Effects of flavone from Galium Verum L on arteriosclerosis endothelial cells via TGF-β/Smad3 signaling pathway
Objective It is to investigate the repair effect of flavone from Galium Verum L(FGVL)on arteriosclerosis endothelial cells based on transforming growth factor-β(TGF-β)/Smad3 and c-Jun amino-terminal kinase(JNK)signaling pathway.Methods Twenty-four adult male rabbits were randomly divided into normal group,model group,low-dose FGVL group and high-dose FGVL group,with 8 rabbits in each group.The rabbits of all groups except for the normal group were prepared to establish models of atherosclerotic occlusion of lower limbs.After successfully modeling,the low-dose FGVL group and high-dose FGVL group were given 45 mg/kg and 180 mg/kg of FGVL by gavage,respectively,the normal group and model group were given the same volume of normal saline by gavage.The rabbits in each group were gavaged for 2 weeks and then were executed,their right iliofemoral artery was taken to isolate and culture endothelial cells.The protein expressions of TGF-β1,Smad3,JNK and phosphorylated JNK(p-JNK)in the endothelial cells were detected by Western blot,and the contents of inflammatory factors[C-reactive protein(CRP),soluble intercellular adhesion molecule-1(sI-CAM-1),tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)],nitric oxide(NO),and endothelin-1(ET-1)in the endothelial cells were respectively determined by enzyme-linked immunoassay,nitrate reduction,and radioimmunoas-say.Results The protein expressions of TGF-β1,Smad3,JNK and p-JNK,and the contents of CRP,sICAM-1,TNF-α,IL-1 β and ET-1 in the endothelial cells of the model group were significantly higher than those of the normal group(all P<0.05),the above indicators of the low-dose and high-dose FGVL groups were significantly lower than those of the model group(all P<0.05),and the above indicators of the high-dose FGVL group were significantly lower than those of the low-dose FGVL group(all P<0.05).The content of NO in the endothelial cells of the model group was significantly lower than that of the normal group(P<0.05),the content of NO in the endothelial cells of the low-dose and high-dose FGVL groups were significantly higher than that of the model group(both P<0.05),and the high-dose FGVL group was signifi-cantly higher than the low-dose FGVL group(P<0.05).Conclusion Flavone from Galium Verum L can alleviate inflam-matory response,protect vascular endothelial cells,inhibit proliferation and apoptosis of smooth muscle cells,and improve vascular endothelial function,and the mechanism may be related to the inhibition of TGF-β/Smad3 and JNK signaling path-way.
transforming growth factor-βSmad3flavone from Galium Verum Lendothelial cells