Nitric Oxide Production Inhibition and Anti‑Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh

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. Materials and 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 H37Rv 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). Conclusion: 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.