Publications (9)25.34 Total impact
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Article: Characterizing the cytoprotective activity of sarracenia purpurea L., a medicinal plant that inhibits glucotoxicity in PC12 cells.
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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. · 2.24 Impact Factor -
Article: BC-spiro-estradiols. Synthesis and estrogen receptor binding affinity of four new estradiol isomers.
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ABSTRACT: The synthesis of four new isomers of estradiol in which the ring A to ring C planes are perpendicular to each other as a result of a spiro BC ring junction is described. Heterocyclic analogs and carbocyclic homologs of these compounds are also reported. Estrogen receptor binding studies show that the spiro compounds with the natural stereochemistry at C9 bind almost as strongly as estradiol but with greater β to α selectivity. These studies show that the estrogen receptors can readily accommodate isomers of estrogen with substantially different fixed shapes than the native ligand.Bioorganic & medicinal chemistry letters 04/2012; 22(11):3713-7. · 2.65 Impact Factor -
Article: A-CD estrogens. I. Substituent effects, hormone potency, and receptor subtype selectivity in a new family of flexible estrogenic compounds.
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ABSTRACT: Long-term use of estrogen supplements by women leads to an increased risk of breast and uterine cancers. Possible mechanisms include metabolism of estradiol and compounds related to tumor-initiating quinones, and ligand-induced activation of the estrogen receptors ERα and ERβ which can cause cancer cell proliferation, depending on the ratio of receptors present. One therapeutic goal would be to create a spectrum of compounds of variable potency for ERα and ERβ, which are resistant to quinone formation, and to determine an optimum point in this spectrum. We describe the synthesis, modeling, binding affinities, hormone potency, and a measure of quinone formation for a new family of A-CD estrogens, where the A-C bond is formed by ring coupling. Some substituents on the A-ring increase hormone potency, and one compound is much less quinone-forming than estradiol. These compounds span a wide range of receptor subtype selectivities and may be useful in hormone replacement therapy.Journal of Medicinal Chemistry 01/2011; 54(2):433-48. · 4.80 Impact Factor -
Article: Triterpenoids from the bark of Ruptiliocarpon caracolito.
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ABSTRACT: Five spirocaracolitone triterpenoids were isolated from the dichloromethane-soluble fraction of the bark of Ruptiliocarpon caracolito, and their structures were determined mainly by application of 1D and 2D NMR spectroscopy. Two known CD-spirotriterpenoids were also isolated from the same source. This brings the total number of known CD-spirotriterpenoids from this source to 17. The discovery of such a large number of closely-related compounds in a single species represents an excellent example of phytochemical redundancy as a defense mechanism.Phytochemistry 08/2010; 71(11-12):1418-22. · 3.35 Impact Factor -
Article: A RP-HPLC-DAD-APCI/MSD method for the characterisation of medicinal Ericaceae used by the Eeyou Istchee Cree First Nations.
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ABSTRACT: Ericaceae medicinal plants are traditionally used by the Eeyou Istchee Cree and other northern peoples of North America to treat type 2 diabetic symptoms. Because of the importance of phenolics as potential cures for degenerative diseases including type 2 diabetes, an analytical method was developed to detect them in the leaf extracts of 14 Ericaceae plants. To develop an optimised method which is applicable to a relatively large number of Ericaceae plants using their leaf extracts. For this purpose phenolics with a wide range of polarity, including a glucosylated benzoquinone, two phenolic acids, three flavanols, a flavanone, a flavone and five flavonols, were included in this study. Characterisation of phytochemicals in extracts was undertaken by automated matching to the UV spectra to those of an in house library of plant secondary metabolites and the authentication of their identity was achieved by reversed phase-high-performance chromatography-diode array detection-atmospheric pressure chemical ionisation/mass selective detection. Twenty-six phenolics were characterised within 26 min of chromatographic separation in 80% ethanol extracts of 14 Ericaceae plants. The calibration curves were linear within 0.5-880 microg/g dry mass of the plant with regression values better than 0.995. The limits of detection ranged from 0.3 for microg/mL for (+)-catechin to 2.6 microg/mL for chlorogenic acid. This is a first study dealing with relatively large number of Ericaceae extracts and is applicable to other plants of same family.Phytochemical Analysis 02/2010; 21(4):328-39. · 2.63 Impact Factor -
Article: Characterisation of phenolics in Flor-Essence--a compound herbal product and its contributing herbs.
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ABSTRACT: Commercially available herbal mixture FE, a proprietary natural health product manufactured by Flora Manufacturing and Distributing Ltd (Flora), is a unique North American traditional herbal product. FE is a chemically complex mixture of eight herbs and has not been subjected to phytochemical analysis. To develop analytical methods to undertake detailed phytochemical analyses of FE, and its eight contributing herbs, including burdock (Arctium lappa L.), sheep sorrel (Rumex acetosella L.), Turkish rhubarb (Rheum palmatum L.), slippery elm Muhl. (Ulmus rubra), watercress (Nasturtium officinale R. Br.), red clover (Trifolium pratense L.), blessed thistle (Cnicus benedictus L.) and kelp (Laminaria digitata Lmx.). The identification was undertaken by a combination of reversed phase high performance liquid chromatography-diode array detection-atmospheric pressure chemical ionisation-mass selective detection (RP-HPLC-DAD-APCI-MSD) analysis and phenolics metabolomic library matching. New separation methods facilitated the identification of 43 markers in the individual herbs which constitute FE. Sixteen markers could be identified in FE originating from four contributing herbs including four caffeoyl quinic acids, three dicaffeoyl quinic acids and two caffeic acid derivatives from A. lappa, luteolin-7-O-glucoside, luteolin, five apigenin glycosides and apigenin from R. acetocella and N. officinale and sissostrin from T. pretense. A validated method for quantitative determination of three markers is reported with good intraday, interday and interoperator repeatability using a reliable alcohol based extraction technique. FE and its contributing herbs predominantly contain phenolics. This methodology can be applied to further develop full-scale validation of this product.Phytochemical Analysis 07/2009; 20(5):395-401. · 2.63 Impact Factor -
Article: Deconstructing estradiol: removal of B-ring generates compounds which are potent and subtype-selective estrogen receptor agonists.
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ABSTRACT: Estradiol and related estrogens have been widely used as supplements to relieve menopausal symptoms, but they lead to an increased risk of breast and endometrial cancer. Here we report the synthesis of a new family of compounds where we have removed the B-ring from the steroid ABCD structure, and functionalized the A-ring. These A-CD compounds show a preferential affinity for the estrogen receptor subtype ERbeta. Some show binding affinities which are greater than estradiol. The presence of electron-withdrawing substituents on the A-ring should reduce the tendency of these compounds to form carcinogenic metabolites, so they might lead to a safer approach to hormone replacement therapy.Bioorganic & medicinal chemistry letters 01/2009; 19(4):1250-3. · 2.65 Impact Factor -
Article: Vulture restaurants and their role in reducing diclofenac exposure in Asian vultures
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ABSTRACT: The provision of supplementary food at vulture restaurants is a well-established tool in the conservation of vulture species. Among their many applications, vulture restaurants are used to provide a safe food source in areas where carcasses are commonly baited with poisons. Rapid and extensive declines of vultures in the Indian subcontinent have been attributed to the toxic effects of diclofenac, a pharmaceutical used in the treatment of livestock, to which vultures are exposed while feeding on the carcasses of treated animals. A vulture restaurant was established at the Oriental White-backed Vulture Gyps bengalensis colony at Toawala, in Punjab province Pakistan, to test the effectiveness of the technique in modifying ranging behaviour and mortality at the colony. Six male vultures were fitted with satellite transmitters to describe variation in movement and home-range during periods when safe food was alternately available and withheld at the vulture restaurant. There was considerable variation in individual home-range size (minimum convex polygons, MCP, of 1,824 km 2 to 68,930 km 2), with birds occupying smaller home-ranges centred closer to the restaurant being more successful in locating the reliable source of food. Fixes showed that 3 of the tagged vultures fed at the vulture restaurant and the home-range of each bird declined following their initial visit, with a 23–59% reduction in MCP. Mean daily mortality during provisioning was 0.072 birds per day (8 birds in 111 days), compared with 0.387 birds per day (41 birds in 106 days) during non-provisioning control periods. Vultures tended to occupy greater home-ranges, cover greater distances each day and spend proportionately more time in the air during the late brooding and post-breeding seasons. Attendance at the vulture restaurant also declined during this period with fewer birds visiting less often and no tagged vultures visiting the vulture restaurant at all. These findings indicate that vulture restaurants can reduce, but not eliminate, vulture mortality through diclofenac exposure and represent a valuable interim measure in slowing vulture population decline locally until diclofenac can be withdrawn from veterinary use.Bird Conservation International 01/2008; 17(1):63-77. · 1.25 Impact Factor -
Article: Spirocaracolitone triterpenoids from the bark of Ruptiliocarpon caracolito.
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ABSTRACT: Six new triterpenoids named spirocarcolitones (G-L), which belong to a novel class of CD-spiro triterpenoids, were isolated from the dichloromethane-soluble fraction of the bark of Ruptiliocarpon caracolito. The structures of these natural products were established using mainly 1D and 2D NMR spectroscopy. One known CD-spiro triterpenoid and canophyllol were also isolated from the same source.Journal of Natural Products 09/2007; 70(8):1228-32. · 3.13 Impact Factor
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Institutions
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2007–2012
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University of Ottawa
- Department of Chemistry
Ottawa, Ontario, Canada
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