Pharmacokinetic and pharmacodynamic investigations of select natural products and nutraceuticals for human and veterinary health

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dc.contributor.authorMartinez, Stephanie
dc.contributor.examiningcommitteeBurczysnki, Frank (Pharmacy) Gong, Yuewen (Pharmacy) Beta, Trust (Food Science) Lefebvre, Jean (Laval University)en_US
dc.contributor.supervisorDavies, Neal (Pharmacy)en_US
dc.date.accessioned2016-03-22T15:32:51Z
dc.date.available2016-03-22T15:32:51Z
dc.date.issued2013-01en_US
dc.date.issued2013en_US
dc.date.issued2014-08en_US
dc.date.issued2015-05en_US
dc.date.issued2015-07en_US
dc.date.issued2015-09en_US
dc.date.issued2013en_US
dc.date.issued2013en_US
dc.date.issued2013en_US
dc.date.issued2013en_US
dc.degree.disciplinePharmacyen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractNatural products are teeming with potential therapeutic agents. One group of compounds, polyphenols, from plants, exhibit anti-cancer, anti-inflammatory and anti-oxidant activities. Four polyphenolic compounds and their enantiomers were investigated in this thesis; the stilbene, 3-methoxypterostilbene, a structural analog of resveratrol, and the chiral prenylflavonoids from hops (Humulus lupulus L.); 8-prenylnaringenin, 6-prenylnaringenin and isoxanthohumol. A high performance liquid chromatography method for 3-methoxypterostilbene and enantiospecific liquid chromatography-mass spectrometry assays for the three prenylflavonoids were developed and validated. The methods allowed for quantification of these four polyphenols in biological samples and plant-based materials. Content analysis studies of 3-methoxypterostilbene and the three prenylflavonoids in traditional Chinese medicinal plants and hops-containing nutraceuticals were carried out, respectively. The pharmacokinetics of these four compounds were delineated through intravenous and oral administration in rats. 3-Methoxypterostilbene demonstrated greater bioavailability in rats than reported values for resveratrol. Enantiomeric differences in disposition parameters were observed for the three prenylflavonoids along with differences between compounds despite only small structural differences. The in vitro pharmacodynamics of these four compounds were elucidated including anti-oxidant, anti-inflammatory, anti-diabetic and cytochrome P450 modulation activities. All four compounds demonstrated a range of bioactivities related to chronic diseases and potential drug-botanical interactions. Further studies of polyphenols, especially clinical studies, are needed along with enantiospecific study when applicable to continue delineating the importance of bioactivity, pharmacokinetics and safety. Natural products are further developed into nutraceuticals and sold over-the-counter for both human and veterinary use but are not currently required to demonstrate efficacy prior to marketing. In the final section of this thesis, Phycox®, a multi-component veterinary nutraceutical for joint health was investigated for pharmacological activity in an in vitro model of canine osteoarthritis along with select constituents. A pilot single-dose pharmacokinetic study in dogs was also undertaken. Two liquid chromatography tandem mass spectrometry methods were developed and validated to detect constituents in serum. In vitro study results indicated that Phycox® was able to reduce inflammatory mediators similar to the NSAID, carprofen, and acute pharmacokinetic results revealed that detectable concentrations of glucosamine were evident in serum. It is suggested that further clinical studies of Phycox® are warranted to optimize its usage.en_US
dc.description.noteMay 2016en_US
dc.identifier.citationMartinez SE, Sayre CL, Davies NM. Analysis of 3-methoxypterostilbene in biological fluids by high-performance liquid chromatography: application to pre-clinical pharmacokinetics. Biomed Chromatogr. 2013 Jan;27(1):67-72.en_US
dc.identifier.citationMartinez SE, Sayre CL, Davies NM. Pharmacometrics of 3-methoxypterostilbeneL a component of traditional Chinese medicinal plants. Evid Based Complement Alternat Med. 2013;2013:261468.en_US
dc.identifier.citationMartinez SE, Lakowski TM, Davies NM. Enantiospecific analysis of 8-prenylnaringenin in biological fluids by liquid-chromatography-electrospray ionization mass spectrometry: application to preclinical pharmacokinetic investigations. Chirality. 2014 Aug;26(8):419-26.en_US
dc.identifier.citationMartinez SE, Davies NM. Stereospecific quantitation of 6-prenylnaringenin in commercially available H. lupulus-containing natural health products and dietary supplements. Res Pharm Sci .2015 May-Jun;10(3):182-91.en_US
dc.identifier.citationMartinez SE, Chen Y, Ho EA, Martinez SA, Davies NM. Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis. Can J Vet Res. 2015 Jul;79(3):241-9.en_US
dc.identifier.citationMartinez SE, Davies NM. Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat. Mol Nutr Food Res. 2015 Sep;59(9):1674-89.en_US
dc.identifier.citationMartinez SE, Davies NM, Reynolds JK. Toxicology and Safety of Flavonoids. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013.en_US
dc.identifier.citationTakemoto JK, Martinez SE, Davies NM. Analysis of Flavonoids through Chromatography. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013.en_US
dc.identifier.citationYáñez JA, Sayre CL, Martinez SE, Davies NM. Chiral Methods of Flavonoid Analysis. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013.en_US
dc.identifier.citationYáñez JA, Remsberg CM, Takemoto JK, Vega-Villa KR, Andrews PK, Sayre CL, Martinez SE, Davies NM. Polyphenols and Flavonoids: An Overview. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013.en_US
dc.identifier.urihttp://hdl.handle.net/1993/31166
dc.language.isoengen_US
dc.publisherJohn Wiley & Sons, Ltd.en_US
dc.publisherHindawi Publishing Corporationen_US
dc.publisherWiled Periodicals, Inc.en_US
dc.publisherMedknow Publicationsen_US
dc.publisherCanadian Veterinary Medical Associationen_US
dc.publisherWILEY-VCH Verlag CmbH & Co.en_US
dc.publisherJohn Wiley and Sons, Inc.en_US
dc.publisherJohn Wiley and Sons, Inc.en_US
dc.publisherJohn Wiley and Sons, Inc.en_US
dc.publisherJohn Wiley and Sons, Inc.en_US
dc.rightsopen accessen_US
dc.subjectPharmacokineticsen_US
dc.subjectPharmacodynamicsen_US
dc.subjectFlavonoidsen_US
dc.subjectNatural productsen_US
dc.subjectVeterinary nutraceuticalen_US
dc.subjectStilbenesen_US
dc.subjectMethods of analysisen_US
dc.subjectChiral flavonoidsen_US
dc.subjectHumulus lupulus L.en_US
dc.subjectContent analysisen_US
dc.titlePharmacokinetic and pharmacodynamic investigations of select natural products and nutraceuticals for human and veterinary healthen_US
dc.typedoctoral thesisen_US
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