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Ethnopharmacological Relevance: Salvadora persica L. (miswak) is traditionally used to ensure oral hygiene Muslim people in developing countries where it is growing. The antibacterial properties of Salvadora persica L. originating from various geographic areas have already been reported. However, they have never been tested for samples originating from Hoggar, where extreme weather conditions could lead to different properties for this Salvadora persica L. ecotype., Aim of the Study: To assess the in vitro and in vivo antimicrobial activities of methanolic extract of Algerian Hoggar Salvadora persica L. (miswak) on some isolated and identified strains from the oral cavity of school children aged from 6 to 12 with (n=20) and without (n=20) caries., Materials and Methods: After a qualitative and quantitative analysis of dental plaque samples from the selected children, the effect of methanolic extract of Hoggar miswak against oral bacterial and fungal strains isolated from the oral cavity of children with caries was tested by both agar disc diffusion and microdilution methods. The stability and physicochemical parameters of Hoggar Salvadora persica L. mouthwash were also assessed compared. The in vivo antimicrobial effect of Hoggar miswak rinse on dental plaque samples was also tested over a week., Results: Four bacterial genera (Staphylococcus, Streptococcus, Escherichia and Lactobacillus) were commonly identified in all subjects at different colonization levels. A statistically significant difference in colonization levels between the two groups of children was recorded. Hoggar miswak extract more significantly inhibited the growth of Gram negative bacteria from the dental plaque than Gram positive ones. Hoggar Salvadora persica L. mouthwash was stable at 4 °C and 25 °C over the period of conservation (one week) while a temperature of 40 °C induced variations in the physicochemical parameters and considered not suitable for preservation. The in vivo study revealed a significant reduction in bacteria of the oral cavity using miswak mouthwash as compared to placebo., Conclusion: Hoggar miswak extract displayed a strong antimicrobial effect both in vitro and in vivo. Its use as a mouthrinse could therefore be recommended as a preventive measure to preserve from tooth decay., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancers; it belongs to the genus Bryonia (Cucurbitaceae)., Aim of the Study: To investigate the cytotoxic and apoptogenic activities, the phytochemical composition and acute toxicity of the aqueous extract of Bryonia dioica roots growing in Algeria., Materials and Methods: Dried roots of Bryonia dioica were extracted with water (decoction). The cytotoxic effects of the aqueous extract in the Burkitt's lymphoma BL41 cell lines were evaluated by flow cytometry. Apoptosis induction was assessed by two corroborative assays; propidium iodide (PI) staining of cell DNA and flow cytometric light scatter analysis. The mitochondria membrane potential was investigated using a fluorescent dye DIOC6. The expression of caspases-3, -8, -9 and PARP was assessed by Western blot. The phytochemical screening of the roots of Bryonia dioica was performed using qualitative phytochemical standard procedures., Results: The Bryonia dioica aqueous extract induced cell death in a dose-dependent manner. The IC50 of Bryonia dioica aqueous extract was estimated to be approximately 15, 63μg/ml. This was accompanied by induction of apoptosis, activation of caspase-3 and -9, cleavage of PARP and loss of mitochondria membrane potential. Furthermore, the phytochemical screening of roots of Bryonia dioica showed the presence of various bioactive such as polyphenols, sterols and triterpenes, alkaloids, c-heterosides, carbohydrates and saponins., Conclusion: The aqueous extract of Bryonia dioica induces apoptosis in the Burkitt's lymphoma BL41 cell lines via the mitochondrial pathway. The flavonoids, sterols and triterpens detected could be responsible for the cytotoxic and apoptogenic activities of the aqueous extract of Bryonia dioica. These findings suggest that Bryonia dioica could be considered as a promising source for developing novel therapeutics against Burkitt's lymphoma., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Atractylis L gummifera is a plant that causes every year serious and often deadly poisonings. In Morocco, 153 cases of poisoning have been recorded between January 1980 and June 1995 by the Moroccan Antipoison Centre. The ignorance by the clinicians, the fast evolution and the frequency of these poisonings are the origin of diagnosis problems. The solution of those problems is to detect atractyloside and carboxyatractyloside in the biologic liquids. Since several decades, some toxicological analytical methods were established in view of an assay. The aim of our paper is to describe the poisoning by this plant and to review the methods of toxicological analysis used from the colorimetric technique until the news recent chromatographic methods.

The adsorption of Cu(2+), Zn(2+), Cd(2+) and Pb(2+) ions from aqueous solution by Algerian raw diatomite was studied. The influences of different sorption parameters such as contact pH solution, contact time and initial metal ions concentration were studied to optimize the reaction conditions. The metals ions adsorption was strictly pH dependent. The maximum adsorption capacities towards Cu(2+), Zn(2+), Cd(2+) and Pb(2+) were 0.319, 0.311, 0.18 and 0.096 mmol g(-1), respectively. The kinetic data were modelled using the pseudo-first-order and pseudo-second-order kinetic equations. Among the kinetic models studied, the pseudo-second-order equation was the best applicable model to describe the sorption process. Equilibrium isotherm data were analysed using the Langmuir and the Freundlich isotherms; the results showed that the adsorption equilibrium was well described by both model isotherms. The negative value of free energy change ΔG indicates feasible and spontaneous adsorption of four metal ions on raw diatomite. According to these results, the high exchange capacities of different metal ions at high and low concentration levels, and given the low cost of the investigated adsorbent in this work, Algerian diatomite was considered to be an excellent adsorbent.

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.

Metformin is an orally administered drug that lowers blood glucose and improves insulin sensitivity in patients with non insulin-dependent diabetes. Although the antihyperglycemic effect of metformin has been extensively studied, its cellular mechanism(s) of action (including the effect on enterocyte) remains to be defined. This study was designed to examine the effect of metformin on glucose transporters in enterocyte. Na(+)-dependent glucose transporter-1 (SGLT-1) activity was followed as glucose-induced short-circuit current (Isc) in Ussing chambers. The effect of metformin (10 micromol/L, 3 min) on transmural glucose transport was studied in isolated rat jejunal loops. Its impact on abundance of transporters SGLT-1 and GLUT2 in jejunal brush border membranes (BBM) and its effect on the phosphorylation of AMP-activated protein kinase (AMPK) alpha2 subunit was studied by western blot. Acute effect of metformin was also measured in vivo by oral glucose tolerance test (OGTT). Metformin markedly inhibited glucose-induced Isc (approximately 77%) after mucosal addition. In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPKalpha2. This effect of metformin was also observed using non-metabolizable sugar alpha3-O-methyl glucose. Transmural glucose transport measured in vitro was increased by 22% under metformin. Finally, oral metformin markedly increased glucose tolerance in OGTT. In conclusion, metformin slightly increases intestinal glucose absorption by inducing a re-distribution of glucose transporters in BBM through AMPK control in enterocyte. In addition to its action to other splanchnic tissues, this could constitute a peripheral signal contributing to the beneficial effect of metformin on glucose tolerance.

Aim of the Study: Nigella sativa L. (Ranunculaceae) seeds have been used traditionally for centuries, notably for treating diabetes., Materials and Methods: We studied the effects of the crude aqueous extract of Nigella sativa seeds on intestinal glucose absorption in vitro using a short-circuit current technique and in vivo using an oral glucose tolerance test., Results: The aqueous extract of Nigella sativa (0.1 pg/ml to 100 ng/ml) exerted dose-dependent inhibition of sodium-dependent glucose transport across isolated rat jejunum. Maximal inhibition exceeded 80% and IC50 was close to 10 pg/ml. An oral glucose tolerance test was carried out in rats after the initial dose and after a 6-week treatment of Nigella sativa (2 g/(kg day)), and compared to metformin (300 mg/(kg day)). Chronic Nigella sativa treatment improved glucose tolerance as efficiently as metformin. Nigella sativa and metformin also reduced body weight without any toxic effect., Conclusions: To our knowledge, this is the first demonstration that Nigella sativa directly inhibits the electrogenic intestinal absorption of glucose in vitro. Together with the observed improvement of glucose tolerance and body weight in rats after chronic oral administration in vivo, these effects further validate the traditional use of Nigella sativa seeds against diabetes.

Incidence of type II diabetes is rapidly increasing worldwide. In order to identify complementary or alternative approaches to existing medications, we studied anti-diabetic properties of Vaccinium angustifolium Ait., a natural health product recommended for diabetes treatment in Canada. Ethanol extracts of root, stem, leaf, and fruit were tested at 12.5 microg/ml for anti-diabetic activity in peripheral tissues and pancreatic beta cells using a variety of cell-based bioassays. Specifically, we assessed: (1) deoxyglucose uptake in differentiated C2C12 muscle cells and 3T3-L1 adipocytes; (2) glucose-stimulated insulin secretion (GSIS) in beta TC-tet pancreatic beta cells; (3) beta cell proliferation in beta TC-tet cells; (4) lipid accumulation in differentiating 3T3-L1 cells; (5) protection against glucose toxicity in PC12 cells. Root, stem, and leaf extracts significantly enhanced glucose transport in C2C12 cells by 15-25% in presence and absence of insulin after 20 h of incubation; no enhancement resulted from a 1 h exposure. In 3T3 cells, only the root and stem extracts enhanced uptake, and this effect was greater after 1 h than after 20 h; uptake was increased by up to 75% in absence of insulin. GSIS was potentiated by a small amount in growth-arrested beta TC-tet cells incubated overnight with leaf or stem extract. However, fruit extracts were found to increase 3H-thymidine incorporation in replicating beta TC-tet cells by 2.8-fold. Lipid accumulation in differentiating 3T3-L1 cells was accelerated by root, stem, and leaf extracts by as much as 6.5-fold by the end of a 6-day period. Stem, leaf, and fruit extracts reduced apoptosis by 20-33% in PC12 cells exposed to elevated glucose for 96 h. These results demonstrate that V. angustifolium contains active principles with insulin-like and glitazone-like properties, while conferring protection against glucose toxicity. Enhancement of proliferation in beta cells may represent another potential anti-diabetic property. Extracts of the Canadian blueberry thus show promise for use as a complementary anti-diabetic therapy.

Type II diabetes is a major health problem worldwide. Some populations, such as aboriginal peoples, are particularly at risk for this disease. In the Cree Nation of Quebec, Canada, prevalence in adults is approaching 20%, and the consequences are compounded by low compliance with modern medicine. In 2003, we conducted an ethnobotanical study of Cree medicinal plants used for the treatment of symptoms of diabetes. This served as the basis for a project designed to identify efficacious complementary treatment options more readily accepted by this population. The present study assesses the in vitro anti-diabetic potential of extracts from the 8 most promising plants to emerge from the ethnobotanical study. Cell-based bioassays were employed to screen for (i) potentiation of glucose uptake by skeletal muscle cells (C2C12) and adipocytes (3T3-L1); (ii) potentiation of glucose-stimulated insulin secretion (GSIS) and insulin production by pancreatic beta cells (INS 832/13); (iii) potentiation of triglyceride accumulation in differentiating 3T3-L1 cells; (iv) protection against glucose toxicity and glucose deprivation in pre-sympathetic neurons (PC12-AC). Additionally, anti-oxidant activity was measured biochemically by the diphenylpicrylhydrazyl (DPPH) reduction assay. All plant extracts potentiated basal or insulin-stimulated glucose uptake to some degree in muscle cells or adipocytes. Adipocyte differentiation was accelerated by 4 extracts. Five extracts conferred protection in PC12 cells. Three extracts displayed free radical scavenging activity similar to known anti-oxidants. None of the plant extracts enhanced GSIS or insulin content in INS 832/13 beta cells. It is concluded that the Cree pharmacopoeia contains several plants with significant anti-diabetic potential.

We investigated the response of bone-specific resorption markers in fasting urine samples from postmenopausal women with low daily dietary calcium (Ca) intake (<800 mg/day) who received either Ca supplementation (1200 mg/day, n = 18) or placebo (n = 14) for 2 months. We measured urinary hydroxyproline, total pyridinoline, and deoxypyridinoline by HPLC, and free deoxypyridinoline (i-F-Dpd) and N- and C-telopeptide fragments of type I collagen (NTX and CTX) by immunoassays. Before supplementation, the urine concentrations of bone resorption markers in the 32 subjects were not statistically different from those measured in 21 subjects with daily dietary Ca intake >800 mg/day. In contrast to the placebo group, Ca supplementation decreased all collagen-related degradation markers except i-F-Dpd as early as the first month. The magnitude of response after 2 months of Ca supplementation, expressed as mean percentage of decrease from baseline values or as individual Z scores, was greatest for the telopeptide assays. Furthermore, the percentage of change assessed at 2 months was greater than the within-person biological variability (CV) assessed in the placebo-treated women for NTX and CTX, whereas for the other markers the percentage of change was very close of the within-person CVs. We conclude that cross-linked telopeptide fragments of type I collagen most sensitively reflect the change in bone resorption after Ca supplementation.

The measurement of urinary deoxypyridinoline (DPD) constitutes a specific and sensitive marker of bone resorption. Total and free forms of DPD are determined by chromatographic method (HPLC) after or without hydrolysis of urine, respectively. Pyrilinks-D, a new immunoassay, allows to assess directly the free forms and needs an appropriate hydrolysis step for measuring the total form. We have compared the values of free (F), total (T) and conjugated (NF) forms of DPD determined by HPLC and Pyrilinks-D, in elderly women (n = 21, mean age: 83.5 +/- 1.5 years) with vitamin D insufficiency (25 OH D < 6 ng/mL) and Ca insufficiency responsible for a secondary hyperparathyroidism (iPTH = 45.3 +/- 22.7 pg/mL) and in healthy elderly women (n = 25, mean age: 76.6 +/- 3.1 years) with a normal vit D status (25 OH D > 10 ng/mL) as control group. We have also measured DPD during the course of vit D and Ca supplementation. At baseline, the HPLC and Pyrilinks-D values of DPD/Cr are highly correlated (DPD-T: r = 0.92, p < 0.001 and DPD-F: r = 0.76, p < 0.001), DPD-F and -NF values are correlated with those of DPD-T, while DPD-F and -NF are not correlated between themselves. In elderly with vit D insufficiency, the values obtained with Pyrilinks-D as compared to control subjects, show a significant increase of urinary excretion of DPD-F (8.5 +/- 3.1 vs 5.7 +/- 1.9 nmol/mmol, Cr, p < 0.0001), DPD-T (16.8 +/- 10.2 vs 9.9 +/- 3.5 nmol/mmol, Cr; p < 0.001) and DPD-NF (8.3 +/- 9.0 vs 4.5 +/- 3.3 nmol/mmol, Cr, p < 0.05). The administration of 800 IU of vit D and 1 g of elemental Ca during a course of 6 months normalize the iPTH values (24.4 +/- 11.8 and 30.9 +/- 14.6 pg/mL at 3 and 6 months). Simultaneously, the urinary excretion at 3 and 6 months of DPD-T (12.9 +/- 6.0 and 13.6 +/- 6.5 nmol/mmol, Cr) and of DPD-NF (4.5 +/- 3.3 and 5.5 +/- 4.8 nmol/mmol Cr) assessed by Pyrilinks-D as well as by HPLC decreased significantly, while no change was seen with DPD-F assessed by both methods. The decreases expressed as percent of baseline values were about 20% for DPD-T and more than 30% for DPD-NF, while DPD-F levels remain unchanged. We conclude that the Pyrilinks-D immunoassay presents reliable characteristics and allows to assess either free or total forms of DPD, like the HPLC technique. It constitutes an excellent reflection of bone resorption in elderly with vit D insufficiency. However its application to monitor therapy like vit D and Ca supplementation, needs a hydrolysis step to determine DPD-T which appears in this study more sensitive to the treatment than DPD-F.