This product is isolated and purified from the herbs of Alstonia yunnanensis
Cur-19-en-17-al, 2,16-didehydro-, (15β,19E)-/(19E)-2,16,19,20-Tetradehydrocuran-17-al/Norfluorocurarine/Curan-17-al, 2,16,19,20-tetradehydro-, (19E)-/(15β,19E)-2,16-Didehydrocur-19-en-17-al
Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.
473.0±45.0 °C at 760 mmHg
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For Reference Standard and R&D, Not for Human Use Directly.
provides coniferyl ferulate(CAS#:6880-54-2) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia), has been found to reduce prostatic hyperplasia (PH) induced with testosterone (T), but not PH induced with dihydrotestosterone (DHT), in rodents, suggesting the inhibition of prostate 5α-reductase activity.
The aims of this study were to assess whether D-004 inhibits prostate 5α-reductase activity in vitro and to examine the effects of D-004 on enzyme kinetics.
This experimental study was conducted at the Pharmacology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. Soluble rat prostate preparations were used as the source of 5α-reductase, and (3H)-DHT production was measured to determine prostate 5α-reductase activity. Cell-free rat prostate homogenates were pre-incubated with carboxymethyl cellulose 2% alone (control tubes) or D-004 (0.24-125 μg/mL) suspended in the vehicle (treated tubes) for 10 minutes prior to adding the labeled substrate (3H)-T Once the reaction was stopped, sterols were extracted with chloroform and aliquots were applied on silica gel plates developed in benzene-acetone (4:1, v/v). Areas containing DHT were scraped and radioactivity was counted. The median inhibitory concentration (IC50) was determined by measuring the conversion of T to DHT The apparent Michaelis-Menten constant (Km) and Vmax values before and after adding D-004 were determined in kinetic studies using labeled T (0.5-25 μmol/L).
Compared with controls, D-004 significantly and dose-dependently inhibited the enzymatic reaction at doses of 1.95 to 125.0 μg/mL) (all, P < 0.05). The IC50 of D-004 required to inhibit 5a-reductase activity was 2.25 μg/mL. Enzyme inhibition was noncompetitive, since D-004 lowered the Vmax from 15.3 to 10.0 nmol DHT/min · mg−1 protein, while the Km (4.54 μmol/L) was almost unaffected.
D-004 dose-dependently and noncompetitively inhibited in vitro 5α-reductase activity in soluble fractions of rat prostate. Although the extent of the maximal inhibition was high and the value of IC50 was low, the relevance of such inhibition requires further study in vivo.
D-004, free fatty acids, prostate hyperplasia, prostate 5α-reductase inhibitors
In vitro effect of D-004, a lipid extract of the fruit of the cuban royal palm (Roystonea regia), on prostate steroid 5α-reductase activity
L. Yohani Perez, PharmD,* Roberto Menendez, PhD, Rosa Ma, PhD, and Rosa M. Gonzalez, BS
Policosanol is a mixture of long-chain primary aliphatic alcoholspurified from sugar cane wax that has cholesterol lowering and antiplatelet effects. Omega-3 fatty acids (FA) have triglyceride lowering and antiplatelet effects. Combination treatment with policosanol and omega-3 FA (Ω23FA) has been associated with significant inhibition of platelet aggregation in rabbits compared with either drug alone.
The aim of this study was to investigate the effects of combination treatment with Ω3FA (1 g/d) and policosanol (Ω3FA+Poli) compared with Ω3FA (1 g/d) plus placebo (Ω3FA+Pla) on platelet aggregation in human patients with hypercholesterolemia.
This randomized, double-blind, clinical study at the Surgical Medical Research Center (Havana City, Cuba) recruited outpatients from lipid clinics, with some atherosclerotic risk factors. Outpatients of both sexes aged 20 to 75 years with serum total cholesterol (TC) levels ≥5 and <6 mmol/L were eligible to enroll. They were included in the study at the end of a 4-week diet stabilization period if their platelet aggregation to arachidonic acid (AA) was ≥50% and serum TC level remained ≥5 mmol/L. Patients were then evenly randomized to receive Ω3FA (1 g/d) + placebo or Ω3FA (1 g/d) + policosanol (10 mg/d) to be taken PO with the evening meal for 21 days. Treatment was assigned according to a randomization code using balanced blocks and a 1:1 allocation ratio. Inhibition of platelet aggregation to AA was the primary efficacy variable, while effects on platelet aggregation to collagen and epinephrine and on lipid profile were secondary variables. Drug compliance and adverse events (AEs) were monitored. Tolerability was assessed using physical examinations and laboratory test results.
Sixty-four subjects were initially enrolled. Fifty-four patients (30 women, 24 men; mean [SD] age, 58.4  years, [range, 40-70 years]) met the inclusion criteria and were randomized to treatment; 2 groups of 27. After 21 days, platelet aggregation to AA was significantly inhibited in the 2 groups. Ω3FA+Poli inhibited platelet aggregation to all agonists by ≥20%. Platelet aggregation to AA 1.0 and 1.5 mM was inhibited with combination treatment (39.6% and 33.9%, respectively; both P < 0.001 vs baseline; P < 0.001 and P < 0.01, respectively, vs Ω3FA+Pla) and with Ω3FA+Pla (11.0% and 13.3%; both, P < 0.001). Combination treatment was more effective in inhibiting platelet aggregation to AA 1.0 and 1.5 mM in 28.6% (P < 0.001) and 20.6% (P < 0.01), respectively. Platelet aggregation to collagen 1 μg/mL was significantly inhibited with combination treatment and with Ω3FA+Pla compared with baseline (43.2% and 15.1%, respectively; both, P < 0.001), but the effects of combination treatment were significantly greater (P < 0.01). Platelet aggregation to epinephrine 0.1 mM was inhibited with Ω3FA+Poli and Ω3FA+Pla (34.8% and 20.1%; both, P < 0.001), with similar results for both groups. Bleeding time did not change significantly for either group and Ω3FA+Pla did not significantly change the lipid profile. Combination treatment did significantly reduce levels of low-density lipoprotein cholesterol (LDL-C) (17.4%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla) and TC (10.1%; P < 0.001 vs baseline, P < 0.05 vs Ω3FA+Pla), increase high-density lipoprotein cholesterol (HDL-C) levels (18.0%; P < 0.001 vs baseline), but did not significantly change triglyceride levels. Three patients (2 from the Ω3FA+Poli group and 1 from the Ω3FA+Pla group) withdrew from the trial, though none were due to AEs. Two patients receiving combination treatment reported mild AEs (headache). All treatments were well tolerated.
In these patients, policosanol (10 mg/d) administered concomitantly with Ω3FA (1 g/d) enhanced the inhibition of platelet aggregation to AA and collagen, but not to epinephrine, compared with Ω3FA+Pla, without significantly affecting bleeding time. Concomitant treatment was also associated with reduced levels of LDL-C and TC and raised HDL-C levels. All treatments were well tolerated.
policosanol, omega-3 fatty acids, platelet aggregation, antiplatelet drugs, cholesterol-lowering drugs
Effects of combination treatment with policosanol and omega-3 fatty acids on platelet aggregation: A randomized, double-blind clinical study
Gladys CastaNo, PhD,1 Maria L. Arruzazabala, PhD,2 Lilia Fernandez, PhD,2 Rosa Mas, PhD,2,** Daisy Carbajal, PhD,2 Vivian Molina, PhD,2 Jose Illnait, PhD,1 Sarahi Mendoza,1 Rafael Gamez, PhD,1 Melbis Mesa,1 and Julio Fernandez, PhD2
D-004, a lipid extract of the fruit of Roystonea regia, contains a mixture of fatty acids—mainly oleic, lauric, palmitic, and myristic acids, with oleic acid being among the most abundant—that has been found to reduce the risk for prostatic hyperplasia (PH) induced with testosterone (T) in rats. The pharmacokinetic profile of D-004 has not been reported.
The objective of this study in rats was to assess plasma levels, tissue distribution, and excretion of total radioactivity (TR) after single-dose administration of oral D-004 radiolabeled with (3H)-oleic acid, as a surrogate for the pharmacokinetics of D-004.
This experimental study was conducted at the Pharmacology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. Single doses of suspensions of (3H)-oleic acid 0.16 μCi/mg mixed with D-004 400 mg/kg (radioactive dose/animal 7.2 μCi) were given orally to male Wistar rats weighing 150 to 200 g assigned to the treated or control group. Three rats were euthanized at each of the following times: 0.25, 0.5, 1, 1.5, 2, 4, 8, 24, 48, 72, 96, and 144 hours after study drug administration. After administration, the rats euthanized at the last experimental time point were housed individually in metabolism cages. Urine and feces samples were collected daily. At each time point, blood samples were drawn and plasma samples were obtained using centrifugation. After euthanization, tissue samples (liver, lungs, spleen, brain, kidneys, adipose tissue, muscle, stomach, small and large intestines, adrenal glands, heart, testes, prostate, and seminal vesicles) were quickly removed, washed, blotted, and homogenized. Plasma (100 μL), tissue aliquots (100 mg), feces (10 mg), and urine (100μL) were dissolved and TR was measured. Samples were assayed in duplicate. Results were expressed in μgEq of radio-labeled oleic acid per milliliter of plasma or urine or gram of tissue or feces. Plasma, tissue, feces, and urine samples of rats that did not receive (3H)-oleic acid were used as controls. Excretion was expressed as the percentage of the radioactivity excreted via each route with respect to the total radioactive dose administered to each rat.
A total of 50 rats were included in the experiment (mean age, 4 weeks; mean weight, 310 g). Absorption was rapid; mean Cmax was 195.56 (31.12) μgEq/mL, and mean Tmax was 2 hours. Thereafter, a biphasic decay of TR was found: a rapid first phase (t1/2α, 1.33 hours), followed by a slower second elimination phase (t1/2β, 36.07 hours). Radioactivity was rapidly and broadly distributed throughout the tissues, with more accumulating in the prostate than elsewhere. In the first 8 hours, accumulation of TR was greatest in the prostate, followed by the liver, small intestine, and plasma. Subsequently, TR increased in the small intestine, while it decreased in the liver and plasma. In contrast, over the periods of 24 and 144 hours after administration, TR increased in the adipose tissue, while it decreased in the other tissues and plasma. During those intervals, TR was greatest in the prostate, followed by adipose tissue. Mean peak radioactivity in the prostate (562.41 μgEq/g) was reached at 4 hours and decreased slowly thereafter. The prostate had the highest values of t1/2β and cumulative AUC compared with the other tissues and plasma. Mean (SD) TR was similar in feces (33.48% [4.90%]) and urine (28.96% [5.32%]), with total excretion being 62.40% (5.90%) of the administered dose.
In this experimental study, after single-dose administration of oral D-004 radiolabeled with (3H)-oleic acid in rats, TR was rapidly and widely distributed across the tissues, with the prostate having the highest accumulation of radioactivity. Excretion of TR was limited, with similar amounts being excreted in feces and urine. The broad distribution of radiolabeled oleic acid and/or its metabolites suggests (SD) pharmacokinetic rationale for the effectiveness of D-004 in reducing the risk for PH induced with T in rats.
oleic acid pharmacokinetics, D-004, Roystonea regia lipid extract, royal palm lipid extract
Plasma levels, tissue distribution, and excretion of radioactivity after single-dose administration of (3H)-oleic acid added to D-004, a lipid extract of the fruit of Roystonea regia, in rats
L. Yohani Perez, PhamD,* Roberto Menendez, PhD, Rosa Mas, PhD, and Rosa M. Gonzalez, BS