Structurally diversified ent-kaurane and abietane diterpenoids from the stems of Tripterygium wilfordii and their anti-inflammatory activity.

[Display omitted] • Four underscribed ent -kaurane and three undescribed abietane diterpenoids were isolated from T. wilfordii. • Compounds 1 and 2 were a pair of C-19 epimers of ent -kaurane diterpenoids. Compound 3 possessed a rare naturally occurring 1,3-dioxacyclohexane moiety. • Abietane diterpenoids 7 – 13 showed significant activity to inhibit NO production. • Compounds 7 and 8 significantly suppressed the protein expression of iNOS and COX-2. Four undescribed ent -kaurane diterpenoids, wilkaunoids A − D (1 – 4), and three undescribed abietane diterpenoids, wilabinoids A − C (13 – 15), along with thirteen known ones (5 – 12 and 16 – 20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electronic circular dichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent -kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 possessed a rare naturally occurring 1,3-dioxacyclohexane moiety. Compounds 13 and 15 represented the first example of abietane diterpenoids with an isovalerate substitution from the genus of Tripterygium. The possible biosynthetic pathways of 1 – 3 were postulated. The effect of 1 – 20 on nitric oxide production was examined in lipopolysaccharide-stimulated RAW 264.7 cells. Abietane diterpenoid quinones 7 – 13 (IC 50 : 1.9–10.2 μM) exhibited the significant activity to inhibit nitric oxide production versus positive control (NG-monomethyl- l -arginine acetate salt, IC 50 = 24.9 μM). The structure activity relationship of 7 – 13 in inhibiting nitric oxide production was then discussed. The most potent 7 and 8 were found to significantly suppress the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins, showing a good anti-inflammatory potential. The findings provided some valuable insights for the discovery and structural modification of abietane diterpenoids towards anti-inflammatory lead compounds. [ABSTRACT FROM AUTHOR]