Andrograpalides A-N, structurally diverse ent-labdane diterpenoids with anti-inflammatory activities from the leaves of Andrographis paniculata.

Andrograpalides A-N (1-14), fourteen previously undescribed ent-labdane-type diterpenoids, together with a previously undescribed naturally occurring diterpenoid (15) and two known analogues (16-17), were isolated from the leaves of Andrographis paniculata. Their structures were unambiguously elucidated via extensive spectroscopic analysis, electronic circular dichroism analysis, and X-ray crystallographic studies. Structurally, compounds 1-8 and 16 are rare cases of 19-nor labdane-type diterpenoids with an unusual C19 carbon skeleton. Notably, compounds 1 and 2 feature an unusual hydroperoxy group at C-4. In addition, the isolated compounds were evaluated for their anti-inflammatory effects in lipopolysaccharide-induced RAW 264.7 cells. Compound 12 exhibited the most significant anti-inflammatory activity, as indicated by the lowest nitric oxide production rate, and the remarkable reduced protein expression of inducible nitric oxide synthase and cyclooxygenase-2.