EFFECTS OF D-005, A LIPID EXTRACT FROM COROJO PALM (Acrocomia crispa) FRUITS, ON α 1-ADRENOCEPTORS MEDIATED RESPONSES
AMBAR OYARZÁBAL YERA
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
VIVIAN MOLINA CUEVAS *
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
ROSA MAS FERREIRO
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
YAZMÍN RAVELO CALZADO
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
YOHANI PÉREZ GUERRA
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
ROXANA SIERRA
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
VICTOR GONZÁLEZ CANAVACIOLO
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
SONIA JIMÉNEZ DESPAIGNE
Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba
*Author to whom correspondence should be addressed.
Abstract
Enhanced stimulation of bladder and prostatic α1-adrenoreceptors (α1-ADR) triggers lower urinary tract symptoms. Phenylephrine (PHE) induces α1-ADR-mediated smooth muscle contractions In vitro and urodynamic dysfunction in rats. Extracts from saw palmetto and Roystonea regia fruits antagonize α1-ADR responses. Effects of Acrocomia crispa (AC), an endemic Cuban palm, are unexplored. This study investigates the effects of D-005, a lipid extract of AC fruits, on PHE-induced contractions in vas deferens and PHE-induced contractions urodynamic dysfunction in rats. In vitro study: Preparations of rat vas deferens were incubated with Tyrode´s solution (control), tamsulosin 0.1 mg/mL or D-005 (125-500 mg/mL). Contractions were induced with PHE (1 x10-6 - 3x10-4 mol/L) or KCl (50 mmol/L). In vivo study: Rats were randomized into a negative vehicle control and seven PHE (5 mg/kg)-injected groups: positive control, D-005 (5, 25, 50, 200, 400 mg/kg) and tamsulosin (0.4 mg/kg). Volume voided per micturition (VM) and urinary total volumes (UTV) were measured. Tamsulosin inhibited PHE-induced contractions and did not change KCl-induced contractions. D-005 (250 and 500 μg/mL, not 125 mg/mL) inhibited significantly and markedly contractions to all PHE concentrations and modestly KCl-induced contractions. PHE lowered significantly VM and UTV in positive controls versus the negative control group. Tamsulosin increased VM (78%) and UTV (78%) versus the positive control group. D-005 (25 - 800 mg/kg, not 5 mg/kg) increased significantly and dose dependently VM versus the positive control. All doses increased significantly UTV. In conclusion, D-005 inhibited PHE-induced contractions in vas deferens of rats and ameliorated PHE-induced urodynamic dysfunction in rats, thus antagonizing α1-ADR-mediated responses.
Keywords: D-005, Acrocomia crispa, vas deferens, lower tract urinary symptoms, α1-adrenoreceptors, phenylephrine responses