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.