Abstract
Many traditional medicines are of plant origin and are made up of extracts from multiple plants. As a result, identifying the key bioactives in these mixtures and their mode of action is a difficult process. Generally, the approach to this problem has been one of fractionation and testing of individual compounds from these mixtures. However, very often, this standard purification and testing approach fails to recapitulate the full bioactivity of the original complex mixture. Presumably, this is because the compounds in these mixtures do not act individually, but rather in combination with other compounds. We have elected to tackle this problem using a systems biology approach that relies on identifying pathways that are perturbed by unfractionated complex mixtures, and using that information to infer a mode of action for the mixture in question. Our primary tool for this approach is transcriptome profiling using next generation sequencing. An illustration of the value of this approach is the work we have carried out on Compound Kushen Injection (CKI), an injectable Traditional Chinese Medicine based on extracts from the roots of Sophora flavescens and Smilax glabra, used in oncology in China, that contains over 21 compounds based on HPLC fractionation [1] . We have extended this work to additional cancer cell lines identifying core genes/pathways with common expression changes, confirming pathways that affect cell cycle as principal targets of this injection.
Published Version
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