Effects Of Traditional Chinese Medicine Sterols And Their Molecular Analogues On Cholesterol Crystallization And Absorption

Cholesterol is an essential lipid for life.Too high or too low cholesterol levels are harmful to humans.However,hypercholesterolemia caused by excessive cholesterol level in the body is one of the important risk factors for atherosclerosis,stroke and coronary heart disease.It reports that sterol active substances in Chinese herbal medicine,as molecular analogues of cholesterol,can affect the absorption and metabolism of cholesterol in the body,especially phytosterols,which can lower plasma cholesterol levels,but the exact mechanism is still unclear.In this paper,through the combination of in vitro and in vivo experiments,sterols,sterol ester derivatives,and saponins in Chinese herbal medicine(such as glycyrrhizic acid)were selected for experiments,and various substances were discussed in different systems.The effect on cholesterol solubility,crystallization and absorption,and explored the association between cholesterol solubility and oral absorption were explored.The research content of this thesis is divided into the following three parts:1.The effect of sterols on the crystallization and absorption of cholesterol.Taking stigmasterol,β-sitosterol and ergosterol as research objects,experiments were carried out in 95%ethanol,model bile and animal,respectively,to determine the change of cholesterol solubility in the supernatant,the change of crystal product morphology,crystal form and melting point.Changes of serum lipid index,AST and ALT activities in rats,changes in liver lipid index and histopathological observation of rat liver and aortic arch.Studies have shown that stigmasterol andβ-sitosterol can increase cholesterol solubility in 95%ethanol and reduce cholesterol solubility in model bile solution,while ergosterol has no significant effect;β-sitosterol can co-precipitate with cholesterol when the ratio to cholesterol is 50%,while stigmasterol has no such effect;β-sitosterol has better hypolipidemic effect in rats than stigmasterol,and ergosterol has no significant effect on lowering cholesterol in the body.2.The effect of sterol esters on the crystallization and absorption of cholesterol.The effects of sterol ester derivatives on cholesterol crystallization were studied with cholesteryl acetate,cholesteryl propionate,cholesteryl succinate,cholesteryl myristate and synthetic water-soluble sterol esters(PEG-SI,NH2-SI).The change of cholesterol solubility in the supernatant,the change of crystal product morphology,crystal form and melting point,the change of serum lipid index,AST and ALT activity in rats,the change of liver lipid index and histopathological observation of rat liver and aortic arch.Studies have shown that the four sterol ester derivatives and two watersoluble sterol esters can increase the solubility of cholesterol in 95%ethanol,among which the effect of cholesteryl succinate is more significant;cholesteryl acetate,cholesteryl myristate,succinic acid Cholesterol ester and aminositosterol can reduce cholesterol solubility in model bile,but cholesteryl propionate and PEG-SI have no obvious effect;water-soluble sterol ester can decrease serum lipid index(TC,TG,LDL-C),AST,ALT activity,and can improve the pathological condition of the liver and aortic arch;NH2-SI is superior to PEG-SI in lowering blood lipids.3.The effect of saponins on cholesterol crystallization.Glycyrrhizic acid was used as a representative substance of traditional Chinese medicine saponin to study its effect on cholesterol crystallization.The change of cholesterol solubility in the supernatant,the change of crystal product morphology,crystal form and melting point,serum lipid index,AST and ALT activity in rats were studied.Changes in rat liver lipid index and histopathological observation of rat liver and aortic arch.Studies have shown that glycyrrhetinic acid can increase cholesterol solubility in 95%ethanol solution,while glycyrrhizic acid has no obvious effect;glycyrrhizic acid and glycyrrhetinic acid can reduce the solubility of cholesterol in model bile at high mass ratio;glycyrrhizic acid can decrease the levels of serum TC,LDL-C and liver TC in rats,glycyrrhetinic acid can reduce the levels of TC and TG in rat liver.Glycyrrhizic acid and glycyrrhetinic acid can improve the pathological condition of liver and aorta and improve the pathological condition of liver and aorta.The hypolipidemic effect of glycyrrhizic acid is better than that of glycyrrhetinic acid.