Nitric oxide inhibitory isopimarane-type diterpenes from Orthosiphon stamineus of Indonesia

A methanolic extract of Orthosiphon stamineus yielded six new highly oxygenated isopimarane-type diterpenes, orthosiphols U-Z (1-6), and 15 previously reported diterpenes. The isolated diterpenes all showed significant dose-dependent inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Orthosiphols A (7), B (8), D (9), and X (4) showed more potent inhibitory activities than a positive control, N(G)-monomethyl-l-arginine (l-NMMA), and 1 displayed the strongest activity with an IC(50) value of 6.4 microM.