[show abstract][hide abstract] ABSTRACT: Evidence supports the health promoting benefits of berries, particularly with regard to the prevention and management of chronic diseases such cardio- and cerebrovascular disease, diabetes and Alzheimer's disease. Two related pathophysiological features common to many of these conditions are oxidative stress and the accumulation of advanced glycation endproducts (AGEs). Whereas antioxidant properties are well-established in several species of berries and are believed central to their protective mechanisms, few studies have investigated the effects of berries on AGE formation. Here, employing a series of complementary in vitro assays, we evaluated a collection of wild berry extracts for 1) inhibitory effects on fluorescent-AGE and Nε- (carboxymethyl)lysine-albumin adduct formation, 2) radical scavenging activity and 3) total phenolic and anthocyanin content. All samples reduced AGE formation in a concentration-dependent manner that correlated positively with each extract's total phenolic content and, to a lesser degree, total anthocyanin content. Inhibition of AGE formation was similarly related to radical scavenging activities. Adding antiglycation activity to the list of established functional properties ascribed to berries and their phenolic metabolites, our data provide further insight into the active compounds and protective mechanisms through which berry consumption may aid in the prevention and treatment of chronic diseases associated with AGE accumulation and toxicity. As widely available, safe and nutritious foods, berries represent a promising dietary intervention worthy of further investigation.
Journal Plant for Human Nutrition 01/2014; · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interactions between conventional drug and traditional medicine therapies may potentially affect drug efficacy and increase the potential for adverse reactions. Cree traditional healing is holistic and patients may use medicinal plants simultaneously with the conventional drugs. However, there is limited information that these medicinal plants may interact with drugs and additional mechanistic information is required.
In this study, extracts from traditionally used Cree botanicals were assessed for their potential interaction that could alter the disposition of two blood glucose lowering drugs, gliclazide (Diamicron) and repaglinide (Gluconorm) though inhibition of either metabolism or transport across cell membranes.
The effect of 17 extracts on metabolism was examined in a human liver microsome assay by HPLC and individual cytochrome P450s 2C9, 2C19, 2C8 and 3A4 in a microplate fluorometric assay. Gliclazide, rhaponticin and its aglycone derivative, rhapontigenin were also examined in the fluorometric assay. The effect on transport was examined with 11 extracts using the intestinal epithelial Caco-2 differentiated cell monolayer model at times up to 180min.
Both blood glucose lowering medications, gliclazide and repaglinide traversed the Caco-2 monolayer in a time-dependent manner that was not affected by the Cree plant extracts. Incubation of the Cree plant extracts inhibited CYP2C9, 2C19, 2C8 and 3A4-mediated metabolism, and the formation of four repaglinide metabolites: M4, m/z 451-A, m/z 451-B and the glucuronide of repaglinide in the human liver microsome assay. Gliclazide caused no significant inhibition. Likewise, rhaponticin had little effect on the enzymes causing changes of less than 10% with an exception of 17% inhibition of CYP2C19. By contrast, the aglycone rhapontigenin showed the greatest effects on all CYP-mediated metabolism. Its inhibition ranged from a mean of 58% CYP3A4 inhibition to 89% inhibition of CYP2C9. While rhaponticin and the aglycone did not show significant effects on repaglinide metabolism, they demonstrated inhibition of gliclazide metabolism. The aglycone significantly affected levels of gliclazide and its metabolites.
These studies demonstrate that the Cree plant extracts examined have the potential in vitro to cause drug interactions through effects on key metabolic enzymes.
Journal of ethnopharmacology 10/2013; · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: From the leaves of Sarracenia purpurea, collected in Mistissini, Quebec, Canada, four goodyerosides and three phenolics and nine known compounds, were isolated. The structures of the compounds were determined by mass spectrometry, including HRMS, and by 1D and 2D NMR spectroscopy.
[show abstract][hide abstract] ABSTRACT: Populus balsamifera L. (BP) is a medicinal plant stemming from the traditional pharmacopoeia of the Cree of Eeyou Istchee (CEI-Northern Quebec). In vitro screening studies revealed that it strongly inhibited adipogenesis in 3T3-L1 adipocytes, suggesting potential antiobesity activity. Salicortin was identified, through bioassay-guided fractionation, as the active component responsible for BP's activity. The present study aimed to assess the potential of BP and salicortin at reducing obesity and features of the metabolic syndrome, in diet-induced obese C57Bl/6 mice. Mice were subjected to high fat diet (HFD) for sixteen weeks, with BP (125 or 250 mg/kg) or salicortin (12.5 mg/kg) introduced in the HFD for the last eight of the sixteen weeks. BP and salicortin effectively reduced whole body and retroperitoneal fat pad weights, as well as hepatic triglyceride accumulation. Glycemia, insulinemia, leptin, and adiponectin levels were also improved. This was accompanied by a small yet significant reduction in food intake in animals treated with BP. BP and salicortin (slightly) also modulated key components in signaling pathways involved with glucose regulation and lipid oxidation in the liver, muscle, and adipose tissue. These results confirm the validity of the CEI pharmacopoeia as alternative and complementary antiobesity and antidiabetic therapies.
Evidence-based Complementary and Alternative Medicine 01/2013; 2013:172537. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: We determined the capacity of putative antidiabetic plants used by the Eastern James Bay Cree (Canada) to modulate key enzymes of gluconeogenesis and glycogen synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase) and glycogen synthase (GS) activities were assessed in cultured hepatocytes treated with crude extracts of seventeen plant species. Phosphorylation of AMP-dependent protein kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western blot. Seven of the seventeen plant extracts significantly decreased G6Pase activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin. This action involved both Akt and AMPK phosphorylation. On the other hand, several plant extracts activated GS, Larix laricina and A. balsamea, far exceeding the action of insulin. We also found a significant correlation between GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In summary, three Cree plants stand out for marked effects on hepatic glucose homeostasis. P. glauca affects glucose production whereas L. laricina rather acts on glucose storage. However, A. balsamea has the most promising profile, simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies thus confirm that the reduction of hepatic glucose production likely contributes to the therapeutic potential of several antidiabetic Cree traditional medicines.
Evidence-based Complementary and Alternative Medicine 01/2013; 2013:189819. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The purple pitcher plant, Sarracenia purpurea L., is a widely distributed species in North America with a history of use as both a marketed pain therapy and a traditional medicine in many aboriginal communities. Among the Cree of Eeyou Istchee in northern Quebec, the plant is employed to treat symptoms of diabetes and the leaf extract demonstrates multiple anti-diabetic activities including cytoprotection in an in vitro model of diabetic neuropathy. The current study aimed to further investigate this activity by identifying the plant parts and secondary metabolites that contribute to these cytoprotective effects. METHODS: Ethanolic extracts of S. purpurea leaves and roots were separately administered to PC12 cells exposed to glucose toxicity with subsequent assessment by two cell viability assays. Assay-guided fractionation of the active extract and fractions was then conducted to identify active principles. Using high pressure liquid chromatography together with mass spectrometry, the presence of identified actives in both leaf and root extracts were determined. RESULTS: The leaf extract, but not that of the root, prevented glucose-mediated cell loss in a concentration-dependent manner. Several fractions elicited protective effects, indicative of multiple active metabolites, and, following subfractionation of the polar fraction, hyperoside (quercetin-3-O-galactoside) and morroniside were isolated as active constituents. Phytochemical analysis confirmed the presence of hyperoside in the leaf but not root extract and, although morroniside was detected in both organs, its concentration was seven times higher in the leaf. CONCLUSION: Our results not only support further study into the therapeutic potential and safety of S. purpurea as an alternative and complementary treatment for diabetic complications associated with glucose toxicity but also identify active principles that can be used for purposes of standardization and quality control.
BMC Complementary and Alternative Medicine 12/2012; 12(1):245. · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Purpose – Research projects involving traditional knowledge are finding new ways of dealing with intellectual property rights and commercialisation. Influenced by calls for fair and equitable protocols involving access and benefit sharing regimes, researchers are developing new standards of practice. Here this paper aims to explore the process by which the CIHR Team in Aboriginal Antidiabetic Medicine (TAAM) came to address these issues within the scope of participatory action research. Design/methodology/approach – A case study method is applied in order to highlight key events and topics. The legally binding research agreement developed for this project is used to illustrate examples of how the needs of First Nations stakeholders and of researchers are met. Findings – The paper finds that strong research partnerships are characterized by accountability, adaptability, transparency, good and frequent communication and ultimately, trust. Researchers should be prepared to take a more “human” approach in their studies as the establishment of personal relationships are as important as the research itself. Proposals should include both monetary and intangible outcomes where possible, which reflect aboriginal culture and decision. Practical implications – This paper can help others to understand the needs of aboriginal peoples with regard to research. It also provides links to protocols and the legal research agreement used by TAAM that can serve as an adaptable template for future work. Originality/value – Publicising the research agreement and experiences herein is meant to contribute to a body of knowledge that will one day lead to new research norms when dealing with aboriginal peoples and traditional knowledge.
Journal of Enterprising Communities People and Places in the Global Economy 08/2012; 6(3):251-270.
[show abstract][hide abstract] ABSTRACT: 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 Sarracenia purpurea (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 6 (isorhamnetin-3-O-glucoside), 8 [kaempferol-3-O-(6″-caffeoylglucoside], and 11 (quercetin-3-O-galactoside) potentiated glucose uptake in vitro, which suggests they represent active principles of S. purpurea (EC(50) values of 18.5, 13.8, and 60.5 μM, respectively). This is the first report of potentiation of glucose uptake by compounds 6 and 8, while compound 11 (isolated from Vaccinium vitis) was previously shown to enhance glucose uptake. Treatment of H4IIE liver cells with the new compound 1, 6'-O-caffeoylgoodyeroside, decreased hepatic glucose production by reducing glucose-6-phosphatase enzymatic activity (IC(50) = 13.6 μM), which would contribute to lowering glycemia and to the antidiabetic potential of S. purpurea.
Journal of Natural Products 06/2012; 75(7):1284-8. · 3.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetes is a growing epidemic worldwide, especially among indigenous populations. Larix laricina was identified through an ethnobotanical survey as a traditional medicine used by Healers and Elders of the Cree of Eeyou Istchee of northern Quebec to treat symptoms of diabetes and subsequent in vitro screening confirmed its potential.
We used a bioassay-guided fractionation approach to isolate the active principles responsible for the adipogenic activity of the organic extract (80% EtOH) of the bark of Larix laricina. Post-confluent 3T3-L1 cells were differentiated in the presence or absence of the crude extract, fractions or isolates of Larix laricina for 7 days, then triglycerides content was measured using AdipoRed reagent.
We identified a new cycloartane triterpene (compound 1), which strongly enhanced adipogenesis in 3T3-L1 cells with an EC(50) of 7.7 μM. It is responsible for two thirds of the activity of the active fraction of Larix laricina. The structure of compound 1 was established on the basis of spectroscopic methods (IR, HREIMS, 1D and 2D NMR) as 23-oxo-3α-hydroxycycloart-24-en-26-oic acid. We also identified several known compounds, including three labdane-type diterpenes (compounds 2-4), two tetrahydrofuran-type lignans (compounds 5-6), three stilbenes (compounds 7-9), and taxifolin (compound 10). Compound 2 (13-epitorulosol) also potentiated adipogenesis (EC(50) 8.2 μM) and this is the first report of a biological activity for this compound.
This is the first report of putative antidiabetic principles isolated from Larix laricina, therefore increasing the interest in medicinal plants from the Cree pharmacopeia.
Journal of ethnopharmacology 04/2012; 141(3):1051-7. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: ETHNOBOTANICAL RELEVANCE: : In previous in vitro bioassay studies, Populus balsamifera L. (Salicaceae), a medicinal plant ethnobotanically identified from the traditional pharmacopoeia of the Cree of Eeyou Istchee (Eastern James Bay area of Canada), exhibited a strong anti-obesity potential by potently inhibiting adipogenesis in 3T3-L1 adipocytes. The aim of the study is to evaluate the effectiveness of this plant extract in mitigating the development of obesity and the metabolic syndrome in diet-induced obese (DIO) C57BL/6 mice.
Mice were subjected for eight weeks to a standard diet (CHOW), a high fat diet (HFD; DIO group), or HFD to which Populus balsamifera was incorporated at 125 and 250 mg/kg.
The results showed that Populus balsamifera decreased in a dose-dependent manner the weight gain of whole body, retroperitoneal fat pad and liver as compared to DIO controls and reduced the severity of hepatic macrovesicular steatosis and triglyceride accumulation. This plant extract also decreased glycemia in the second half of the feeding period and improved insulin sensitivity by diminishing insulin levels and the leptin/adiponectin ratio, as well as augmenting adiponectin levels. These effects were associated with slightly but significantly reduced food intake with 250 mg/kg Populus balsamifera as well as with an increase in energy expenditure (increase in skin temperature and increased expression of uncoupling protein-1; UCP-1). Data also suggest other mechanisms, such as inhibition of adipocyte differentiation, decrease of hepatic inflammatory state and potential increase in hepatic fatty acid oxidation.
Taken together, these results confirm the potential of Populus balsamifera as a culturally adapted therapeutic approach for the care and treatment of obesity and diabetes among the Cree.
Journal of ethnopharmacology 04/2012; 141(3):1012-20. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Harvesting of medicinal plants from wild populations is increasing worldwide, however, studies on sustainable harvesting techniques are lacking. In this exploratory study, we investigated the impact of leaf harvesting on Rhododendron groenlandicum (Oeder) Kron & Judd, a North American temperate shrub, used traditionally as a medicinal plant by the Cree Nation. The species is widely distributed, but Crees are worried that commercial harvesting could threaten local plant populations. Our study was conducted near the Cree Nation of Mistissini (James Bay, Northern Quebec). Three leaf harvest regimes were tested in 2008 and 2009: no harvest, all leaves harvested, and only old leaves harvested; each treatment was performed on 30 plants. The harvesting of all leaves had a negative impact on stem elongation after the first harvest, while leaf production and stem radial growth decreased after the second harvest. Two-thirds of the plants also died following the second regime of harvesting all leaves. The harvesting of old leaves had no significant impact on growth, leaf production, or survival of R. groenlandicum, even after 2 years of harvest. These results lead to the conclusion that sustainable harvest of this species is possible, but further study is required to make definite recommendations.
[show abstract][hide abstract] ABSTRACT: Eight commercial grape seed products (GSPs) were assessed for their inhibition of the formation of advanced glycation end-products in vitro. All 8 commercial GSPs included in this study were potent inhibitors of advanced glycation end-product formation with IC(50) values ranging from 2.93 to 20.0 µg/mL. Total procyanidin content ranged from 60% to 73%. HPLC-DAD-ELSD results indicate that (+)-catechin, (-)-epicatechin, procyanidin B1, and procyanidin B2 were predominant and ubiquitously present in all the products under study, while gallic acid and procyanidin B4 were present in relatively minor amounts. The IC(50) values correlated with total phenolic content, and multiple regression analysis indicated that IC(50) is a linear function of the concentration of gallic acid and procyanidins B1, B2, and B4. Based on this study, GSPs have the potential to complement conventional diabetes medication toward disease management and prevention.
Canadian Journal of Physiology and Pharmacology 02/2012; 90(2):167-74. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Canadian Aboriginals, like others globally, suffer from disproportionately high rates of diabetes. A comprehensive evidence-based approach was therefore developed to study potential antidiabetic medicinal plants stemming from Canadian Aboriginal Traditional Medicine to provide culturally adapted complementary and alternative treatment options. Key elements of pathophysiology of diabetes and of related contemporary drug therapy are presented to highlight relevant cellular and molecular targets for medicinal plants. Potential antidiabetic plants were identified using a novel ethnobotanical method based on a set of diabetes symptoms. The most promising species were screened for primary (glucose-lowering) and secondary (toxicity, drug interactions, complications) antidiabetic activity by using a comprehensive platform of in vitro cell-based and cell-free bioassays. The most active species were studied further for their mechanism of action and their active principles identified though bioassay-guided fractionation. Biological activity of key species was confirmed in animal models of diabetes. These in vitro and in vivo findings are the basis for evidence-based prioritization of antidiabetic plants. In parallel, plants were also prioritized by Cree Elders and healers according to their Traditional Medicine paradigm. This case study highlights the convergence of modern science and Traditional Medicine while providing a model that can be adapted to other Aboriginal realities worldwide.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:893426. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Larix laricina K. Koch is a medicinal plant belonging to traditional pharmacopoeia of the Cree of Eeyou Istchee (Eastern James Bay area of Canada). In vitro screening studies revealed that, like metformin and rosiglitazone, it increases glucose uptake and adipogenesis, activates AMPK, and uncouples mitochondrial function. The objective of this study was to evaluate the antidiabetic and antiobesity potential of L. laricina in diet-induced obese (DIO) C57BL/6 mice. Mice were subjected for eight or sixteen weeks to a high fat diet (HFD) or HFD to which L. laricina was incorporated at 125 and 250 mg/kg either at onset (prevention study) or in the last 8 of the 16 weeks of administration of the HFD (treatment study). L. laricina effectively decreased glycemia levels, improved insulin resistance, and slightly decreased abdominal fat pad and body weights. This occurred in conjunction with increased energy expenditure as demonstrated by elevated skin temperature in the prevention study and improved mitochondrial function and ATP synthesis in the treatment protocol. L. laricina is thus a promising alternative and complementary therapeutic approach for the treatment and care of obesity and diabetes among the Cree.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:296432. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: The antidiabetic activities of different extracts and fractions of Balanites aegyptiaca were tested in cultured C2C12 skeletal muscle cells and 3T3-L1 adipocytes. An 18-h treatment with 200 µg/mL of the sugars fraction (A1) showed the highest activity as it increased basal glucose uptake by 52% in muscle cells; which is twice the activity of 100 nM insulin [insulin equivalent (IE) = 2.0 ± 0.07]. The dichloromethane (E) and ethyl acetate (F) successive extracts exerted 37 and 41% increase in the glucose uptake, respectively. Only E and F accelerated the triglyceride accumulation in pre-adipocytes undergoing differentiation, comparably with 10 µM rosiglitazone [rosiglitazone equivalent (RE) was 1.6 ± 0.3 and 0.7 ± 0.1, respectively). Gas chromatography (GC) analysis of A1 revealed the presence of xylose, rhamnose, sorbitol, fructose, galactose and glucose. The active extracts E and F were standardized by high-performance liquid chromatography (HPLC) to contain 0.031 and 0.239% of rutin, 0.007 and 0.004% of isorhamnetin, respectively.
[show abstract][hide abstract] ABSTRACT: The antidiabetic activities of the aqueous (AqEx) and ethanolic (AlEx) extracts of Cleome droserifolia (Forssk.) Del., were tested in cultured C2C12 skeletal muscle cells and 3T3-L1 adipocytes. An 18-h treatment with the AqEx increased basal glucose uptake by 33% [insulin equivalent (IE)=1.3±0.04] in muscle cells comparable to a 25.5% increase caused by 100 nM insulin (IE=1±0.03). Fractionation of the tested AqEx yielded hexane (HxFr), chloroform (ClFr) and ethyl acetate (EtFr) fractions which exerted 38, 52 and 35% increase in the glucose uptake corresponding to an IE of 1.5±0.06, 2.0±0.04 and 1.4±0.04, respectively. Only the ClFr and EtFr accelerated the triglyceride accumulation [rosiglitazone equivalent (RE) was 0.9±0.13 and 0.63±0.12, respectively] in pre-adipocytes undergoing differentiation comparably with 10 μM rosiglitazone. Six terpenoids (C1-C6) and three flavonol glycosides (F1-F3) were isolated from the active ClFr and EtFr, respectively, and identified. C5, C2 and C4 had an IE of 0.86±0.05, 1.01±0.04 and 0.9±0.08, while F1, F2 and F3 gave an IE of 1.3±0.05, 2.3±0.05 and 2.0±0.04, respectively. We could conclude that the reported antihyperglycemic activity of Cleome droserifolia is attributed to significant insulin-like effects in peripheral tissues, and that compounds F2 and F3, being highly active, could be used as bioactive markers to standardize the C. droserifolia herbal extract.
Phytomedicine: international journal of phytotherapy and phytopharmacology 09/2011; 19(1):38-41. · 2.97 Impact Factor