Effect of D-004, a lipid extract from the Cuban royal palm fruit, on in vitro and in vivo effects mediated by alpha-adrenoceptors in rats.

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 alpha1-adrenoceptors.

Methods: In vitro effects were investigated by adding D-004 (125-500 microg/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 microg/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 microg/kg) [0.1mL/100g], with 5 minutes' interval between doses.

Results: D-004 and Saw palmetto (125-500 microg/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 microg/mL) were weaker (p < 0.05) than in preparations containing Saw palmetto (500 microg/mL). At 125 microg/mL, D-004 inhibited the contractions induced by NA 1 and 32 x 10(-6) mol/L by 70.8% and 28.5%, respectively, and Saw palmetto by 56.2% and 10.7%, respectively. At 500 microg/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) microg/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 microg/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 microg/kg) but not with high doses (2 and 4 microg/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 alpha1-adrenoceptors deserves further investigation, including comparative studies versus specific defined alpha1-adrenoceptor antagonists.