Open Access2-Phenylnaphthalene Derivatives Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Mediators by Downregulating of MAPK/NF-κB Pathways in RAW 264.7 Macrophage Cells
Author(s) -
Chi-Fen Chang,
Kang-Chun Liao,
Chen Ch
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0168945
Subject(s) - p38 mitogen activated protein kinases , nitric oxide , nitric oxide synthase , lipopolysaccharide , chemistry , biochemistry , tumor necrosis factor alpha , cell culture , microbiology and biotechnology , mapk/erk pathway , macrophage , nf κb , kinase , signal transduction , biology , enzyme , immunology , in vitro , genetics , organic chemistry
The anti-inflammatory pharmacological effect of eight 2-phenylnaphthalenes ( PNAP - 1 − PNAP - 8 ) on lipopolysaccharide (LPS)-induced RAW 264.7 (a mouse cell line) was investigated. Among them, 6,7-dihydroxy-2-(4′-hydroxyphenyl)naphthalene ( PNAP - 6 ) and 2-(4′-aminophenyl)-6,7-dimethoxynaphthalene ( PNAP - 8 ) exhibited the best anti-inflammatory activity in this study. PNAP - 6 and PNAP - 8 not only significantly decreased the expression of inducible nitric oxide synthase and cyclooxygenase-II, but also inhibited the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS stimulated cells. Moreover, PNAP - 6 and PNAP - 8 inhibited nuclear factor (NF)-κB activation by decreasing the degradation of IκB and nuclear translocation of NF-κB subunit (p65). In addition, PNAP - 6 and PNAP - 8 also attenuated the phosphorylation of ERK, p38, and JNK. These results suggest that PNAP - 6 and PNAP - 8 exert anti-inflammatory activities by down regulating NF-κB activation and the mitogen-activated protein kinase signaling pathway in LPS-stimulated Raw 264.7 cells. This is the first study demonstrating that PNAPs can inhibit LPS-induced pro-inflammatory mediators in macrophages cells.