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Cardiovascular effects of mollic acid glucoside, a 1alpha-hydroxycycloartenoid saponin extractive from Combretum molle R Br ex G Don (Combretaceae) leaf.

ABSTRACT: The cardiovascular effects of mollic acid glucoside (MAG), a 1alpha-hydroxycycloartenoid saponin extractive from Combretum molle R Br ex G Don (Combretaceae) leaf, have been investigated in some experimental animal paradigms. The plant extract (MAG, 5-80 microg/ml) produced concentration-dependent, significant (p < 0.05-0.001) negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. MAG also significantly reduced (p < 0.05-0.001) or abolished, in a concentration-dependent manner, the rhythmic, spontaneous contractions of portal veins isolated from healthy, normal Wistar rats. Like acetylcholine (ACh, 10-(8)-10-(5) M), the plant extract (5-80 microg/ml) produced concentration-related relaxations of rat isolated endothelium-containing thoracic aortic rings pre-contracted with noradrenaline (NA, 10-10(-10)-(5) M). The vasorelaxant effects of MAG in the aortic rings were markedly inhibited or annulled by N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor. Furthermore, MAG (2.5-40 mg/kg iv) caused dose-related, transient but significant reductions (p < 0.05-0.001) in the systemic arterial blood pressures and heart rates of anaesthetised normotensive and hypertensive rats. The results of this laboratory animal study indicate that MAG caused bradycardia, vasorelaxation and hypotension in the mammalian experimental models used. The vasorelaxant action of MAG was endothelium dependent, and was therefore possibly dependent on the synthesis and release of nitric oxide (NO). The findings of this study suggest that Combretum molle leaf may be used as a natural supplementary remedy in essential hypertension and in certain cases of cardiac dysfunctions in rural African communities.

SUBMITTER: Ojewole JA

PROVIDER: S-EPMC3974560 | biostudies-literature | 2008 May-Jun

REPOSITORIES: biostudies-literature

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Cardiovascular effects of mollic acid glucoside, a 1alpha-hydroxycycloartenoid saponin extractive from Combretum molle R Br ex G Don (Combretaceae) leaf.

Ojewole J A JA

Cardiovascular journal of Africa 20080501 3

The cardiovascular effects of mollic acid glucoside (MAG), a 1alpha-hydroxycycloartenoid saponin extractive from Combretum molle R Br ex G Don (Combretaceae) leaf, have been investigated in some experimental animal paradigms. The plant extract (MAG, 5-80 microg/ml) produced concentration-dependent, significant (p < 0.05-0.001) negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectiv ...[more]

PMID: 18568171

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Project description:Background:Combretum micranthum (CM) (Combretaceae) is widely used in traditional medicine throughout West Africa for the treatment of diabetes, hypertension, inﬂammation, malaria and liver ailments. In our recent research we demonstrated that CM has nephroprotective potentials in diabetes mellitus, hypertension and renal disorders. However, to the best of our knowledge, no systematic study concerning its toxicity proﬁle has been reported. Aim of the study:The study carried out to evaluates the potential toxicity of the hydroalcoholic extract from leaves of the CM, through the method of acute and sub-chronic oral administration in rats. Materials and methods:During the acute toxicity study, male and female rats were orally administrated with CM extract at single doses of 5000 mg/kg (n = 5/group/sex). Abnormal behaviour, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. For sub-chronic toxicity study, the extract was administered orally at doses of 500 and 1000 mg/kg (n = 5/group/sex) daily to Wistar rats for 28 days. The general behaviour and body weight of the rats was observed daily. A biochemical, haematological, macroscopical and histopathological examinations of several organs were conducted at the end of the treatment period. The CM extract was subjected to Fourier transform infrared spectrophotometric examination in order to detect the presence or absence of cyanide toxic compounds. Results:The absence of absorbance peaks between the 2220-2260 cm-1 region of FT-IR spectrum of CM, indicating the absence of cyanide groups. This suggested that the CM extract may not contain toxic substances. During the acute toxicity test, no mortality or adverse effects were noted at the dose of 5000 mg/kg. In the subchronic study, the CM extract induced no mortality or treatment-related adverse effects with regard to body weight, general behaviour, relative organ weights, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. Conclusion:The present study revealed that oral administration of CM extract for 28 days, at dosage up to 1000 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the extract was estimated to be more than 5000 mg/kg.

Project description:BACKGROUND:Combretum molle R.B/G. Don (Combretaceae) is a graceful deciduous shrub, distributed especially in tropical Africa and used in traditional medicine in the treatment of malaria, diabetes, and bacterial, liver and cardiovascular deseases. To our knowledge, no long-term toxicity studies of C. molle has ever been realized yet. METHODS:The long-term toxicity study was conducted in accordance with OECD 408 guidelines with slight modifications. In fact, rats were divided in groups and treated orally with CMAE at doses of 62.5, 125 and 250?mg/kg for 6?months. The general behavior and signs of toxicity of the rats were daily observed. Body weight, food and water intake were recorded every 2?months for 6?months. At the end of treatment period, urine and blood samples were collected for hematological, biochemical and antioxidant estimations. Immediately, internal organs were collected and weighed. RESULTS:The results showed that no mortality and visible signs of the toxicity were recorded in all experimental animals. The administration of CMAE had no significant effects on body weight, organ weights, serum electrolyte, and food and water intake. However, all doses of CMAE produced an increase in high density lipoprotein cholesterol, white blood cells, platelets, glutathione, and a decrease in low density lipoprotein cholesterol and malondialdehyde rate. CMAE at doses of 125 and 250?mg/kg decreased in serum proteins and the activity of aspartate amino transferase, and increased the activity of catalase. In addition, CMAE (250?mg/kg) significantly decreased the alanine aminotransferase activity and the level of triglycerides, very low density cholesterol, total proteins and creatinine, and increased in renal clearance, red blood cells, hemoglobin, hematocrit and superoxide dismutase activity. CONCLUSIONS:At the end of this study, no signs of major intoxication was noted during 6?months of treatment. These results suggest that long-term consumption of CMAE at the therapeutic dose (250?mg/kg) presents low risks to human health.

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Dataset Information

Cardiovascular effects of mollic acid glucoside, a 1alpha-hydroxycycloartenoid saponin extractive from Combretum molle R Br ex G Don (Combretaceae) leaf.

Publications

Cardiovascular effects of mollic acid glucoside, a 1alpha-hydroxycycloartenoid saponin extractive from Combretum molle R Br ex G Don (Combretaceae) leaf.

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