Molecular mechanisms of inhibitory activities of tanshinones on lipopolysaccharide-induced nitric oxide generation in RAW 264.7 cells

The effects of four tanshinones isolated from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) were tested for their inhibition of nitric oxide production in macrophage cells, and the underlying molecular mechanisms studied. Of the four tanshinones used, 15, 16-dihydrotanshinone-I, tanshinone-IIA and cryptotanshinone, but not tanshinone I, demonstrated significant inhibition of the LPS-induced nitric oxide production in RAW 264.7 cells, with calculated IC50 values of 5, 8, and 1.5 muM, respectively. Tanshinones exerted inhibitory activities on the LPS-induced nitric oxide production only when applied concurrently with LPS, and tanshinone-IIA and cryptotanshinone were found to inhibit LPS-induced NF-kappaB mobilization and extracellular-regulated kinase (ERK) activation, respectively. These results suggest that tanshinones inhibit LPS-induced nitric oxide generation by interfering with the initial stage of LPS-induced expression of certain genes. NF-kappaB and ERK could be the molecular targets for tanshinones for the inhibition of LPS-induced nitric oxide production in macrophage cells.