Study On Activity To HMG-CoA Reductase And Security Evaluation Of Hawthorn Fruit

Hyperlipidemia is a dangerous factor of cardio-cerebrovascur diseases, inducing coronary heart disease and atherosclerosis. It is widely acknowledged that lowering the level of total cholesterol (TC), low-density lipopro-tein cholesterol (LDL-C), and triglycerides (TG) can interfere with the progression of atherosclerosis and reduce cardiovascular events in patients with atherosclerosis and cardio-cerebrovascular diseases The most widely used lipid-lowering drugs are a class of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) inhibitors. HMG-CoA Reductase is the key enzyme of cholesterol synthesis. Statins, a competitive inhibitor of HMGR most widely used in clinics, reduce TC, LDL-C, apolipoprotein B, and TG levels, but they are associatedwith undesirable side effects such as severe myopathy and statin-associated memory loss. Hawthorn is widely used as a food and traditional medicine in treating hyperlipidemia with a low toxicity. However, there had been no reports on the active components of HMGR inhibitors in hawthorn fruit and their lipid-lowering efficacy.In this study, extract of hawthorn fruit were separated and purified using HMGR as the target to research the inhibition to HMGR and the lipid-lowering efficacy of active components and evaluated the toxicity of obtained extract.The results were as follows:(1) Seperation and purification of Hawthorn extracts using HMGR as a target purifying simple substances, such as quercetin(â… ), hyperoside(â…¡), rutin(â…¢), chlorogenic acid(â…£) etc. Especially inhibition rate of simple substances was lower than mixture obviously. The result indicated that there was synergistic effect among the active compounds of Hawthorn Fruit. it is unknown that which ratio active compounds mixed by will educe the best effect. This problem need further study.Ursolic acid did not influence the activity of HMG-CoA Reductase, it has been indefinited that ursolic acid with hypso-concentration could inhibited HMG-CoA reductase efficiently or not. In principle, but, ursolic acid was not the activity compound inhibiting HMG-CoA reductase from Hawthorn Fruit.(2) Evalution for the toxicity of the extracts:LD₅₀ of Hawthorn extracts is bigger than 10g·Kg^-1, that is, Hawthorn extracts has no actue toxicity. In sperm abnormality test, bone marrow cell micronucleus test and ninety days feeding study, there's no significant difference on measured index between the dosage groups and the normal control.