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D-004, a lipid extract of Roystonea regia fruits, has been shown to reduce Testosterone, but not dihydrotestosterone-induced prostate hyperplasia in rodents. Inhibition of prostate 5?-reductase seems to explain these effects of D-004. Finasteride, an inhibitor of 5?-reductase used to treat benign prostate hyperplasia (BPH), has been shown to produce drug-induced depression and to increase mouse immobility in the forced swim test (FST). In this study, therefore, we investigated the effect of D-004 on the immobility in the FST and the tail suspension test (TST) in mice. Also, its effects on other behavioural tests (grip strength, open field activity and rotarod test) were investigated. Mice were randomized into five groups: three groups orally treated with D-004 (250, 500 and 1000 mg/kg) or vehicle (control group), and a fifth group that received intraperitoneally (IP) imipramine 20 mg/kg for 30 days. In the FST, D-004 (250, 500 and 1000 mg/kg) produced a statistically significant reduction in immobility (51, 58, and 65%, respectively, versus the control group), whereas imipramine reduced FST immobility by 69%. In the TST, D-004 (250 and 500 mg/kg) significantly, but modestly (21%) reduced the immobility versus the control group, although less than imipramine (50%). The lowest dose of D-004 (50 mg/kg), however, was ineffective. D-004 did not alter the results of other behavioural tests. In conclusion, D-004 (250-1000 mg/kg) administered orally for 30 days reduced the immobility in the FST and the TST in mice, and had no effect on other behavioural tests in mice.

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Increased platelet aggregation contributes to vascular risk. D-003, a mixture of high molecular weight sugarcane wax acids, has shown antiplatelet effects in experimental models and healthy volunteers. This randomised, double-blinded, placebo-controlled study investigated the effects of titrated doses of D-003 (5-20 mg/d) on platelet aggregation in hypercholesterolemic patients. After a 4-week baseline phase, 56 patients were randomised to D-003 5 mg/d or placebo. The doses were doubled every 15 days if arachidonic acid (AA)-induced platelet aggregation was not inhibited at least by 15%. AA (0.75 and 1.5 mmol/L) and collagen (1 microg/mL)-induced platelet aggregation, laboratory and physical safety indicators were assessed at baseline and every 15 days thereafter, when adverse events (AE) were also reported. No significant change of platelet aggregation was found in the placebo group. After 15, 30 and 45 on therapy, D-003 reduced platelet aggregation induced with both AA 0.75 mmol/L (18.1%, 19.0% and 30.3%, respectively) and AA 1.5 mmol/L (17.0%, 16.3% and 22.5%, respectively), and also collagen-induced platelet aggregation (26.6%, 20.8% and 29.4%) (p < 0.01 at days 15 and 30 versus placebo, p < 0.0001 at study completion). The mean inhibition of platelet aggregation with D-003 at day 15, at which all patients had received the lowest dose, was over 15%. Nineteen out of 28 D-003 randomised patients (67.9%) required dose titration to achieve such goal. At trial completion, the mean estimated dose was 11.6 mg/d. D-003 lowered low-density lipoprotein (22.0 %), total cholesterol (14.7%) and raised high-density lipoprotein-cholesterol (10.9%) (p < 0.0001 versus placebo). Six patients (2 placebo, 4 D-003) withdrew from the trial, none due to AE. D-003 did not modify the safety indicators with respect to placebo. Four patients (2 placebo, 2 D-003-treated) reported AE: pruritus and increased blood pressure (2 placebo) and rash and polyphagla (2 D-003). In conclusion, D-003 (5-20 mg/d) given as doses titrated every 15 days (5-20 mg/d) inhibited AA- and collagen-induced platelet aggregation in hypercholesterolemic patients and was well tolerated.

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5-alpha-Reductase inhibitors, alpha1-adrenoreceptors blockers and herbal drugs, like lipid extracts from saw palmetto fruits, are used to treat benign prostatic hyperplasia (BPH). D-004, a lipid extract from the Royal palm fruits, prevented prostate hyperplasia (PH) induced with testosterone and the atypical PH induced with phenylephrine (PHE) in the rat, its effect in this last model being comparable to that of saw palmetto, but lesser than that of tamsulosin (CAS 106133-20-4). It was investigated whether single doses of D-004, tamsulosin and their combined therapy can prevent urodynamic changes induced with PHE in the rat. Firstly, the effects of PHE on rat volume voided per micturition (VM) were explored in rats that were distributed in three groups: a negative control and two groups injected s. c. with PHE (5 and 10 mg/kg, respectively). In the other two experiments, rats were distributed in four groups: a negative control and three groups injected with PHE (a positive control and two groups treated with either tamsulosin 0.05 and 0.1 mg/kg, or D-004 400 and 800 mg/kg. In another experiment, the effects of the combined therapy were assessed using four groups: a negative control, a positive control and three groups treated orally with tamsulosin 0.05 mg/kg, D-004 400 mg/kg or D-004 400 mg/kg + tamsulosin 0.05 mg/kg, respectively. Sixty min later, all rats (except negative controls) were injected s. c. with PHE (5 mg/kg), and all (including the negative controls) received a fluid-loading dose. Thirty min later, they were placed in metabolic cages and theVM was measured for 1 h. The VM was significantly reduced with PHE (5 and 10 mg/kg), the high dose producing anuria in 50% of the rats. The reduction of VM was significantly and dose-dependently prevented with tamsulosin (0.05 and 0.1 mg/kg) (42.9% and 60.3%, respectively) and with D-004 (400 and 800 mg/kg) (25.2% and 43.1%, respectively). The inhibition reached (70.9%) with the combined therapy was greater than that reached with each monotherapy and also greater than the sum (56.8%) of the inhibitions reached with tamsulosin (35%) or D-004 (21.8%) alone. In conclusion, tamsulosin (0.05 and 0.1 mg/kg) and D-004 (400-800 mg/kg) dose-dependently inhibited the VM reduction induced with PHE, their combined therapy producing the greater effects.

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BACKGROUND: Benign prostatic hypertrophy is the nonmalignant, uncontrolled growth of prostatic epithelial cells and stroma that, left untreated, may lead to difficult urination and other complications. A common treatment of BPH is lipid extract from saw palmetto fruit, and lipid extract from Cuban Royal palm (a palm of the same family) fruit is being studied for this use. One study found that the latter, D-004, at 100 to 400 mg/kg daily prevented prostatic hypertrophy (PH) induced with testosterone (T) in a rat model. OBJECTIVES: This study comprised 2 experiments in a rat model. The first assessed the effects of different doses of D-004 on T-induced PH; the second investigated the effects of D-004 on PH induced with dihydrotestosterone (DHT). METHODS: In experiment 1, rats were distributed in 6 groups of 10 rats each. One group received an SC injection of soy oil and oral treatment with Tween 65/water vehicle (negative control). The other 5 groups received an SC injection of T 3 mg/kg daily and oral treatment with vehicle (positive control) or D-004 at 50, 200, 400, or 800 mg/kg daily suspended in vehicle. In experiment 2, rats were distributed in 3 groups of 10 rats each. A negative control group received treatment as in experiment 1. Positive controls received an SC injection of DHT 1.5 mg/kg and vehicle orally. The third group received an SC injection of DHT and oral treatment with D-004 at 800 mg/kg suspended in vehicle. All treatments were given for 14 days. At sacrifice, prostates were removed and weighed. Mean prostatic weights and prostatic/body weight ratios were calculated. RESULTS: In experiment 1, in the groups receiving D-004 at 200, 400, or 800 mg/kg daily, prostatic weight was significantly lower compared with the positive control group (P < 0.05, P < 0.01, and P < 0.001, respectively); this effect was not seen in the group receiving 50 mg/kg daily. In the groups receiving D-004 at 400 and 800 mg/kg daily, prostatic/body weight ratio was significantly lower compared with positive controls (both, P < 0.05); this effect was not seen in the groups receiving 50 or 200 mg/kg daily. In experiment 2, prostatic weight and prostatic/body weight ratio in the group receiving D-004 were similar to those of positive controls. Body weight was not affected in any of the groups receiving D-004. CONCLUSIONS: This study of rats with T- or DHT-induced PH suggests that D-004 at 200 to 800 mg/kg daily administered orally prevents T-induced PH, and that D-004 at 800 mg/kg daily does not prevent DHT-induced PH.

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Policosanol is a natural mixture of higher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum officinarum, L.) wax, whose main component is octacosanol. Policosanol (5-200 mg/kg) orally administered for 4 weeks to normocholesterolemic New Zealand rabbits significantly reduced total cholesterol and low density lipoprotein cholesterol (LDL-C) serum levels in a dose dependent manner. Serum triglyceride levels of treated and control animals were significantly different, but the reduction observed was not dose-dependent. High density lipoprotein cholesterol (HDL-C) levels remained unchanged. Results indicate that the reduction in total cholesterol values induced by policosanol is mainly mediated through a decrease in LDL-C levels(AU)

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Policosanol is a natural mixture of higher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum officinarum, L.) wax, whose main component is octacosanol. Policosanol (5-200 mg/kg) orally administered for 4 weeks to normocholesterolemic New Zealand rabbits significantly reduced total cholesterol and low density lipoprotein cholesterol (LDL-C) serum levels in a dose dependent manner. Serum triglyceride levels of treated and control animals were significantly different, but the reduction observed was not dose-dependent. High density lipoprotein cholesterol (HDL-C) levels remained unchanged. Results indicate that the reduction in total cholesterol values induced by policosanol is mainly mediated through a decrease in LDL-C levels

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En este trabajo se estudio el efecto de la administración oral de Policosanol (mezcla de alcoholes de alto molecular cuyo componente fundamental es el octacosanol) sobre los lípidos y lipoproteínas séricos de conejos Nueva Zelanda normocolesterolémicos. El tratamiento oral con Policosanol (5 mg/kg/día) durante 4 semanas provocó una disminución significativa de los niveles séricos de colesterol, triglicéridos y LDL-C, sin producir cambios significativos en los valores de HDL-. El contenido de colesterol hepático de los animales tratados resultó significativamente menor que el de los controles

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