TitleStudies on Nrf2-targeted phytochemicals
NameWang, Hu (author), Kong, Ah Ng Tony (chair), Hatefi, Arash (internal member), Michniak-Kohn, Bozena B. (internal member), Nomeir, Amin A. (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionPrevention has been regarded as a superior approach in dealing with diseases. Huang-Di Ne-Jing, a manuscript believed being written by the ancient Chinese emperor, indicated: "… the Saint treats those ill-to-be rather than those being ill" (Chapter 1, Introduction) Cancer, as it takes as long as 20 to 30 years to develop from initiated cells to malignant tumor, allows precious opportunities to prevent its occurrence and delay its progression. In the past centuries, fruitful searching for natural and synthetic cures of cancer enriched our understanding and empowered our treatment options for this disease. Phytochemicals have been sought after as handy and effective reagents for such task, along with the proposed and accepted mechanisms and pathways (Chapter 2, Plants vs. Cancer). To understand the nature of Nrf2, we studied the role of Nrf2 in suppressing LPS-induced inflammation in mouse peritoneal macrophages via ex vivo approach (Chapter 3, Role of Nrf2 in inflammation suppression by DHA/EPA in mouse peritoneal macrophages). To enable further preclinical in vivo research of sulforaphane, an Nrf2 initiator and an anti-carcinogenesis agent enlisted by National Cancer Institute, a highly sensitive and robust bioanalytical method was developed, validated, and applied to the pharmacokinetic studies in rats (Chapter 4, Bioanalytical Method for Sulforaphane). A follow-up study, linking the pharmacokinetics and pharmacodynamics, enlightened how sulforaphane drives Nrf2-related gene expression of phase II drug metabolism enzymes in rat lymphocytes (Chapter 5, PK/PD studies of sulforaphane in rat following intravenous administration). From the review of the current research frontier on natural phytochemicals for cancer chemoprevention and treatment, to the Nrf2 role elucidation at the molecular level; from the bioanalytical method characterization and its application to in vivo studies, to modeling the pharmacokinetics in blood plasma and the pharmcodynamics of mRNA effects in lymphocytes, our studies contributed to the better understanding of Nrf2 and to the application potentials of the phytochemicals for their druggability. We wish to further the discovery and development research: to prevent the patients from being patients, the ultimate goal of a pharmaceutical research scientist.
NoteIncludes bibliographical references
Noteby Hu Wang
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.