Protective Effect of Policosanol on Endothelium and Intimal Thickness Induced by Forceps in Rabbits

Miriam Noa,Rosa Mas,Carlos Lariot 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.3

Presented at the XIIth International Symposium onDrugs Affecting Lipid Metabolism, Baylor University, Houston,1995.44. Pomerantz KB, Hajjar DP: Eicosanoids in regulation of arterialsmooth muscle cell phenotype, proliferative, capacity and cho-lesterol metabolism. Arteriosclerosis1989;9:413429.45. Menndez R, Fraga V, Amor AM, Gonzlez RM, Ms R: Oraladministration of policosanol inhibits in vitro copper ion-inducedrat lipoprotein peroxidation. Physiol Behav1999;67:17.46. Menndez R, Ms R, Amor AM, et al.: Effects of policosanoltreatment on the susceptibility of low density lipoprotein (LDL)isolated from healthy volunteers to oxidative modification in vitro.Br J Clin Pharmacol2000;50:255262.47. Matrisian LM: The matrix degrading metalloproteinases. Bioes-says1992;14:455463.48. Bennett M, Evan G, Schwartz S: Apoptosis of human vascularsmooth muscle cells derived from normal vessels and coronaryatherosclerotic plaques. J Clin Invest1995;95:22662274.POLICOSANOL ON INTIMA OF ARTERIES IN RABBITS 45949. Angelini A, Visona A, Pettenazzo E, Calabrese F, Yacoub A: Pro-liferation and cellular death (apoptosis) in an animal model of ac-celerated atherosclerosis. Atherosclerosis1997;134:267276.50. Br PR: Apoptosisthe cell’s silent exit. Life Sci1996;59:

Lack of Protective Effect of D-003, a Mixture of High-Molecular-Weight Primary Acids from Sugar Cane Wax, on Liver Damage Induced by Galactosamine in Rats

Miriam Noa,Sarah Mendoza,Rosa Mas,Nilda Mendoza 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.3

D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, whereinoctacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and pre-vents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- andparacetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galac-tosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this studywas to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigatedthe effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive controlgroup, and three groups treated with galactosamine and D-003 (5, 25, and 100 mg/kg). To induce liver damage, galactosamine(800 mg/kg) was injected intraperitoneally 30 minutes after dosing with vehicle or D-003. Twenty-four hours later, rats weresacrificed, and livers were immediately removed for histopathological studies. Livers from positive controls showed the char-acteristic pattern of galactosamine-induced damage. Galactosamine significantly reduced the percentage of normal hepato-cytes, increasing both necrotic or lipid-rich hepatocytes compared with negative controls. D-003, however, did not increasethe percentage of normal hepatocytes compared with positive controls, indicating that treatment was not effective for pre-venting the hepatic injury induced with galactosamine. Likewise, D-003 failed to change the content of necrotic and lipid-rich hepatocytes relative to positive controls. It is concluded that D-003 did not protect against the histological changes ofgalactosamine-induced hepatotoxicity.

Evaluation of the effect of D-002, a mixture of beeswax alcohols, on osteoarthritis symptoms

Roberto Puente,José Illnait,Rosa Mas,Daisy Carbajal,Sarahí Mendoza,Julio César Fernández,Meilis Mesa,Rafael Gámez,Pablo Reyes 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.2

Background/Aims: Nonsteroidal anti-inflammatory drugs relieve osteoarthritis(OA) symptoms but cause adverse effects. D-002, a mixture of beeswax alcohols,is effective against experimental OA. A pilot study found that D-002 (50 mg/day)for 8 weeks improves OA symptoms. The aim of this study was to investigate theeffects of D-002 (50 to 100 mg/day) administered for 6 weeks on OA symptoms. Methods: Patients with OA symptoms were double-blindly randomized to D-002(50 mg) or placebo for 6 weeks. Symptoms were assessed by the Western Ontarioand McMaster Individual Osteoarthritis Index (WOMAC) and the visual analogscale (VAS) scores. Patients without symptom improvement at week 3 were titratedto two daily tablets. The primary outcome was the total WOMAC score. WOMACpain, joint stiffness and physical function scores, VAS score, and use of rescuemedications were secondary outcomes. Results: All randomized patients (n = 60) completed the study, and 23 experienceddose titration (two in the D-002 and 21 in the placebo groups). At study completion,D-002 reduced total WOMAC (65.4%), pain (54.9%), joint stiffness (76.8%), andphysical function (66.9%) WOMAC scores, and the VAS score (46.8%) versusplacebo. These reductions were significant beginning in the second week, andbecame enhanced during the trial. The use of rescue medication by the D-002(6/30) group was lower than that in the placebo (17/30) group. The treatment waswell tolerated. Seven patients (two in the D-002 and five in the placebo group)reported adverse events. Conclusions: These results indicate that D-002 (50 to 100 mg/day) for 6 weeksameliorated arthritic symptoms and was well tolerated.

Preventive Effect of D-002, a Mixture of Long-Chain Alcohols from Beeswax, on the Liver Damage Induced with CCl4 in Rats

Sarahi Mendoza,Miriam Noa,Yohani Perez,Rosa Mas 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.2

Effects of D-003 (10 mg/day) on Bone Mineral Density of the Lumbar Spine and Femoral Neck in Postmenopausal Women: A Randomized, Double-Blinded Study

( Alfredo Ceballos ),( Gladys Castano ),( Sarahi Mendoza ),( Juan Gonzalez ),( Rosa Mas ),( Lilia Fernandez ),( Jose Illnait ),( Meilis Mesa ),( Rafael Gamez ),( Julio Cesar Fernandez ),( Ricardo Tell 대한내과학회 2011 The Korean Journal of Internal Medicine Vol.26 No.2

Background/Aims: Increased osteoclast activity is a pivotal finding in osteoporosis. This increase is mediated via the mevalonate-to-cholesterol pathway, which is involved in producing the intermediates required for osteoclast activity. D-003, a mixture of high molecular weight sugarcane wax acids, has been shown to inhibit cholesterol synthesis prior to mevalonate production, resulting in a reduction of bone loss and resorption in ovariectomized rats. Moreover, previous studies have demonstrated that short-term D-003 treatment reduces urinary excretion of deoxypyridinoline/creatinine in postmenopausal women. Methods: We performed a double-blinded, placebo-controlled study to investigate the effects of D-003 (10 mg/day) treatment for 3 years on bone mineral density (BMD) in 83 postmenopausal women with low BMD. Results: Over 3 years, D-003 treatment increased lumbar spine BMD (5.1%, p < 0.01) and improved osteoporosis-related quality of life scores as compared with placebo-treated controls. D-003 was also well tolerated; the frequency of adverse events in the bone, joints, or muscle with D-003 treatment (p < 0.05) was lower than in the placebo group. Conclusions: D-003 treatment (10 mg/day) for 3 years increased lumbar spine BMD and produced clinical improvements in postmenopausal women with low BMD. Further studies, however, will be required to confirm these results. (Korean J Intern Med 2011;26:168-178)

Effects of In Utero Exposure to D-004, a Lipid Extract from Roystonea regia Fruits, in the Male Rat: A Comparison with Finasteride

Ariadne Gutie´rrez Martı´nez,Balia Pardo,Rafael Ga´mez,Rosa Mas,Miriam Noa,Gisela Marrero,Maikel Valle,Haydee Garcı´a,Dayisell Curveco,Nilda Mendoza,Edy Goicochea 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.12

D-004 is a lipid extract obtained from Cuban royal palm fruits, consisting of a mixture of free fatty acids, that prevents prostate hyperplasia induced with testosterone in rodents. This study investigated the possible alterations due to D-004 of androgen-dependent development after exposure in utero and compared them with those due to finasteride. Rats were randomized into five experimental groups: a control group, three groups treated with D-004 at 500, 750, or 1,000 mg/kg/day,respectively, and a group treated with finasteride (10 mg/kg/day). Male rats were treated 10 weeks before and during mating. Female rats were treated for 15 days prior mating, during mating, during pregnancy, and until lactation (day 21) except for those treated with finasteride, which were only administered the drug on gestational days 12–21. All male offspring were monitored individually until necropsy after postnatal day 90. The results of the present study indicate that D-004 induced no alterations in androgen-dependent development after the exposure in utero. Also, the current study demonstrated a permanent reduction in anogenital distance and retention of nipples in adult male rats exposed to finasteride during late gestation. Significant alterations induced by exposure to finasteride were mainly in tissues dependent on dihydrotestosterone during development.

Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease

José Illnait,Iván Rodríguez,Sarahí Mendoza,Yolanda Fernández,Rosa Mas,Mirtha Miranda,Jesús Piñera,Julio César Fernández,Meilis Mesa,Lilia Fernández,Daisy Carbajal,Rafael Gámez 대한내과학회 2013 The Korean Journal of Internal Medicine Vol.28 No.4

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is intimately related to insulin resistance and ranges from a benign course to liver fibrosis and cirrhosis. NAFLD management mainly involves dietary modification and weight loss. Although no fully successful pharmacological intervention is available, alternative therapies to treat NAFLD have shown promising results. Experimental studies have shown that D-002, a mixture of beeswax alcohols with antioxidant effects, is hepatoprotective. The aim of this study was to investigate the efficacy and safety of D-002 in patients with NALFD. Methods: Fifty patients with NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks. The primary endpoint was a significant ultrasonography-detected reduction of liver fat infiltration versus a placebo. Secondary endpoints were decreases in the homeostatic model assessment (HOMA) index,insulin levels, serum liver enzymes, increases in plasma total antioxidant status (TAS) and improved clinical symptoms versus the placebo recipients. Results: At randomization, all indicators were comparable in both groups. At study completion, seven (28.0%) D-002-patients, but none of the placebo recipients,exhibited a normal liver echo pattern on ultrasonography (p < 0.01). Also,D-002 significantly reduced (p < 0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased the TAS, but did not affect other parameters. The proportion of D-002-patients (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three patients in each group withdrew from the study. Conclusions: D-002 (100 mg/day) improved ultrasonographic findings, indicators of insulin resistance, plasma TAS and clinical evolution on NAFLD patients. Further studies, however, are needed to confirm these results.