Evaluation Of The Cardiovascular Activity And Toxicity Study Of Alstonia Scholaris Bark Extracts

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Date
2016-03
Authors
Bello, Idris
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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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Cardiovascular
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