Mechanisms underlying the antihypertensive effect of Alstonia scholaris

Bello, Isabelle Cenci di; Usman, Nasiba Salisu; Mahmud, Rohela; Asmawi, Mohd Zaini

doi:10.1016/j.jep.2015.09.031

Cited by 21 publications

(10 citation statements)

References 39 publications

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“…The antihypertensive mechanism of action of some plants has also been studied. Alstonia scholaris has been shown to have antihypertensive activity by inhibiting calcium ion channels [10].…”

Section: Introductionmentioning

confidence: 99%

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Sholikhah

Mustofa

Nugrahaningsih

et al. 2020

BioMed Research International

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The polyherbal formulation containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol ex. Maton has been used for hypertension treatment empirically. Our previous study showed its blood pressure-lowering effect on a rat model of hypertension. However, toxicity data were not available for this polyherbal formulation. This study is aimed at evaluating the acute and subchronic oral toxicity of the polyherbal formulation in rats. The acute toxicity study was conducted on 6 female Wistar rats using the fixed-dose method for the treatment group and 5 female Wistar rats for the control. The single dose of 2,000 mg/kg of the polyherbal formulation was given orally. There were no significant toxic effects and no death observed until the end of the study, and it was showed that the lethal dose 50% (LD50) of the polyherbal formulation was estimated to be more than 2,000 mg/kg. The macroscopic and microscopic examination of vital organs showed no symptoms of toxicity. At the subchronic toxicity study, the polyherbal formulation with 3 dose variations of 252 mg/kg, 1,008 mg/kg, and 4,032 mg/kg was administered for 91 days orally. The lowest dose of 252 mg/kg is equivalent to the daily recommended dose for a human. There were no significant toxic effects observed at all doses on physical sign and symptoms, weight gain, food intake, hematological parameters, biochemical parameters, and macroscopic and microscopic examination of organs. These findings showed that the short- and long-term oral administration of the polyherbal formulation is safe to use within its dose recommendation.

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“…The antihypertensive mechanism of action of some plants has also been studied. Alstonia scholaris has been shown to have antihypertensive activity by inhibiting calcium ion channels [10].…”

Section: Introductionmentioning

confidence: 99%

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Sholikhah

Mustofa

Nugrahaningsih

et al. 2020

BioMed Research International

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“…A. scholaris has been investigated for its anti-inflammatory, analgesic [ 5 ], antidiabetic, antihyperlipidemic [ 6 ], anti-malarial [ 7 ], and anti-microbial effects [ 8 ], in addition to it theraputic potential against other diseases. Boiled decoctions of this herb have been reported to treat several diseases, such as asthma, hypertension, lung cancer and pneumonia; and also as remedies for fever [ 9 , 10 , 11 ]. The present study evaluates the acute and subacute oral toxicity of the methanol extract of Alstonia scholaris in experimental animals.…”

Section: Introductionmentioning

confidence: 99%

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

et al. 2016

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Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD) rats. The methanolic extract of Alstonia scholaris stem bark (ASME) was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg) for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.). Histopathological studies revealed slight degeneration (lesion) and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg). The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

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“…Vasorelaxation assay was conducted as described by Bello et al. [ 15 ]. The SHR was immobilized in the carbon dioxide (CO 2 ) gas chamber and then exsanguinated.…”

Section: Methodsmentioning

confidence: 99%

“…2.6. Isolated rat thoracic aortic rings preparation and vasorelaxation study of V. pubescens extracts Vasorelaxation assay was conducted as described by Bello et al [15]. The SHR was immobilized in the carbon dioxide (CO 2 ) gas chamber and then exsanguinated.…”

Section: Antihypertensive Studymentioning

confidence: 99%

Antihypertensive activity and vascular reactivity mechanisms of Vitex pubescens leaf extracts in spontaneously hypertensive rats

Asmawi

Dewa

Mahmud

2020

Heliyon

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Background Vitex pubescens has been used traditionally in hypertension treatment but not yet scientifically assessed. The objective of the study is to investigate the antihypertensive and vasorelaxant activities of V. pubescens , study its underlying pharmacological mechanisms, and identify the relevant vasoactive compounds. Methods Successive extractions of V. pubescens leaf were carried out to produce petroleum ether (VPPE), chloroform (VPCE), methanol (VPME), and water (VPWE) extracts. Spontaneously hypertensive rats (SHRs) received a daily oral administration of the extracts (500 mg/kg/day; n = 6) or verapamil (15 mg/kg/day; n = 6) for 2 weeks, while the systolic and diastolic blood pressures were measured using non-invasive tail-cuff method. Vasorelaxation assays of the extracts were later conducted using phenylephrine (PE, 1 μM) pre-contracted aortic ring preparation. Mechanisms of vasorelaxation by the most potent fraction were studied using vasorelaxation assays with selected blockers/inhibitors. GC-MS was conducted to determine the active compounds. Results VPPE elicited the most significant diminution in systolic and diastolic blood pressure of treated SHRs and produced the most significant vasorelaxation in the aortic rings. Vasorelaxant effects of F2-VPPE were significantly reduced in endothelium-denuded aortic rings by glibenclamide (1 μM), whereas calcium chloride and PE-induced contractions were significantly suppressed. Endothelium removal of the aortic rings or incubation with indomethacin (10 μM), atropine (1 μM), methylene blue (10 μM), propranolol (1μM) and L-NAME (10 μM) did not significantly alter F2-VPPE-induced vasorelaxation. Seven compounds were identified using GC-MS, including spathulenol. Conclusion F2-VPPE exerted its endothelium-independent vasorelaxation by inhibition of vascular smooth muscle contraction induced by extracellular Ca +2 influx through trans-membrane Ca +2 channels and/or Ca +2 release from intracellular stores, and by activation of K ATP channels. The vasorelaxation effects of V. pubescens could be mediated by the compound, spathulenol.

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Mechanisms underlying the antihypertensive effect of Alstonia scholaris

Cited by 21 publications

References 39 publications

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

Antihypertensive activity and vascular reactivity mechanisms of Vitex pubescens leaf extracts in spontaneously hypertensive rats

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