Magnolol potently suppressed lipopolysaccharide-induced iNOS and COX-2 expression via downregulating MAPK and NF-κB signaling pathways

Magnolol is a hydroxylated biphenyl compound from the bark of Magnolia officinalis that has been reported to have various biological properties including anti-inflammation. However, the molecular mechanism of anti-inflammation remains unclear although it has been suggested that magnolol inhibits NO production in murine macrophage. In this study, we investigated the inhibitory effects of magnolol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Co-treatment with magnolol significantly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression. Western blot analysis and reporter assay showed that magnolol reduced translocation of the p50 and p65 subunit by reducing the degradation and phosphorylation of inhibitor κB (IκB), and subsequent transcriptional activity of NF-κB. We also found that magnolol blocked LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, Jun N-terminal kinase (JNK) 1/2 and phosphatidylinositiol 3-kinase (PI3 K)/Akt signaling but no p38 mitogen-activated protein kinase (MAPK). These results suggest that magnolol inhibits iNOS and COX-2 protein and gene expression by blocking the activation of NF-κB through interference with activation of PI3K/Akt and MAPK signaling. These findings suggest that magnolol may have potential to be developed into an effective anti-inflammatory agent.

► Magnolol reduced translocation of the p50 and p65 subunit by reducing the degradation and phosphorylation of inhibitor κB (IκB), and subsequent the transcriptional activity of NF-κB.
► Magnolol blocked LPS-induced phosphorylation of ERK 1/2, JNK 1/2, and PI3K/Akt signaling but no p38 MAPK.
► Magnolol may have potential to be developed into an effective anti-inflammatory agent.