Anti-inflammatory effect of 4-O-methylhonokiol, a novel compound isolated from Magnolia officinalis through inhibition of NF-κB

The bioactive constituents isolated from the bark of Magnolia officinalis such as magnolol, honokiol and obovatol have anti-inflammatory properties through the inactivation of NF-κB which is an important factor in the regulation of inflammatory reaction. We recently isolated a novel neolignan compound, 4-O-methylhonokiol, from M. officinalis. In the present study, we investigated whether or not 4-O-methylhonokiol inhibits inflammatory reaction through the inhibition of NF-κB activity. The results showed that 4-O-methylhonokiol (2.5–10 μM) inhibited LPS (1 μg/ml)-induced NO generation in macrophage Raw 264.7 cells in a concentration-dependent manner with IC50 value 9.8 μM. The inhibition of NO generation by 4-O-methylhonokiol was consistent with the inhibitory effect on the expression as well as transcriptional activity of inducible nitric oxide synthase (iNOS). In addition, 4-O-methylhonokiol inhibited the LPS-induced transcriptional and DNA binding activities of NF-κB as well as p50 and p65 translocation into the nucleus. Topical application of 4-O-methylhonokiol (0.1–1 mg/ear) inhibited 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema formation, NF-κB activity, and iNOS and COX-2 expression. The present results provided evidence that 4-O-methylhonokiol has anti-inflammatory properties through inhibition of the NF-κB pathway, and suggested that 4-O-methylhonokiol can be used as an anti-inflammatory agent.