Anti-inflammatory activity of labdanediol-derived diterpenes

• González-Cofrade, Laura ^[1] ; Cuadrado, Irene ^[1] ; Estévez-Braun, Ana ^[2] ; Hortelano, Sonsoles ^[3] ; Heras, Beatriz de las ^[1]
  1. [1] Universidad Complutense de Madrid

     Universidad Complutense de Madrid

     Madrid, España

     
  2. [2] Universidad de La Laguna

     Universidad de La Laguna

     San Cristóbal de La Laguna, España

     
  3. [3] Instituto de Investigaciones en Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII)

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• Localización: Dianas: revista de dianas terapéuticas, ISSN-e 1886-8746, Vol. 9, Nº. 1, 2020 (Ejemplar dedicado a: Actas del V Congreso de Señalización Celular, SECUAH 2020 / coord. por María José Carmena Sierra, Alberto Domingo Galán)
• Idioma: inglés
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• Resumen

  • Inflammation is a protective physiological response triggered by microbial infection or tissue injury with a key role in the pathogenesis of several chronic diseasease, due to the up-regulation and overproduction of proinflammatory mediators and the dysregulation of the NLRP3 inflammasome. Terpenes are bioactive natural products with great therapeutic potential. In this work, a series of ten novel labdanes derivatives (LB1-LB10) from the diterpene labdanediol isolated from Oxylobus glanduliferus was synthetized and evaluated for anti-inflammatory potential in lipopolysaccharide (LPS)-treated J774A.1 macrophages. Inhibitory effects of the non-toxic compounds on nitric oxide (NO) release were evaluated. Labdanediol derivative LB5 was selected as the most active inhibitor (IC50= 10 µM). LB5 also significantly inhibited the protein expression of Nitric Oxide Synthase-2 (NOS-2) and Cyclooxygenase-2 (COX-2) enzymes and the gene expression at the transcriptional level of NOS-2, COX-2 and inflammatory cytokines (IL-6, TNFα). Regulation of NLRP3 inflammasome pathway seems not to be involved in the anti-inflammatory activity of these compounds, as IL-1β levels in LPS/ATP-stimulated macrophages were not significantly reduced by treatment with these derivatives. In summary, we have identified a novel labdanediol derivative (LB5) with potential anti-inflammatory activity so it can be considered as a promising starting point for the development of new anti-inflamatory agents. Further experiments will be performed to elucidate the molecular mechanisms involved.