Isomeranzin suppresses inflammation by inhibiting M1 macrophage polarization through the NF-κB and ERK pathway.
Macrophage polarization plays an important role in inflammation. Regulation of the polarization has been reported to be effective therapeutics for various kinds of inflammatory diseases. The aims of the present study were to investigate the anti-inflammatory property of isomeranzin isolating from Murraya exotica as well as potential molecular mechanisms. Results showed that isomeranzin specifically reduced the M1 macrophage-associated pro-inflammatory cytokines through down-regulation of NF-κB and ERK signals. Immunoprecipitation and RNA silencing indicated suppression of isomeranzin in NF-κB activation was relying on the decreasing of TRAF6 ubiquitination. In vivo studies showed isomeranzin evidently inhibited LPS-induced sepsis for rising survival rate, improving tissue damage and lessening inflammatory cytokines. In accordance with in vitro studies, isomeranzin significantly blocked expression of p-p65 and p-ERK in lung and liver tissues. Moreover, isomeranzin ameliorated DSS and TNBS-induced colitis due to its anti-inflammatory effects. Taken together, isomeranzin suppressed inflammatory diseases by controlling M1 macrophage polarization through the NF-κB and ERK pathway.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Ge
G
Xu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Lili
L
Feng
The Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
Pingping
P
Song
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Fang
F
Xu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Ang
A
Li
School of Pharmaceutical Sciences, Nanjing Tech University, No 5. Xinmofan Road, Nanjing 210009, China.
Yubin
Y
Wang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Yan
Y
Shen
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Xuefeng
X
Wu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Qiong
Q
Luo
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Xingxin
X
Wu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
Yang
Y
Sun
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China. Electronic address: xudongwu@nju.edu.cn.
Xudong
X
Wu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China. Electronic address: molpharm@163.com.
Qiang
Q
Xu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003374:Coumarins / Q000494:pharmacology*; D016264:Dextran Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D032101:Murraya / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D000067996:RAW 264.7 Cells; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D003374:Coumarins; D016328:NF-kappa B; C000616632:isomeranzin; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases
Anti-inflammation; Isomeranzin; M1 macrophage polarization; NF-κB signals