Date of Award
Doctor of Philosophy in Pharmaceutical Sciences
Biomedical and Pharmaceutical Sciences
Complex carbohydrates exist in almost all species of plants, animals and microorganisms. Because of their physiochemical properties, they have been traditionally applied as emulsifiers and stabilizers in food, cosmetics, textiles and as pharmaceutical ingredients. Complex carbohydrates generally exist as a layer of thick, sequential, hydrous polymers consisting of monosaccharides and non-carbohydrate substituents such as acetate, pyruvate, and phosphate. While complex carbohydrates are generally believed to serve as structural support or energy sources for the producing organisms, their potential biomedical properties have been less investigated. Our understanding of the biological activities of complex carbohydrates is further complicated since most have been tested after only rough purification and their structural characteristics need to be further elucidated. In order to establish structure-activity relationships for these molecules, careful structural studies need to be undertaken.
In Manuscript I, a group of oligosaccharides isolated from North American cranberries (Vaccinium macrocarpon) was investigated for their inhibition on the biofilm formation by uropathogenic bacterium Escherichia coli CFT073. Most urinary tract infections (UTIs) are associated with E. coli that could form biofilm along the urinary tract, especially on the bladder wall, to prevent eradication by the urinal and immune system. Intake of cranberry juice is traditionally believed to have preventive effects against UTIs but the molecular mechanism is still unclear. In contrast to the role that phenolic secondary metabolites might play in preventing UTIs, carbohydrate constituents in cranberry have not been previously investigated. In this study, we identified certain oligosaccharides that are capable for reducing biofilm formation by uropathogenic E. coli.
In Manuscript II, a chemically characterized oligosaccharide-enriched fraction purified from the North American cranberries (Vaccinium macrocarpon) was evaluated for its capability of inhibiting the formation of advanced glycation end-products (AGEs) and antioxidant effects. AGEs are glycation adducts formed via non-enzymatic glycation occurred between carbohydrates and proteins. Long term in vivo accumulation of AGEs is involved in many chronic diseases. The oligosaccharide-enriched fraction inhibited AGE formation in with comparable activity to a synthetic anti-glycating agent. In the 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay, Cranf1b-CL showed antioxidant activity superior to the synthetic commercial antioxidant, butylated hydroxytoluene.
In Manuscript III, a Rhamnogalacturonan-I type pectic polysaccharide was isolated from ginseng root aqueous extract and shown to prevent biofilm formation by P. aeruginosa both in vivo and in vitro. Mechanistic study on the polysaccharide exhibited its inhibitory effect on the intracellular cyclic di-GMP level of P. aeruginosa, suggesting that this polysaccharide inhibits the biofilm formation by altering a core biochemical signaling process in P. aeruginosa to interrupt the biofilm formation and promote the biofilm dispersal.
In Manuscript IV, the polymeric substances from maple syrup were investigated. By ethanol precipitation and anion exchange chromatography, polysaccharides including inulin, rhamnogalacturonan, arabinogalactan and dextran were extracted and purified, among which inulin was isolated from maple syrup for the first time. The structures of these polysaccharides were analyzed by glycosyl composition analysis, glycosyl linakge analysis and NMR. Further investigations should be focused on the biological activities of maple syrup polysaccharides and their contributions to the overall health benefits of maple syrup.
Sun, Jiadong, "Investigations on Biologically Active Carbohydrates from Natural Sources" (2016). Open Access Dissertations. Paper 531.