Methyl-1-hydroxy-2-naphthoate, a novel naphthol derivative, inhibits lipopolysaccharide-induced inflammatory response in macrophages via suppression of NF-κB, JNK and p38 MAPK pathways

The anti-inflammatory effect of methyl-1-hydroxy-2-naphthoate (MHNA), a novel naphthol derivative, was evaluated in the lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages. The release of nitric oxide (NO), interleukin-1beta (IL-1 beta) and interleukin-6 (IL-6) were detected by the Griess reagent and ELISA methods. The protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by Western blotting. The mRNA expressions of IL-1 beta, IL-6, iNOS and COX-2 were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappa B) pathways were detected by Western blotting, reporter gene assay and electrophoretic mobility shift assay. MHNA significantly inhibited the release of NO, IL-1 beta and IL-6 as well as the protein expression of iNOS and COX-2 in LPS-stimulated macrophages. It also inhibited the mRNA expression of iNOS, COX-2, IL-1 beta and IL-6. Further studies indicated that MHNA inhibited LPS-induced increases in NF-kappa B DNA-binding activity and NF-kappa B transcriptional activity as well as I kappa B-alpha degradation and NF-kappa B translocation in a dose-dependent manner. Meanwhile, the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) induced by LPS were decreased by MHNA. MHNA inhibits the LPS-induced inflammatory response in murine macrophages via suppression of NF-kappa B and MAPKs signaling pathways activation.