Ursolic Acid Suppresses IL-6 Induced C-reactive Protein Expression In HepG2 And Its Protective Effects On The Human Umbilical Vein Endothelial Cell Injury Induced By CRP

Objective:To investigate the inhibitory effects of UA on the expression of CRP induced by IL-6 on HepG2 and the protective effects on the human umbilical vein endothelial caused by CRP.Methods:(1) To investigate the inhibitory effects of UA on the expression of CRP in HepG2:HepG2 were divided into control group, IL-6 (30 ng/ml) group and UA (6.5,12.5,25μmol/L) with IL-6 (30 ng/ml) co-incubation groups. Cells were treated with drug for 48 h, MTT assayed the OD values in each group. After that, cells were collected for western blotting and RT-PCR methods to detect CRP protein expression and mRNA expression. (2) Protective effects of UA on HUVEC injured by CRP: HUVEC were divided into control group, CRP group and UA (5,10,20μmol/L)with CRP (25μg/ml) co-incubation groups. Cells were treated with drug for 24 h; MTT measured the OD values to assay the cell survival in each group. After that, cells were collected for western blotting and RT-PCR methods to detect VCAM-1, LOX-1 protein expression and VCAM-1 mRNA expression.Results:(1) Results of inhibitory effects of UA on the expression of CRP in HepG2 Compared with control group, the cell viability is significantly lower in IL-6 group. But in groups added UA (12.5,25μmol/L), the viability is significantly higher than that in IL-6 group (P<0.01). Compared with control group, IL-6 group can significantly increase CRP protein and mRNA expression in HepG2, and this effect of IL-6 can be decreased by UA (6.25,12.5,25μmol/L) markedly in a dose-dependent manner (P<0.01). (2) Results of the Protective effects of UA on HUVEC damaged by CRP:Compared with control group, CRP can obviously increase the proliferation of HUVEC. Compared with CRP group, UA(10,20μmol/L)can significantly decreased the proliferation of HUVEC caused by CRP (P<0.01). Compared with control group, CRP can obviously increase VCAM-1 protein and its mRNA expression in HUVEC, and this effect of CRP can be inhibited by UA (10,20μmol/L) in a dose-dependent manner (P<0.01). CRP can obviously increase LOX-1 protein expression in HUVEC, Also this effect of CRP can be decreased by UA (5,10,20μmol/L) in a dose-dependent manner (P<0.01)Conclusion:Both on mRNA and protein levels, UA can reduce the over expression of CRP in HepG2 cells induced by IL-6. Also UA can decrease the increased expression of VCAM-1 and LOX-1 in HUVEC caused by CRP. We speculate that UA may inhibit the hepatic synthesis of CRP to reduce CRP levels in blood and prevent the other inflammatory cytokines from injuring endothelial cells, so it may play against myocardial ischemia and atherosclerosis and other cardiovascular diseases.