Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264.7 cells: possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways.

Research paper by Seon Il SI Jang, Hyung Jin HJ Kim, Young-Jun YJ Kim, Seung-Il SI Jeong, Yong-Ouk YO You

Indexed on: 27 Jun '06Published on: 27 Jun '06Published in: European Journal of Pharmacology


Nuclear factor kappaB (NF-kappaB) activation by NF-kappaB-inducing kinase (NIK)-IkappaB alpha kinase (IKK) pathway and mitogen-activated protein kinases (MAPKs) pathway are important in inflammation. We recently found that the tanshinone IIA, a diterpene isolated from Salvia miltiorrhiza (S. miltiorrhiza), reduced the production of pro-inflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). However, little is known about the inhibitory mechanisms of tanshinone IIA on the production of pro-inflammatory mediators. To investigate the inhibitory mechanism, we determined the inhibitory effects of tanshinone IIA on the activation of NF-kappaB and IkappaB alpha phosphorylation, and also examined phosphorylation of NIK and IKK as well as the activation of MAPKs such as p38 MAPK (p38), extracellular signal-regulated kinases 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in RAW 264.7 cells stimulated with LPS. Tanshinone IIA inhibited NF-kappaB-DNA complex, NF-kappaB binding activity, and the phosphorylation of IkappaB alpha in a dose dependent manner. Tanshinone IIA also inhibited the translocation of NF-kappaB from cytosol to nucleus. Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the tanshinone IIA in a dose dependent manner. These results suggest that tanshinone IIA may inhibit LPS-induced IkappaB alpha degradation and NF-kappaB activation via suppression of the NIK-IKK pathway as well as the MAPKs (p38, ERK1/2, and JNK) pathway in RAW 264.7 cells and these properties may provide a potential mechanism that explains the anti-inflammatory activity of tanshinone IIA.