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Isolation of gingerols and shogaols from ginger and evaluation of their chemopreventive activity on prostate cancer cells and anti-inflammatory effect on 12-O-tetradecanoylphorbol-13-acetate-induced mouse ear inflammation

Posted on:2008-01-09Degree:Ph.DType:Thesis
University:Rutgers The State University of New Jersey - New BrunswickCandidate:Ramji, DivyaFull Text:PDF
GTID:2444390005979237Subject:Agriculture
Abstract/Summary:
Ginger, obtained from the rhizome of Zingiber officinale (Family Zingiberaceae), has been used extensively as a spice and in traditional medicine. The compounds in ginger primarily responsible for its medicinal properties are the gingerols. Gingerols can undergo dehydration, during storage and processing, to form the corresponding shogaols. Studies conducted so far have primarily focused on the biological activities of ginger and 6-gingerol. The main objectives of this research were to evaluate the anti-inflammatory and chemopreventive activities of gingerols and shogaols.;The crude ginger extract was subjected to column chromatography to obtain a mixture of gingerols, a mixture of shogaols, 6-gingerol, 8-gingerol and 6-shogaol which were characterized using high pressure liquid chromatography and nuclear magnetic resonance spectroscopy.;The anti-inflammatory activity of 6-gingerol and 6-shogaol was evaluated using the 12-O-tetradecanoylphorbol-13-acetate-induced mouse ear inflammatory model. Both 6-gingerol and 6-shogaol inhibited ear edema as well as the levels of proinflammatory cytokines.;The primary focus of this study was to evaluate the chemopreventive potential of these compounds on prostate cancer cells (LNCaP and PC-3). We hypothesized that gingerols and shogaols exhibit their chemopreventive potential through the modulation of the intrinsic pathway of apoptosis. Cell viability studies indicated that, among the compounds tested, 6-shogaol, 8-gingerol and shogaol mixture were the most effective in inhibiting cell growth in both cell lines. Morphological assessment, cell cycle, Annexin V staining and western blot analysis showed that 8-gingerol and 6-shogaol induced apoptosis in both the cell lines. Western blot analysis further confirmed our hypothesis that 8-gingerol and 6-shogaol induced apoptosis through activation of the intrinsic pathway of apoptosis as seen by caspase-9 cleavage. In addition, 8-gingerol and 6-shogaol induced the production of reactive oxygen species (ROS) which correlated well with the induction of apoptosis. This suggests that production of ROS could be one of the mechanisms of apoptosis induction by these compounds.;In conclusion, our study shows for the first time that gingerols and shogaols isolated from ginger were able to inhibit the growth of prostate cancer cells. 6-shogaol and 8-gingerol were able to induce apoptosis in both cell lines by activation of the intrinsic pathway of apoptosis.
Keywords/Search Tags:Ginger, Cell, Apoptosis, 6-shogaol, Intrinsic pathway, Chemopreventive, Induced, Anti-inflammatory
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