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Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2

(Willd.) DC., a large woody vine native to the Amazon and Central American
rainforests has been used medicinally by indigenous peoples since ancient times and has
scientifically proven immunomodulating, anti-inflammatory, cytotoxic and antioxidant activities.
Several inflammatory mediators that are implicated in vascular permeability and shock are
produced after Dengue Virus (DENV) infection by monocytes, the primary targets for virus
replication. Here we assessed the immunoregulatory and antiviral activities from
samples, which were tested in an in vitro DENV infection model. DENV-2 infected human
monocytes were incubated with
hydro-alcoholic extract or either its pentacyclic
oxindole alkaloid-enriched or non-alkaloid fractions. The antiviral activity was determined by
viral antigen (DENV-Ag) detection in monocytes by flow cytometry. Our results demonstrated an inhibitory activity by both extract and alkaloidal fraction, reducing DENV-Ag+ cell rates
in treated monocytes. A multiple microbead immunoassay was applied for cytokine determination
(TNF-α, IFN-α, IL-6 and IL-10) in infected monocyte culture supernatants. The alkaloidal
fraction induced a strong immunomodulation: TNF-α and IFN-α levels were significantly
decreased and there was a tendency towards IL-10 modulation. We conclude that the alkaloidal fraction was the most effective in reducing monocyte infection rates and cytokine levels. The
antiviral and immunomodulating
pentacyclic oxindole alkaloids
displayed novel properties regarding therapeutic procedures in Dengue Fever and might be further
investigated as a promising candidate for clinical application.

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