Larval Cytotoxic and Subacute Toxicity of Gardenia ternifolia, Rourea coccinea, and Cassytha filiformis Used in Traditional Medicine of Benin (West Africa).

The use of medicinal plants in traditional medicine is a common practice in developing countries. However, this unregulated or irrational use may pose a risk of toxicity to humans in the short and/or long term. Recent studies reported interesting ethnopharmacological, antioxidant, and phytochemical data on some medicinal plants used in the traditional treatment of male infertility in Benin. Unfortunately, very little data exist on the long-repeated dose toxicity of these medicinal plants. This study was aimed at evaluating the larval cytotoxicity and subacute toxicity of the hydroethanolic extract of Cassytha filiformis whole plant, Gardenia ternifolia roots, and Rourea coccinea leaves. The subacute toxicity of these plants was evaluated in male Wistar albino rats at three different doses (200, 400, and 800 mg/kg) according to the OECD 407 guidelines. Hematological and biochemical examinations and the histological study of the liver and kidneys were carried out. Larval cytotoxicity was assessed by the sensitivity of Artemia salina larvae to different concentrations of the studied plants extracts. The mean lethal concentration (LC50) was determined by the probit method. Subacute toxicity data indicated that there was no mortality or structural alterations of the liver and kidneys in the lot of treated animals. However, significant alterations in certain hematological and biochemical parameters (hematocrit, ASAT, and uremia) were noted. These abnormalities were observed in the lot of rats treated with Rourea coccinea and Cassytha filiformis extracts. Larval cytotoxicity data indicate that the studied plants extracts are not cytotoxic (LC50 > 0.1 mg/mL). These data suggest that the use in traditional medicine of studied plants at high doses and repeated over a long period of time requires special attention.

Moringa olifeira Lam. Stimulates Activation of the Insulin-Dependent Akt Pathway. Antidiabetic Effect in a Diet-Induced Obesity (DIO) Mouse Model.

We investigated the antidiabetic effect of Moringa olifeira Lam. in a diet-induced obesity (DIO) mouse model. Six mice were randomly selected as normal controls. Moringa olifeira Lam. leaf extract at a dose of 200, 400 or 600 mg/kg body weight, glibenclamide (Glib) at the dose of 10 mg/kg (positive control) and distilled water at 10 ml/kg (control group) were administered orally by gastric intubation, and each group consisted of six mice. Insulinsensitive tissues (liver, skeletal muscle) were collected to investigate antidiabetic effects and examine the plant's molecular mechanisms. Moringa olifeira Lam. leaf extract prevented weight gain. It also reduced blood glucose in DIO mice. Glib and Moringa olifeira Lam. leaf extract, 400 mg/kg, treatments restored insulin levels towards normal values (P < 0.05 versus diabetic control group). Western immunoblot analysis of different tissues, collected at the end of the study, demonstrated that Moringa olifeira Lam. stimulated activation of the insulin-dependent Akt pathway and increased the protein content of Glut 4 in skeletal muscle. The improvement of hepatic steatosis observed in DIO-treated mice was associated with a decrease in the hepatic content of SREBP-1, a transcription factor involved in de novo lipogenesis. The hepatic PPARα protein content in the plant extract- treated mice remained significantly higher than those of the control group (P < 0.05). In conclusion, this study provides the first evidence for direct action of Moringa olifeira Lam. on pancreatic ß-cells, enhancing glucose-stimulated insulin secretion. This correlated with hypoglycaemic effects in diabetic mice associated with restored levels of plasma insulin.

Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

[Contribution of ATP-dependent potassium channels, nitric oxide and prostaglandins in increase of diaphgram arteriolar blood fow during diaphgram contraction]. / Contribution des canaux potassiques ATP-dépendant, du monoxyde d'azote et des prostaglandines dans l'augmentation du débit artériolaire lors de la contraction du diaphragme.

ATP-sensitive potassium (K(ATP)) channels and nitric oxide (NO) have been suggested to contribute in mediating active hyperemia in diaphragm. However, no data is available in the current literature concerning their comparative contributions to arteriolar dilation during muscle contraction. The aim of this study was therefore to examine, by video microscopy in rats, the effects of superfusing the muscle with Krebs solution alone (group C), or Krebs solution containing either glybenclamide (3mdeltaM, a blocker of K(ATP), group GLY), or Nwdelta-nitro-L-arginine (300 mdeltaM, a NO synthase inhibitor, group NNA), or mefenamic acid (50 mdeltaM, a prostaglandin synthesis inhibitor, group MA) on second and third order of diaphragm (A2 and A3 respectively) arteriolar dilation elicited by 3 min muscle stimulation (40 Hz, train duration: 300 milliseconds, 90 cycles per min). In group C, A2 diameters increased by 67.5 +/- 1.9% referring to baseline at the end of the stimulation. This increase was significantly reduced in groups GLY and NNA (16.7 +/- 2.5% and 47.3 +/- 2.2% respectively, p < 0.001 as compared to group C) and was more important in group GLY than in group NNA (p < 0.001). By contrast, no difference in post-contraction diameter was observed between groups C and MA. Similar results were observed in A3 vessels. These results indicate that K(ATP) are more important mediators of functional diaphragm arteriolar dilation in rat than NO, whereas prostaglandins are not involved in this phenomenon.

Modulation of adipokines and cytokines in gestational diabetes and macrosomia.

CONTEXT/OBJECTIVE: Not much is known about the implication of adipokines and different cytokines in gestational diabetes mellitus (GDM) and macrosomia. The purpose of this study was to assess the profile of these hormones and cytokines in macrosomic babies, born to gestational diabetic women. DESIGN/SUBJECTS: A total of 59 women (age, 19-42 yr) suffering from GDM with their macrosomic babies (4.35 +/- 0.06 kg) and 60 healthy age-matched pregnant women and their newborns (3.22 +/- 0.08 kg) were selected. METHODS: Serum adipokines (adiponectin and leptin) were quantified using an obesity-related multiple ELISA microarray kit. The concentrations of serum cytokines were determined by ELISA. RESULTS: Serum adiponectin levels were decreased, whereas the concentrations of leptin, inflammatory cytokines, such as IL-6 and TNF-alpha, were significantly increased in gestational diabetic mothers compared with control women. The levels of these adipocytokines were diminished in macrosomic babies in comparison with their age-matched control newborns. Serum concentrations of T helper type 1 (Th1) cytokines (IL-2 and interferon-gamma) were decreased, whereas IL-10 levels were significantly enhanced in gestational diabetic mothers compared with control women. Macrosomic children exhibited high levels of Th1 cytokines and low levels of IL-10 compared with control infants. Serum IL-4 levels were not altered between gestational diabetic mothers and control mothers or the macrosomic babies and newborn control babies. CONCLUSIONS: GDM is linked to the down-regulation of adiponectin along with Th1 cytokines and up-regulation of leptin and inflammatory cytokines. Macrosomia was associated with the up-regulation of Th1 cytokines and the down-regulation of the obesity-related agents (IL-6 and TNF-alpha, leptin, and adiponectin).