Dissertation
Dissertation > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology

Study on Effective Site Clusters of Xiaoyu Tablet and Their Mechanisms of Blood-lipid Regulation

Author XueJie
Tutor XieMeiLin;GuZhenLun
School Suzhou University
Course Pharmacology
Keywords Radix Salviae Fructus Crataegi effective site of blood-lipid regulation pharmacodynamics mechanism
CLC R285
Type Master's thesis
Year 2004
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Aim: To determine the effective sites of blood-lipid regulation from the extracts of Radix Salviae Miltiorrhizae(SM) or Fructus Crataegi(FC) in xiaoyu tablet and their mechanisms. Methods: In our studies, the effects of each extract of SM or FC on the blood lipid of hyperlipidemic rats were observed by orthogonal experimental design. Then we examined their absorptions in rat serum by HPLC. In order to understand their mechanisms of blood-lipid regulation, We used the amphotercin B cell model and RT-PCR method to examine the effects of the serum-drugs of SM and FC extracts and their effective monomers, including danshensu, protocatechualdehyde, ursolic acid, quercetin and rutin, on cholesterol biosynthesis in CHO cells and the expressions of CYP7AmRNA and DGATmRNA in BRL cell line. At last we utilized the system of lipase activity assay in vitro to determine whether they could increase lipase activity. Results: 75% ethanol and ammonia extracts of SM obviously decreased serum TC and LDL-C levels in hyperlipidemic rats, meanwhile 75% ethanol extract of SM obviously decreased serum TG level too, and ammonia extract of SM significantly decreased the ratio of LDL-C/HDL-C. Acetone extract of FC markedly decreased serum TC, LDL-C and LDL-C/HD-C ratio in hyperlipidemic rats, also obviously decreased serum TG. Petroleum ether and anhydrous alcohol extracts of FC had no obvious effects on serum TC, TG, LDL-C and LDL-C/HDL-C ratio, moreover the high dose of petroleum ether extract of FC had a tendency to increase serum TC, LDL-C and LDL-C/HDL-C ratio. The result also showed the extracts of SM or FC had no obvious effects on increasing serum HDL-C in hyperlipidemic rats. Danshensu and protocatechualdehyde, the water soluble ingredients of SM, were absorbed to blood in rats by oral, and 75% ethanol and ammonia extracts of SM, sodium danshensu and protocatechualdehyde, obviously increased OD in the experiment of amphotercin B cell model and the expression of CYP7AmRNA in BRL cell line. In addition, 75% ethanol extract of SM also obviously increased serum lipase activity. However the triterpene of FC was not detectable in rat blood, and the extracts of FC had no direct effect on blood-lipid regulation by themselves, but they were in coordination with the extracts of SM. Furthermore ursolic acid was able to increase the expression of CYP7AmRNA, quercetin and rutin, the flavonoids of FC, also increased OD in the experiment of amphotercin B cell model. Conclusion: The effective sites of blood-lipid regulation in xiaoyu tablet are 75% ethanol extract of SM , ammonia extract of SM and acetone extract of FC, anhydrous alcohol extract of FC is an assistant site, the best matching of them is 72: 22: 27: 48, and petroleum ether extract of FC may be an antagonistic site. The extracts of SM, danshensu and protocatechualdehyde, had ablood-lipid regulation by inhibiting cholesterol biosynthesis and increasing CYP7AmRNA expression when they were absorbed to blood. And 75% ethanol extract of SM could reduce serum TG level by increasing lipase activity. The extracts of FC and ursolic acid maybe take this action chiefly by inhibiting the absorption of exogenous lipid, but ursolic acid also increased CYP7AmRNA expression, and quercetin and rutin inhibited cholesterol biosynthesis if they could be absorbed.

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