Abstract
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 adminis¬tered lovastatin (10 mg·kg−1·d−1), XZK (1200 mg·kg−1·d−1), F1 (27.5 mg·kg−1·d−1), F2 (11.3 mg·kg−1·d−1) or F3 (35 mg·kg−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 elimination 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%, sig¬nificantly reduced intestinal absorption of cholesterol by inhibiting the transcription of NPC1L1, and elevated excretion of TC, FC and CE by 96%, 72% and 101%, respectively. Administration of F2 showed pharmacological effects similar to those of lovastatin.
Conclusion:
Isoflavones and phytosterols in XZK exert cholesterol-lowering effects in HFD mice through mechanisms that differ from those of lovastatin. Isoflavones and phytosterols act in a complimentary manner: through enhancing the elimination of bile acids and reducing intestinal cholesterol absorption, respectively.
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Acknowledgements
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).
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Supplementary information is available at Acta Pharmacologica Sinica's website.
Supplementary information
Supplementary Information, Figure S1
Fecal BA composition in C57BL/6 male mice. (DOCX 56 kb)
Supplementary Information, Table S1
List of primers used to amplify mRNA by real-time PCR (DOCX 12 kb)
Supplementary Information, Table S2
Body weight, Food intake and Liver weight in C57BL/6 male mice. (DOCX 12 kb)
Supplementary Information, Table S3
Changes of plasma atherogenic indices in C57BL/6 male mice. (DOC 85 kb)
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Feng, D., Sun, Jg., Sun, Rb. et al. Isoflavones and phytosterols contained in Xuezhikang capsules modulate cholesterol homeostasis in high-fat diet mice. Acta Pharmacol Sin 36, 1462–1472 (2015). https://doi.org/10.1038/aps.2015.98
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DOI: https://doi.org/10.1038/aps.2015.98
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