Antiviral and Immunomodulatory Effects of Norantea brasiliensis Choisy on Dengue Virus-2.
OBJECTIVE
Severe dengue fever is a result of exacerbated immune responses and no specific treatments are available. We evaluated the antiviral and immunomodulatory effects of Norantea brasiliensis Choisy.


METHODS
Human adherent monocytes infected in vitro with dengue virus (DENV)-2 were incubated with the crude ethanol extract from leaves (NB1) or 3 derived fractions: dichloromethane (NB3), ethyl acetate (NB5), and butanolic (NB6) partitions. The antiviral and immunomodulatory activities were determined by intracellular detection of DENV antigen within monocytes and by secreted NS1 viral protein and cytokines.


RESULTS
The crude extract alone exhibited both antiviral activities (intracellular and secreted antigens) and all fractions derived from this extract modulated NS1 production. Regarding the immunomodulatory effect, among the secreted factors, TNF-α was inhibited by NB3 and NB6; IL-6 was inhibited by NB1, NB3, and NB6; IL-10 by NB1 and NB3; and IFN-α by NB6. The crude extract (NB1) presented the best antiviral effect, whereas the dichloromethane fraction (NB3) presented an immunomodulatory effect in the inflammatory and anti-inflammatory cytokines.


CONCLUSIONS
During in vitro DENV infection, N. brasiliensis Choisy exerts both antiviral and immunomodulatory effects that are likely associated, considering that less viral load may lead to less immunostimulation.
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Luciana Gomes
LG
Fialho
Vagner Pereira
VP
da Silva
Sônia Regina Nogueira Ignácio
SR
Reis
Elzinandes Leal
EL
Azeredo
Maria Auxiliadora Coelho
MA
Kaplan
Maria Raquel
MR
Figueiredo
Claire Fernandes
CF
Kubelka
D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003716:Dengue Virus / Q000187:drug effects* / Q000276:immunology; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D019684:Magnoliopsida / Q000737:chemistry*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects*; D017361:Viral Nonstructural Proteins / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
D000956:Antigens, Viral; D000998:Antiviral Agents; D016207:Cytokines; D000431:Ethanol; D016753:Interleukin-10; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; D000093242:Interleukin-6 Inhibitors; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C079340:NS1 protein, Dengue virus type 2