The Study Of Pharmacodynamics And Mechanism Of Polyphenols From Rubus Suavissimus S.lee

Objective: To study the effect of polyphenols from Rubus suavissirnus S．Lee(RSLP) on hyperlipidemia rats, spontaneous hypertensive rats (SHR) anddiabetic mice induced by Alloxan, and to explore the mechanism ofanti-hyperlipidemia, anti-hypertensive and hypoglycemic effects.Method:1. Prepare the RSLP with the water extraction, and extract thepolyphenols with macroporous resin.2. Acute toxicity was studied in oral administration.3. The hyperlipidemia rats were induced by high-fat diet. The SD rat-s were seperated into the Control group, Model group, Simvastatin group,RSLP-L group, RSLP-M group and RSLP-H group. The Control groupwas fed the basal diet, and the other groups were fed high-fat diet. Afteradministration for12weeks, the contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST)and fatty acid synthase (FAS) in serum and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) in liver were d-etected, and the Hermatoxylin-eosin staining of liver pathology in each gr-oup were observed.4. The noninvasive blood pressure analysis system was used to detectthe blood pressure. The normal Wistar rats were randomly divided intoControl group, normal RSLP high-dose group (RSLP-NH). The spontaneou-s hypertension rats were divided into Model group, Simvastatin g-roup, RSLP-L group, RSLP-M group and RSLP-H group. SBP, DBP, HR, bodyweight and organ index were observed after administration for8weeksand withdrawal for2weeks. The contents of NO, NOS, T-SOD, MDA,GSH-Px and ANP in serum were measured.5. The diabetic mice were established by intravenous injection of Alloxan.Normal mice were separated into Control group, RSLP-NH group. Thehyperglycemic mice were randomly divided into Model group, metforminhydrochloride group (MH), RSLP-L group, RSLP-M group and RSLP-H group.The effects of body weight, morphology, organ index, fasting blood glucoseand glucose tolerance were observed，and the contents of insulin，TG and TC inserum and NO, NOS in liver were measured.Results:1. The maximum tolerated dose of RSLP in acute toxicity was57.5g·Kg-1BW，and the maximum tolerated multiple was143times adults’(50kg)recommended daily dosage, indicating that it is safe.2. Compared with the Control group, the TC, TG and LDL-C levels inserum of Model group were significantly increased (P<0.05or P<0.01), and theHDL-C was significantly decreased (P<0.01), indicating the modeling wassuccessful.①RSLP could significantly reduce the body weight ofhyperlipidemia rats (P<0.05or P<0.01), lower liver index (P<0.05or P<0.01), and improve kidney index (P<0.05or P<0.01).②RSLP could significantlydecrease the TC, TG, LDL-C, and increase HDL-C in serum of RSLP groups(P<0.05or P<0.01).③RSLP could significantly reduce activities of ALT, AST,and FAS in serum (P<0.05or P<0.01);④RSLP could elevate the activities ofGSH-Px, SOD and reduce MDA level in liver(P<0.05or P<0.01);⑤RSLPcould protect the liver cell in rats.3. The blood pressure of SHR was significantly higher than that of theControl group, which could be used for anti-hypertensive studies.①RSLPcould significantly reduce the SBP and DBP of SHR (P<0.05or P<0.01), buthad no effect on HR(P>0.05).②RSLP could elevate GSH-Px, SOD levels andreduce the activity of MDA in liver (P<0.05or P<0.01);③RSLP could reduceNO, NOS and ANP contents in serum (P<0.05or P<0.01).4. The fasting glucose of diabetic mice induced by alloxan wassignificantly higher than Control group, which could be used for hypoglycemicstudy.①RSLP could reduce diabetic mice symptoms of eating, drinking, andurinary more.②RSLP could reduce fasting blood glucose levels in diabeticmice (P<0.05or P<0.01), and lower their glucose tolerance (P<0.05or P<0.01).③RSLP could increase serum insulin(P<0.05or P<0.01), lower levels of TC,TG, NO and NOS in serum of diabetic mice (P<0.05or P<0.01).Conclusion:1. The acute toxicity study showed that RSLP was safe.2. RSLP had antihyperlipidemic effect on the hyperlipidemia rats inducedby high-fat diet. It can reduce the overweight triggered by hyperlipidemia,decrease liver index, and increase kidney index. TC, TG and LDL-C levels wereelevated, and HDL-C was reduced. And can significantly reduce activities ofserum ALT, FAS and AST.3. RSLP can significantly reduce the SBP and DBP of SHR, but have no significant effect on HR. It can increase GSH-PX, SOD, NO, NOS levels, andreduce MDA, ANP content in serum.4. RSLP can significantly reduce fasting glucose and glucose tolerance ofdiabetic mice, lower TC, TG in serum and NO, NOS in liver, and elevate levelsof serum insulin.