Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2 Sonia Regina I.N. Reis a , Ligia M.M. Valente b , André L. Sampaio c , Antonio C. Siani d , Mariana Gandini a , Elzinandes L. Azeredo a , Luiz A. D'Avila e , José L. Mazzei e , Maria das Graças M. Henriques c , Claire F. Kubelka a, ⁎ a Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil b Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Brazil c Departamento de Farmacologia Aplicada, Instituto de Tecnologia em Fármacos, FIOCRUZ, Brazil d Laboratório de Produtos Naturais, Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Brazil e Departamento de Processos Orgânicos, Escola de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Received 2 September 2007; received in revised form 20 November 2007; accepted 27 November 2007 Abstract Uncaria tomentosa (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 activ- ities. 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 U. tomentosa- derived samples, which were tested in an in vitro DENV infection model. DENV-2 infected human monocytes were incubated with U. tomentosa 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 in vitro inhibitory activity by both extract and alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead immunoassay was applied for cytokine determina- tion (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 © 2007 Elsevier B.V. All rights reserved. KEYWORDS Uncaria tomentosa; Dengue; Cytokines; Immunomodulator; Alkaloids; Antiviral ⁎ Corresponding author. Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365 Rio de Janeiro, Brazil, CEP 21040- 360. Tel.: +55 21 25984354; fax: +55 21 25984373. E-mail address: claire@ioc.fiocruz.br (C.F. Kubelka). 1567-5769/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2007.11.010 www.elsevier.com/locate/intimp International Immunopharmacology (2008) 8, 468–476