title: Desoxyrhapontigenin, a potent anti-inflammatory phytochemical, inhibits LPS-induced inflammatory responses via suppressing NF-κB and MAPK pathways in RAW 264.7 cells.
abstract: 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 50μM concentrations) significantly inhibited nitric oxide (NO) production, nuclear factor kappa B (NF-κB) activation, the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Therefore, the anti-inflammatory 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-α) and interleukin-6 (IL-6), but also PGE2 release. As assayed by electrophoretic mobility shift assays (EMSAs), desoxyrhapontigenin also produced the dose-dependent inhibition of the LPS-induced activation of NF-κB and AP-1. Moreover, desoxyrhapontigenin inhibited the protein expression of myeloid differentiation primary response gene 88 (MyD88), IκB kinase (IKK) phosphorylation and the degradation of IκBα. 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 25mg/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-κB and Akt activation.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Ran Joo
authors.initials: RJ
authors.lastname: Choi
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jaemoo
authors.initials: J
authors.lastname: Chun
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Salman
authors.initials: S
authors.lastname: Khan
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea. Electronic address: kims@snu.ac.kr.
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002351:Carrageenan / Q000008:administration & dosage; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012250:Rheum / Q000276:immunology; D027343:Rhizome; D013267:Stilbenes / Q000008:administration & dosage* / Q000009:adverse effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C439024:3,5-dihydroxy-4'-methoxystilbene; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013267:Stilbenes; D018808:Transcription Factor AP-1; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Desoxyrhapontigenin; Inflammation; MAPK; NF-κB; Stilbenes