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, NG-monomethyl-l-arginine (l-NMMA), and 1 displayed the strongest activity with an IC50 value of 6.4 μM.