University of SaskatchewanHARVEST
  • Login
  • Submit Your Work
  • About
    • About HARVEST
    • Guidelines
    • Browse
      • All of HARVEST
      • Communities & Collections
      • By Issue Date
      • Authors
      • Titles
      • Subjects
      • This Collection
      • By Issue Date
      • Authors
      • Titles
      • Subjects
    • My Account
      • Login
      JavaScript is disabled for your browser. Some features of this site may not work without it.
      View Item 
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item

      Local effects of Linoorbitides and enterolactone On intestinal epithelial functions

      Thumbnail
      View/Open
      ALMOUSA-DISSERTATION-2017.pdf (2.613Mb)
      Date
      2017-03-20
      Author
      Almousa, Ahmed A. 1985-
      ORCID
      0000-0001-5183-1988
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
      Show full item record
      Abstract
      The use of natural products is becoming increasingly popular worldwide. Flaxseed is a source of natural products that are rich with bioactives and have been reported to modulate inflammation, blood pressure, glucose levels and lipid profiles in both humans and animals. Currently, several known bioactives including fibers, lignans, alpha-linolenic acid, and linoorbitides (LOBs) are believed to impart those pharmacological activities. Previous studies have focused on the ability of flaxseed bioactives to provide their pharmacological action in the systemic circulation. However, our increasing understanding of their pharmacokinetics and chemical structures, suggests enhanced abundance of LOBs and lignans at the level of the intestinal epithelium due to the potential lack of permeation of LOBs, and susceptibility of lignans to enterohepatic circulation. Our aim in this work is to evaluate the effects of the lignan enterolactone (ENL) and LOBs on intestinal epithelium function and how it might influence associated pathologies like inflammatory bowel disease (IBD) and hypercholesterolemia. We first assessed LOBs and ENL effects on barrier integrity (a pathological hallmark of IBD) in vitro using a monoculture transwell system, and the potential mechanisms involved in maintenance of the barrier. Next, we examined their effect in a coculture system that more closely simulates the intact intestinal mucosa. These studies triggered the evaluation of pyruvate kinase M-2 (PKM2) as a possible biomarker of IBD. Lastly, we evaluated the effect of lignans on cholesterol metabolism in a human intestinal epithelial cell line (Caco-2). Our barrier integrity assessments of LOBs and ENL in the monoculture system identified differential effects of LOBs and ENL, and both showed increased protein levels of anti-inflammatory peroxisome proliferator-activated receptor gamma (PPAR-γ) and tight junction protein zonula, occludin (ZO-1). Further, in newly diagnosed IBD patients, PKM2 was indicative of disease presence with less variation than other biomarkers like fecal calprotectin and fecal lactoferrin. Lastly, altered cholesterol trafficking was observed in Caco-2 cells, an effect best attributed to the glucuronic acid conjugated form of enterolactone. These studies confirmed the importance of the flaxseed bioactives, ENL and LOBs in maintaining barrier integrity and modulation of cholesterol metabolism. More importantly, and due to their increased abundance at the level of the intestinal epithelium, those effects are crucially important in IBD and hypercholesterolemia. However, these effects remain to be evaluated in an animal models of colitis and dyslipidemia.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Pharmacy and Nutrition
      Program
      Pharmacy
      Supervisor
      Alcron, Jane; Krol, Edward S.
      Committee
      Blackburn, David; Bandy, Brian; Fowler, Sheryl; Muir, Alister
      Copyright Date
      March 2017
      URI
      http://hdl.handle.net/10388/7781
      Subject
      Intestinal function
      Enterolactone
      Linoorbitides
      Barrier Integrity
      Cholesterol Trafficking
      Collections
      • Graduate Theses and Dissertations
      University of Saskatchewan

      University Library

      The University of Saskatchewan's main campus is situated on Treaty 6 Territory and the Homeland of the Métis.

      © University of Saskatchewan
      Contact Us | Disclaimer | Privacy