TNF-α inhibitory diterpenoids from the Chinese mangrove plant Excoecaria agallocha L.

Chemical examination of the stems and twigs of the mangrove plant Excoecaria agallocha L. resulted in the isolation of six ent-kaurane diterpenoids named agallochaols K-P (1-6), an atisane-type diterpenoid agallochaol Q (7), along with eight known diterpenoids (8-15). Their structures were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR spectroscopic data with those reported in literature, in association with the biogenetic relationship with the X-ray structure of 9. Compounds 1, 5-7, 9-10, and 13 showed anti-inflammatory potency to suppress expression of NF-κB and AP-1 targeted genes including TNF-α and IL-6 induced by lipopolysaccharide (LPS) in mouse macrophages Raw 264.7 cells. In addition, compounds 1, 5-7, 9-10, and 13 block NF-κB activation, while compounds 1 and 7 block AP-1 activation dramatically, indicating these compounds possess an anti-inflammatory potential in vitro.