Evaluation Of The Cardiovascular Activity And Toxicity Study Of Alstonia Scholaris Bark Extracts
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Date
2016-03
Authors
Bello, Idris
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
The aim of the present study was to investigate the antihypertensive effect of Alstonia
scholaris (pulai) bark extracts and its pharmacological mechanism of actions. Successive
extraction was carried out to obtain methanol (ASME) and water (ASWE) extract of the bark
after defatting with petroleum ether. The antihypertensive effect of these extracts were
evaluated on spontaneous hypertensive rats (SHR). Daily oral administration of ASME (1000
mg/kg for 2 weeks) exhibited a significant decrease in the blood pressure (p < 0.05) of the
rats compared to control SHR. By means of liquid-liquid fractionation technique, the aqueous
ASME solution was successively fractionated using dichloromethane, ethyl acetate and nbutanol.
All the fractions (0.125 – 4 mg/mL) gave a dose-dependent vasorelaxation on aortic
ring preparations pre-contracted with phenylephrine (PE; 1 μM) or potassium chloride (80
mM). The n-butanol fraction (NBF-ASME) was the most potent fractions (Rmax = 106.4 ±
0.045 %). Pre-incubation of aortic rings with NBF-ASME (0.5, 1 and 2 mg/mL) significantly
inhibit the contractile response of the aortic rings to PE-induced contraction (p<0.05-0.001).
Removal of endothelium and incubation with L-NAME, indomethacin, atropine, and
propranolol did not significantly affect the relaxation effect of NBF-ASME. Furthermore, of
the K+ channel blockers, TEA showed slight inhibitory activity while glibenclamide showed
no inhibitory effect. However, aortic rings pretreated with ODQ showed a significant
suppression of the relaxation curve of NBF-ASME (p<0.01-0.001). In Ca2+-free solution,
NBF-ASME inhibits the release of intracellular Ca2+ from the sarcoplasmic reticulum. NBFASME
also inhibits CaCl2-induced contraction in endothelium-denuded aortic rings in a concentration-dependent manner. The result suggested that A. scholaris act via blocking
calcium channels, direct activation of soluble guanylate cyclase and possibly by also
inhibiting the formation of inositol 1, 4, 5-triphosphate. The acute and subacute toxicity of
methanol extract of A. scholaris (ASME) was also evaluated. In the acute toxicity study,
single dose of ASME 2,000 mg/kg was found to be non-toxic. In subacute toxicity study, SD
rats of either sex were administered three doses of ASME (250, 500 and 1000 mg/kg/day) for
28 days. ASME 250 mg/kg, did not produce any significant difference in all the parameters
when compared to control rats. Some significant changes in body weight, hematological and
biochemical parameters were observed in experimental groups of rats at the dose of 500 and
1000 mg/kg with two animals died at the highest dose. Histopathological study revealed
slight degeneration (lesion) and centrilobular necrosis in the liver. These results demonstrated
that daily oral administration of ASME at 500 mg/kg and above is toxic and may be fatal to
the animal primarily due to liver damage..
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Keywords
Cardiovascular