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A Multivariate Approach to Integration of Ethnobotanical, Pharmacological, and Phytochemical Analyses of Cree and Squamish Traditional Herbal Medicines for Anti-Diabetes Use

This thesis investigated the integration of pharmacological and phytochemical data of medicinal plants from the Cree of Eeyou Istchee in Northern Quebec. Data from these 17 plant extracts were assessed for patterns of biological activity and chemical signals that could be explained by taxonomic or plant organ groupings. The Squamish medicinal plant Oplopanax horridus (Sm.) Miq. was also assessed for enzyme inhibition activity across multiple extracts and for bioactive compounds using an untargeted metabolomics approach.
A comprehensive data set was assembled documenting the relative activities on the 17 plant extracts in 69 cell-free and cell-based bioassays covering activity on glucohomeostasis, effects of hyperglycemia, and capacity for enzyme inhibition. Multivariate analysis suggests that the leaf part extracts are particularly associated with antioxidant and antiglycation activities, while another discrete group of extracts associate strongly with other sets of glucohomeostasis assays. The activity of extracts on enzyme inhibition appears to be the factor most strongly driving the majority of activity patterns, likely because extracts that interact strongly with more metabolic enzymes will have more effects on other targets in the body.
The phytochemical profiles of the Cree medicinal plants were assessed in two ways. First, spectroscopic and chromatographic data for the plant extracts was compared to a database of phytochemical standards using a proprietary Waters software, UNIFI, to match known signals of chemical standards to unidentified peaks in the plant extracts. Second, similarly collected spectroscopic data for the Cree plant extracts was processed using the software MZMine for multivariate analysis in R, revealing the chemical diversity of the bark extracts in relation to the fruit and leaf extracts. Additionally, marker signals were determined for major sample groupings, and the capacity for this analytical approach to be used to tentatively identify unique compounds was demonstrated.
Through bioassay guided fractionation of the O. horridus inner bark extract using the CYP 3A4 inhibition assay, the DCM subfraction midway through the non-polar elution on open column chromatography was determined to be the most potent. This fraction contained 10 major peaks on HPLC-DAD analysis. The hot water extract was found to have negligible activity on CYP 3A4 inhibition.
Together, this research provides the first integrated look at the pharmacological and phytochemical data from across the Cree anti-diabetic medicinal plants in a statistical way, as well as providing a first look at O. horridus for inclusion in the anti-diabetes project.

Identiferoai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/39248
Date27 May 2019
CreatorsHall, Braydon
ContributorsHarris, Cory Steven
PublisherUniversité d'Ottawa / University of Ottawa
Source SetsUniversité d’Ottawa
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf

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