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. 2013 Dec;17(4):1125-33.
doi: 10.1016/j.intimp.2013.10.001. Epub 2013 Oct 14.

(E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one ameliorates the collagen-arthritis via blocking ERK/JNK and NF-κB signaling pathway

Xiuxia Li  1 , Fei Peng, Caifeng Xie, Wenshuang Wu, Xiaolei Han, Lijuan Chen
Affiliations

(E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one ameliorates the collagen-arthritis via blocking ERK/JNK and NF-κB signaling pathway

Xiuxia Li et al. Int Immunopharmacol. 2013 Dec.

Abstract

Our previous report has shown a natural pyranochalcones-derived compound, (E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one (5b), that exerted protection against carrageenan-induced hind paw edema and adjuvant-induced arthritis. In this study, collagen-induced arthritis (CIA) model was used to further examine the anti-arthritic effects of 5b in vivo; the underlying molecular mechanisms of action were also investigated using a murine monocytic cell line, RAW264.7 cells. Here we showed that oral administration of 5b (20mg/kg) significantly suppressed the progression of arthritis. Improvement in disease severity was accompanied by inhibition of CD68-positive cells in knee joint and reduced pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in serum. In vitro, 5b suppressed expressions of iNOS, cyclooxygenase-2 (COX-2), TNF-α, IL-6 and IL-1β as well as productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated macrophages. This compound also significantly suppressed LPS-induced NF-κB activation, including phosphorylation of I-κB, degradation of I-κB, and nuclear translocation of p65 and p50. Treatment with 5b also blocked LPS-induced expression of TLR4 remarkably, suppressed degradation of IRAKs and phosphorylations of JNK and ERK, but had little effect to p38 kinase activation. These findings indicated that 5b might be a therapeutic agent for rheumatoid arthritis, and exerted an anti-inflammatory effect mainly through mediating TLR4, NF-κB and ERK/JNK signaling pathways in monocytes.

Keywords: (E)-3-(3, 4-Dimethoxyphenyl)-1-(5-hydroxy-2, 2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one; 5b; CIA; CMC; COX-2; Collagen-induced arthritis (CIA); DMSO; ELISA; EMSA; ERK; H&E; IFA; IKKα; IL-1β; IL-6; IRAKs; IκB kinase α; IκBα; JNK; LPS; MAPK; NF-κB; NO; NSAIDs; RA; TNF-α; c-Jun-N-terminal kinase; carboxymethylcellulose sodium; collagen induced arthritis; cyclooxygenase-2; dimethylsulfoxide; electrophoretic mobility-shift assay; enzyme-linked immunosorbent assay; extracellular signal-regulated kinase; hematoxylin and eosin; iNOS; incomplete Freund's adjuvant; inducible nitric oxide synthase; inhibitor kappa B-alpha; interleukin 6; interleukin-1 receptor associated kinases; interleukin-1β; lipopolysaccharide; mitogen-activated protein kinase; nitric oxide; non-steroidal anti-inflammatory drugs; nuclear factor-κB; p38; p38 MAP kinase; rheumatoid arthritis; tumor necrosis factor-α.

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