Effect Of Policosanol On Activity Of LDL-R

Policosanol is a natural mixture of higher primary aliphatic alcohols isolated and purified from sugar cane wax or honey wax,its main effective ingredient is octacosanol[CH₃(CH₂)₂₆CH₂OH].Many animals studies and clinical tests revealed that policosanol had the pharmacodynamic effcets of decreasing cholesterol and anti-platelet Its side effects was very slight,so policosanol may become a prospective drug with great utilities for prevention and therapies for hypercholesterolemia and other cardiovascular diseases.The previous studies have showed that policosanol had effects on decreasing cholesterol level in clinic cases.Some research reports showed that policosanol can significantly decrease the activity of HMG-CoAR,which is the key enzyme of the cholesterol synthesis.Is there another way to decreasing cholesterol? This experiment explore the effect of policosanol on activity of LDL-R which is a key way to metabolize and decrease cholesterol.Objective Explore the effect of policosanol on activity of LDL-R and mechanism of policosanol decrease cholesterol.Methods 1.In vitro experiment:cells cultivated experiments using conventional methods to observe the direct effect of policosanol on mononuclear cells LDL-R.The cells were divided into six groups including negative control group,solvent control group,policosanol group and positive control group. LDL-R activity was analysed by fluorescence flow cytometry and labeled by the fluorescent reagent DiI.2.In vivo experiment:28 patients with hypercholesterolemia whom identified by the national standard of National Guidelines for Prevention and Treatment of Adult Dyslipidemia and Diagnostic randomly assigned to policosanol treatment group(20mg.d^-1) and control group.The blood samples taking from the patients were collected to determine lipid levels(including serum TC,TG,HDL-C and LDL-C),antioxidation capability(including serum MDA,SOD and GSH-PX ),and LDL-R activity in human mononuclear cells before and after 4 weeks policosanol treatment.Results 1.In vitro experiment:Policosanol 5～20μg.ml^-1 obviously activated the activity of LDL-R in human mononuclear cells,policosanol levels and the activity of LDL-R in human mononuclear cells showed significantly dose-response relationship in vitro study.2.In vivo experiment:After 4 weeks treatment,policosanol treatment group's TC and LDL-C lowed 6.4%and 11.6%respectively,LDL-R activity increased 95.0%in human mononuclear cells,SOD and GSH-PX increased 43.9%and 14.0%,MDA lowed 35.3%comparing with before treatment group; policosanol treatment group's TC and LDL-C lowed 5.2%and 12.0% respectively,LDL-R activity increased 61.9%in human mononuclear cells, SOD increased 29.6%,MDA lowed 35.7%comparing with control group.Conclusions 1.Policosanol can significantly decrease cholesterol level in patients with high blood levels of TC and LDL-C level;2.Policosanol up-regulates the activity of the LDL-R in the mononuclear cells.3.Plicosanol has exact effects on enhangcing the function of antioxidation.It suggest that the machanisms of policosanol decreasing the levels of total cholesterol should include the increasing of LDL-R activity in the body.