Effect of D-003 on Isoproterenol-Induced Myocardial Necrosis in Rats

Daisy Carbajal,Miriam Noa,Vivian Molina,Maria Lourdes Arruzazabala,Rosa M?,Sarah?Mendoza,Jorge Gonz?ez 한국식품영양과학회 2003 Journal of medicinal food Vol.6 No.1

D-003 is a mixture of high-molecular-weigh t aliphatic primary acids purified from sugar canewax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isopro-terenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objec-tive of this study was to determine whether D-003 shows protective effects against ISO-in-duced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25 40mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5 20mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investi-gated. D-003 administered as single doses dose-dependen tly decreased necrosis area, percentof infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, butonly the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment withASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs wasunchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necro-sis indicators in a dose-dependen t maner, with results effective from 25 mg/kg to the high-est dose tested, indicating that the repeated dose scheme was more effective to prevent thedamage. It is concluded that D-003 shows a protective effect on the myocardial necrosis in-duced by ISO in rats.13

Effect D-003 on Intravascular Platelet Aggregation Induced with Collagen in Rats

Vivian Molina,Daisy Carbajal,Lourdes Arruzazabala,Rosa M?s 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.2

D-003 is a mixture of higher aliphatic primary acids purified from sugar-cane (Saccharum officinarumL.) waxthat inhibits platelet aggregation induced ex vivoby addition of agonists to platelet-rich plasma (PRP) of rats, guinea pigs,and healthy human volunteers. Because the ex vivoplatelet aggregation model does not mimic properly platelet aggregationoccurring inside the arteries, since all blood factors regulating the formation of a platelet aggregate or thrombus are not pre-sent in PRP, this work was undertaken in order to investigate the effects of different oral doses of D-003 on platelet aggre-gation induced by collagen in vivoin rats. Effects of single (5, 25, 100, and 200 mg/kg) or repeated doses (1, 5, 25, 100, and200 mg/kg during 10 days) of D-003 on in vivo platelet aggregation in rats were studied. D-003 (5200 mg/kg) orally ad-ministered as single or repeated doses inhibited significantly and dose-dependently collagen-induced platelet aggregation inrats. The minimal dose investigated effective in both single and repeated administration schemes was 5 mg/kg. The highestdose assessed in both cases was 200 mg/kg, causing inhibitions of 61.5% (single doses) and 74.4% (repeated doses). Thus,the effects of repeated doses were more pronounced than those obtained with single administration. The mean 50% effectivedose of D-003 in both schemes was 2.3 mg/kg, which indicates a promising anti-thrombotic potential of D-003.

Therapeutic Effect of D-002 (Abexol) on Gastric Ulcer Induced Experimentally in Rats

Vivian Molina,Daisy Carbajal,Lourdes Arruzazabala,Rosa M? 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.1

D-002 is a mixture of higher aliphatic primary alcohols isolated from beeswax, wherein triacontanol is themost abundant alcohol, with antioxidant and anti-ulcer properties. Since compounds with cytoprotective and antioxidant ef-fects can improve healing of gastroduodenal ulcer induced by noxious agents, this work investigated the healing effect of D-002 on acute and chronic gastric ulcers induced with indomethacin and acetic acid, respectively, in rats. Acute gastric ulcerwas induced with single oral doses of indomethacin (20 mg/kg). Treatments with D-002 at 50, 100, and 200 mg/kg or vehi-cle were administered 3 hours after ulcer induction. Three hours later, rats were sacrificed, and the stomach was removed forquantifying the lesions. Chronic gastric ulcer was induced by 50 .L of 80% acetic acid application on the anterior serosalsurface of the glandular stomach during 20 seconds. Twenty-four hours later D-002 at 50, 100, and 200 mg/kg or vehicle wasadministered for 5 days. At the end of the treatment, animals were fasted for 24 hours and sacrificed, the stomachs were re-moved, and the lesions were quantified. D-002 orally administered at 100 and 200 mg/kg acutely significantly healed gastriculcers induced with indomethacin by 39% and 56% compared with positive controls, respectively. Also, D-002 at 200 mg/kg,but not at 50 or 100 mg/kg, administered orally for 5 days after ulcer induction exerted a significant healing effect (65.8%inhibition) in gastric ulcers induced with acetic acid. In conclusion, this work demonstrated that D-002 administered after ul-cer induction induced effective healing of acute and chronic gastric ulcers provoked by, respectively, indomethacin and aceticacid.

Effect of D-003, a Mixture of Very-Long-Chain Aliphatic Acids Purified from Sugarcane Wax, on Cerebral Ischemia in Mongolian Gerbils

Vivian Molina,Miriam Noa,Lourdes Arruzazabala,Daisy Carbajal,Rosa M? 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.4

D-003 is a mixture of very-high-molecular-weight aliphatic acids purified from sugar cane wax (Saccharumofficinarum), which inhibits platelet aggregation and lipid peroxidation. The objective of the present study was to evaluatethe effect of D-003 on cerebral ischemia induced by ischemia-reperfusion (I-R) in Mongolian gerbils. Two experimental se-ries were conducted. The first series investigated the effects of D-003 on cerebral edema, neurological symptoms, and mor-tality in Mongolian gerbils with cerebral ischemia induced by I-R, while the second series investigated the effects on histo-logical markers of cerebral injury, such as edema intensity (vacuolization) and cerebral necrosis. Animals were randomlydistributed in five experimental groups: a sham-operated group experiencing surgical handling except the clamping and orallytreated with Tween/water vehicle and four groups subjected to the I-R surgical procedure. One of these groups was treatedwith the same vehicle, and the other three groups received D-003 at 25, 100, and 200 mg/kg, respectively. All treatments wereadministered for 14 days. D-003 (200 mg/kg) significantly reduced the cerebral edema and clinical symptoms provoked by I-R compared with the positive control group, whereas lower doses (25 and 100 mg/kg) were not effective. Positive controlanimals showed an injury profile characterized by swelling (tissue vacuolization) and necrosis of neurons in all areas of thebrain studied (frontal cortex, hippocampus, and striatum). The results of the histological study were consistent with those ob-served by determining cerebral edema and symptoms observation. Thus, D-003 at 200 mg/kg significantly reduced histolog-ical markers of brain injury (swelling and necrosis) compared with the control group. It is concluded that D-003 administeredorally at 200 mg/kg for 14 days protected against cerebral damage caused by bilateral cerebral ischemia in Mongolian ger-bils.

D-003 and Warfarin Interaction on the Bleeding Time and Venous Thrombosis Experimentally Induced in Rats

Mar? Lourdes Arruzazabala,Vivian Molina,Daisy Carbajal,Rosa M? 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.2

D-003 is a mixture of higher aliphatic primary acids isolated and purified from sugarcane wax, the main component of which is octacosanoic acid. D-003 exhibits a cholesterol-lowering effect as well as antiplatelet and antithrombotic effects in experimental models. Warfarin is a coumarin derivative with anticoagulant activity that acts as a vitamin K antagonist. Since in clinical practice warfarin and D-003 could be administered together, the objective of this study was to evaluate the effects of the simultaneous administration of both drugs on the bleeding time and the venous thrombosis experimentally induced in rats. The combined therapy of minimally effective doses of D-003 and warfarin produced an antithrombotic effect significantly higher than those produced by each monotherapy. Likewise, the prolongation of bleeding time induced by warfarin was increased by the simultaneous administration with D-003, showing a synergistic effect between both drugs.

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.

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.