Anti-inflammatory effect of isopimarane diterpenoids from Kaempferia galanga.

Two new isopimarane diterpenes, 1α-hydroxy-14α-methoxyisopimara-8(9),15-diene (7) and 1α,14α-dihydroxyisopimara-8(9),15-diene (9) and eight known isopimarane diterpenes including (-)-sandaracopimaradiene (1), 6β-acetoxysandaracopimaradiene-9α-ol (2), sandaracopimaradiene-7β,9α-diol (3), sandaracopimaradiene-1α,9α-diol (4), 6β-acetoxysandaracopimaradiene-9α-ol-1-one (5), 6β-acetoxysandaracopimaradiene-1α,9α-diol (6), 6β,14α-dihydroxyisopimara-8(9),15-diene (8), and 6β,14β-dihydroxyisopimara-8(9),15-diene (10) were isolated from hexane fraction of Kaempferia galanga ethanol extract. Compounds 5, 6, 8, and 9 exerted the good anti-inflammatory effect on lipopolysaccharide-stimulated nitric oxide production from RAW264.7 cells with IC₅₀ of 11.2, 7.7, 14.3, and 12.1 μM, respectively. These four compounds inhibited nitric oxide synthase (iNOS) mRNA expression. Compounds 5 and 6 also suppressed cyclooxygenase 2 (COX-2) mRNA expression; in addition, compound 6 had mild inhibitory effect on TNF-α mRNA. Among these compounds, 5 dramatically inhibited iNOS and COX-2 mRNA expression. The influential structures were proposed to be oxygen substitute at C-1, C-6, and α-OH at C-14.