A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Zoledronic acid (ZA), the gold standard treatment for breast cancer‐derived osteolytic bone lesions, induces apoptosis in mature osteoclasts. Curcumin, a plant‐dervied component of turmeric (Curcuma longa), inhibits osteoclast differentiation. This study aimed to determine the in vitro and in vivo effects of ZA and curcuminoids, alone and combined, on osteoclast differentiation and survival, breast cancer cell growth, breast cancer cell‐induced osteolytic bone lesion area, and bone mineral density (BMD). Curcuminoids, but not ZA, inhibited osteoclast formation at doses that did not alter precursor viability, as assessed by osteoclastogenesis assays using murine RAW 264.7 cells. Combined curcuminoids and ZA did not differ from curcuminoids alone in their effects on osteoclast survival/formation. The half maximal inhibitory concentration (IC50) for ZA alone was 4 μM, while the IC50 for curcuminoids plus ZA was 6μM. Curcuminoids and ZA inhibit in vitro cell viability of human breast cancer‐ derived MDA‐MB‐231 cells, as assessed by MTT assays. The IC50 of ZA alone was projected to be 1.0677 x 10^4 μM, while the IC50 for curcuminoids alone (9.1 x 10^1 μM), was close to the IC50 for curcuminoids plus ZA (1.31 x 10^2 μM curcuminoids with 300 μM ZA). In vivo effects of ZA (2 μg/kg/d) and curcuminoids (25 mg/kg/d), alone and combined, on osteolytic bone lesions dervied from innoculation with MDA‐MB‐231 cells were assessed. Radiographically‐evident osteolytic bone lesion area did not differ between treatment groups, with a trend towards decreased osteolytic lesion area in mice treated with ZA. BMD In non‐responders, without bone or pericardiac tumors, assessed by dual energy x‐ray absorptiometry, was increased in mice administered ZA. Thus, for the first time, the combined in vitro effects of ZA and curcuminoids on osteclast formation and survival were demonstrated, as well as the combined effects of ZA and curcuminoids on bresat cancer‐derived osteolytic bone lesions and BMD.

Methods for the determination of boron are reviewed. A thorough investigation of the curcumin method was undertaken. Factors such as spectral absorption, boron volatilisation and the effects of pH, the stability of reagents and colour solutions, the drying of reaction products and the interference from certain elements, were investigated. A study of the efficiency of extracting boron from plant material using an ashing procedure is presented. The modified curcumin method for the determination of boron in plant material is described. The statistical accuracy and precision of the modified method is presented. The modified method was used to determine the boron content in citrus and pineapple leaf samples obtained from various parts of the Eastern Cape.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (M.S.)--The University of North Carolina at Greensboro, 2008. / Directed by Joel Bowen; submitted to the Dept. of Chemistry and Biochemistry. Title from PDF t.p. (viewed Aug. 26, 2009). Includes bibliographical references (p. 88-90).

BACKGROUND:Ginger (Zingiber officinale) and turmeric (Curcuma longa) accumulate important pharmacologically active metabolites at high levels in their rhizomes. Despite their importance, relatively little is known regarding gene expression in the rhizomes of ginger and turmeric.RESULTS:In order to identify rhizome-enriched genes and genes encoding specialized metabolism enzymes and pathway regulators, we evaluated an assembled collection of expressed sequence tags (ESTs) from eight different ginger and turmeric tissues. Comparisons to publicly available sorghum rhizome ESTs revealed a total of 777 gene transcripts expressed in ginger/turmeric and sorghum rhizomes but apparently absent from other tissues. The list of rhizome-specific transcripts was enriched for genes associated with regulation of tissue growth, development, and transcription. In particular, transcripts for ethylene response factors and AUX/IAA proteins appeared to accumulate in patterns mirroring results from previous studies regarding rhizome growth responses to exogenous applications of auxin and ethylene. Thus, these genes may play important roles in defining rhizome growth and development. Additional associations were made for ginger and turmeric rhizome-enriched MADS box transcription factors, their putative rhizome-enriched homologs in sorghum, and rhizomatous QTLs in rice. Additionally, analysis of both primary and specialized metabolism genes indicates that ginger and turmeric rhizomes are primarily devoted to the utilization of leaf supplied sucrose for the production and/or storage of specialized metabolites associated with the phenylpropanoid pathway and putative type III polyketide synthase gene products. This finding reinforces earlier hypotheses predicting roles of this enzyme class in the production of curcuminoids and gingerols.CONCLUSION:A significant set of genes were found to be exclusively or preferentially expressed in the rhizome of ginger and turmeric. Specific transcription factors and other regulatory genes were found that were common to the two species and that are excellent candidates for involvement in rhizome growth, differentiation and development. Large classes of enzymes involved in specialized metabolism were also found to have apparent tissue-specific expression, suggesting that gene expression itself may play an important role in regulating metabolite production in these plants.

Thesis (M.S.)--University of Wyoming, 2007. / Title from PDF title page (viewed on June 11, 2009). Includes bibliographical references (p. 36-40).

An increasing number of studies show that nutritional antioxidants such as vitamin E and polyphenols are capable of blocking neuronal death in vitro and may have therapeutic properties in animal models of neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases. In the present study, the neuroprotective ability of one such polyphenolic antioxidant, curcumin, was investigated. Curcumin is the yellow curry spice derived from turmeric, and is widely used as a dietary component and herbal medicine in India. Most neurological disorders are postulated to have an oxidative or excitototoxic basis. Thus the effects of curcumin on oxidative stress in the rat brain were investigated. Curcumin, administered to the rat in vivo and in vitro, was able to exert protective effects on oxidative damage in the brain, induced by cyanide, a mitochondrial inhibitor. Curcumin also offered protection against quinolinic acid induced lipid peroxidation, and this protection was extended to lipid peroxidation induced by metals such as lead and cadmium in the rat brain. Experiments conducted on the pineal gland revealed an increased production of the neuroprotective hormone melatonin in presence of curcumin in vivo. The hippocampus is functionally related to vital behaviour and intellectual activities and is known to be a primary target for neuronal degeneration in the brains of patients with Alzheimer’s disease. Histological studies were undertaken to assess the effects of curcumin on lead induced toxicity on the rat hippocampus, the results of which show that curcumin affords significant protection to the hippocampus of the lead treated rats. This study also sought to elucidate possible mechanisms by which curcumin exerts its neuroprotective capabilities. Curcumin was found to inhibit the action of cyanide on the mitochondrial electron transport chain, one of the most common sources of free radicals. Electrochemical, UV/VIS and Infrared spectroscopy were used to characterise interactions between curcumin and the metals lead, cadmium, iron (II) and iron (III). Curcumin was shown to directly chelate these metals with the formation and isolation of two new curcumin complexes with lead, and one complex each with cadmium and iron (III). These results suggest chelation of toxic metals as a mechanism of neuroprotection afforded by curcumin. The need for neuroprotective agents is urgent considering the rapid rise in the elderly population and the proportionate increase in neurological disorders. The findings of this study indicate that curcumin, a well-established dietary antioxidant, is capable of playing a bigger role in neuroprotection, which needs to be further explored and exploited.

Turmeric extract or active component curcumin may have anti-inflammatory effects in people with chronic inflammatory diseases. The effect of turmeric or curcumin on a wide range of inflammatory markers has not been evaluated in a systematic review. We performed a systematic review of randomized controlled trials (RCTs)evaluating the effects of oral turmeric or curcumin on inflammatory markers (CRP, hsCRP, IL-1, IL-6, TNF)in patients with a wide range of chronic inflammatory diseases. Pubmed, EMBASE, Scopus, the Web of Science, and the Cochrane library were evaluated until June 2018. Random effects meta-analyses with inverse variance methods and stratified by turmeric or curcumin were performed. Effects were expressed as mean differences (MD)and their 95% confidence intervals (CI). Risk of bias of RCTs was evaluated with the Cochrane tool. Nineteen RCTs were identified; included patients had rheumatic diseases, advanced chronic kidney disease with hemodialysis, metabolic syndrome, and cardiovascular diseases. Turmeric was the intervention in 5 RCTs (n = 356)and curcumin/curcuminoids in 14 RCTs (n = 988). Follow up times ranged between 4 and 16 weeks. One RCT had high risk of bias. In comparison to controls, turmeric or curcumin did not significantly decrease levels of CRP (MD -2.71 mg/L, 95%CI -5.73 to 0.31, p = 0.08, 5 studies), hsCRP (MD -1.44 mg/L, 95%CI -2.94 to 0.06, p = 0.06, 6 studies), IL-1 beta (MD -4.25 pg/mL, 95%CI -13.32 to 4.82, p = 0.36, 2 studies), IL-6 (MD -0.71 pg/mL, 95%CI -1.68 to 0.25, p = 0.15), and TNF alpha (MD -1.23 pg/mL, 95%CI -3.01 to 0.55, p = 0.18, 7 studies). There were no differences between turmeric and curcumin interventions. High heterogeneity of effects was observed for all markers across studies, except hsCRP. Other inflammatory markers such as IL-1 alpha, TNF beta, IL-17, and IL-22 had scarce data. Turmeric or curcumin did not decrease several inflammatory markers in patients with chronic inflammatory diseases. / Revisión por pares

Soils in irrigated fields are impacted by irrigation water quality. Salts in the irrigation water may accumulate in the soil depending on amount of leaching, the quality of water and type of ions present. Salinity is an environmental hazard that is known to limit agriculture worldwide. The quality of irrigation water is thus of concern to agriculturists. More so is the impact it has on productivity. The objective of this study was to quantify the impact due to use of ground water of such quality, with respect to salinity, as found in Berambadi watershed of Southern India, under farmers‟ field conditions. Turmeric (Curcuma Longa L.) was used for the study, based on salt sensitivity, under furrow irrigation. Study sites were selected basing on quality of water, with respect to salinity, crop and irrigation method. Samples of both soil and water were collected from each site and analyzed in the laboratory. The samples were analysed for salinity, alkalinity, pH and Cations of Magnesium, Sodium, Calcium and potassium as well as Chlorides and Sulfates. In addition soil was analysed for texture and Organic matter content. Non destructive plant monitoring for Leaf area (Index), number of leaves and plant height was done up to 210 days from planting. Profile, up to 80 cm depth, soil moisture was monitored at six plots using TDR and surface, up to 6cm depth, soil moisture for all the plots using Theta probe. Potential yield was obtained using STICS 6.9 crop model while field yield was estimated from rhizomes average weight of three plants. For both potential and observed yield estimation, a plant density of 9 plants per M2 was used. The quality parameters in water were correlated to soil parameters and to crop growth and ultimate yield. Impact due to salinity was then identified and quantified using relative yield. Identified quality problems in terms of turmeric response were, salinity, alkalinity and pH there was significant positive correlation between irrigation water salinity and soil salinity. Some wide scatter was observed and could be indicative of irrigation management practices, soil texture difference and other local variations. Observed turmeric yield was significantly negatively correlated to soil salinity. There was a monotonically increasing gap between simulated and observed yield as salinity increased. The maximum observed yield was 71% of the potential. The highest impact due to salinity was observed at 2.1 dS/m amounting to 44 % yield reduction. Excessive chlorosis due to iron deficiency occurred at 24.5% as CaCO3 and pH 7.5. Irrigation water pH was normal as per the guidelines. Soil pH was not so varied; it ranged between 7.1-7.9 except for one site where it was 6. Within the 7.1-7.9 range there was no effect on crop and yield observed. Interaction of stress factors observed was between salinity and alkalinity. The other was rhizome rot disease. Loss of yield to salinity was significant but farmers have no specific plans to leach out salts nor do they have an idea that ground water quality can actually negatively impact productivity. Salinity in irrigation water was in the moderately saline range. While that in the soil was low to slightly saline but could increase given the management practices.

published_or_final_version / abstract / Chinese Medicine / Master / Master of Philosophy