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  • Platycodon grandiflorum is a member of

    2021-10-27

    Platycodon grandiflorum is a member of the genus Platycodon and is commonly known as balloon flower. In East Asia, P. grandiflorum is used for the treatment of asthma, coughs, inflammatory diseases, pulmonary tuberculosis, and diabetes (Takagi and Lee, 1972). Furthermore, recent studies have reported that P. grandiflorum extracts exert various pharmacological effects against diseases, such as obesity, diabetes, hyperlipidemia, inflammation, and allergies (Ashok and Ali, 1999, Finkel and Holbrook, 2000, Halliwell, 2006, Han et al., 2000, 2002; Zhao et al., 2008). Ginseng is a popular health supplement in South Korea and has long been used for improving health. Ginseng contains several pharmacological ingredients called ginsenosides, which include Rb1, Rb2, Rb3, Rg3, Rh2, Rg1, Rg2, Rh1, and Ro (Chen et al., 2014). Various studies have demonstrated the pharmacological effects of ginseng. Interestingly, ginseng extracts contain numerous bioactive compounds; however, most studies have investigated individual compounds present in ginseng extracts. Despite their importance for the identification of new pharmacological targets, the mechanisms underlying the therapeutic effects of these whole extracts remain to be elucidated. HDAC (Histone deacetylases) is an enzyme that removes acetyl group from N-terminal lysine residue of histone. It induces gene silencing and repression and thus play key role in the regulation of cell cycle, proliferation. In this study, we evaluated the therapeutic efficacies of P. grandiflorum and ginseng extract using CMAP-based gene Benztropine mesylate analysis. Our results using lung cancer cell lines showed that P. grandiflorum and ginseng extracts have good potential for repurposing as novel HDAC (histone deacetylase) inhibitors. Further, our workflow represents a novel approach for repositioning multi-compound-containing plant extracts for the development of therapeutic strategies for new diseases.
    Materials and methods
    Results
    Discussion Transcriptome analysis has emerged as an indispensable method for investigating the interactions between proteins and their underlying regulatory mechanisms. Analysis of large-scale genome and transcriptome sequence data using NGS technologies has proven effective in predicting novel protein-based bioactive compounds in plants (Han et al., 2016). Although the genomic technologies have been used for distinguishing between species, strain or bioactive genes, our findings can be used to identify the effective cellular targets of compounds from the plant extracts. All substances, including natural compounds, plant extracts, and chemical drugs, induce changes in cellular gene expression when administrated into cells or the body. Given that the development of diseases is triggered by aberrant gene expression patterns, certain compounds exhibit potential for therapeutic treatment against diseases. Our current Benztropine mesylate findings demonstrated that gene expression similarity could be used to identify associations between compounds and specific diseases. Thus, the association between disease and drugs and gene expression could serve as an effective approach to understand the mechanisms of action of the components present in medicinal herbs. CMAP, which compares the gene expression profiles, can be employed to identify cellular perturbations induced by novel compounds that are similar to those induced by known therapeutic agents (Lamb et al., 2006, Smalley et al., 2010). In the present study, we utilized gene-pattern analysis algorithm, CMAP, to identify the inhibitory effects of P. grandiflorum and ginseng extract on histone deacetylase (HDAC) activity. The gene expression profiles obtained in a previous study (Kwon et al., 2013) were used as query for comparisons using the CMAP database. P. grandiflorum and ginseng extract have received great research interest because the induced DEGs showed a considerably higher degree of overlap with the DEGs induced upon treatment with HDAC inhibitors than those induced by other drugs. P. grandiflorum and ginseng extract significantly inhibited HDAC activity (Fig. 3A and B) in human lung cancer cells and induced p21 expression (Fig. 3C). Interestingly, P. grandiflorum and ginseng extract additionally enhanced DNA damage-induced apoptosis (Fig. 4). Thus, the above findings suggested that P. grandiflorum and ginseng extract could serve as novel HDAC inhibitors in lung cancer cells.