Man Ricky Y K, Lynn Edward G, Cheung Filly, Tsang Patricia S Y, O Karmin
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, China.
Mol Cell Biochem. 2002 Apr;233(1-2):153-8. doi: 10.1023/a:1017487815091.
Hyperlipidemia is a well-known risk factor for atherosclerosis and statins are widely used to treat patients with elevated levels of lipids in their plasma. Notwithstanding the proven benefits of statin drugs on both primary and secondary prevention of heart disease, the high cost of statin treatment, in addition to possible side effects such as liver function abnormalities, may limit their widespread use. We conducted a study on a natural product as an alternative to statin treatment. Cholestin, a dietary supplement, is prepared from rice fermented with red yeast (Monascus purpureus), which has been shown to significantly decrease total cholesterol levels in hyperlipidemic subjects. Our objective was to determine the cellular effect of Cholestin on cholesterol synthesis in human hepatic cells (HepG2) and the mechanism by which it caused a change in lipid metabolism. Cholestin had a direct inhibitory effect on HMG-CoA reductase activity (78-69% of control). Cholesterol levels in HepG2 cells treated with Cholestin (25-100 microg/mL) were significantly reduced in a dose-dependent manner (81-45% of control, respectively). This reduction was associated with decreased synthesis and secretion of both unesterified cholesterol (54-31 and 33-14% of control, respectively) and cholesteryl ester (18-6 and 37-19% of control, respectively). These results indicate that one of the anti-hyperlipidemic actions of Cholestin is a consequence of an inhibitory effect on cholesterol biosynthesis in hepatic cells and provide the first documentation of a biomolecular action of red yeast rice.
高脂血症是动脉粥样硬化的一个众所周知的危险因素，他汀类药物被广泛用于治疗血浆脂质水平升高的患者。尽管他汀类药物在心脏病的一级和二级预防方面已被证明具有益处，但他汀类药物治疗成本高昂，此外还可能有诸如肝功能异常等副作用，这可能会限制它们的广泛使用。我们开展了一项关于一种天然产物作为他汀类药物治疗替代物的研究。Cholestin是一种膳食补充剂，由红曲（紫红曲霉）发酵的大米制备而成，已证明其可显著降低高脂血症患者的总胆固醇水平。我们的目的是确定Cholestin对人肝细胞（HepG2）胆固醇合成的细胞效应以及它引起脂质代谢变化的机制。Cholestin对HMG-CoA还原酶活性有直接抑制作用（为对照的78 - 69%）。用Cholestin（25 - 100微克/毫升）处理的HepG2细胞中的胆固醇水平以剂量依赖方式显著降低（分别为对照的81 - 45%）。这种降低与未酯化胆固醇（分别为对照的54 - 31%和33 - 14%）和胆固醇酯（分别为对照的18 - 6%和37 - 19%）的合成及分泌减少有关。这些结果表明，Cholestin的抗高脂血症作用之一是对肝细胞胆固醇生物合成产生抑制作用的结果，并首次记录了红曲米的生物分子作用。
