Networking the active compounds from Chinese Medicines and molecular targets in mammalian cells for drug discovery in the Post-Genomic Era

Abstract

Chinese traditional medicines are often composed of multiple medicinal herbs, sometimes non-herbal materials for treating various diseases. The adherent chemical complexity and mechanistic elusiveness are two major factors hindering the modernization and globalization of this long-history medicine. The recently evolved transcriptomics, proteomics, phytomics and metabolomics have made it possible to dissect the networks between the chemical ingredients of medicinal herbs and protein targets in different cells of human body. This presentation will take our recent work on a famous post-stroke rehabilitation formulation ISF-1 as an example to provide a tentative roadmap for the molecular characterization of complex herbal medicine formulation. Our strategy involves three major steps: 1) to investigate the biological response fingerprints (BioReF) and proteomic response fingerprints (ProReF) of complex herbal medicine formulations in various cell models. The protein targets are selected from the transcriptomic or proteomic profiles based on the impact on human health; 2) to isolate the corresponding active compounds from the complex herbal medicine formulations for selected protein targets through a bioactivity-guided fractionation procedure; 3) to further examine the molecular mechanisms by which the bioactive botanical compounds regulated specific protein targets as well as the intracellular signalling pathways in cell models and animal models. Such a technology platform should be generally useful for other scientists to understand the molecular pharmacology behind the clinical use of a variety of Chinese medicine formulations against human diseases. The resulted knowledge represents useful information to develop quality control metric as well as to define potential intracellular protein targets for drug discovery.