Kaurane diterpenes from Isodon japonicus inhibit nitric oxide and prostaglandin E2 production and NF-κB activation in LPS-stimulated macrophage RAW264.7 cells

A methanolic extract of the whole plant of Isodon japonicus (Labiatae) showed potent inhibition on the LPS-induced nitric oxide (NO) and prostaglandin E-2 (PGE(2)) production in RAW264.7 cells. Four known kaurane diterpenes were isolated by activity-guided fractionation and their structures were identified as kamebanin (1), kamebacetal A (2), kamebakaurin (3), excisanin A (4), All compounds also inhibited the LPS-induced NF-kappaB activation as assessed by NF-kappaB reporter assay and electrophoretic mobility shift assay (EMSA). Compounds 2-4 showed comparable inhibitory effects on the LPS-induced production of NO and PGE(2), and activation of NF-kappaB without affecting cell viability. These results suggest that kaurane diterpenes could exert their inhibitory effects on the production of NO and PGE(2) through the suppression of NF-kappaB activation, and be partially responsible for the anti-inflammatory activities of the genus Isodon.