with target prediction of tyrosinase and finally resulted in a series of disturbances. Moreover, the prediction also validated the target on a metabolic level. The present investigation demonstrated that global metabolome analysis could provide a novel strategy for deciphering the potential drug targets of natural products.