机构地区:[1]Key Lab of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China [2]Institute of Biotechnology for TCM Research School of Traditional Chinese Medicine, China Phar- maceutical University, Nanjing 210009, China [3]Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China
出 处:《Acta Pharmacologica Sinica》2015年第12期1462-1472,共11页中国药理学报(英文版)
基 金:The study was financially supported by the National Natural Science Foundation of China (81373481), Jiangsu Provincial Promotion Foundation for the Key Lab of Drug Metabolism and Pharmacokinetics (Grant No BM2012012) and the Key Technology Projects of China "Creation of New Drugs" (No 2015ZX09501001).
摘 要:Aim: Xuezhikang (XZK), an extract of red yeast rice, has been widely used in traditional Chinese medicine to treat cardiovascular disease. Three fractions F1, F2 and F3 (primarily containing isoflavones, monacolins or phytosterols, respectively) are extracted from Xuezhikang capsules. In this study we evaluated the lipid-lowering effects of these fractions and explored the potential mechanisms of actions, Methods: Mice treated with a high-fat diet (HFD) were orally administered Iovastatin (10 mg·k-1·d-1), XZK (1200 mg·k-1·d-1), F1 (27.5 mg·k-1·d-1), F2 (11.3 mg·k-1·d-1) or F3 (35 mg·k-1·d-1) for 10 weeks. Lipids were measured using commercial enzymatic kits, and the mRNA and protein levels of genes involved in cholesterol and bile acid homeostasis were evaluated using qRT-PCR and Western blot analysis, respectively. Results: XZK increased the fecal excretion of lipids and bile acids, reduced serum TC, TG and LDL-C levels by 40%, 55% and 46%, respectively, and increased serum HDL-C by 31%. Administration of F1 repressed serum TC and TG by 24% and 52%, respectively, and elevated hepatic synthesis of CYP7A1. It also increased hepatic elimJnation of bile acids in the fecal excretions by 79% through upregulating BSEP and downregulating NTCP. Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPClL1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively. Administration of F2 showed pharmacological effects similar to those of Iovastatin. Conclusion: Isoflavones and phytosterols in XZK exert cholesterol-lowering effects in HFD mice through mechanisms that differ from those of Iovastatin. Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.Aim: Xuezhikang (XZK), an extract of red yeast rice, has been widely used in traditional Chinese medicine to treat cardiovascular disease. Three fractions F1, F2 and F3 (primarily containing isoflavones, monacolins or phytosterols, respectively) are extracted from Xuezhikang capsules. In this study we evaluated the lipid-lowering effects of these fractions and explored the potential mechanisms of actions, Methods: Mice treated with a high-fat diet (HFD) were orally administered Iovastatin (10 mg·k-1·d-1), XZK (1200 mg·k-1·d-1), F1 (27.5 mg·k-1·d-1), F2 (11.3 mg·k-1·d-1) or F3 (35 mg·k-1·d-1) for 10 weeks. Lipids were measured using commercial enzymatic kits, and the mRNA and protein levels of genes involved in cholesterol and bile acid homeostasis were evaluated using qRT-PCR and Western blot analysis, respectively. Results: XZK increased the fecal excretion of lipids and bile acids, reduced serum TC, TG and LDL-C levels by 40%, 55% and 46%, respectively, and increased serum HDL-C by 31%. Administration of F1 repressed serum TC and TG by 24% and 52%, respectively, and elevated hepatic synthesis of CYP7A1. It also increased hepatic elimJnation of bile acids in the fecal excretions by 79% through upregulating BSEP and downregulating NTCP. Administration of F3 decreased serum TC, TG and LDL-C levels by 33%, 29% and 39%, respectively, and increased serum HDL-C by 28%, significantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPClL1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively. Administration of F2 showed pharmacological effects similar to those of Iovastatin. Conclusion: Isoflavones and phytosterols in XZK exert cholesterol-lowering effects in HFD mice through mechanisms that differ from those of Iovastatin. Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.
关 键 词:HYPERLIPIDEMIA cholesterol-lowering medication red yeast rice Xuezhikang Iovastatin ISOFLAVONES phytosterols CHOLESTEROL bile acids traditional Chinese medicine
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