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Nonsteroidal antiinflammatory drugs include the traditional drugs and more selective COX-2 inhibitors. Traditional nonsteroidal antiinflammatory drug use is hampered by their gastrotoxicity, while COX-2-inhibitors increase the cardiovascular risk. The search of safer substances for managing inflammatory conditions is updated, a challenge wherein dual COX/5-LOX inhibitors have a place. This review summarizes the benefits of D-002, a mixture of higher aliphatic beeswax alcohols, on joint health and gastric mucosa. D-002 elicits gastroprotection through a multiple mechanism that involves the increased secretion and improved quality of the gastric mucus, the reduction of hydroxyl radical, lipid peroxidation, protein oxidation, neutrophil infiltration and the increase of antioxidant enzymes on the gastric mucosa. Consistently, D-002 inhibits NSAIDs, ethanol, pylorus-ligation and acetic acid-induced gastric ulceration in rats, and has reduced gastrointestinal symptoms in clinical studies. Early results found that D-002 was effective in the cotton pellet-induced granuloma and carrageenan-induced pleurisy model in rats, lowering pleural leukotriene B4 levels without causing gastrointestinal ulceration. However, D-002 effects on inflammation received little attention for years. Recent data have shown that D-002 inhibited both COX and 5-LOX activities with a greater affinity for 5-LOX and could act as a dual COX/5-LOX inhibitor. This mechanism might explain efficacy in experimental inflammatory and osteoarthritic models as well as clinical efficacy in osteoarthritic patients while supporting the lack of D-002 gastrotoxicity, but not the gastroprotective effects, which appear to be due to multiple mechanisms. In summary oral D-002 intake could help manage inflammatory conditions that impair joint health, while offering gastroprotection. [ABSTRACT FROM AUTHOR]

BACKGROUND: and objective: Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Saw palmetto (Serenoa repens), the dwarf American palm (Arecaceae family), is commonly used to treat BPH. The Cuban royal palm (Roystonea regia) also belongs to the Arecaceae family, and 200–400mg of D-004, a lipid extract from its fruits, administered orally for 14 days has been shown to prevent testosterone- but not dihydrotestosterone-induced prostatic hyperplasia in rats. D-004 (125–250 μg/mL) added to preparations of rat vas deferens caused a marked, dose-dependent and significant inhibition of noradrenaline-induced smooth muscle contraction, a response mediated through α1-adrenoceptors, and was more effective in these respects than Saw palmetto. However, the in vivo effects of D-004 and Saw palmetto on the hypertensive response induced by noradrenaline were modest (albeit significant), and neither treatment affected resting blood pressure or heart rate in rats. The differential effects of D-004 in in vitro and in vivo models could be related to a differential affinity for adrenoceptor subtypes or to different bioavailabilities in vascular and urogenital targets. Phenylephrine injected into rodents induces prostatic hyperplasia with all the characteristic morphological changes of the condition but does not result in enlargement of the prostate. Therefore, this phenylephrine-induced change in rat prostate tissue is called atypical prostatic hyperplasia. It serves as an in vivo model of prostatic hyperplasia induced by stimulation of α1-adreno- ceptors. The objective of this study was to determine whether D-004 can inhibit induction of atypical prostatic hyperplasia by phenylephrine in rats. METHODS: Rats were randomly distributed into five groups (ten rats/group). One group was a negative control and received oral vehicle only. The other four groups were injected subcutaneously with phenylephrine (2 mg/kg): of these groups, one was a positive control receiving the vehicle, and the other three groups were treated with D-004 or Saw palmetto (both 400 mg/kg) or tamsulosin 0.4 mg/kg. All active treatments were given orally for 28 days. After completion of treatment, rats were placed unrestrained in metabolic cages and micturition studies were performed. The rats were later killed and their prostates removed and weighed. Prostate samples were processed for histological study, with histological changes being assessed according to a scoring system. Bodyweight was measured at baseline and at weekly intervals. RESULTS: Histological examination of positive control rats revealed features of atypical prostatic hyperplasia, with piling-up, papillary and cribiform patterns and budding-out of epithelial cells. Micturition assessment revealed that phenylephrine significantly lowered both the total volume of urine in 1 hour and the volume per micturition; the latter was considered the main efficacy variable. D-004 and Saw palmetto extracts significantly prevented this reduction in volume per micturition by 70.5% and 68.6%, respectively, while tamsulosin totally abolished the reduction in micturition induced by phenylephrine (100% inhibition).& [ABSTRACT FROM AUTHOR]

Background: Benign prostatic hyperplasia (BPH) is the non-malignant, uncontrolled growth of glandular and stromal elements of the prostate gland. Lipid extracts from Saw palmetto (Arecaceae) fruits are widely used to treat BPH. The Cuban royal palm (Roystonea regia) is a member of the same family. Previous studies have found that D-004, a lipid extract from the R. regia fruit, administered orally at 200–800 mg/day for 14 days, prevented testosterone- but not dihydrotestosterone- induced prostate hyperplasia in rats. Objective: To determine whether D-004 can inhibit noradrenaline (NA) [norepinephrine]- and acetylcholine (ACh)-induced smooth muscle contraction in rat vas deferens and to investigate the in vivo effects of D-004 on NA pressure- elevating effects in rats, an effect mediated by vascular α1-adrenoceptors. Methods: In vitro effects were investigated by adding D-004 (125–500 μg/mL) to preparations of rat vas deferens suspended in an organ, bath containing Tyrode's solution, in which in vitro contractions were induced by NA or ACh, Negative and positive controls containing Tyrode's solution alone or with Saw palmetto extracts (125–500 μg/mL), respectively, were included. To assess the in vivo effects of D-004 on arterial blood pressure, rats were randomly distributed to one of five groups (ten rats/group): these consisted of a negative control group receiving the vehicle, two groups treated with D-004 (400 and 800 mg/kg) and two other groups treated with Saw palmetto (400 and 800 mg/kg). All treatments were orally administered. Rats were anaesthetised with sodium thiopental. Heart rate and blood pressure were registered in baseline conditions. Immediately afterwards, rats were injected intravenously over 5 seconds with successive doses of NA (1, 2 and 4 μg/kg) [0.1 mL/100g], with 5 minutes' interval between doses. Results: D-004 and Saw palmetto (125–500 μg/mL) significantly (p « 0.05) and dose dependently inhibited contractions induced by NA in rat vas deferens versus control. D-004 was more effective in inhibiting NA-induced contractions than Saw palmetto. The contractions induced by NA in preparations with D-004 (500 μg/mL) were weaker (p « 0,05) than in preparations containing Saw palmetto (500 μg/mL). At 125 μg/mL, D-004 inhibited the contractions induced by NA 1 and 32 ⊗ 10-6 mol/L by 70.8% and 28.5%, respectively, and Saw palmetto by 56.2% and 10.7%, respectively. At 500 μg/mL, D-004 inhibited these contractions by 100.0% and 71.3%, and Saw palmetto by 80.0% and 42.7%, respectively. The inhibitory concentrations of 50% (IC50) for NA contractions were 148.34 (D-004) and 188.38 (Saw palmetto) μg/mL. D-004 and Saw palmetto significantly (p « 0.05) and to a similar extent inhibited ACh-induced contractions, but less effectively than contractions induced by NA, since at 125 μg/mL they were ineffective. At a dose of 800 mg/kg, but not at 400 mg/kg, D-004 and Saw palmetto inhibited the pressure-elevating effects induced with low (1 μg/kg) but not with high doses (2 and 4 μg/kg) of NA. Conclusions: D-004 and Saw palmetto extracts inhibited in vitro the contractile responses to NA and ACh in rat vas deferens, and were more effective in inhibiting NA than ACh contractions. The in vivo effects of D-004 and Saw palmetto on the hypertensive response induced by NA were significant but modest. These results are preliminary as the relevance of the effects of D-004 on α1-adrenoceptors deserves further investigation, including comparative studies versus specific defined α1-adrenoceptor antagonists. [ABSTRACT FROM AUTHOR]

Background: D-003 is a mixture of long-chain aliphatic primary acids purified from sugarcane wax with experimentally demonstrated antiplatelet effects. D-003 shows hypocholesterolaemic effects in rabbits and healthy volunteers, lowering serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), but increasing high-density lipoprotein-cholesterol (HDL-C). Objective: To investigate the effects of D-003 administered for 10 days on platelet aggregation in healthy volunteers. Participants: Healthy men and women aged 20-55 years. Methods: The present double-blind, randomised, placebo-controlled study investigated the effects of D-003 (5, 10 and 20 mg/day), on platelet aggregation induced by arachidonic acid (AA) [0.75 and 1.5 mmol/L], collagen (1 mg/L) and adenosine diphosphate (ADP) [1 and 2 μmol/L]. The reversibility of the effects was also investigated. Forty-one subjects were randomised to receive placebo or D-003 at 5, 10 and 20 mg/day for 10 days followed by a washout period of 7 days. At baseline and after active treatment and washout completion, platelet aggregation, lipid profile and safety indicators were assessed. Results: D-003 significantly, markedly and reversibly inhibited platelet aggregation induced by AA 0.75 and 1.5 mmol/L in a dose-dependent manner. D-003 at 10 mg/day significantly inhibited (p < 0.05) aggregation induced by AA 0.75 mmol/L from 60.4-21.0% and that induced by AA 1.5 mmol/L from 61.5-26.8%. The dosage of 20 mg/day inhibited platelet aggregation induced by AA 0.75 mmol/L from 57.2-11.2%, and platelet aggregation induced by AA 1.5 mmol/L from 65.1- 21.6%. D-003 at 10 and 20 mg/day also inhibited platelet aggregation induced by collagen 1 mg/L, the effect being moderate, not dose related and reversible after washout. Platelet aggregation induced by ADP and coagulation time were unaffected by the treatment. D-003 at 5 mg/day was ineffective in inhibiting platelet aggregation. TC and triglycerides remained unchanged after therapy, as was expected for such a short duration of administration. Nevertheless, D-003 (10 and 20 mg/day) significantly (p < 0.05 vs baseline and placebo ) raised HDL-C by 20%, an effect that was not dose dependent and was partially reversible after washout. As a consequence, final values of LDL-C were lower (p < 0.05) in the 20 mg/day group than in the placebo group. No significant changes in lipid profiles occurred with placebo. No drug-related changes in safety indicators were observed. Four subjects, one from each group, withdrew from the study, none because of adverse events (AEs). No patients reported AEs during the study. Conclusions: D-003 at 10 and 20 mg/day for 10 days significantly inhibited AA- and collagen-induced platelet aggregation, without changes in ADP-induced platelet aggregation or coagulation time. The effects on AA-induced aggregation were marked, dose dependent and reversible, whereas the effects on collagen-induced aggregation were moderate and not dose dependent. D-003 (10 and 20 mg/day) also significantly but not dose dependently raised HDL-C. D-003 was well tolerated, with no AEs being reported and no changes in safety indicators being observed. The effects described suggest that D-003 is a promising agent with concomitant antiplatelet and lipid-profile modifying effects, and is potentially useful for the treatment and/or prevention of atherothrombotic disorders. Clinical investigation of D-003 is justified and further studies are needed to demonstrate such a hypothesis. [ABSTRACT FROM AUTHOR]

The effect of disodium 4-chloro-2,2-iminodibenzoate (CCA) on IgE antibody response was examined in CH/A and (BALB/c×C57BL/6J) F1 hybrid mice immunized with low doses of ovalbumin (OA) adsorbed on aluminium hydroxide gel. CCA administered orally at the doses of 5 and 50 mg/kg/day reduced IgE antibody production in these mice as determined by PCA test. High doses of CCA (100 mg/kg/day) given from day 7 before immunization of C57BL mice and during 1 week after immunization of mice with OA and Bordetella Pertussis Vaccine reduced the mortality of these mice subjected to anaphylactic shock on day 7 of immunization. CCA treatment was ineffective in anaphylactic shock of C57BL mice immunized with very high dose of OA, known to elicit little or no IgE antibody production but high IgG antibody response. The treatment of OA-immunized Guinea pigs with one oral dose of CCA (100 mg/kg) did not reduce mortality in protracted anaphylactic shock. Our results demonstrate that CCA inhibits IgE production as well as IgE mediated hypersensitivity reactions in mice. [ABSTRACT FROM AUTHOR]