Herbacetin inhibits THP-1 foam cell formation via ERK/NF-κB signaling pathway
Objective To investigate whether Herbacetin impacts oxidized low density lipoprotein(ox-LDL)-triggered foam cell formation,inflammation as well as lipid deposition in THP-1 macrophages via extracellular signal-regulated kinase(ERK)/nuclear factor kappa B(NF-κB)signaling pathway.Methods After being differentiated into macrophages by induction with Phorbol 12-myristate 13-acetate(PMA),THP-1 monocytes were exposed to oxidized low density lipoprotein(ox-LDL)to stimulate foam cell formation.After being treated by varying concentrations of Herbacetin(10,20 and 40 μmol/L),THP-1 cells were categorized into control group,ox-LDL group,ox-LDL+Herbacetin 10 μmol/L group,ox-LDL+Herbacetin 20 μmol/L group and ox-LDL+Herbacetin 40 μmol/L group.After being pretreated by ERK agonist LM22B-10 or ERK inhibitor PD-98059,cells were intervened by 40 μmol/L Herbacetin and were categorized into control group,ox-LDL group,ox-LDL+Herbacetin 40 μmol/L group,ox-LDL+Herbacetin 40 μmol/L+LM22B-10 group and ox-LDL+Herbacetin 40 μmol/L+PD-98059 group.CCK-8 method assayed cell viability.Oil Red O staining estimated foam cell formation.Western blot examined the expression of proteins implicated in reverse cholesterol transport and ERK/NF-κB signaling.Liquid scintillation counting appraised cholesterol efflux.Corresponding biochemical kits examined total cholesterol(TC)and free cholesterol(FC)concentrations.After cultivation with DiI-labeled ox-LDL,the capability of cells to take up ox-LDL was detected.ELISA estimated the levels of inflammatory cytokines.Results Herbacetin effectively ameliorated ox-LDL-elicited formation of THP-1 macrophage-derived foam cells,lipid deposition as well as inflammation in a concentration-dependent manner.Besides,Herbacetin blocked ERK/NF-κB pathway and LM22B-10 partially reversed the impacts of Herbacetin on ox-LDL-stimulated THP-1 macrophages.Conclusion Herbacetin might protect against ox-LDL-provoked foam cell proliferation,inflammation and lipid deposition in macrophages,the mechanism of which might be related to the down-regulation of ERK/NF-κB pathway.
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