Structure and anti-inflammatory activity of neo-clerodane diterpenoids from Scutellaria barbata.

Herein, 13 previously undescribed neo -clerodane diterpenoids (1 – 13) and 27 known analogs (14 – 40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC 50 value of 10.6 μM. Structure–activity relations of these neo -clerodane diterpenoids revealed that the α, β -unsaturated- γ -lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF- κ B signaling by inhibiting IκBα phosphorylation. [Display omitted] • 40 neo -clerodane diterpenoids was isolated from Scutellaria barbata. • Absolute configurations of 13 undescribed compounds were assigned. • Compound 36 showed potent anti-inflammatory activity by inhibiting NF-κB pathway. • Structure–activity relations of 40 neo -clerodane diterpenoids were discussed. [ABSTRACT FROM AUTHOR]