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Molecular Mechanisms of Inhibitory Activities of Tanshinones on Lipopolysaccharide-Induced Nitric Oxide Generation in RAW 264.7 Cells  

Choi, Hong-Seok (Department of Pharmacology, College of Pharmacy, Drug Development Research Center , Chonnam National University)
Cho, Dong-Im (Department of Pharmacology, College of Pharmacy, Drug Development Research Center , Chonnam National University)
Choi, Hoo-Kyun (College of Pharmacy, Chosun University)
Im, Suhn-Yong (Department of Biological Sciecnces, Chonnam National University)
Ryu, Shi-Yong (Korea Research Institute of Chemical Technology)
Kim , Kyeong-Man (Department of Pharmacology, College of Pharmacy, Drug Development Research Center , Chonnam National University)
Publication Information
Archives of Pharmacal Research / v.27, no.12, 2004 , pp. 1233-1237 More about this Journal
Abstract
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 $IC_{50}$ values of 5, 8, and 1.5 ${\mu}M$ , 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-$_KB$ 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-$_KB$ and ERK could be the molecular targets for tanshinones for the inhibition of LPS-induced nitric oxide production in macrophage cells.
Keywords
Tanshinones; Nitric oxide; Lipopolysaccharide; Nf-$_KB$; ERK;
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