title: Possible mechanisms of action of the aqueous extract of Artocarpus altilis (breadfruit) leaves in producing hypotension in normotensive Sprague-Dawley rats.
abstract: OBJECTIVE
  Artocarpus altilis (Parkinson) Fosberg (Moraceae) (breadfruit) leaves are used as an antihypertensive remedy. We investigated the possible mechanisms of action of its aqueous extract and its effect on cytochromes P450 (CYP) enzyme activities.
  
  
  METHODS
  Intravenous administration of an aqueous leaf extract (20.88-146.18 mg/kg) of A. altilis on mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized normotensive Sprague-Dawley rats. Recordings of the contractile activity of the aortic rings to the extract (0.71-4.26 mg/mL) were studied using standard organ bath techniques. Inhibitions of human CYP3A4 and CYP2D6 enzyme activities were evaluated by means of a fluorometric assay in 96 well plates using heterologously expressed microsomes.
  
  
  RESULTS
  A. altilis caused significant (p < 0.05) hypotensive and bradycardiac responses unaffected by atropine (2 mg/kg) and mepyramine (5 mg/kg), but attenuated by propranolol (1 mg/kg) and N(G)-nitro-L-arginine methyl ester (5 mg/kg). The extract (0.71-4.26 mg/mL) significantly (p < 0.05) relaxed phenylephrine (10⁻⁹-10⁻⁴ M) and 80 mM KCl-induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca²⁺ dose-response curves in Ca²⁺-free Kreb's solution. Moderate inhibitions of cytochrome P450s (CYP3A4 and CYP2D6) enzyme activities with IC₅₀ values of 0.695 ± 0.187 and 0.512 ± 0.131 mg/mL, respectively, were produced.
  
  
  CONCLUSIONS
  A. altilis exhibits negative chronotropic and hypotensive effects through α-adrenoceptor and Ca²⁺ channel antagonism. Drug adversity effects are unlikely if the aqueous leaf extract is consumed with other medications reliant on CYP3A4 and CYP2D6 metabolism. This study thus provides scientific evidence for the use of the breadfruit in the treatment of hypertension.
authors: Department of Basic Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica. chukwuemeka.nwokocha@uwimona.edu.jm
authors: Chukwuemeka R
authors: CR
authors: Nwokocha
authors: Daniel U
authors: DU
authors: Owu
authors: Michca
authors: M
authors: McLaren
authors: JeAnn
authors: J
authors: Murray
authors: Rupika
authors: R
authors: Delgoda
authors: Karen
authors: K
authors: Thaxter
authors: Garsha
authors: G
authors: McCalla
authors: Lauriann
authors: L
authors: Young
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D031622:Artocarpus / Q000737:chemistry*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D020834:Ethnopharmacology; D006801:Humans; D066298:In Vitro Techniques; D007563:Jamaica; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; D014665:Vasodilator Agents; D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human; D019389:Cytochrome P-450 CYP2D6