Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 35, Issue 1, Pages 65-71Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.35.65
Keywords
interferon; Janus kinase: signal transducer and activator of transcription; emodin; quercetin; luteolin
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Funding
- Chinese Academy of Sciences (West Light Foundation)
- National Natural Sciences Foundation of China [90713002]
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Type I interferons (IFN-alpha/beta) have been widely used in the treatment of many viral and malignant diseases by activation of the Janus kinase/signal transducer and activator of transcription JAK/STAT) signaling pathway, but the side effects of protein-based IFN therapy severely limit their clinical use. Discovering small molecules to activate the JAK/STAT pathway will greatly facilitate the development of new drugs which have similar pharmacological function to IFNs but with fewer side effects. To screen a natural products-based library, we established a cell-based screening assay using human hepatoma HepG2 cells stably transfected with a plasmid where the luciferase reporter activity is driven by interferon a-stimulated response element (ISRE), the motif specifically recognized by type I IFN-induced activation of JAK/STAT pathway. Among 1,431 natural product compounds screened, four compounds (emodin, quercetin, apigenin and luteolin) were identified as activators of the JAK/STAT pathway. Further studies demonstrated that these four compounds could increase the endogenous antiviral gene expression regulated by the IFN-activated JAK/STAT pathway. The identified small molecule activators are valuable for structural modification and warrant further investigation for use in new antiviral drugs as IFN mimics or adjuvants.
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