Kaurane Diterpenes from Isodon japonicus Inhibit Nitric Oxide and Prostaglandin E2 Production and NF-κB Activation in LPS-Stimulated Macrophage RAW264.7 Cells

Abstract

A methanolic extract of the whole plant of Isodon japonicus (Labiatae) showed potent inhibition on the LPS-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) 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-κB activation as assessed by NF-κB reporter assay and electrophoretic mobility shift assay (EMSA). Compounds 2 - 4 showed comparable inhibitory effects on the LPS-induced production of NO and PGE₂, and activation of NF-κB without affecting cell viability. These results suggest that kaurane diterpenes could exert their inhibitory effects on the production of NO and PGE₂ through the suppression of NF-κB activation, and be partially responsible for the anti-inflammatory activities of the genus Isodon.