Chenopodium ambrosioides induces an endothelium-dependent relaxation of rat isolated aorta.

OBJECTIVE: This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action. METHODS: The vasorelaxant effect and the mode of action of various extracts from the leaves of C. ambrosioides were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, ethyl acetate and methanol fractions were analyzed, using thin-layer chromatography and high-performance liquid chromatography techniques, for their polyphenolic content. RESULTS: The various active extracts of C. ambrosioides at four concentrations (10-3, 10-2, 10-1 and 1 mg/mL) relaxed the contraction elicited by phenylephrine, in a concentration-dependent manner. This effect seems to be endothelium-dependent, since the vasodilatory effect was entirely absent in denuded aortic rings. The vasorelaxant effect of the methanol fraction (MF) of C. ambrosioides at 1 mg/mL was also inhibited by atropine and tetraethylammonium. This effect remained unchanged by Nω-nitro-l-arginine methyl ester hydrochloride and glibenclamide. The preliminary phytochemical analysis showed that the leaves of C. ambrosioides are rich in phenolic and flavonoid derivatives. CONCLUSION: These results suggest that the MF of C. ambrosioides produces an endothelium-dependent relaxation of the isolated rat aorta, which is thought to be mediated mainly through stimulation of the muscarinic receptors, and probably involving the opening of Ca2+-activated potassium channels.

Antihypertensive and vasorelaxant effects of aqueous extract of Artemisia campestris L. from Eastern Morocco.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. AIM OF THE STUDY: This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated. MATERIAL AND METHODS: the chemical content of AcAE was determined by using HPLC and NMR techniques. The antihypertensive effect was assessed indirectly by tail-cuff method on L-NAME induced hypertensive rats, while the hypotensive action was monitored intravenously by invasive method on normotensive rats. The vasorelaxant effect and vascular mechanism of action were studied in the presence of antagonists and blockers on aorta isolated from normotensive rats. On the other side, the acute toxicity was studied by oral feeding of extract to the mice. RESULTS: The global phytochemical profile of AcAE reveals the presence of several polyphenols as main components. A. campestris L. infusion was characterized by mono- and di-cinnamoyl compounds, with 3,5-dicaffeoylquinic (isochlorogenic A) acid being the main compound, followed by 5-caffeoylquinic (chlorogenic) acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant compound among flavonoids. The daily treatment with AcAE at 150mg/kg/day prevented the installation of hypertension on L-NAME hypertensive rats, and reduced SBP from 172mmHg up to 144mmHg. At the dose 40mg/kg, AcAE provoked reduction of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), without affecting the heart rate. Also, AcAE (10-2-2mg/ml) relaxed the precontracted aorta by 95.8±1.3%. The denudation and preincubation of aorta with atropine, calmidazolium, L-NAME, hydroxycobalamin, ODQ, 8-RP-Br-PET-cGMP, thapsigargin and verapamil attenuated the vasorelaxant response, while the pre-treatment with 4-AP, TEA, glibenclamide and BaCl2 did not alter this effect. The oral administration of AcAE (0-6g/kg) reveals no mortality or toxicity. CONCLUSIONS: our study proved that AcAE possess an important antihypertensive, hypotensive and vasorelaxant effect, which is mediated via calmodulin-NO-cGC-PKG pathway, and via inhibition of calcium influx through voltage-operated calcium channels and activation of intracellular calcium mobilization into sarcoplasmic reticulum. Therefore, our findings give first evidence about the traditional use of A. campestris L. as antihypertensive plant.

Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive.

BACKGROUND: Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day). METHODS: Treatment with L-NAME alone caused a progressive increase in SBP. After 4 weeks, the value of SBP reached 160±2mmHg which shows the installation of hypertension. Enalapril prevented the increase in SBP, which remained normal at 123±1mmHg after 4 weeks of treatment. The administration of MeOH-extract along with L-NAME prevented the increase in SBP as well, which remained constant at 115±1mmHg after 4 weeks of treatment. In ex-vivo models, MeOH-extract produced a relaxation of pre-contracted ring aorta (54 ± 2% of relaxation at 3g/L). But, when the rings were denuded, MeOH-extract failed to relax pre-contracted rings of aorta. Phytochemical study of I. viscosa MeOH-extract revealed the presence of phenolic compounds, such as cynarin and chlorogenic acid. RESULTS: The present results suggest that I. viscosa MeOH-extract has an antihypertensive, predominantly mediated by an endothelium-dependent vasodilatory effect. Cynarin and chlorogenic acid, which have a strong vasorelaxant effect may be involved in the antihypertensive effect of the plant extract. The bioinformatic POM analysis confirms the therapeutic potential of cynarin and chlorogenic acids as inhibitors of various biotargets. Based on the results, the coordination of these phytochemicals with calcium and transition metals should be studied, for better scope at antihypertensive drug development.

Platelet anti-aggregant property of some Moroccan medicinal plants.

It is known that blood platelets may present some dysfunction linked to cardiovascular pathologies such as arterial hypertension. The aim of this work is to examine the in vitro anti-aggregant effect of five medicinal plants among which three were reported as antihypertensive in oriental Morocco: Arbutus unedo (Ericaceae), Urtica dioïca (Urticaceae), and Petroselinum crispum (Apiaceae). The two other plants were Cistus ladaniferus (Cistaceae) and Equisetum arvense (Equisetaceae). The results obtained showed that all extracts produced a dose-dependent inhibition of thrombin and ADP-induced aggregation. The calculated IC50 (half-maximal inhibition of thrombin and ADP-induced aggregation) was found to be identical in all plant extracts while Urtica dioïca had a higher IC50 value. The effect of plants could be related in part to the polyphenolic compounds present in their extracts suggesting their involvement in the treatment or prevention of platelet aggregation complications linked to cardiovascular diseases. Phytochemical separation must be carried out to identify the active principles responsible for the anti-aggregant effect and elucidate their mechanisms of action.

Hypotensive property of Chenopodium ambrosioides in anesthetized normotensive rats.

BACKGROUND: The leaves of Chenopodium ambrosioides L. (Chenopodiaceae) are widely used in Moroccan traditional medicine to treat diabetes and hypertension. The goal of the present work is to investigate the hypotensive properties of different extract and fractions of the plant in anesthetized normotensive rats and to elucidate the mechanism underlying this effect. METHODS: The hypotensive effect of aqueous extract (AqE) of the leaves of C. ambrosioides L., methanolic (MF), ethyl acetate (AcF), and aqueous (AqF) Soxhlet fractions, administrated intravenously, was evaluated in anesthetized rats. The recorded signals of blood pressure and heart rate were visualized and analyzed by using an acquisition card "National Instrument" and software Labview 6.1. RESULTS: Intravenous administration of AqE of the leaves of C. ambrosioides L. induces a dose-dependent hypotension. A similar effect was obtained with MF, AcF, and AqF. Atropine (1 mg/kg), used to block cholinergic system, significantly reduced the hypotensive response to MF and AcF suggesting the presence of the cholinomimetic-muscarinic components in these fractions. However, the blood pressure lowering effect of MF and AcF in rats pretreated with L-NAME 20 mg/kg was unchanged showing that the release of NO is not implicated in the hypotensive action of this plant. CONCLUSIONS: The present study demonstrates that extracts from leaves of C. ambrosioides induce hypotensive effect that may be partially associated with its cardiac effects. These results may partly explain the traditional use of leaves of C. ambrosioides L. for the treatment of disorders such as hypertension.

Epidemiology of hypertension and its relationship with type 2 diabetes and obesity in eastern Morocco.

The major objectives of this work are to estimate the hypertension (HT) frequency in the east of Morocco and to study the relationship between HT, type 2 diabetes and obesity. Our sample is composed of 1628 adults aged 40 years and older, recruited voluntarily by using the convenience sampling method through 26 screening campaigns in urban and rural areas of the east of Morocco. We enumerated 516 hypertensive people (31.7%), without significant difference between women (32.5%) and men (30.2%). The known hypertensive people represent 10.1% of the whole sample. The frequency of HT, increases with age and it is more marked in rural (39.9%) than in urban areas (29%) (p < 0.001). It is significantly very high in diabetic subjects (69.9%) than among the non-diabetic ones (27.4%) (p < 0.001). The odd ratio (OR) of the diabetics to HT is 6.16 (IC95% [4.33-8.74]). Among the obese persons, HT is present at (40.8%) vs. (30.2%) among the subjects of normal weight (p < 0.05). The OR of the obese to HT is 1.6 (IC95% [1.26 - 2.04]). In conclusion, our results show a high frequency of HT in the east of Morocco; it affects nearly one third of the adult population aged 40 years and older. The relations between type 2 diabetes and obesity have also been identified and estimated.

Anti-diarrhoeal activity of crude aqueous extract of Rubia tinctorum L. roots in rodents.

The anti-diarrhoeal effect of aqueous extract of Rubia tinctorum L. (Rubiaceae) roots in rodents was examined. At doses 300, 600 and 800 mg/kg aqueous extract protected rats, in a dose-dependent fashion, against castor oil-induced diarrhoeal dropping by 37, 59 and 64% respectively. Furthermore, it has significantly inhibited by 41% the gastrointestinal transit of charcoal in mice at 800 mg/kg dose of extract. These data suggest that Rubia tinctorum showed antidiarrhoeal activity by inhibiting intestinal motility which was concordant with its use in traditional medicine.