dianas 9(1) > González-Cofrade etal

dianas | Vol 9 Num 1 | marzo 2020 | e202003c01

Anti-inflammatory activity of labdanediol-derived diterpenes.

Laura González-Cofrade^1, a, Irene Cuadrado¹, Ana Estévez-Braun², Sonsoles Hortelano³, Beatriz de las Heras¹

1. Departamento de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia, Universidad Complutense de Madrid.  2. Instituto Universitario de Bio-Orgánica "Antonio González". Universidad de La Laguna, Tenerife, Spain.  3. Unidad de Terapias Farmacológicas, Instituto de Investigaciones en Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, España.

a. lagonz11@ucm.es

V Congreso de Señalización Celular, SECUAH 2020.
16-18 de marzo, 2020. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: Inflammation, diterpenes, macrophages

Abstract

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.