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

The Constitutive Expression of Type X Collagen in Mesenchymal Stem Cells from Osteoarthritis Patients Is Reproduced in a Rabbit Model of Osteoarthritis

The expression of type X collagen (COL X), a late-stage chondrocyte hypertrophy marker in human mesenchymal stem cells (MSCs) from osteoarthritis (OA) patients poses a major setback to current cartilage and intervertebral disc tissue engineering efforts. However, it is not yet clear whether COL X is expressed by all human bone marrow stem cells or if it is related to age, gender, site, disease status, or drug therapy. In the current study, we report that COL X expression is upregulated in MSCs from rabbits in a surgical instability model of OA (anterior cruciate ligament transection (ACLT)) when compared to control rabbit MSCs. Thus COL X expression in OA is a common phenomenon that is due to the disease process itself and not to other environmental factors. It is, therefore, critical to understand MSC phenotype in OA patients, as these cells are essential clinically for biological repair of cartilage lesions using autologous stem cells

Antidiabetic Compounds from <i>Sarracenia purpurea</i> Used Traditionally by the Eeyou Istchee Cree First Nation

Through ethnobotanical surveys, the CIHR Team in Aboriginal Antidiabetic Medicines identified 17 boreal forest plants stemming from the pharmacopeia of the Cree First Nations of Eeyou Istchee (James Bay region of Northern Quebec) that were used traditionally against diabetes symptoms. The leaves of <i>Sarracenia purpurea</i> (pitcher plant), one of the identified Cree plants, exhibited marked antidiabetic activity in vitro by stimulating glucose uptake in C2C12 mouse muscle cells and by reducing glucose production in H4IIE rat liver cells. Fractionation guided by glucose uptake in C2C12 cells resulted in the isolation of 11 compounds from this plant extract, including a new phenolic glycoside, flavonoid glycosides, and iridoids. Compounds <b>6</b> (isorhamnetin-3-<i>O</i>-glucoside), <b>8</b> [kaempferol-3-<i>O</i>-(6″-caffeoylglucoside], and <b>11</b> (quercetin-3-<i>O</i>-galactoside) potentiated glucose uptake in vitro, which suggests they represent active principles of <i>S. purpurea</i> (EC₅₀ values of 18.5, 13.8, and 60.5 μM, respectively). This is the first report of potentiation of glucose uptake by compounds <b>6</b> and <b>8</b>, while compound <b>11</b> (isolated from <i>Vaccinium vitis</i>) was previously shown to enhance glucose uptake. Treatment of H4IIE liver cells with the new compound <b>1</b>, 6′-<i>O</i>-caffeoylgoodyeroside, decreased hepatic glucose production by reducing glucose-6-phosphatase enzymatic activity (IC₅₀ = 13.6 μM), which would contribute to lowering glycemia and to the antidiabetic potential of <i>S. purpurea.</i