Utilization of gene expression signature for quality control of traditional chinese medicine formula Si-Wu-Tang

Abstract

The current study utilized a combined pharmacokinetic and genomic approach to demonstrate the feasibility of a new quality control method by using a panel of special differentially expressed genes (DEGs) as unique fingerprint to serve as marker of in vivo bioactivity for a representative traditional Chinese medicine (TCM) formula, Si-Wu-Tang (SWT). The method involves firstly obtaining possible in vivo active components, i.e., the "absorbable" components from the permeate of the Caco-2 monolayer model to simulate oral administration of two specific SWT products (CU-SWT, J-SWT), their component single herbs (Angelicae, Chuanxiong, Paeoniae, and Rehmanniae), and a standard mixture of active compounds (ferulic acid, ligustilide, senkyunolide A). Then, these respective absorbable components were incubated with MCF-7 cells to determine the gene expression profile using microarray processing/analysis as well as real-time PCR. From the available DEGs identified following the incubation, the magnitude of change in DEGs by real-time PCR was found to be consistent with that by microarray. The designated DEGs from the CU-SWT permeate were found to be distinct from other 19 products. Furthermore, the changes in the DEGs resulting from MCF-7 cells treated by eight replicate extracts of CU-SWT on three separate days were consistent. These results demonstrated sufficient specificity and consistency of the DEG panel which could serve as a unique bioactive "fingerprint" for the designated SWT product. The present method for DEG determination may be applied to other TCM products and with further definitive study can potentially provide a unique method for quality control of TCM in the future. © 2013 American Association of Pharmaceutical Scientists.