Helveticoside is a biologically active component of the seed extract of Descurainia sophia and induces reciprocal gene regulation in A549 human lung cancer cells

Bu-Yeo Kim, Jun Lee, No Soo Kim

Although the pharmacological activities of the seed extract of Descurainia sophia have been proven to be useful against cough, asthma, and edema, the biologically active components, particularly at the molecular level, remain elusive. Therefore, we aimed to identify the active component of an ethanol extract of D. sophia seeds (EEDS) by applying a systematic genomic approach. After treatment with EEDS, the dose-dependently expressed genes in A549 cells were used to query the Connectivity map to determine which small molecules could closely mimic EEDS in terms of whole gene expression. Gene ontology and pathway analyses were also performed to identify the functional involvement of the drug responsive genes. In addition, interaction network and enrichment map assays were implemented to measure the functional network structure of the drug-responsive genes. A Connectivity map analysis of differentially expressed genes resulted in the discovery of helveticoside as a candidate drug that induces a similar gene expression pattern to EEDS. We identified the presence of helveticoside in EEDS and determined that helveticoside was responsible for the dose-dependent gene expression induced by EEDS. Gene ontology and pathway analyses revealed that the metabolism and signaling processes in A549 cells were reciprocally regulated by helveticoside and inter-connected as functional modules. Additionally, in an ontological network analysis, diverse cancer type-related genes were found to be associated with the biological functions regulated by helveticoside. Using bioinformatic analyses, we confirmed that helveticoside is a biologically active component of EEDS that induces reciprocal regulation of metabolism and signaling processes. Our approach may provide novel insights to the herbal research field for identifying biologically active components from extracts.