Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts
Laboratorio de Bioquímica, Centro de Productos Naturales, Centro Nacional de Investigación Científica, Havana, Cuba. Archives of Medical Research
(Impact Factor: 2.65).
01/2001; 32(1):8-12. DOI: 10.1016/S0188-4409(00)00265-4
Cholesterol biosynthesis is strictly controlled by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase.
Transfer of cultured fibroblasts to a lipid-depleted medium (LDM) up-regulates the enzyme levels. This, in turn, is followed by an accelerated biosynthesis of cholesterol.
Exposure of Vero fibroblasts to LDM and policosanol (0.5-50 microg/mL), a new cholesterol-lowering drug purified from sugarcane (Saccharum officinarum L.) wax, decreased in a dose-dependent manner cholesterol biosynthesis from [14C]-acetate and 3H-water, but not from [14C]-mevalonate.
This suggests an effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis. When enzyme activity was measured in the presence of various concentrations of policosanol (0.5-50 microg/mL), reductase was not suppressed. Therefore, there was no evidence for a competitive or noncompetitive inhibition of enzyme activity. However, after treatment of intact cells with policosanol (50 microg/mL) in the presence of LDM, a suppressive effect on enzyme activity was observed, suggesting a modulatory effect of policosanol on reductase activity. The previous inhibition of enzyme up-regulation by policosanol suggests to date a depression of de novo synthesis of HMG-CoA reductase and/or stimulation of its degradation. However, the exact mechanism by which policosanol inhibits the activity of HMG-CoA reductase still remains unclear. Further studies are needed to clarify the precise mechanism of its inhibitory action on cholesterol biosynthesis.
Available from: Yi‐Chen Chia
- "In recent years, high purity (98%) of tetracosanol has sold at about US$75 per kg in Taiwan and China.Tetracosanol may be an economical and riskless pharmaceutical composition that comprises insulin or an insulin analogue in combination with tetracosanol for treatment of DM. Moreover, reports have also suggested that 5–20 mg per day of policosanol (including tetracosanol) lowers total cholesterol and low-density lipoprotein (LDL) and increases high-density lipoprotein (HDL) (Aneiros et al., 1995; Menendez et al., 2001). Furthermore, its effect on antiinflammatory activity is mediated by policosanol (Montserrat-de la Paz, Garcia-Gimenez, Angel-Martin, Perez-Camino, & Fernandez Arche, 2014; Ng et al., 2005). "
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ABSTRACT: In this study, we investigated whether tetracosanol, an aliphatic alcohol isolated from Saccharum sinense, enhances insulin receptor kinase activity to exhibit an insulin synergistic effect in vitro and in vivo. The insulin plus tetracosanol enhanced insulin receptor kinase showed that AKT activity was down-regulated by S961 in differentiated L6 myotubes. Meanwhile, insulin plus tetracosanol restored the ability of glucose transporter translocation and glucose uptake in differentiated myotubes with S961-induced insulin resistance in vitro. The modification of carbon chain lengths and the hydroxyl group of tetracosanol showed that it served as a critical chemical structure for the glucostasis effect in vivo. This study provides new evidence to show that tetracosanol can improve glycaemic control via insulin receptor kinase activity induced and leads to the enhancement of glucose transporter translocation to improve glucose uptake. The hydroxyl group of tetracosanol plays a critical role for insulin receptor kinase activity.
Journal of Functional Foods 04/2015; 14. DOI:10.1016/j.jff.2015.01.033 · 3.57 Impact Factor
Available from: Muhammad Umair Arshad
- "It has been recommended that PC might reduce the synthesis of HMG- CoA reductase or enhance its degradation (Menendez et al., 2001). Menendez et al. (2001) intended that PC diminishes the action of HMG-CoA reductase by disquieting the physicochemical attributes of definite cellular organelle membranes. PC alters their analogous acids into the endoplasmic reticulum (ER) and influences peroxisome (Hargrove et al., 2004) as peroxisome and ER hold the highest levels of HMG-CoA reductase (Olivier and Krisans, 2000). "
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ABSTRACT: In the era of nutrition, much focus has been remunerated to functional and nutraceutical foodstuffs. The health endorsing potential of such provisions is attributed to affluent phytochemistry. These dynamic constituents have functional possessions that are imperative for cereal industry. The functional and nutraceutical significance of variety of foods is often accredited to their bioactive molecules. Numerous components have been considered but wheat straw and its diverse components are of prime consideration. In this comprehensive dissertation, efforts are directed to elaborate the functional and nutraceutical importance of wheat straw. Wheat straw is lignocellulosic materials including cellulose, hemicellulose and lignin. It hold various bioactive compounds such as policosanols, phytosterols, phenolics, and triterpenoids, having enormous nutraceutical properties like anti-allergenic, anti-artherogenic, anti-inflammatory, anti-microbial, antioxidant, anti-thrombotic, cardioprotective and vasodilatory effects, antiviral, and anticancer. These compounds are protecting against various ailments like hypercholesterolemia, intermittent claudication, benign prostatic hyperplasia and cardiovascular diseases. Additionally, wheat straw has demonstrated successfully, low cost, renewable, versatile, widely distributed, easily available source for the production of biogas, bioethanol, and biohydrogen in biorefineries to enhance the overall effectiveness of biomass consumption in protected and eco-friendly environment. Furthermore, its role in enhancing the quality and extending the shelf life of bakery products through reducing the progression of staling and retrogradation is limelight of the article.
Critical reviews in food science and nutrition 01/2013; 53(3):287-95. DOI:10.1080/10408398.2010.528080 · 5.18 Impact Factor
Available from: Dev K Singh
- "The ability of policosanol to prevent the up-regulation of HMG-CoA reductase activity in these cells in response to lipid-depleted media suggested that policosanol suppresses HMG-CoA reductase synthesis or enhances enzyme degradation. Similar results were obtained with D-003 (Menendez et al., 2001), although neither study measured HMG-CoA reductase protein levels. Our studies explored that policosanol and identify the active component(s) of this natural product inhibits cholesterol synthesis by inhibiting HMGCoA reductase enzyme (Singh et al., 2006). "
Biochemistry, 03/2012; , ISBN: 978-953-51-0076-8
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