Int J Tissue React 1998;20(4):119-24. Effect of policosanol on platelet aggregation in type II hypercholesterolemic patients. Arruzazabala ML, Mas R, Molina V, Carbajal D, Mendoza S, Fernandez L, Valdes S. Center of Natural Products, National Center for Scientific Research, Havana, Cuba.
Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects proved in experimental models and healthy volunteers. This study reports the results of a 4-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation in type II hypercholesterolemic patients. Patients started or continued on a step-one cholesterol-lowering therapy for 4 weeks and those with total cholesterol > 5.0 mmol/L despite dietary conditions were randomized to receive under double-blind conditions placebo or policosanol (10 mg/day) for 30 days. Both groups were similar at randomization. Effects of policosanol on platelet aggregation induced by arachidonic acid (3.2 mM), collagen (0.5-1 microgram/ml) and ADP (0.5-1 uM) were determined at baseline and after 30 days of treatment. Policosanol significantly reduced platelet aggregation induced by arachidonic acid and collagen, meanwhile it only inhibited significantly the platelet aggregation induced by the lowest doses of ADP (0.5 uM). No adverse events occurred during the trial. Only one patient (placebo) discontinued from the study because of arthralgia.
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Int J Cardiol 1998 Dec 1;67(2):125-32. Effect of policosanol on intimal thickening in rabbit cuffed carotid artery. Noa M, Mas R, Mesa R. Laboratory of Histology, Center of Natural Products, National Center for Scientific Research, Havana, Cuba.
We studied the effect of policosanol on smooth muscle cell proliferation in the cuffed carotid artery of the rabbit. Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, with cholesterol lowering effects proved in experimental models and patients with type II hypercholesterolemia. It acts by inhibiting cholesterol biosynthesis. The positioning of a nonocclusive silicone collar around the rabbit carotid artery results in the formation of a neointima. We wished to determine whether policosanol orally administered prevented intimal thickening. Collars were placed around the left carotid for 15 days. The contralateral artery was sham operated. We included three experimental groups: a control received vehicle and two others policosanol at 5 and 25 mg Kg until sacrificed. Samples of arteries were examined by light and electron microscopy. To evaluate intimal thickening the cross-sectional area of intima and media were measured. Neointima was significantly reduced in policosanol-treated animals compared with controls. The smooth muscle cell proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen and a significant reduction was observed in policosanol treated rabbits. It is concluded that policosanol has a protective effect on the neointima formation in this experimental model.
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Int J Clin Pharmacol Ther 1998 Sep;36(9):469-73. Long-term therapy with policosanol improves treadmill exercise-ECG testing performance of coronary heart disease patients. Stusser R, Batista J, Padron R, Sosa F, Pereztol O. Clinical Research Center, Havana University, Playa, Cuba.
This study examined the effects of long-term lipid-lowering therapy with policosanol on the clinical evolution, and exercise-ECG testing responses of 45 coronary heart disease (CHD) patients with myocardial ischemia, documented by exercise 201T1-myocardial perfusion scintigraphy, in an overall randomized, double-blind, placebo-controlled trial, made for different test endpoints. Fifteen patients were treated with 5 mg of policosanol twice daily; another 15 patients were administered the same drug dose plus 125 mg aspirin; and the other 15 patients received placebo plus equal aspirin dose. They were followed for 20 months, previous baseline observations, with treadmill exercise-ECG, besides serum lipid test. Beneficial changes on proportions among the 2 policosanol groups and the placebo group, showed an increment on functional capacity class, a decrement on rest and exercise angina, and a significant decrease in cardiac events, and in ischemic ST segment response, especially in the policosanol plus aspirin group (p = 0.05, X2(2df) = 5.8; p = 0.04, p = 0.02; Fisher). After treatment, sets of mean changes revealed an increase on maximum oxygen uptake, and a decline on double product simultaneously in both policosanol groups (p < or = 0.02, p < or = 0.002; Pillais, Hotellings' T2), while the placebo group was impaired. Aerobic functional capacity percent showed an increment in policosanol groups (p < or = 0.05, paired T). Lipid levels improved as other endpoints already reported. A supposed ergogenic effect of octacosanol, policosanol's main active compound, was not detected with this design. These results show that policosanol-treated CHD patients improved clinical evolution, and exercise-ECG responses, owing to the amelioration of myocardial ischemia, even more when administered with aspirin.
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Pharmacol Res 1998 Aug;38(2):89-91. Interaction policosanol-warfarin on bleeding time and thrombosis in rats. Carbajal D, Arruzazabala ML, Valdes S, Mas R. Center of Natural Products, CNIC, Playa, Havana, Cuba.
Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. This study investigated the effects of the concomitant administration of policosanol and warfarin on bleeding time and experimentally-induced venous thrombosis in rats. Policosanol did not change the bleeding time, meanwhile warfarin alone and the combination policosanol + warfarin induced a moderate, but significant prolongation of the bleeding time. The addition of policosanol to warfarin therapy did not enhance the prolongation of the bleeding time induced by warfarin alone. A significant reduction of thrombus weight was observed after policosanol or warfarin monotherapies. When the combination was used instead of either drug alone, no significant benefits were observed on the reduction of thrombus weight.
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Teratog Carcinog Mutagen 1998;18(1):1-7. Evaluation of peri- and post-natal toxicity of Policosanol in rats. Rodriguez MD, Garcia H. Department of Toxicology, National Center for Scientific Research, Havana, Cuba.
The effects of Policosanol, a newly developmented hypocholesterolemic drug administered during the perinatal and postnatal periods, were studied in Sprague-Dawley rats. This compound was administered orally to female rats at dose levels of 0 (control), 5, 50, and 500 mg/kg/day, from day 15 of pregnancy to day 21 after parturition. The animals were allowed to deliver and their offspring were examined for postnatal growth and development. No signs of toxic effects related to the test material were observed in the dams F0 during pregnancy and lactation. No adverse effects were observed on the postnatal growth, behaviours, or reproductive ability of pups F1. The physical and sensorial development of pups F2 was also normal. These results confirm that Policosanol does not affect the reproductive performance or fetal/neonatal development.
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Arch Med Res 1998 Spring;29(1):21-4. Erratum in: Arch Med Res 1998 Winter;29(4):361. Effect of policosanol on arterial blood pressure in rats. Study of the pharmacological interaction with nifedipine and propranolol. Molina Cuevas V, Arruzazabala ML, Carbajal Quintana D, Mas Ferreiro R, Valdes Garcia S. Centro de Productos Naturales, CNIC, Havana, Cuba.
BACKGROUND: Policosanol is a natural mixture of higher aliphatic primary alcohols isolated from sugar cane wax (Saccharum officinarum, L) with cholesterol-lowering effects demonstrated in experimental models and in patients with type II hyperlipoproteinemia. The purpose of this study is to determine the effect of policosanol on arterial blood pressure and its interaction with propranolol and nifedipine. METHODS: Single doses of policosanol (25, 50 and 200 mg/kg) orally administered to spontaneously hypertensive rats (SHR) did not significantly change arterial pressure. RESULTS: The study on pharmacological interactions between policosanol (200 mg/kg) and both antihypertensive agents revealed that pretreatment with high doses of policosanol significantly increased propranolol-induced hypotensive effects, while the effects of nifedipine remained unchanged. CONCLUSIONS: Our results show that policosanol does not antagonize the hypotensive effect of beta-blockers but it can increase the hypotensive effect of beta-blockers without modifying cardiac frequency.
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Prostaglandins Leukot Essent Fatty Acids 1998 Jan;58(1):61-4. Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers. Carbajal D, Arruzazabala ML, Valdes S, Mas R. Center of Natural Products, CNIC, Cubanacan Habana, Cuba.
Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and patients with type II hypercholesterolemia. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. This study reports the results of a 2-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation and thromboxane B2 and prostacyclin (6 keto PGF1alpha) production after stimulation with collagen in healthy volunteers. The volunteers were on a placebo-baseline period for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10 mg/day) for 15 days. Platelet aggregation was determined at baseline and after 15 days of treatment. Significant reductions of arachidonic acid and collagen-induced platelet aggregation were observed. Thromboxane, but not prostacyclin, generation induced by collagen was also inhibited by policosanol.
