Desoxyrhapontigenin, a potent anti-inflammatory phytochemical, inhibits LPS-induced inflammatory responses via suppressing NF-κB and MAPK pathways in RAW 264.7 cells

This study investigates the anti-inflammatory effects of a stilbene compound, desoxyrhapontigenin, which was isolated from Rheum undulatum. To determine the anti-inflammatory effects of this compound, lipopolysaccharide (LPS)-induced RAW 264.7 macrophages were treated with different concentrations of six stilbene derivatives. The results indicated that compared with other stilbene compounds, desoxyrhapontigenin (at 10,30 and 50 mu M concentrations) significantly inhibited nitric oxide (NO) production, nuclear factor kappa B (NP-kappa B) activation, the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Therefore, the antiinflammatory mechanism of desoxyrhapontigenin was investigated in detail. The results of this investigation demonstrated that desoxyrhapontigenin suppressed not only LPS-stimulated pro-inflammatory cytokine secretions, including the secretions of tumor necrosis factor alpha (TNF-alpha) and interleuldn-6 (IL-6), but also PGE(2) release. As assayed by electrophoretic mobility shift assays (EMSAs), desoxyrhapontigenin also produced the dose-dependent inhibition of the LPS-induced activation of NF-kappa B and AP-1. Moreover, desoxyrhapontigenin inhibited the protein expression of myeloid differentiation primary response gene 88 (MyD88), I kappa B ldnase (IKK) phosphorylation and the degradation of I kappa B alpha. Activations of p-JNK1 and p-Akt were also significantly inhibited, and phosphorylation of p38 and ERK was down-regulated. A further study revealed that desoxyrhapontigenin (5 and 25 mg/kg, i.p.) reduced paw swelling in carrageenan-induced acute inflammation model in vivo. On the whole, these results indicate that desoxyrhapontigenin showed anti-inflammatory properties by the inhibition of iNOS and COX-2 expression via the down-regulation of the MAPK signaling pathways and the inhibition of NF-kappa B and Akt activation. (C) 2013 Elsevier B.V. All rights reserved.