Abdelkhaleq Legssyer

Phytotherapy of hypertension and diabetes in oriental Morocco

In order to select the main medicinal plants used in folk medicine to treat arterial hypertension and/or diabetes, a survey was undertaken in different areas of oriental Morocco. The patients (370 women and 256 men) were divided into three groups: diabetics (61%), hypertensives (23%) and hypertensive diabetic persons (16%). On average, 67.51% of patients regularly use medicinal plants. This proportion is perceptibly the same in all groups and does not depend on sex, age and socio-cultural level. This result shows that phytotherapy is widely adopted in northeastern Morocco. For diabetes, 41 plants were cited, of which the most used were Trigonella foenum-graecum L. (Leguminosae), Globularia alypum L. (Globulariaceae), Artemisia herba-alba Asso. (Compositae), Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) and Tetraclinis articulata Benth. (Cupressaceae). In the hypertensions therapy 18 vegetal species were reported, of which the most used were Allium sativum L. (Liliaceae), Olea europea L. (Oleaceae), Arbutus unedo L. (Ericaceae), Urtica dioica L. (Urticaceae) and Petroselinum crispum A.W. Hill (Apiaceae). Among the 18 species used for hypertension, 14 were also employed for diabetes. Moreover, these two diseases were associated in 41% of hypertensives. These findings suggest that hypertension observed in this region would be in a large part related to diabetes.

Antihyperglycemic activity of the aqueous extract of Urtica dioica.

When administered 30 min before glucose loading, the aqueous extract of Urtica dioica (nettle) (250 mg/kg) showed a strong glucose lowering effect. The decrease of glycemia has reached to 33+/-3.4% of the control value 1 h after glucose loading. This effect was persistent during 3 h. In contrast, nettle did not show hypoglycemic effect in alloxan-induced diabetic rats. The amount of glucose absorbed in a segment jejunum in situ was 8.05+/-0.68 mg in presence of nettle extract vs. 11.11+/-0.75 mg in control rats during 2 h (P<0.05). The results indicate that nettle has a significant antihyperglycemic effect in OGTT model. This effect may be caused in part by the reduction of intestinal glucose absorption. LD(50) is 3.5 g/kg (i.p.).

Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats

Many cardiovascular diseases are associated with an increase in blood platelet activity. In Morocco, parsley (Petroselinum crispum, Apiaceae) is one of the medicinal herbs used to treat cardiovascular diseases such as arterial hypertension. In this study, crude aqueous extract (CAE) of parsley was evaluated for its anti-platelet activity in experimental animals on platelet aggregation in vitro and ex vivo; and on bleeding time in vivo. The in vitro aggregation was monitored after pre-incubation of platelets with CAE. The bleeding time and ex vivo aggregation were performed after oral treatment. CAE inhibited dose dependently platelet aggregation in vitro induced by thrombin, ADP, collagen and epinephrine. The oral administration of CAE (3g/kg) inhibited significantly (p<0.001) platelet aggregation ex vivo and prolonged bleeding time (p<0.001) without changes in the platelet amount. The prolongation of bleeding time by CAE may be attributed to the observed inhibition of platelet aggregation. These effects could be related in part to the polyphenolic compounds present in the extract. These results support the hypothesis that the dietary intake of parsley may be benefit in the normalization of platelet hyperactivation, in the nutritional prevention of cardiovascular diseases and are potentially interesting in the development of new prevention strategies.

Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I. Cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats

Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

Hypertensive effects of oral administration of the aqueous extract of Solanum torvum fruits in L-NAME treated rats: evidence from in vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE Solanum torvum fruits are commonly used in Cameroonian traditional medicine for treatment of arterial hypertension. It has been previously shown that intravenous administration of aqueous extract from dried fruits (AEST) reduced blood pressure. AIM The present work evaluates acute toxicity and effects of oral administration of AEST in chronic arterial hypertension induced by L-NAME. Effects of AEST were also evaluated on isolated aorta. MATERIALS AND METHODS AEST (200 mg/kg/day, p.o.) was given solely or concomitantly with L-NAME (40 mg/kg/day, p.o.) for 30 consecutive days. Animal body weight, systolic blood pressure and heart rate were measured before stating the treatment and at the end of each week. Urinary volume and urinary sodium and potassium contents were quantified before and at days 1, 15 and 30 of the treatment. Aorta from treated animals was tested for their sensitivity to noradrenaline and carbachol. Aorta from normal untreated rats was used to evaluate the in vitro vascular effect of AEST. RESULTS The results showed that AEST did induce neither mortality nor visible signs of toxicity. When given solely or in co-administration with L-NAME, AEST significantly reduced animals body weight. It amplified the hypertensive and cardiac hypertrophy effect of L-NAME and did not affect these parameters in normotensive animals. AEST increased the sensitivity to noradrenaline in normotensive and significantly reduced it in hypertensive animals. AEST significantly increased urinary volume and sodium excretion in L-NAME treated animals while reducing the sodium excretion in normotensive. In vitro, AEST induced a potent partial endothelium-dependent contraction of aortic ring; contractions that were partially antagonized by prazosin and verapamil and were not relaxed by carbachol. CONCLUSION These results suggest that oral chronic administration of AEST induced potentiation of arterial hypertension and cardiac hypertrophy in L-NAME treated rats. These effects may result from a reduction in sensitivity to vasorelaxant agents and increase in hypersensitivity to contractile factors. AEST possess potent in vitro vasocontractile activity that may result from activation of both alpha(1)-adrenergic pathway and calcium influx.

Prevention of Chemically Induced Diabetes Mellitus in Experimental Animals by Virgin Argan Oil

The argan tree plays an important socioeconomic and ecologic role in South Morocco. Moreover, there is much evidence for the beneficial effects of virgin argan oil (VAO) on human health. Thus, this study investigated whether administering VAO to rats can prevent the development of diabetes. VAO extracted by a traditional method from the almonds of Argania spinosa (2 mL/kg) was administered orally (for 7 consecutive days) to rats before and during intraperitoneal alloxan administration (75 mg/kg for 5 consecutive days). An alloxan diabetic‐induced untreated group and treated by table oil were used as control groups. Body mass, blood glucose and hepatic glycogen were evaluated. In the present study, subchronic treatment with VAO at a dose of 2 mL/kg, before the experimental induction of diabetes, prevented the body mass loss, induced a significant reduction of blood glucose and a significant increase of hepatic glycogen level (p < 0.001) compared with the untreated diabetic group. In conclusion, the present study shows that argan oil should be further investigated in a human study to clarify its possible role in reducing weight loss in diabetics, and even in inhibiting the development or progression of diabetes. This antidiabetic effect could be due to the richness of VAO in tocopherols, phenolic compounds and unsaturated fatty acids. Copyright

Antidiabetic effect of some medicinal plants of Oriental Morocco in neonatal non-insulin-dependent diabetes mellitus rats

The goal of the present study is to test the effect of water extract (WE) of four medicinal plants used as antidiabetics in Eastern Morocco (Arbutus unedo: Au, Ammoïdes pusilla: Ap, Thymelaea hirsuta: Th, and Urtica dioïca: Ud). These plants are used in cooking to bring out the flavor in a dish or to complement it. The first experiment was realized in order to determine the antidiabetic effect of the WE of these plants during 5 weeks’ treatment. Seven groups of Wistar rats were used: Healthy controls, neonatal streptozotocin (n-stz) induced-diabetic rats (90 mg/kg; intraperitoneally [i.p.]), n-stz + tolbutamide (400 mg/l), and 4 groups n-stz + WE of plants (400 mg/l, drink water). The percentages of Plasma glucose lowering effect were, respectively for Au, Ap, Th, Ud and tolbutamide: 31.6 % p<0.01, 27.4 % p<0.05, 38.2 % p<0.01, 13 % and 33.9 % p<0.05 when compared with untreated diabetic controls. In a second experiment, oral glucose tolerance tests were carried out in n-stz induced-diabetic rats. The i.p. administration of the water extract (WE) of Ap and Ud (150 mg/kg) 30 minutes before the glucose overload (2 g/kg) showed a significant reduction glycemia, respectively of 36 % at 60 min (p<0.05) and 50 % at 180 min (p<0.05) after glucose overload compared with controls. In contrast, the effect of WE of Au and Th (150 mg/kg, i.p.) was not significant. The in vitro study of glucose utilization by isolated rat hemidiaphragm suggests that these extracts in combination with insulin potentiate its activity and enhance the utilization of glucose. In conclusion, it seems that these plants possess antidiabetic activity.

Antihypertensive and endothelium-dependent vasodilator effects of aqueous extract of Cistus ladaniferus.

Cistus ladaniferus L. (Cistaceae) is a medicinal plant originated from the Mediterranean region which exerts different pharmacological effects. In the present study, our goal was to examine whether the plant possessed antihypertensive properties. Aqueous extract of Cistus leaves (AEC, 500mg/kg/day) reduced systemic blood pressure (SBP) in two animal models of hypertension, the l-NAME and renovascular two kidney-one clip (2K-1C) hypertensive rats. In the former, AEC prevented the increase in SBP when co-administered with l-NAME during four weeks (164+/-3mm Hg in l-NAME vs. 146+/-1mm Hg in l-NAME+AEC, p<0.001). In the latter, AEC reversed the increase in SBP when administered during four weeks after installation of the hypertension (146+/-5mm Hg with AEC vs. 179+/-6mm Hg without, p<0.05). AEC treatment also reversed the endothelial dysfunction observed in both animal models of hypertension. A direct effect on cardiac and vascular tissue was also tested by examining the contractile effects of AEC in rat isolated aortic rings and Langendorff perfused hearts. AEC (10mg/L) had no effect on left ventricular developed pressure and heart rate in isolated perfused heart. However, AEC produced a strong relaxation of pre-contracted rat aortic rings (80+/-2% relaxation, n=25). When the rings were denuded from endothelium or were incubated with 1mM Nomega-nitro-l-arginine (l-NNA), the relaxant effect of AEC was lost. We conclude that C. ladaniferus possesses antihypertensive properties which are mainly due to an endothelium-dependent vasodilatory action.

Effect of Argan Oil on Platelet Aggregation and Bleeding Time: A Beneficial Nutritional Property

Platelet hyperactivity is one of the most important factors responsible for thrombosis and incidence of cardiovascular diseases. In this study, we investigated the effect of argan oil (0.2, 0.5, 1 and 2 %) on blood platelet aggregation (in vitro and ex vivo) and on tail bleeding time (in vivo) on rats. The in vitro aggregation was monitored after pre-incubation of platelets with argan oil for one minute. The in vivo bleeding time and ex vivo aggregation were performed after 4 weeks of oral treatment (10 ml/Kg/day). Argan oil was found to possess a maximum inhibition of the in vitro (46.4±4.3 %) and ex vivo platelet aggregation induced by different agonists (43.4±5.51 %). The ex vivo aggregation inhibition was not accompanied by a change in the platelets amount, neither in the bleeding time (5.5±0.3 min). These results suggest that argan oil may probably act directly on the common and an ultimate step of aggregation: attachment of fibrinogen to GpIIb/IIIa platelet receptors without affecting platelet adhesiveness to the vascular endothelium. These findings give evidence that the dietary intake of argan oil may be beneficial in the normalization of platelet hyperactivation and in the nutritional prevention of cardiovascular diseases.

Antidiabetic Activity Assessment of Argania spinosa Oil

Background: Argan or Argania spinosa (L.) Skeels, of the family sapotaceae which is an endemic species of the western south Morocco is used for its antidiabetic activity in local traditional medicine. All the parts of the plants are used to prepare remedies against various diseases. Recently, some studies suggest that Argan oil could play a beneficial role in cardiovascular diseases prevention.Aim: The goal of the present work is to show more evidences of the antidiabetic activity of Argan oil extracted from the almonds of Argan tree.Methods: In a first experiment, we tested the antihyperglycemiant effect on oral glucose tolerance test in healthy rats and streptozotocin-induced diabetic rats (60 mg/kg). In the second subchronic study, we tested the effect of the repeated oral administration of Argan oil (2 ml/kg during 15 days) on streptozotocin-induced diabetic rats. Moreover, the effect of Argan oil on the intestinal glucose absorption was tested in a jejunum segment by the technique of the in situ perfusion.Results: In the OGTT experiment of healthy rats and diabetic rats, the intraperitoneal administration of Argan oil (2.5 ml/kg) 30 minutes before the oral glucose loading (1g/kg) induced a significant reduction of glycemia, at 60 minutes and the decrease was persistent until the end of experiments (180 min) when compared to controls. In the subchronic treatment, the results showed a significant improvement of body mass and a significant reduction of the glycemia (55 %, p<0.001) at the end of experiment, when compared with untreated diabetic rats. Moreover, Argan oil reduced significantly (19.3 %, p<0.05) the amount of absorbed glucose in perfused jejunum segment versus controls. This effect was less than that of acarbose (alpha-glucosidase inhibitor).Conclusion: The consumption of Argan oil as a traditional food has the potential to reduce hyperglycemia-induced pathogenesis. It also explains the basis for its traditional use by rural community of western south Morocco.