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(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.
Int Immunopharmacol. 2013 Dec; 17(4):1125-33.II

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.

Authors+Show Affiliations

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China; Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24135236

Citation

Li, Xiuxia, et al. "(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." International Immunopharmacology, vol. 17, no. 4, 2013, pp. 1125-33.
Li X, Peng F, Xie C, et al. (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. Int Immunopharmacol. 2013;17(4):1125-33.
Li, X., Peng, F., Xie, C., Wu, W., Han, X., & Chen, L. (2013). (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. International Immunopharmacology, 17(4), 1125-33. https://doi.org/10.1016/j.intimp.2013.10.001
Li X, et al. (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. Int Immunopharmacol. 2013;17(4):1125-33. PubMed PMID: 24135236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (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. AU - Li,Xiuxia, AU - Peng,Fei, AU - Xie,Caifeng, AU - Wu,Wenshuang, AU - Han,Xiaolei, AU - Chen,Lijuan, Y1 - 2013/10/14/ PY - 2013/02/04/received PY - 2013/09/06/revised PY - 2013/10/01/accepted PY - 2013/10/19/entrez PY - 2013/10/19/pubmed PY - 2014/9/3/medline KW - (E)-3-(3, 4-Dimethoxyphenyl)-1-(5-hydroxy-2, 2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one KW - 5b KW - CIA KW - CMC KW - COX-2 KW - Collagen-induced arthritis (CIA) KW - DMSO KW - ELISA KW - EMSA KW - ERK KW - H&E KW - IFA KW - IKKα KW - IL-1β KW - IL-6 KW - IRAKs KW - IκB kinase α KW - IκBα KW - JNK KW - LPS KW - MAPK KW - NF-κB KW - NO KW - NSAIDs KW - RA KW - TNF-α KW - c-Jun-N-terminal kinase KW - carboxymethylcellulose sodium KW - collagen induced arthritis KW - cyclooxygenase-2 KW - dimethylsulfoxide KW - electrophoretic mobility-shift assay KW - enzyme-linked immunosorbent assay KW - extracellular signal-regulated kinase KW - hematoxylin and eosin KW - iNOS KW - incomplete Freund's adjuvant KW - inducible nitric oxide synthase KW - inhibitor kappa B-alpha KW - interleukin 6 KW - interleukin-1 receptor associated kinases KW - interleukin-1β KW - lipopolysaccharide KW - mitogen-activated protein kinase KW - nitric oxide KW - non-steroidal anti-inflammatory drugs KW - nuclear factor-κB KW - p38 KW - p38 MAP kinase KW - rheumatoid arthritis KW - tumor necrosis factor-α SP - 1125 EP - 33 JF - International immunopharmacology JO - Int Immunopharmacol VL - 17 IS - 4 N2 - 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. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/24135236/_E__3__34_Dimethoxyphenyl__1__5_hydroxy_22_dimethyl_2H_chromen_6_yl_prop_2_en_1_one_ameliorates_the_collagen_arthritis_via_blocking_ERK/JNK_and_NF_κB_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(13)00369-X DB - PRIME DP - Unbound Medicine ER -