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dc.contributor.authorChen, Wei-Chunen_US
dc.contributor.authorTseng, Chin-Kaien_US
dc.contributor.authorLin, Chun-Kuangen_US
dc.contributor.authorWang, Shen-Nienen_US
dc.contributor.authorWang, Wen-Hungen_US
dc.contributor.authorHsu, Shih-Hsienen_US
dc.contributor.authorWu, Yu-Hsuanen_US
dc.contributor.authorHung, Ling-Chienen_US
dc.contributor.authorChen, Yen-Hsuen_US
dc.contributor.authorLee, Jin-Chingen_US
dc.date.accessioned2018-08-21T05:53:24Z-
dc.date.available2018-08-21T05:53:24Z-
dc.date.issued2018-01-01en_US
dc.identifier.issn2150-5594en_US
dc.identifier.urihttp://dx.doi.org/10.1080/21505594.2017.1421893en_US
dc.identifier.urihttp://hdl.handle.net/11536/144646-
dc.description.abstractDengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice. Then, the anti-DENV activity of lucidone was confirmed by western blotting and quantitative-reverse-transcription-polymerase chain reaction analysis, with an EC50 value of 25 +/- 3 mu M. Lucidone significantly induced heme oxygenase-1 (HO-1) production against DENV replication by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed antiviral interferon response. The inhibitory effect of lucidone on DENV replication was attenuated by silencing of HO-1 gene expression or blocking HO-1 activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its anti-DENV activity. Taken together, the mechanistic investigations revealed that lucidone exhibits significant anti-DENV activity in in vivo and in vitro by inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease activity to induce the anti-viral interferon (IFN) response. These results suggest that lucidone is a promising candidate for drug development.en_US
dc.language.isoen_USen_US
dc.subjectDengue virusen_US
dc.subjectlucidoneen_US
dc.subjectheme oxygnase-1en_US
dc.subjectviral replicationen_US
dc.subjectinterferon responseen_US
dc.titleLucidone suppresses dengue viral replication through the induction of heme oxygenase-1en_US
dc.typeArticleen_US
dc.identifier.doi10.1080/21505594.2017.1421893en_US
dc.identifier.journalVIRULENCEen_US
dc.citation.volume9en_US
dc.citation.spage588en_US
dc.citation.epage603en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000426967300024en_US
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