title: Uncaria tomentosa alkaloidal fraction reduces paracellular permeability, IL-8 and NS1 production on human microvascular endothelial cells infected with dengue virus.
abstract: Dengue is the major Arbovirus in the world, annually causing morbidity and death. Severe dengue is associated with changes in the endothelial barrier function due to the production of inflammatory mediators by immune cells and by the endothelium. Dengue virus (DENV) replicates efficiently in human endothelial cells in vitro and elicits immune responses resulting in endothelial permeability. Uncaria tomentosa (Willd.) DC.(Rubiaceae), known as cat's claw, has been used in folk medicine for the treatment of a wide-array of symptoms, and several scientific studies reported its antiviral, immunomodulatory, anti-inflammatory and antioxidant properties. Here we infected a human lineage of dermal microvascular endothelial cells (HMEC-1) with DENV-2 and treated it with an alkaloidal fraction from U. tomentosa bark (AFUT). We showed antiviral and immunomodulatory activities of U. tomentosa by determining the NS1 antigen and IL-8 in supernatant of DENV-2 infected HMEC-1. Furthermore, by measurement of transendothelial electrical resistance (TEER) we demonstrated, for the first time, that a plant derivative contributed to the reduction of paracellular permeability in DENV-2 infected HMEC-1. We also showed that IL-8 contributed significantly to the induction of permeability. Although further investigations should be conducted before a new drug can be suggested, our in vitro data support evidence that AFUT could be potentially useful in developing a treatment for severe dengue.
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil. raimundojunior@yahoo.com.br
authors.forename: Raimundo Sousa
authors.initials: RS
authors.lastname: Lima-Junior
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil.
authors.forename: Cintia da Silva
authors.initials: Cda S
authors.lastname: Mello
authors.affiliation: lnstituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Siani
authors.affiliation: Instituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, C.T., Bl.A, 21941-909, Rio de Janeiro, RJ, Brazil.
authors.forename: Ligia M Marino
authors.initials: LM
authors.lastname: Valente
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil.
authors.forename: Claire Fernandes
authors.initials: CF
authors.lastname: Kubelka
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D020948:Cat's Claw / Q000737:chemistry*; D002478:Cells, Cultured; D003716:Dengue Virus / Q000187:drug effects*; D042783:Endothelial Cells / Q000276:immunology / Q000821:virology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D010539:Permeability; D024301:Plant Bark / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis*
chemical_list: D000470:Alkaloids; D016209:Interleukin-8; C079340:NS1 protein, Dengue virus type 2; D017361:Viral Nonstructural Proteins