The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content

The antidiabetic effect of N. sativa seed ethanol extract (NSE) was assessed in Meriones shawi after development of diabetes. Meriones shawi were divided randomly into four groups: normal control, diabetic control, diabetic treated with NSE (2 g eq plant/kg) or with metformin (300 mg/kg) positive control, both administered by daily intragastric gavage for 4 weeks. Glycaemia and body weight were evaluated weekly. At study's end, an Oral Glucose Tolerance Test (OGTT) was performed to estimate insulin sensitivity. Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed. ACC phosphorylation and Glut4 protein content were determined in liver and skeletal muscle. NSE animals showed a progressive normalization of glycaemia, albeit slower than that of metformin controls. Moreover, NSE increased insulinemia and HDL-cholesterol, compared to diabetic controls. Leptin and adiponectin were unchanged. NSE treatment decreased OGTT and tended to decrease liver and muscle triglyceride content. NSE stimulated muscle and liver ACC phosphorylation and increased muscle Glut4. These results confirm NSE's previously reported hypoglycaemic and hypolipidemic activity. More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression

Cytotoxicity of alkaloids isolated from Peganum harmala seeds

Abstract: Ethnopharmacological relevance: Peganum harmala is used in traditional medicine to treat a number of diseases including cancer. Our preliminary studies show that the alkaloidal extract of PH seed is cytotoxic to several tumor cell lines in vitro and has antitumor effect in a tumor model in vivo. The present investigation was aimed at extending our previous studies in identifying the components in P. harmala seedextract responsible for the cytotoxic effects, and study the cytotoxic and antiproliferative activity of isolated alkaloids and total alkaloidal fraction (TAF) in several tumor cell lines. Four alkaloids: harmalicidine, harmine, peganine (vasicine) and vasicinone were isolated from the P. harmala seedextract and their activity and that of TAF were tested a) for their cytotoxic activity against four tumor cell lines [three developed by us by chemical-induction in Wistar rats: 1) Med-mek carcinoma ; 2) UCP-med carcinoma ; 3) UCP-med sarcoma] ; and 4) SP2/O-Ag14, and b) for antiproliferative effect on cells of Jurkat, E6-1 clone (inhibition of incorporation of { 3 H-thymidine} in cellular DNA). The alkaloids and TAF inhibited the growth of tumor cell lines to varying degrees; Sp2/O-Ag14 was the most sensitive, with IC 50 values (concentration of the active substance that inhibited the growth of the tumor cells by 50%) ranging between 2.43 µg/mL and 19.20 µg/mL, while UCP-med carcinoma was the least sensitive (range of IC 50 = 13.83 µg/mL to 59.97 µg/mL). Of the substances evaluated, harmine was the most active compound (IC 50 for the 4 tumor cell lines varying between 2.43 µg/ml and 18.39 µg/mL), followed by TAF (range of IC 50 = 7.32 µg/mL to 13.83 µg/mL); peganine was the least active (IC 50 = 50 µg/mL to > 100 µg/ml). In terms of antiproliferative effect, vasicinone and TAF were more potent than other substances: the concentration of vasicinone, and TAF needed to inhibit the incorporation of { 3 H-TDR} in the DNA cells of Jurkat, E6-1 clone by 50% (IC 50 ) were 8.60 ± 0.023 µg/mL and 8.94 ± 0.017 µg/mL, respectively, while peganine was the least active (IC 50 >100 µg/mL). The IC 50 values for harmalacidine (27.10 ± 0.011 µg/mL) and harmine (46.57 ± 0.011 µg/mL) were intermediate. The harmala alkaloids inhibited the growth of four tumor cell lines, and proliferation of Jurkat cells with varying potencies. Harmine was the most potent in inhibiting cell growth, and vasicinone was most active as antiproliferating substance. The TAF had significant cytotoxic as well as antiproliferating activity

Effet diurétique de l'infusion de fleurs de Lavandula officinalis

Diuretic activity of the flowers infusion of Lavandula officinalis. The diuretic activity of an infusion of Lavandula officinalis was studied in the Wistar rat. Thus, the kinetic of hydroelectrolyte elimination in response to the oral administration of an infusion of pharmaceutical lavender flowers were measured in the rats. Experiments were completed under similar conditions using a synthetic pharmacological diuretic, Diamox. The aqueous extract of this aromatic plant accelerated the elimination of the water overload. At the peak of the diuretic response, urinary osmolarity was significantly less than that of controls (111 $\pm$ 14 vs. 195 $\pm$ 1l mosmol$\cdot$kg$^{-1}$). Sodium excretion was moderate following administration of the infusion when compared to the synthetic diuretic. The stability of the aldosterone concentrations in the plasma and the absence of correlation with plasma sodium concentrations, coupled with the observed clearance of the free water (0.055 $\pm$ 0.007 vs. 0.045 $\pm$ 0.012 mL$\cdot$min$^{-1}$) show that the increase in diuresis and the moderate increase in sodium excretion are of tubular origin. The result of the phytochemical analysis of hexane extracts in the infusion and in urine indicated that four or five chemical factors may be involved in the diuretic effect of lavender.Les effets diurétiques d'une infusion de lavande ont été recherchés chez le rat Wistar. Pour cela, la cinétique des éliminations hydroélectrolytiques en réponse à une administration par voie orale d'une infusion de fleurs de lavande officinale a été mesurée chez des rats. Les expérimentations ont été réalisées dans les mêmes conditions avec un diurétique pharmacologique de synthèse (le Diamox). L'extrait aqueux de cette plante aromatique accélère l'élimination de la surcharge hydrique. Au maximum de la réponse diurétique, l'osmolarité urinaire diminue significativement par rapport aux témoins (111 $\pm$ 14 vs. 195 $\pm$ 11 mosmol$\cdot$kg$^{-1}$). L'excrétion sodique est modérée avec le traitement à l'infusion de lavande par rapport aux effets du diurétique de synthèse. La stabilité de l'aldostéronémie, l'absence de corrélation avec le taux de sodium plasmatique, ainsi que l'augmentation de la clearance de l'eau libre chez les animaux ayant reçu l'infusion de lavande (0,055 $\pm$ 0,007 vs. 0,045 $\pm$ 0,012 mL$\cdot$min$^{-1}$) montrent que l'augmentation de la diurèse et l'élévation modérée de la natriurèse sont d'origine tubulaire. D'après les résultats de l'étude phytochimique des extraits hexaniques de l'infusion et des urines, quatre à cinq composés chimiques ont été identifiés mais dont l'implication partielle ou totale reste à démontrer dans l'effet diurétique observé de la lavande