Study On The Pharmacodynamics And Mechanism Of Phenolic Extracts From Dracula Radix In Improving Atherosclerosis

Atherosclerosis,regarded as a leading cause of death,is the underlying pathogenesis of the maj or coronary heart disease event,and the underlying pathogenesis of atherosclerosis is complicated.Hyperlipidemia is generally accepted as a cause of atherosclerosis.The high levels of cholesterol in blood could cause increased WBV,enhance the arterial stenosis,cause the thrombus,thus induce the progression of atherosclerosis.Besides,the injury and the further dysfunction of vascular endothelial cells are generally regarded as the primary event in the pathogenesis of atherosclerosis.Meanwhile,it is generally accepted that the progression of atherosclerosis is associated with chronic inflammation in the arterial vessel wall.The medical treatment of atherosclerosis is mainly by such mechanisms as lipid lowering,anti-inflammatory,antioxidant,and antithrombotic.Meanwhile,the traditional Chinese medicine,based on the traditional Chinese medicinal theory,also exerted a unique advantage on the treatment of atherosclerosis for its combined treatment.Chinese dragon’s blood,the red resin of Dracaena cochinchinensis(Lour.)S.C.Chen,has been used to improve perfusion,alleviate blood stasis,relieve pain,and stop bleeding in traditional Chinese medicine for thousands of years.Previous phytochemical investigations have revealed that the main biological activities of Chinese dragon’s blood come from its phenolic compounds.Previous pharmacological investigations have revealed that its phenolic compounds can affect the hemorheological properties,such as inhibiting the thrombin inhibitory,and inhibiting the aggregation of platelet.Besides,not only its therapeutic effect on cardiovascular diseases,such as myocardial ischemia and focal cerebral ischemia,but also its activity on anti-inflammatory and antioxidant,has been reported.However,the definitive evidence of the anti-atherosclerotic effect of Chinese dragon’s blood has not been clearly investigated.The aim of this study is to investigate the anti-atherosclerotic effect of the total phenolic extract of Chinese dragon’s blood(DBE)and the underlying mechanisms in high-fat diet(HFD)-induced ApoE-/-mice.The ApoE-/-mice,suffering from hyperlipidemia and atherosclerosis,was induced by HFD.This study indicated that DBE could recover the abnormal hemorheological parameters and improve the erythrocyte function,although it did not improve the dyslipidemia.Further investigation indicated that DBE exerted anti-atherosclerotic effect in ApoE-/-mice suffering from HFD-induced hypercholesterolemia,and the possible mechanisms for its effect on improving effect of endothelial dysfunction was investigated in vitro.Several results were obtained.1.DBE improved erythrocyte function and abnormal hemorheological parameters in ApoE-/-mice suffering from HFD-induced hypercholesterolemia.DBE recovered the abnormal hemorheological parameters in HFD-induced ApoE-/-mice by reducing the whole blood viscosity(WBV)at high rate(200 s-1)(P<0.05)and improving erythrocyte deformability(P<0.05)and erythrocyte osmotic fragility(P<0.001).Furthermore,DBE was found to be able to markedly reduce the level of MDA on erythrocyte membrane(P<0.001),and DBE at low,middle,and high doses markedly reduce the plasma MDA level(P<0.05,P<0.05,and P<0.01,respectively).2.The effect of DBE on atherosclerotic lesions of the aortic sinus in ApoE-/-mice suffering from HFD-induced hypercholesterolemia and the underlying mechanisms.DBE at low,middle,and high doses markedly decreased the atherosclerotic lesion areas of the aortic sinus in HFD-induced ApoE-/-mice by 26.4%(P<0.05),30.1%(P<0.05),and 46.5%(P<0.01),respectively.Furthermore,DBE appeared to restore the diminished NO production of ox-LDL-stimulated HUVECs(P<0.001)and inhibited the adhesion between monocytes and endothelial cells(P<0.01).Further investigations indicated that DBE dose-dependently increased the expression level of eNOS protein in ox-LDL-stimulated HUVECs(P<0.001).Meanwhile,DBE could reduce the expression levels of VCAM-1 and COX-2 protein in ox-LDL-stimulated HUVECs in a dose-dependent manner.DBE at high dose was associated with a significant decrease in MCP-1 protein expression(P<0.01).Besides,the MAPKs/IKK/IκB/NF-κB signalling pathway was regulated by DBE.These results implied the following conclusions.DBE could reduce lipid peroxidation on plasma,reduce lipid peroxidation on erythrocyte membranes,ameliorate erythrocyte osmotic fragility and deformability,reduce WBV at high rate,thus improve the abnormal hemorheological parameters in ApoE-/-mice suffering from HFD-induced hypercholesterolemia.DBE appeared to alleviate ox-LDL-stimulated dysfunction of HUVECs,and inhibit the adhesion of monocytes to HUVECs via the MAPKs/IKK/IκB/NF-κB signaling pathway,thus decrease atherosclerotic lesions of the aortic sinus in ApoE-/-mice suffering from HFD-induced hypercholesterolemia.The improving effects of DBE on the hemorheological properties and the endothelial dysfunction suggest the potential of DBE for use as an effective agent against atherosclerosis.