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  • Tunicamycin br Results br Discussion br Conclusions br Ackno


    Acknowledgments The basic studies were funded in part by a grant of the Clinical Research, Endocrinology and Metabolism Merck Research Laboratories, Medical School Grant Committee for Ezetimibe, Rahway, NJ, USA.
    Introduction Elevated cholesterol, particularly low density lipoprotein p(LDL) cholesterol, is a well defined risk factor for the development of atherosclerosis [1] through the formation of atherosclerotic lesions [2]. Atherosclerosis is associated with cardiovascular disease (CVD), the leading cause of mortality and disability in developed countries. Cholesterol levels are maintained and regulated by cholesterol Tunicamycin and synthesis, which have a reciprocal relationship, and by cholesterol elimination into the bile. Therefore, the proper evaluation of absorption, synthesis and trafficking of cholesterol throughout the body is critical to health research. Plasma cholesterol can be synthesized hepatically or extra-hepatically, or absorbed from the intestine, derived from dietary or biliary sources. Statins, a family of HMG-CoA reductase inhibitors, have been shown to effectively reduce cholesterol synthesis, achieving plasma LDL cholesterol lowering of up to 60% [3] and a CVD risk reduction of one-third [4]. Although efficacious in lowering LDL-C levels, statin use is associated with adverse events including muscle cramping and rhabdomyolysis [5]. Therapies which reduce cholesterol by inhibiting intestinal cholesterol or bile acid absorption are also available. Plant sterols/stanols, dietary fibre, and bile acid sequestrants have been shown to be effective in treating hyperlipidemia, with LDL cholesterol reductions of 10–15, 8.5–13 and 5–30%, respectively [6]. Use of Ezetimibe, a potent cholesterol absorption inhibitor, led to the discovery of the Niemann–Pick C1 Like 1 (NPC1L1) protein and its role in cholesterol absorption [7]. NPC1L1, a novel sterol transporter highly expressed in the jejunum, is essential for the absorption of cholesterol. NPC1L1 null mice display reduced cholesterol absorption by upwards of 90% [8]. Ezetimibe has been demonstrated to lower LDL cholesterol levels by 16–19% [9]. The wide range of cholesterol lowering response seen after each treatment is likely the product of genetic factors which modify cholesterol synthesis and absorption, as well as modulate the effectiveness of each intervention [10], [11], [12]. Given this considerable genetic heterogeneity, a need exists for the precise measurement of cholesterol synthesis and absorption as well as their response to different dietary, pharmaceutical and lifestyle interventions.
    Methods to assess cholesterol absorption
    Methods of assessment of cholesterol synthesis Cholesterol synthesis contributes substantially more to circulating cholesterol pools than cholesterol absorption, yielding approximately 700–900mg/day [24], [55]. This synthesis has been shown to undergo diurnal periodicity, maintaining cholesterol levels during fasting [56]. Accurate assessment of cholesterol synthesis is essential to the field of cholesterol research (Table 3).
    Introduction Berberine (BBR) is a plant alkaloid, which is the principal bioactive compound of Coptis Chinensis and many other medicinal plants. BBR possesses a wide range of biological and pharmacological functions. It has been used for thousands of years in traditional Chinese medicine to treat various diseases, such as infectious diseases and gastrointestinal disorders, without apparent side-effects being reported from home remedies and clinical uses [1], [2]. The cholesterol-lowering effect of BBR was reported back to the 1980s, with an observation that BBR lowered the intracellular cholesterol in cultured human aortic intimal cells [3]. However, this potential health benefit had not been paid serious attention until 2004 when BBR was found to markedly lower blood cholesterol levels in vivo in humans and hamsters [4]. Since then, several studies have repeatedly demonstrated the lowering effects of BBR on blood total cholesterol (T-C), LDL cholesterol (LDL-C), or nonHDL cholesterol (nonHDL-C) [5], [6], [7], [8], [9], [10], whereas the mechanism of action remains to be further elucidated [4], [5].