Combination therapy has proven to be a popular treatment strategy for tighter diabetes control. Since the preliminary evidence is suggestive of complementary actions of American (AG) and Korean Red Ginseng (KRG) in improving glycemia, this project was designed to investigate the therapeutic potential of AG and KRG in combination. Following a randomized, double-blind, placebo-controlled parallel design in a population with diabetes at two centres, the combined use of AG and KRG for 12 weeks was safe, but did not significantly affect glycemic control, blood lipids or blood pressure. However, there was a trend toward lower glycated hemoglobin by 0.7% (p=0.1) and office systolic blood pressure by 5 mm Hg (p=0.052) compared to placebo. These findings encourage further investigation of the mechanism and roles of AG, KRG and their effective components. They also highlight limitations in ginseng research and the need to impose strict regulations to facilitate its standardization.

Combination therapy has proven to be a popular treatment strategy for tighter diabetes control. Since the preliminary evidence is suggestive of complementary actions of American (AG) and Korean Red Ginseng (KRG) in improving glycemia, this project was designed to investigate the therapeutic potential of AG and KRG in combination. Following a randomized, double-blind, placebo-controlled parallel design in a population with diabetes at two centres, the combined use of AG and KRG for 12 weeks was safe, but did not significantly affect glycemic control, blood lipids or blood pressure. However, there was a trend toward lower glycated hemoglobin by 0.7% (p=0.1) and office systolic blood pressure by 5 mm Hg (p=0.052) compared to placebo. These findings encourage further investigation of the mechanism and roles of AG, KRG and their effective components. They also highlight limitations in ginseng research and the need to impose strict regulations to facilitate its standardization.

Matrix metalloproteinase (MMP) induced extra cellular matrix (ECM) degradation is a crucial process involved in the development of many chronic inflammatory diseases, including cardiac remodeling and cancer metastasis. In cardiac remodeling, the presence of pathological stimuli leads to elevated MMP-9 expression and impairment of cardiac performance, which subsequently develops into heart failure. While in tumorgenesis, MMP-9 has been found to play key roles in metastasis, as it can break physical barriers for the tumor. Therefore, searching for agents targeting MMP-9 is a new direction for the treatment of cardiac remodeling and cancer metastasis. Chinese herbal medicine is becoming increasingly used worldwide in recent decades. In the past twenty years, as many highly selective and sensitive bioassays were introduced into the bioactive compounds screening from herbal medicine, more than one hundred new drug candidates have been identified. Therefore, herbal medicine is a potential source of bioactive compounds. Panax notoginseng (PNG) is one of the most common traditional Chinese medicines to treat cardiovascular diseases, and it was also reported to have anti-cancer effect. We hypothesized that it contains bioactive compounds that could inhibit MMP-9 activity in cardiomyocytes and cancer cells. In order to examine the effect of PNG on cardiac remodeling and cancer metastasis, we employed TNF-α induced MMP-9 in H9c2 cell (a rat cardiomyocyte) and HepG-2 cell (a human hepatoma cell) as an in vitro assay, respectively. PNG was first extracted by four different extraction methods according to the polarity of the solvent. The most effective fraction in suppressing MMP-9 activity in TNF-α induced H9c2 cell was chosen for further separation by silica gel column chromatography and high performance liquid chromatography (HPLC) until a single compound was isolated. According to the result of spectroscopic analysis by NMR, the compound was identified as ginsenoside Rb1. For the bioactivity assays, real-time quantitative polymerase chain reaction (QPCR) and Enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA and protein expression of MMP-9, respectively. We also examined the MMP-9 activity by gelatin zymography. The results showed that both of the PNG extract obtained from 10% ethanol extraction method (PNG-3) and purified Compound P (ginsenoside Rb1) showed significant inhibitory effect on MMP-9 expression and activity in H9c2 cells and HepG-2 cells. We further examined the molecular mechanisms of the inhibitory effect of PNG-3. H9c2 and HepG-2 cells were pretreated with different kinase inhibitors followed by the activation by TNF-α. The results showed the protein kinase R (PKR) inhibitor could inhibit TNF-α induced MMP-9 in both of the two cell lines. Furthermore, the results of Western blot showed the PNG-3 suppressed the phosphorylation of eIF-2α which is a down-stream effector of PKR in TNF-α stimulated H9c2 and HepG-2 cells, respectively. Therefore, PNG-3 may act through PKR to regulate TNF-α induced MMP-9 activity. In summary, bioactivity guided fractionation is an effective way of isolating bioactive compounds from medicinal herbs. In addition, PNG containing ginsenoside Rb1 may be a potential candidate of MMP-9 inhibition for the treatment of cardiac remodeling and cancer metastasis. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

University of Macau / Institute of Chinese Medical Sciences

Obligate shade plants possess adaptations that enable them to photosynthesise in the low light environment of the forest floor. Adaptations that facilitate light scavenging may compromise capacity for high rates of photosynthesis. This study compares the responses of obligate shade and facultative shade plant species upon exposure to elevated light. The obligate shade plants were two commercially grown medicinal herb species of ginseng, Panax ginseng C.A. Meyer and Panax quinquefolius L.; and goldenseal - Hydrastis canadensis L. Comparison was made to Arabidopsis thaliana and Pisum sativum L. as facultative shade species. Panax ginseng (Korean ginseng) and Panax quinquefolius (American ginseng) are obligate shade plants found in broadleaf forests of Eastern Asia and North America, respectively. Studies on these plants have shown optimal growth at light intensities between 200-300 [mu]mol photons. m⁻�. s⁻�, or 10-15% of full sunlight, and at intensities greater than 500 [mu]mol photons. m⁻�. s⁻� characteristic photoinbibitory symptoms develop. An atypical response to methyl viologen in photosynthetic electron transport assays was observed in ginseng in both isolated thylakoid membranes and whole leaves. No correlation was found between detectable superoxide dismutase activity and altered methyl viologen reactions. In a mutagenesis study using the model cyanobacterium Synechocystis sp. PCC 6803, a unique amino acid residue in the terminal electron acceptor PsaC, found only in ginseng, was changed and found to have no effect on methyl viologen reactions. Electron transfer to methyl viologen was examined in both isolated thylakoid membranes and whole leaves using chlorophyll a fluorescence and the apparent ability for methyl viologen to act as an electron acceptor was observed to differ between ginseng species. Obligate shade species were observed to possess alternate pools of photosystem II centres that potentially provide a mechanism to maximise photosynthetic gain under low light and during short periods of increased illumination. In experiments designed to identify physiological processes that contribute to increased susceptibility to photoinhibition in obligate shade plants, responses were observed and characterised following a moderate increase in illumination (140 to 400 [mu]mol photons. m⁻� . s⁻�) using chlorophyll a fluorescence induction curve analysis. The obligate shade species exhibited varied responses to elevated light and showed increased susceptibility, to photoinhibition. Photoprotective non-photochemical dissipative capacity was quantified and found to be comparable between all species studied.

Thesis (Ph.D.) -- McMaster University, 2001. / Includes bibliographical references. Also available via World Wide Web.

Thesis (Ph. D.)--Michigan State University. Dept. of Food Science and Human Nutrition, 2008. / Title from PDF t.p. (viewed on Mar. 27, 2009). Includes bibliographical references. Also issued in print.

Thesis (M.S.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains vi, 98 p. : ill., map. Vita. Includes abstract. Includes bibliographical references.

Thesis (M.S.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains vii, 51 p. : ill. Includes abstract. Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 81-93). Also available in print.