Zeylleucapenoids A-H, Halimane-type and Labdane-type Diterpenoids with Anti-inflammatory Activity from Leucas zeylanica

Eight new diterpenoids (1-8) characterized as halimane-type and labdane-type skeletons, and four known (9-12) compounds, were isolated from Leucas zeylanica. Their structures were determined by comprehensive spectroscopic analysis, X-ray crystal diffraction and computational calculations. Compounds 1 and 2 represent structurally unique 6/6/6-fused tricyclic halimane-type diterpenoids. Compounds 8 and 12 exhibit nontoxic effects for zebrafish embryo, while they display efficient reduction against NO production in a dose-dependent manner and strongly suppress the secretion of LPS-induced TNF-α and IL-6 cytokines in RAW264.7 macrophages. In addition, marked reductions of iNOS and COX-2 in protein were observed. Molecular docking analysis indicated that both 8 and 12 have high affinities with the target amino acid residues on protein-binding sites, which may be a possible mechanism contributing to the anti-inflammatory potential of these molecules.