Liver is one of the most important organs in the body that maintains the homeostasis of metabolism, immunity, detoxification and hematopoiesis. A large number of acute and chronic intoxications and diseases can influence the normal functions of the liver, leading to irreversible liver damage and even cancer. Currently, applying herbs or herbal derivatives in the prevention and therapy of acute and chronic liver injury receive numerous attentions since they hold great potentials as food supplements in the treatment strategy of liver injuries. There were two major hypotheses of this current work namely: a)In CCl4-inducedacute liver injury animal model, whether pre-treatment with garlic derived S-allylmercaptocysteine (SAMC)or Wolfberry derived Lycium barbarum polysaccharides (LBP)could reduce liver injury, oxidative stress and inflammation partly through a NF-κB-dependent pathway. SAMC or LBP could also promote liver regeneration after acute damage. b)In non-alcoholic steatohepatitis (NASH)-induced chronic liver injury animal model, whether administration of SAMC or LBP along with high-fat diet induction could attenuate liver injury, lipid metabolism dysfunction, fibrosis, oxidative stress, inflammation, apoptosis and transcription factors activities in the liver. In this study, SAMC and LBP were applied in a carbon tetrachloride (CCl4) induced mice acute liver injury model and a high-fat diet induced non-alcoholic steatohepatitis model. In the acute model, an eight-hour CCl4treatment induced severe acute liver injury. Pre-treatment with SAMC or LBP (1) attenuated hepatic histological injury; (2) reduced serum ALT level; (3) ameliorated oxidative stress; (4) reduced expression of inflammatory mediators and chemokines; (5) promoted liver regeneration; and (6) decreased NF-κB activity. Vehicle-treated SAMC or LBP did not exhibit obvious adverse effects on healthy mice. In the chronic NASH model, when compared with control rats, NASH rats showed typical clinical features of human NASH patients, including increased liver injury, lipid content, oxidative stress, inflammation, and apoptosis. In comparison, SAMC or LBP co-treated NASH rats showed (1) reduced fat accumulation, cellular necrosis, collagen formation, as well as reduced serum ALT and free fatty acids levels; (2) restored insulin resistance related kinase phosphorylation status which had been altered during NASH; (3) reduced pro-fibrogenic factors; (4) restored antioxidant enzymes, as well as attenuated end-products of lipid peroxidation and NO production through a cytochrome P450 2E1-dependent pathway; (5) reduced hepatic pro-inflammatory mediators and chemokines production; (6) diminished activities of nuclear transcription factors (NF-κB and AP-1); and (7) ameliorated hepatic cellular apoptosis through a p53-dependentpathwaywhich was under the regulation of LKB1/AMPK axis and PI3K/Akt axis. In conclusion, our data demonstrated that SAMC or LBP consumption protects the liver from acute injury caused by CCl4and chronic damages caused by a high-fat diet. These effects were mainly mediated by the amelioration of hepatic oxidative stress, inflammation, and cell death. In the NASH model, SAMC or LBP also improved hepatic lipid metabolism, fibrosis, and apoptosis. Therefore, the present study proposed that both garlic and Wolfberry, which are novel hepatoprotective herbal products, can be taken as part of the daily dietary supplements in the prevention of acute and chronic liver injury. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

This study investigated potential apoptotic and anti-proliferative effects of the phytochemicals, genistein and anthocyanin extract, as single and combined treatments in MCF-7 human breast cancer cells. Cells were exposed to single and combined treatments with the phytochemiclas for 48 and 72 hours. Cell viability was assessed using the MTT bioassay. Apoptosis induction was assessed using acridine orange ethidium bromide and rhodamine 123 ethidium bromide fluorescence assays. Both singe and combination treatments induced dose- and time-dependent apoptotic cell death in MCF-7 cells. The percentage of apoptosis was higher in combination treatments than single treatments with either phytochemical, although the difference was not statistically significant. The combination of genistein and anthocyanin extract peaked in efficacy at 48 hours of treatment, to exhibit significantly greater (P<. O5) dose- and time-dependent cell cytotoxicity than single treatments. This study reveals potential chemopreventive implications for the complementary effects of genistein and anthocyanin extract. / by Corine M. Stinson. / Thesis (M.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

This study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) > 10uM genistein > 70uM genistein. The chi-square test for comparing necrosis, apoptosis and life cells showed that Vitamin C could impact genistein-induced apoptosis in LNCaP cells (p = 0.0003). This study forms the basis for in vivo studies of the impact of vitamin C on genistein-induced apoptosis in LNCaP prostate cancer cells. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

An estimated 220,800 new prostate cancer cases and 27,540 deaths are expected to occur in US men by the end of 2015. Despite the increased treatment modes for prostate cancer, there is still no definite cure, and prognosis remains, at best, cautiously optimistic. The explicit amalgamation of two or more cancer therapeutic modalities such as surgery, radiation, and chemotherapy, has been one of the main interests of clinical investigation for several decades. Genistein (GN) and Beta-lapachone (BL) are two of the most promising anticancer phytochemical compounds. However, the anticancer activities of BL have been correlated with the enzyme activity of NQO1. The aim of this study was to investigate the enhancing effects of VLDR derived from a portable pyroelectric crystal generator on the chemopreventive and/or chemotherapeutic effects of GN and BL in NQO1+ PC3 and NQO1± (deficient) LNCaP prostate cancer cells (PCa) in vitro. The combination treat ment-induced cytotoxicity was investigated via MTT and Trypan blue exclusion assays. Dicoumarol (an NQO1 inhibitor) was co-administered to assess the effect of VLDR on NQO1 modulation. Nitro-blue tetrazolium assay was used to assess the intracellular ROS levels. Fluorescence microscopy was also used to assess the mode of cell death. In this study, a novel quantitative modeling approach was employed to comparably assess the cytotoxic effects of specific drugs used alone or in combinations with VLDR and to predict the potential synergistic therapeutic combinations. The data suggests that VLDR induced a rise in ROS levels, followed by upregulation in NQO1 levels. Pharmacodynamic indices were developed to quantify and characterize the combination treatment as synergistic, additive or antagonistic per dose or time-interval. Synergism was found to be dose and time-interval dependent. The major mode of cell death by this combination therapeutic regimen was found to be via apoptosis . In conclusion, our results confirm that VLDR enhanced cytotoxicity effects of both drugs dose- and time-dependently. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

A breast cancer cell line stably transfected with the CYP19 gene had been employed for aromatase inhibition. Among the phytochemicals tested, the major dietary flavonoids, such as genistein and daidzein, produced very weak inhibition. On the other hand, the red clover isoflavone biochanin A, the hydroxychalcone butein and the red grape phytoalexin resveratrol were found to be effective aromatase inhibitors. Cell proliferation assay had shown that they could inhibit ER-positive cell proliferation induced by testosterone, and the inhibitory effect was specifically attributed to the reduction of estrogen synthesis. In another breast cancer cell line SK-BR-3, resveratrol, biochanin A and genistein inhibited CYP19 both in enzyme and promoter I.3/II transcriptional levels. The element responsible for the inhibition of aromatase by these phytoestrogens should fall within the region between -556 to -446 by upstream of exon II. / Breast cancer is one of the most common cancers affecting women. Estrogen plays an important role in breast cancer initiation and development. The majority of breast tumors are initially dependent upon estrogen to support their growth. Most breast cancers occur in the postmenopausal period. However, the intra-tumoral estradiol (E2) is maintained at a high level equivalent to the pre-menopausal status. High intra-tumoral E2 level in postmenopausal women is sustained by the biosynthesis of estrogens in the tumorous tissue. / Genistein and Biochanin A, ranged from 0.1 to 10 muM, might act as estrogen agonist and induced aromatase activity and promoter I.1 transactivation in ERalpha-transfected SK-BR-3 cells. (Abstract shortened by UMI.) / The aromatase enzyme, CYP19, belongs to a family of P450 enzyme. As a final rate-limiting step in estrogen biosynthesis, it catalyzes the conversion of C 19 steroids to estrogens. The expression of CYP19 is tissue-specific, and is regulated by alternate promoter usage. The use of aromatase inhibitors for breast cancer treatment has become a major therapeutic approach. / The consumption of some phytochemicals protects against breast cancer. Yet the mechanisms are far from clear. In my present study, various phytochemicals, including phytoestrogens, monoterpenes and carotenoids, were evaluated for their effect on aromatase. / Wang Yun. / "July 2005." / Adviser: Lai-Kwok Leung. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3716. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 145-169). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.