The aim of this project was to investigate a range of medicinal herbs which have radical scavenging and antioxidant activities and then apply novel mass spectrometric techniques to investigate and analyse active components responsible for their pharmaceutical actions. A sensitive electron capture negative ionization of gas chromatography-mass spectrometry (ECNI-GC-MS) method was developed to assess hydroxyl radical production, as indicated by 3.4-dihydroxyphenylacetic acid (DOPAC) production, which allows excellent evaluation of hydroxyl radical scavenging and antioxidant activity of a number of medicinal Chinese herbs. Melatonin is an effective multiple radical scavenger and antioxidant and has been used in this study for the comparison of radical scavenging activity with medicinal herbs. To analyse active compounds from herbal extracts, mass spectrometric techniques were used to separate components that suppressed hydroxyl radical production from Dimocarpus longan Lour, determine known ginsenosides from ginseng extracts as well as to identify and quantify melatonin in ten herbal extarcts. The results obtained indicated that 1) the utilization of alumina in the ECNI-GC-MS method diminished interferences from ???noise??? products in a Fenton-type reaction, which allows obtaining pure final hydroxyl radical product and this method demonstrated optimal sensitivity and reliability; 2) Aqueous extracts of all herbs analysed showed different levels of hydroxyl radical scavenging activity. Dimocarpus longan Lour, Chrysanthemum morifolium Ramat, Lonicera hypoglauca Miq, Ginkgo biloba L, Rehmannia flutinosa and Libosch Cornus officinalis Sieb all exhibited stronger inhibitory effect on hydroxyl radical production than melatonin. 3) Aqueous extract of Dimocarpus longan Lour. showed the greatest inhibitory effect on hydroxyl radical production among the other herbs tested. The active fractions of this herb eluted just after the void volume using HPLC suggesting that the active compounds responsible for radical scavenging activity are polar and water soluble. They may belong to phenol group of chemicals. 4) Herbal extracts using non-polar solvents showed no effect on hydroxyl radical production suggesting active compounds in those herbs are water soluble. 5) Different species and origins of ginseng were compared for their radical scavenging activity. Chinese fresh ginseng (Oriental ginseng) showed higher activity than Korean ginseng tablet and American ginseng. Seven known active ginsenosides were identified using HPLC-MS-MS. 6) Melatonin was found at varying concentrations in ten herbs, which may contribute to the radical scavenging activity of herbs, on the other hand, it may provide the justification of clinical use and food resources, particularly for those herbs contain high level of melatonin.

INTRODUCTION Antioxidant micronutrients may help alleviate oxidative stress in cystic fibrosis (CF) lung disease. To determine treatment effect, systematic reviews (SR) synthesize available evidence. Cochrane SRs are known for being methodologically rigourous, however, may have limited generalizability. OBJECTIVES To assess effectiveness of antioxidant micronutrients in CF lung disease using Cochrane and non-Cochrane SR methodology; to determine whether Cochrane SRs trade relevance for rigour METHODS The first SR followed Cochrane-preferred methods, while the non-Cochrane SR employed a broader search strategy and nclusion criteria. Reviews were contrasted regarding yield of search, treatment effect (efficacy and safety) and risk of bias. RESULTS Neither SR had enough data to support or refute efficacy or safety of antioxidant supplementation in CF lung disease. Compared to the Cochrane SR, the non-Cochrane SR had four more included studies, more precise estimates of efficacy, additional harms data and a similar risk of bias. CONCLUSION Broader search strategies and inclusion criteria may improve relevance of Cochrane SRs without compromising rigour. / Clinical Epidemiology

Thesis (Ph.D.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 203-239.

Red raspberries, as an excellent source of dietary antioxidants, were investigated for their effect on oxidative stress in healthy adults. Study 1 measured effects of chronic exposure in a parallel, multi-dose intervention. Subjects consumed one-cup red raspberries (1cR) daily for two-weeks, then were randomized to consume 1cR, 2cR or 4cR for additional two-weeks (n=8, by group). There was a reduction in TBARS, indicating a decrease in lipid peroxidation, after two-weeks of intervention in the 1cR group, but effects were not significant at week 4, or for other treatment groups. Study 2 measured effects of acute exposure using a cross-over design. Subjects (n=8) consumed single treatments of 1cR, 2cR, 4cR, bread and bread plus vitamin C. Post-prandial oxidative stress responses were complex and appeared related to calorie and antioxidant load. Overall there was no clear relationship between red raspberry consumption and protection against oxidative stress.

Thesis (doctoral)--Swedish University of Agricultural Sciences, 2001. / Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 139-149).

Thesis (M.S.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Feb. 2, 2009). Includes bibliographical references (p. 35-48).

Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains ix, 38 p. : ill. Includes abstract. Includes bibliographical references.

published_or_final_version / Pharmacology and Pharmacy / Master / Master of Philosophy

Hyperglycemia is associated with a higher risk for the development of cardiovascular diseases such as atherosclerosis and hypertension. Hyperglycemia-induced generation of reactive oxygen species and the endothelial dysfunction largely account for this phenomenon. Ergothioneine is a naturally occurring amino acid that is abundantly found in mushroom. Numerous benefits have been found associated with ergothioneine such as cation chelating, regulation of gene expression, improvement in immunity and bioenergetics, and of most concern its antioxidative property. The aim of this study was to investigate whether mushroom extract and synthetic ergothioneine can exert protective effect on endothelial cells against oxidative stress. Human umbilical vein endothelial cells served as the cell model. Pyrogallol, hydrogen peroxide and high glucose were used to create the oxidative stress condition in endothelial cells. Biochemical assay was used to measure the viability of the cells. It was found that only the mushroom extract could significantly reduce the cell death induced by pyrogallol. Both the mushroom extract and synthetic ergothioneine significantly decreased the cell death induced by high glucose. However, neither mushroom extract nor synthetic ergothioneine have any positive effect on hydrogen peroxide-induced cell death. These results indicated that mushroom extract and synthetic ergothioneine did exert certain level of protective effect on endothelial cells. However, this protective effect is relatively weak. Besides, it is still unclear if antioxidation is the sole mechanism accounting for the cytoprotective effect of ergothioneine. Further investigation is required to examine if other mechanisms are also involved. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences