Isoflavones and phytosterols contained in Xuezhikang capsules modulate cholesterol homeostasis in high-fat diet mice

• Published in: Acta pharmacologica Sinica 2015-12, Vol.36 (12), p.1462-1472
• Main Authors: Feng, Dong, Sun, Jian-guo, Sun, Run-bin, Ou-Yang, Bing-chen, Yao, Lan, Aa, Ji-ye, Zhou, Fang, Zhang, Jing-wei, Zhang, Jian, Wang, Guang-ji
• Format: Article
• Language: English
• Subjects: Animals; Bile Acids and Salts - genetics; Bile Acids and Salts - metabolism; Biomedical and Life Sciences; Biomedicine; Capsules; Cholesterol - blood; Cholesterol - genetics; Cholesterol - metabolism; Diet, High-Fat; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Gene Expression Regulation - drug effects; Homeostasis - drug effects; Hypolipidemic Agents - chemistry; Hypolipidemic Agents - pharmacology; Immunology; Internal Medicine; Isoflavones - administration & dosage; Isoflavones - chemistry; Isoflavones - pharmacology; Lipid Metabolism - drug effects; Lipids - blood; Liver - drug effects; Liver - metabolism; Male; Medical Microbiology; Mice, Inbred C57BL; Original; original-article; Pharmacology/Toxicology; Phytosterols - administration & dosage; Phytosterols - chemistry; Phytosterols - pharmacology; Vaccine; 大豆异黄酮; 小鼠; 植物甾醇; 胆固醇代谢; 胶囊; 血脂; 饲料喂养; 高脂饲料
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2015.98

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.