title: Nitric Oxide Production Inhibition and Anti-Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh.
abstract: BACKGROUND
  Red algae of the genus Laurencia J. V. Lamouroux are a rich source of secondary metabolites with important pharmacological activities such as anti-tumoral, anti-inflammatory, anti-fungal, anti-viral, anti-leishmanial, anti-helminthic, anti-malarial, anti-trypanosomal, anti-microbial as well as anti-bacterial against Mycobacterium tuberculosis.
  
  
  OBJECTIVE
  In the present study, we evaluated the inhibition of nitric oxide (NO) and tumor necrosis factor-α production and the anti-mycobacterial activity of crude extracts from the red Alga Laurencia dendroidea (from the South-Eastern coast of Brazil). Halogenated sesquiterpenes elatol (1), obtusol (2) and cartilagineol (3), previously isolated from this Alga by our group, were also studied.
  
  
  METHODS
  The lipopolysaccharide-activated macrophage cells (RAW 264.7) were used as inﬂammation model. Cytotoxic effect was determined using a commercial lactate dehydrogenase (LDH) kit and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The growing Mycobacterium inhibition was verified against Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37 Rv strains.
  
  
  RESULTS
  The crude extract from Alga collected at Angra dos Reis, RJ, Brazil, was the most active inhibitor of both mycobacterial growth (half maximal inhibitory concentration [IC50] 8.7 ± 1.4 μg/mL) and NO production by activated macrophages (IC50 5.3 ± 1.3 μg/mL). The assays with isolated compounds revealed the anti-mycobacterial activity of obtusol (2), whereas (-)-elatol (1) inhibited the release of inflammatory mediators, especially NO. To our knowledge, this is the first report describing an anti-mycobacterial effect of L. dendroidea extract and demonstrating the association of this activity with obtusol (2).
  
  
  CONCLUSIONS
  The described effects of active compounds from L. dendroidea are promising for the control of inflammation in infectious diseases and specifically, against mycobacterial infections associated with exacerbated inflammation.
  
  
  CONCLUSIONS
  Inflammation is strongly involved in the pathogenesis of most infectious diseases, including TB. The treatment of TB is based on the use of anti mycobacterial drugs, however the most severe forms of TB, require additional anti inflammatory therapy to prevent excessive inflammation. A combination of these properties in one compound could provide additional therapeutic benefits. In this work, we studied L. dendroidea extracts and purified compounds and demonstrated that the LDA extract and (-)-elatol (1) were potent in inhibiting NO production by macrophages through the specific inhibition of iNOS expression. The LDA and LDM extracts and obtusol (2) were active against virulent strain of M. tuberculosis. This is the first report demonstrating that the anti-inflammatory activities of L. dendroidea were associated with the presence of (-)-elatol (1), whereas anti-mycobacterial activities of L. dendroidea extracts were associated with obtusol (2).
authors.affiliation: Laboratory of Biology of Recognition, Center of Bioscience and Biotechnology, Darcy Ribeiro University of Northern Fluminense, Campos dos Goytacazes-RJ, Brazil; Laboratory of Bioactive Products, School of Pharmacy, Federal University of Rio de Janeiro, Macaé/ IMMT-RJ, Brazil.
authors.forename: Thatiana Lopes
authors.initials: TL
authors.lastname: Biá Ventura
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Group of Natural Products from Aquatic Organisms, Center for Ecology and Socio-Environmental Development, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernanda Lacerda
authors.initials: FL
authors.lastname: da Silva Machado
authors.affiliation: Laboratory of Biology of Recognition, Center of Bioscience and Biotechnology, Darcy Ribeiro University of Northern Fluminense, Campos dos Goytacazes-RJ, Brazil; Laboratory of Bioactive Products, School of Pharmacy, Federal University of Rio de Janeiro, Macaé/ IMMT-RJ, Brazil.
authors.forename: Marlon Heggdorne
authors.initials: MH
authors.lastname: de Araujo
authors.affiliation: Group of Natural Products from Aquatic Organisms, Center for Ecology and Socio-Environmental Development, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Lísia Mônica
authors.initials: LM
authors.lastname: de Souza Gestinari
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carlos Roland
authors.initials: CR
authors.lastname: Kaiser
authors.affiliation: Group of Natural Products from Aquatic Organisms, Center for Ecology and Socio-Environmental Development, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Francisco
authors.initials: F
authors.lastname: de Assis Esteves
authors.affiliation: Laboratory of Biology of Recognition, Center of Bioscience and Biotechnology, Darcy Ribeiro University of Northern Fluminense, Campos dos Goytacazes-RJ, Brazil.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Lasunskaia
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Group of Natural Products from Aquatic Organisms, Center for Ecology and Socio-Environmental Development, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Angélica Ribeiro
authors.initials: AR
authors.lastname: Soares
authors.affiliation: Laboratory of Bioactive Products, School of Pharmacy, Federal University of Rio de Janeiro, Macaé/ IMMT-RJ, Brazil.
authors.forename: Michelle Frazão
authors.initials: MF
authors.lastname: Muzitano
keywords: Anti-inflammatory; Laurencia dendroidea; Rhodomelaceae; anti-mycobacterial; halogenated sesquiterpenes