2. Academic Validation
  3. Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway

Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway

  • PLoS One. 2016 Mar 29;11(3):e0152236. doi: 10.1371/journal.pone.0152236.
Jung-Sheng Yu 1 2,  Wei-Chun Chen 3,  Chin-Kai Tseng 4 5,  Chun-Kuang Lin 6,  Yao-Chin Hsu 1,  Yen-Hsu Chen 7 8 9 10,  Jin-Ching Lee 11 12 13
Affiliations

Affiliations

  • 1 Department of Chinese Medicine, Chi Mei Medical Center, Tainan, 71004, Taiwan.
  • 2 Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40402, Taiwan.
  • 3 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 4 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 5 Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 6 Doctoral Degree Program in Marine Biotechnology, College of Marine Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
  • 7 Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 8 School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Center for Dengue Fever Control and Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 9 Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan.
  • 10 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 11 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 12 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 13 Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan.
PMID: 27023634 DOI: 10.1371/journal.pone.0152236
Abstract

Hepatitis C virus (HCV) infection-induced oxidative stress is a major risk factor for the development of HCV-associated liver disease. Sulforaphane (SFN) is an antioxidant phytocompound that acts against cellular oxidative stress and tumorigenesis. However, there is little known about its anti-viral activity. In this study, we demonstrated that SFN significantly suppressed HCV protein and RNA levels in HCV replicon cells and infectious system, with an IC50 value of 5.7 ± 0.2 μM. Moreover, combination of SFN with anti-viral drugs displayed synergistic effects in the suppression of HCV replication. In addition, we found nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 induction in response to SFN and determined the signaling pathways involved in this process, including inhibition of NS3 protease activity and induction of IFN response. In contrast, the anti-viral activities were attenuated by knockdown of HO-1 with specific inhibitor (SnPP) and shRNA, suggesting that anti-HCV activity of SFN is dependent on HO-1 expression. Otherwise, SFN stimulated the phosphorylation of phosphoinositide 3-kinase (PI3K) leading Nrf2-mediated HO-1 expression against HCV replication. Overall, our results indicated that HO-1 is essential in SFN-mediated anti-HCV activity and provide new insights in the molecular mechanism of SFN in HCV replication.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15005
    99.97%, HCV Inhibitor
    HCV