Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7 macrophages

Ethnopharmacological relevance: Taraxasterol was isolated from the Chinese medicinal herb Taraxacum officinale which has been frequently used as a remedy for inflammatory diseases. Our previous study has shown that taraxasterol inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E-2 (PGE(2)) production in RAW 264.7 macrophages. To elucidate the underlying mechanism responsible for these effects, in the present study, we investigated the effects of taraxasterol on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, and mitogen-activated protein kinases (MAPKs) signaling pathway in LPS-induced RAW 264.7 macrophages. Materials and methods: RAW 264.7 cells were pretreated with 2.5, 5 and 12.5 mu g/ml of taraxasterol 1 h prior to treatment with 1 mu g/ml of LPS. The mRNA expression levels of iNOS and COX-2 were examined by RT-PCR. The protein expression levels of iNOS and COX-2, and the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) MAPKs were measured by Western blot. Results: The mRNA and protein expression levels of iNOS and COX-2 were inhibited by taraxasterol in a concentration-dependent manner. Further studies revealed that taraxasterol suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW 264.7 macrophages. Conclusions: These results indicate that taraxasterol inhibits iNOS and COX-2 expression by blocking ERK1/2 and p38 MAPKs signaling pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.