Pharmacol Res 1997 Oct;36(4):293-7. Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Arruzazabala ML, Valdes S, Mas R, Carbajal D, Fernandez L. Department of Pharmacology, Centre of Natural Products, CNIC, Habana, Cuba.
A randomized, double-blind, placebo-controlled study was conducted in 43 healthy volunteers to compare the effects of policosanol (20 mg day-1), aspirin (ASA) (100 mg day-1) and combination therapy (policosanol 20 mg day-1 plus ASA 100 mg day-1) on platelet aggregation. The healthy volunteers were randomly treated for 7 days. Both, platelet aggregation and coagulation time were measured at baseline and after therapy. When policosanol was administered platelet aggregation induced by ADP (37.3%), epinephrine (32.6%) and collagen (40.5%) were significantly reduced. Meanwhile, aspirin significantly reduced platelet aggregation induced by collagen (61.4%) and epinephrine (21.9%) but not ADP-induced aggregation. Combined therapy significantly inhibited aggregation induced by all the agonists reaching the highest reductions of platelet aggregation induced by collagen (71.3%) and epinephrine (57.5%). Coagulation time did not change significantly in any group. No subject withdrew from the trial. Four volunteers reported mild adverse experiences during the study: three ASA-treated cases referred headache, epigastralgia and nose bleeding, meanwhile one patient receiving combination therapy reported gum bleeding. The present results demonstrate that policosanol (20 mg day-1) is as effective as ASA (100 mg day-1). Moreover, combination therapy shows some advantages compared with the respective monotherapies.
——
J Pharm Pharmacol 1997 Oct;49(10):999-1002. Effect of policosanol on circulating endothelial cells in experimental models in Sprague-Dawley rats and in rabbits. Noa M, Mas R, Mesa R. National Centre for Scientific Research, Havana, Cuba.
The effect of policosanol on circulating endothelial cells has been studied in different experimental models with endothelium damage. Oral administration of 25 mg kg-1 policosanol to Sprague-Dawley rats resulted in significant protection of the endothelial lining against the desquamating effect of citrate. Oral administration of 5 mg kg-1 policosanol to spontaneously hypertensive rats (SHR) resulted in a significant reduction of circulating endothelial cells compared with controls. Moreover, comparison between groups revealed a lower frequency of aortic lesions in policosanol-treated animals than in controls. On the other hand, administration of 5 mg kg-1 policosanol to rabbits with intimal hyperplasia induced by cuff placement in the carotid artery resulted in levels of circulating endothelial cells significantly lower than in controls. These results demonstrate the protective effect of policosanol in different experimental models and suggest its potential for endothelial protection.
——
Arch Med Res 1997 Autumn;28(3):355-60. Effect of policosanol on in vitro and in vivo rat liver microsomal lipid peroxidation. Fraga V, Menendez R, Amor AM, Gonzalez RM, Jimenez S, Mas R. Centro Nacional de Investigaciones Cientificas, Centro de Productos Naturales, Havana, Cuba.
Policosanol, a defined mixture of high molecular weight aliphatic alcohol isolated and purified from sugar cane (Saccharum officinarum, L) wax is a new cholesterol-lowering agent effective in experimental models, healthy volunteers, and patients with type II hypercholesterolemia. Also, policosanol prevents the onset of spontaneously- and experimentally-induced atherosclerotic lesions and cerebral ischemia in Mongolian gerbils. Free radicals are linked to many diseases including atherosclerosis and ischemia/ reoxidation cellular injury. Therefore, in this study the authors evaluate the antioxidant activity of policosanol on rat liver microsomes. The extent of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS). When policosanol was administered orally (100 and 250 mg/kg) for up to 4 weeks, a partial prevention of rat in vitro microsomal lipid peroxidation was noted. The formation of TBARS in microsomes isolated from treated rats was significantly decreased by about 50%, when peroxidation was initiated by Fe3+/ADP/ NADPH, Fe2+/ascorbate and CCl4/NADPH-generating system. Also, oral administration of policosanol in rats provides a partial inhibition of lipid peroxidation, but the mechanism supporting such effect remains to be elucidated. This beneficial effect of policosanol on membrane lipid peroxidation may be useful in protecting to some extent against free radical-associated diseases.
——
Br J Nutr 1997 Jun;77(6):923-32. Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet. Menendez R, Arruzazabala L, Mas R, Del Rio A, Amor AM, Gonzalez RM, Carbajal D, Fraga V, Molina V, Illnait J. Department of Pharmacology, National Center for Scientific Research, Havana, Cuba.
The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugarcane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50 mg/kg) the increases in plasma total cholesterol and LDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125I-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t1/2) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.
——
Toxicol Lett 1997 Feb 7;90(2-3):97-106. Multigeneration reproduction study of policosanol in rats. Rodriguez MD, Sanchez M, Garcia H. Department of Toxicology, National Center for Scientific Research, Havana, Cuba.
The hypocholesterolaemic drug policosanol was administered to Sprague-Dawley rats of both sexes throughout three successive generations at concentrations of 0, 5, 50 and 500 mg/kg bw/day by gavage. For each generation two litters were reared until they were at least 3 weeks old. No clinical signs which could be related to the administration of the test substance were observed in the F0, F1b and F2b parents. There were no differences among groups in the number of animals that conceived, the number of pups born live or dead, the rate of male to female pups, the number of pups that survived until weaning and the pups' body weights through the lactancy. The following test showed no treatment-related effects on F3b offspring: righting on a surface, air righting, corneal, pirmal and pain reflexes, auditory startle and visual placing. The results of the present study did not demonstrate any deleterious effects on the fertility, reproductive performance or development of rats administered policosanol at levels of up to 500 mg/kg bw/day over three successive generations.
