Aqueous extract from leaf of Artocarpus altilis provides cardio-protection from isoproterenol induced myocardial damage in rats: Negative chronotropic and inotropic effects.
BACKGROUND
The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats.


METHODS
Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-h period. Blood pressure readings were taken before and after the administering of ISO using the tail cuff method. ECG was performed on anaesthetized rats. Cardiac contractility was measured in isolated right atrial muscles. Assessment of myocardial infarct (MI) size, heart/body weight ratio, biochemical, hematological and histo-morphological parameters were conducted at the end of seven days. An aqueous extract from leaves of A. altilis was analyzed for organic compounds using UHPLC mass spectrometry.


RESULTS
ISO induced myocardial damage through an elevation of the heart rate (HR), infarct size and ECG distortions. Treatment with AA significantly (p˂0.05) reduced heart/body weight ratio (49%), MI (96%), HR (27%), sympathovagal imbalance (36%) and serum cardiac biomarkers (AST, LDH, HDL, triglycerides and CCK) caused by ISO. AA decreased the beat frequency of isolated right atrium (11%) cause by ISO, an action similar to propranolol (beta-adrenergic antagonist; 20%), but showed no significant changes in the QTc intervals of the ECG (suggesting no cardio-toxic drug-herb interactions), Thirty nine compounds were detected using high resolution LC-MS analysis (HPLC-Orbitrap-APCI-MS) in the extract. Pure compounds, as gallic acid and rutin, presented a higher negative chronotropic effect, similar to propranolol.


CONCLUSIONS
Oral administration of aqueous extract of Artocarpus artilis has cardio-protective functions in myocardial injury, in part, by decreasing the HR, reduced contractility and infarct size. These findings may explain the cardio-protective use of A. altilis in traditional medicine.
Department of Basic Medical Sciences, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica.
Chukwuemeka
C
Nwokocha
Facultad de Ciencias de la Salud, Instituto de EtnoFarmacología (IDE), Universidad Arturo Prat, Chile. Electronic address: clpalaci@unap.cl.
Javier
J
Palacios
Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Casilla 567, Valdivia 5090000, Chile.
Mario J
MJ
Simirgiotis
Department of Basic Medical Sciences, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica.
Jemesha
J
Thomas
Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Jamaica.
Magdalene
M
Nwokocha
Department of Basic Medical Sciences, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica.
Lauriann
L
Young
Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Jamaica.
Rory
R
Thompson
Laboratorio de Fisiología Experimental (EPhyL), Instituto Antofagasta (IA), Universidad de Antofagasta, Antofagasta, Chile.
Fredi
F
Cifuentes
Laboratorio de Química Biológica, Instituto Antofagasta (IA), Universidad de Antofagasta, Antofagasta, Chile.
Adrian
A
Paredes
Natural Products Institute, University of the West Indies, Mona Campus, Jamaica.
Rupika
R
Delgoda
D000818:Animals; D031622:Artocarpus / Q000737:chemistry*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D041743:Herb-Drug Interactions; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D010936:Plant Extracts; D007545:Isoproterenol
Artocarpus altilis; Blood pressure; Electrocardiogram; Isoproterenol; Myocardial infarction; UHPLC