Anti-inflammatory effect of phenylpropanoids from Dendropanax dentiger in TNF-α-induced MH7A cells via inhibition of NF-κB, Akt and JNK signaling pathways

Abstract

The root of Dendropanax dentiger (Harms) Merr. has been used for centuries as an empirical treatment for rheumatoid arthritis (RA) in China without scientific validation. In our recent study, nineteen phenylpropanoids (1–19) with cyclooxygenase-2 inhibitory activities from the ethanol extract of D. dentiger roots, indicated to have a potential anti-RA effect. This study, evaluated the anti-RA effect of 19 phenylpropanoids on tumor necrosis factor (TNF)-α induced inflammation in MH7A cells and clarified their underlying mechanisms. As a result, 16 compounds remarkably suppressed nitric oxide (NO) production at a concentration of 40 μM in TNF-α-induced MH7A cells. Among them, pinoresinol (12) and dendrocoumarin A (1) were the most effective substances, which showed significant inhibitory effect on NO production, with IC50 values of 6.25 ± 0.42 and 7.87 ± 0.67 μM, respectively. Furthermore, pinoresinol and dendrocoumarin A remarkably decreased the levels of interleukin (IL)-2, 6, 8, and interferon-gamma (IFN-γ), as well as prominently reduced the phosphorylation protein levels of nuclear factor kappa B (NF-κB) p65, I-kappa-B-alpha (IkBα), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) by Western blot analysis. Taken together, our findings suggest that pinoresinol and dendrocoumarin A may offer new and safe anti-RA candidates by inhibiting NF-kB, Akt and JNK signaling pathways.