Rhodiola inhibits dengue virus multiplication by inducing innate immune response genes RIG-I, MDA5 and ISG in human monocytes

Arch Virol. 2014 Aug;159(8):1975-86. doi: 10.1007/s00705-014-2028-0. Epub 2014 Mar 4.


Recognition of virus infection by retinoic acid-inducible gene (RIG) I and melanoma differentiation-associated protein (MDA) 5, which are RNA helicases, and interferon-stimulated gene (ISG) 15 activates cascades of signal transduction pathways leading to production of type I interferons and proinflammatory cytokines that orchestrate the elimination of the viruses. However, it has been demonstrated that RNA-helicase-mediated innate immunity plays an essential role in defending the host from infection. In our efforts to identify plant-derived antivirals that selectively enhance ISG- and RNA-helicase-mediated antiviral immune responses, we identified a plant, rhodiola, that significantly promoted ISG, RIG-I and MDA 5 gene expression and an antiviral immune response against dengue virus (DENV) infection. Rhodiola induced interferon (IFN) β and other cytokines, including IL-1β, TNF-α, IL-6 and IL-8, in infected cells. It was also found that rhodiola upregulated phosphorylated eIF-2α, PKR and NF-kB in infected cells. In addition, the number of NK cells was also increased by rhodiola treatment in dengue-virus-infected human PBMCs. Treatment with a crude extract of rhodiola (RAE) resulted in effects in the 20 % range, which is similar to the magnitude of the same effects observed in DENV infections. Taken together, our results imply that rhodiola induces pharmacological modulation of RIG-I, MDA 5 and ISG signal transduction pathways in favor of the induction of a beneficial antiviral immune response against dengue virus, which can be a novel therapeutic strategy for management of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Cytokines / genetics*
  • Cytokines / immunology
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / immunology
  • Dengue / drug therapy
  • Dengue / genetics
  • Dengue / immunology*
  • Dengue / virology
  • Dengue Virus / drug effects*
  • Dengue Virus / physiology
  • Humans
  • Immunity, Innate / drug effects
  • Interferon-Induced Helicase, IFIH1
  • Monocytes / immunology
  • Monocytes / virology
  • Plant Extracts / pharmacology*
  • Rhizome / chemistry
  • Rhodiola / chemistry*
  • Ubiquitins / genetics*
  • Ubiquitins / immunology
  • Up-Regulation / drug effects
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Cytokines
  • Plant Extracts
  • Ubiquitins
  • ISG15 protein, human
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1