Repurposing natural products as novel HDAC inhibitors by comparative analysis of gene expression profiles

Extracts derived from natural products have been used to produce health supplements or therapeutic agents in oriental medicine. Although these extracts contain various bioactive compounds, their applications are generally limited to a few previously known diseases. To effectively expand their use for the treatment of other conditions, systematic analysis should be conducted for repurposing.

The purpose of the present study was to investigate the new therapeutic efficacies of the Platycodon grandiflorum and ginseng extract using the CMAP-based gene expression analysis.

In the present study, we analyzed the expression patterns of differentially expressed genes (DEGs) from extracts as the basis for drug repurposing. Cells were treated with extracts or single compounds derived from nine natural products. DEG analysis indicated that the gene expression patterns of cells treated with P. grandiflorum and ginseng extracts were highly similar to those of cells treated with different types of Histone deacetylase (HDAC) inhibitors. To identify the new mechanism of these extracts, we carried out cell viability assay, TUNEL assay, HDAC enzyme activity assay and immunoblot analysis.

In vitro experiments at the dose of 50 µg/ml of each extract did not affect cell death rate but significantly inhibited HDAC activity. Each extract was found to inhibit HDAC enzymatic activity and induce the expression of the p21. Furthermore, our results revealed that each extract stimulated cell death and inhibited cell proliferation.

These findings demonstrate the HDAC-inhibiting activity of P. grandiflorum and ginseng extracts and further validate the effectiveness of DEG similarity-based repurposing of natural products.