Study On Lipid-lowering Effects Of Total Flavonoids Of Stellera Chamaejasme L.in Experimental Hyperlipidemia Rats

Hyperlipemia is a common form of metabolic disease that causes by the lipid metabolism disorder and resulted the high lipid level in plasma and serum with the symbol of dyslipidemia. Hyperlipemia is the main causes of human cardiovascular and cerebrovascular disease, Non alcoholic fatty liver disease, hypertension, hyperglycemia and obesity. The mortality of Hyperlipemia was increasing and reached 30% in our country during the last few years and became one of the biggest threat of human health. Based on these reasons, it will be significant for the prevention and treatment of cardiovascular and cerebrovascular disease to adjust the serum lipid level and dyslipidemia. As a flavonoid, the total flavonoids of stellera chamaejasmeL. (TFSC) also exhibites various physiological functions. The studies have shown that the flavonoid compounds in diversities of vegetables showed hypolipidemic and antioxidation effects, but the hypolipidemic effect of TFSC has not been reported. In this study, we applied the TFSC on a rat model of hyperlipemia to investigate the function and mechanism of hypolipidemic effect of TFSC, and these results provided the evidences for the development of new lipid-lowering agents.1.We compared the extraction effects of TFSC by ultrasonic-assisted extraction and microwave-assisted extraction through single factor experiment and response surface experiment. The results showed that the ultrasonic-assisted extraction method was more suitable for the TFSC extraction than microwave-assisted extraction. The optimal condition of ultrasonic-assisted extraction of TFSC was material:liquid=1:30,71% ethanol, ultrasonic power 300W,62℃,30 min,3 times extraction. The extraction efficiency was 5.16% and the TFSC purity was 27.5% under this condition.2.We compared the purification effects of 9 macroporous resins on TFSC through the static saturated adsorption rate and the desorption rate. Our results showed that the AB-8 resin has relatively good absorption-desorption performance and suitable for the TFSC isolation and purification. We also analyzed the optimal condition of purification effects of AB-8 resin on TFSC. The best condition was:sample concentration 2.0mg/mL, flow rate of sample injection 2.0BV/h,70% eluent of ethanol. elution flow rate 2.0BV/h, elution volume of ethanol 4.0BV. The purity of TFSC can increased 2.12 times from 27.5% to 58.24%, and reached the purpose of isolation and purification.3.We successfully established a rat model of hyperlipemia by feeding the rat with high lipid diets and analyzed the body weight, the weight of liver, the index of liver and serum lipid level in every second week, we also observed the liver pathological section to confirm the condition of the hyperlipemia.4.We analyzed the molecular mechanisms of lipid-lowering effects of TFSC on the rat model of hyperlipemia by measuring the rat body weight, the weight of liver, the index of liver, lipid index of serum, antioxidation index of serum, liver lipid level, liver antioxidation index, TC and TG in the faeces. We also analyzed the mRNA and protein expression of SREBP-lc and the mRNA expression of FAS、ACC、CYP7A1、CPT-I and PPAR-a in rat liver after 6 weeks intragastric administration of TFSC. The results showed that TFSC significantly reduced the body weight, the weight of liver and the liver index of rat hyperlipemia model; significantly reduced the rat serum TC, TG, LDL-C, AI, and increased in HDL-C level, meanwhile improve the index of hemorheology; significantly increased in T-SOD, GSH-Px activity and reduced in MDA level both in rat serum and liver; significantly upregulated the level of lipidolysis related gene CYP7A1, CPT-I and PPAR-a, and downregulated the level of lipid synthesis related gene FAS, ACC and SREBP-lc in rat liver; but had no effect on GLU and FFA in rat serum.Our studies indicated that TFSC had lowering lipid and hepatoprotective effect, and regulated and improved the balancing effects of free radicals on rat model of hyperlipemia. It’s possible mechanism is that TFSC downregulating the mRNA and protein expression of transcription factor SREBP-lc to regulate the downstream lipid synthesis related genes ACC and FAS expression, meanwhile, TFSC upregulated the level of transcription factor PPAR-ato regulate the downstream lipidolysis related genes CPT-I and CYP7A1 expression, and improved the liver tissue β oxidation and in vivo fatty acid degradation, inhibit fatty acid synthesis, and finally reach the effective regulation of lipid metabolisms of experimental rat model of hyperlipemia.