(E)-Guggulsterone Inhibits Dengue Virus Replication by Upregulating Antiviral Interferon Responses through the Induction of Heme Oxygenase-1 Expression

  • Viruses. 2021 Apr 20;13(4):712. doi: 10.3390/v13040712.
Wei-Chun Chen  1 ,  Chih-Ku Wei  1 ,  Monir Hossen  2 ,  Yao-Chin Hsu  3 ,  Jin-Ching Lee  1  2  4  5  6
Affiliations
  • 1. Department of Biotechnology and PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 2. Graduate Institute of Medicine in College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 3. Chinese Medical Department, Chi-Mei Medical Center, Tainan 71004, Taiwan.
  • 4. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 5. Graduate Institute of Natural Products in College of Pharmacy and Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 6. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
PMID: 33924157 DOI: 10.3390/v13040712
Abstract

Dengue Virus (DENV) Infection, which causes dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is a severe global health problem in tropical and subtropical areas. There is no effective vaccine or drug against DENV Infection. Thus, the development of anti-DENV agents is imperative. This study aimed to assess the anti-DENV activity of (E)-guggulsterone using a DENV infectious system. A specific inhibitor targeting signal molecules was used to evaluate the molecular mechanisms of action. Western blotting and qRT-PCR were used to determine DENV protein expression and RNA replication, respectively. Finally, an ICR suckling mouse model was used to examine the anti-DENV activity of (E)-guggulsterone in vivo. A dose-dependent inhibitory effect of (E)-guggulsterone on DENV protein synthesis and RNA replication without cytotoxicity was observed. The mechanistic studied revealed that (E)-guggulsterone stimulates Nrf2-mediated heme oxygenase-1 (HO-1) expression, which increases the Antiviral interferon responses and downstream Antiviral gene expression by blocking DENV NS2B/3B protease activity. Moreover, (E)-guggulsterone protected ICR suckling mice from life-threatening DENV Infection. These results suggest that (E)-guggulsterone can be a potential supplement for controlling DENV replication.

Keywords
(E)-guggulsterone; DENV; heme oxygenase-1 (HO-1); interferon.
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