Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Pharmacology and Toxicology

Supervisor

Dr. Edmund MK Lui

Abstract

The relationship between American ginseng immunostimulatory and immunoinhibitory effects and the unique bioactive fractions of its different extracts namely aqueous (AQ) and alcoholic (ALC) extracts was investigated. AQ extract up-regulated the production of nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), while ALC extract did not upregulate macrophage function. ALC extract but not AQ extract suppressed lipopolysaccharide (LPS) induced macrophage NO and TNF-α production. Macrophage-stimulating activity of the AQ extract was inhibited in the presence of ALC extract. Fractionation of AQ extract revealed that its crude polysaccharides (PS) are the only immunostimulatory phytochemical. Fractionation study of ALC extract showed that its macromolecule and ginsenoside fractions contribute to the extract’s immunoinhibitory effect. ALC extract which was devoid of PS, was immunoinhibitory whereas the AQ extract which contained PS, was immunostimulatory. These effects may be considered as the paradoxical immunomodulatory actions of ginseng.

Recent studies suggest that ginseng PS also suppress induced proinflammatory responses. Investigation was performed ex vivo and in vivo to determine whether American ginseng roots polysaccharides (AGRPS) stimulates basal innate immune function and at the same time can suppress LPS proinflammatory response. An in vitro mechanistic study was used to identify the fractions responsible for AGRPS immunobioactivities. Orally administered AGRPS exerted immunostimulation and suppressed LPS immune response under basal and LPS proinflammatory conditions ex vivo and in vivo. Similar AGRPS immunostimulatory and immunouppressive effects were observed in vitro, and these AGRPS immunodulatory effects were mediated primarily by acid PS and its species with molecular weights ≥100 kDa and 50 - 100 kDa.

The intestinal absorption of orally administered immunomodulatory AGRPS is yet to be ascertained. Absence of a method to analyze ginseng PS created the need for a novel method to investigate the intestinal absorption of orally administered unlabeled AGRPS into systemic circulation. Perchloric acid-protein precipitation of plasma and high performance size exclusion chromatography (HPSEC) with right angle light scattering detection was used as novel approach to analyze AGRPS in plasma of rats after oral administration of AGRPS. Outcome of this study indicates that orally administered immunomodulatory AGRPS is absorbed from the gastrointestinal tract into systemic circulation.


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