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Curcumin and Its Oxidative Degradation Products: Their Comparative Effects on InflammationZhu, Julia 13 July 2016 (has links) (PDF)
The anti-inflammatory agent curcumin degrades rapidly, leading to speculations that curcumin’s reported effects stem from its degradation products. Curcumin can degrade via hydrolysis, and more recently it was discovered that curcumin can degrade via oxidation at physiological pH. Additionally, bicyclopentadione is the major degradation product from this oxidation reaction. Evidence from the literature suggests that curcumin degrades primarily through oxidation. However, the biology of the oxidation products is not well characterized, and there is debate on whether oxidation intermediates or curcumin itself is more biologically active. To further elucidate the biology of the oxidation products, their effects on inflammation were examined. RAW264.7 murine macrophage cells were stimulated with E. coli lipopolysaccharide (LPS) and treated with curcumin, curcumin’s total oxidative degradation products, and bicyclopentadione. Curcumin strongly decreased LPS-induced nitric oxide production and iNOS expression in a dose dependent manner; total degradation products slightly decreased nitric oxide production and iNOS expression, while bicyclopentadione failed to decrease either. Additionally, curcumin was significantly more effective than either bicyclopentadione or total degradation products in inhibiting COX-2 expression. iNOS and COX-2 arise from the activation of the NF-kB pathway, which curcumin is known to modulate; thus, the oxidation products’ effect on key proteins in this pathway was also examined. Neither total degradation products nor bicyclopentadione inhibited translocation of NF-kB into the nucleus, prevented degradation of IκBα, nor inhibited phosphorylation of IKK as effectively as curcumin. In conclusion, curcumin is significantly more effective at inhibiting inflammation than the oxidation degradation products.
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Adjunct Therapy with Curcumin for the Treatment of Malaria : Studies in a Murine ModelDende, Chaitanya January 2015 (has links) (PDF)
Malaria accounts for 198 million cases worldwide; with a high mortality rate. 584000 deaths were reported in 2013. Malaria is a re-emerging disease globally due to drug resistance, parasite recrudescence and non-availability of a vaccine. Chloroquine, quinine and antifolates served as frontline antimalarial drugs for decades. Development of resistance to chloroquine and antifolates, and the decreased efficacy of mefloquine, and even quinine, in malaria-endemic regions, has led to artemisinin derivatives evolving as frontline drugs. Artemisinin is a potent antimalarial compound and clears around 104 parasites per cycle. Despite being a potent antimalarial, artemisinin derivatives suffer from poor pharmacokinetic properties and short half lives. This has led to the development of artemisinin-based combination therapies (ACTs) using a partner drug with a longer half-life. However, resistance to ACTs has been reported in the last few years, perhaps due to lack of adherence to prescribed regimens or suboptimal treatment and the use of counterfeit drugs. Therefore there is an urgent need to develop an alternative ACT which overcomes these limitations.
This thesis entitled “Adjunct therapy with curcumin for the treatment of malaria: studies in a murine model” describes the antimalarial activity of curcumin and artemisinin and the adjunct role of curcumin in the prevention of parasite recrudescence and cerebral malaria. The thesis is divided into three chapters:
The first chapter entitled “Introduction: Malaria and anti-malarial drugs” consists of a brief introduction of malaria, the parasite life cycle and currently known antimalarial drugs. During the course of infection, the Plasmodium undergoes sporogony in the mosquito, and merogony and schizogony in the human host. All these life cycle stages are briefly described with depictions. A major part of this chapter is dedicated to describe antimalarial compounds under the following headings 1. Quinoline derivatives 2. 4-aminoquinolines 3. Antifolates 4. Artemisinin derivatives 5. Antibiotics and 6. Curcumin.
The second chapter is aimed at examining the ability of curcumin-arteether (a synthetic derivative of artemisinin) combination therapy in preventing parasite recrudescence in a murine model through immunomodulation employing various immunological, molecular biological, and biochemical techniques. The use of suboptimal doses of antimalarial drugs leads to recrudescence or relapse of malaria (reappearance of the parasite in blood after antimalarial regimen). In the present study we have addressed this issue by the use of curcumin as an adjunct molecule with α,β arteether (a synthetic derivative of artemisinin). We have studied recrudescence in a Swiss mice model. A suboptimal dose was standardized by the use of different doses of α,β arteether (AE) ranging from 250µg to 1500 µg. We found 750 µg to be a suboptimal dose and studied the adjunct nature of curcumin when animals were treated with AE suboptimal dose or AE+curcumin (AC) combination treatment and monitored the survival of animals. Our results clearly demonstrate that ~95% of animals treated with the suboptimal AE dose died of recrudescent malaria but there was almost 100% survival of AC-treated animals; these animals were under observation for at least 3 months. We have studied the effect of curcumin in a recrudescence model at the molecular level. Curcumin by itself has antimalarial activity, but only in combination with α,β arteether prevented recrudescence. Our results indicate that curcumin has immunomodulatory activity. Serum cytokine analysis and spleen mRNA analysis for proinflammatory and anti-inflammatory mediators indicate that AC treatment effectively reduced both mRNA and serum cytokine levels of IFNγ, TNFα, IL-12 and effectively increased both mRNA and serum levels IL-10 and antibodies of the IgG subclass. Using TLR2 and IL-10 knockout animals, we have conclusively demonstrated that TLR2 is involved in the production of IL-10, and IL-10 is required for the AC-mediated protection of animals during the recrudescence period. We conclude that curcumin is able to prevent parasite recrudescence essentially by switching the Th1 response to a Th2 response.
The third chapter deals with the study the effect of areether-curcumin (AC) combination therapy in the prevention of Experimental Cerebral Malaria. Although malaria mortality rates have decreased by an impressive 47% between 2000 and 2013, it is still a major affliction of mankind (WHO 2014). Plasmodium falciparum infection causes human cerebral malaria (HCM). The mortality rate in HCM is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. HCM is characterized by a rapid progression from headache, general malaise, and prostration to hemiparesis, ataxia, unrousable coma, and death. Paediatric HCM deaths are mostly due to respiratory arrest. Alternatively, death may be due to parasite-mediated injury to a sensitive location; a small lesion due to parasite in brain stem can cause sudden respiratory arrest. In HCM, cytoadherence of pRBCs in brain microvasculature has been implicated as a major contributing factor for CM pathology. The failure of a large number of adjunct therapies in HCM demands the development of new intervention strategies. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. In this study, we have demonstrated the efficacy of curcumin and PLGA nanocurcumin in the treatment of Experimental Cerebral Malaria (ECM), using the Plasmodium berghei ANKA-infected mouse model (C57BL/6). Curcumin/PLGA nanocurcumin alone can prevent the onset of ECM. We have shown that curcumin/PLGA nanocurcumin can prevent CD8+ T cell, CXCR3+ CD8 T cell and parasite-infected RBC (pRBC) sequestration in the brain. These are also the essential parameters underlying HCM. We have also demonstrated that curcumin effectively inhibits T cell proliferation in spleen. We have explained the anti-inflammatory effects of curcumin by showing the inhibition of NF-B in both brain and spleen, which is a plausible explanation. But, curcumin/PLGA nanocurcumin treated animals died later due to build up of parasitemia in blood and subsequent anemia.
Moreover, a combination therapy with arteether and curcumin given even after the onset of neurological symptoms can completely cure and protect the animals against mortality. We have tested AC-combination after the onset of symptoms to mimic patient conditions in HCM, since the murine regimens reported were not successful in the treatment of HCM. Our results clearly demonstrate that AC treatment even after the onset of symptoms ensures 100% survival. Since the bioavailability of curcumin is reported to be poor, we have also tested the efficacy of PLGA nanocurcumin and find that it is superior to native curcumin in terms of therapeutic effects. It is concluded that curcumin would be an ideal adjunct drug to be used with the artemisinin derivatives to treat malaria, including cerebral malaria.
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Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasiaGattoc, Leda, Frew, Paula M, Thomas, Shontell N, Easley, Kirk A, Ward, Laura, Chow, H-H Sherry, Ura, Chiemi A, Flowers, Lisa 12 1900 (has links)
Background: This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia. Objective: The objective of this study was to assess the safety, tolerability, and pharmacokinetics of intravaginal curcumin in healthy women. Study design: We conducted a 3+3 dose-escalation Phase I trial in a group of women aged 18-45 years. Thirteen subjects were given one of four doses of curcumin powder (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) packed in gelatin capsules, which was administered intra-vaginally daily for 14 days. The primary end point for this study was safety based on severe adverse events regarding laboratory toxicity, clinical findings, and colposcopic abnormalities. We administered an acceptability questionnaire to assess product experience and attributes. Results: No dose-limiting toxicities (0/13) were experienced (95% confidence interval: 0.0%-22.8%) in this study. The pharmacokinetics data demonstrated that curcumin and curcumin conjugates were not measurable in the serum and negligible in the urine of the study participants. Although 23 adverse events occurred during the course of the trial, all events were grade I based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and were resolved by the end of the study in an average of 9 days. Fifty-six percent of the adverse events were related to the study drug, which included genital pruritus (23% of subjects), vaginal discharge (100%), vaginal dryness (15%), abnormal prothrombin (23%), and hypokalemia (8%). Conclusion: Intravaginal curcumin was well tolerated by all subjects and safe. In this Phase I trial, there were no severe adverse events observed at any of the administered dose levels. All adverse events were grade I and did not result in early termination of the study. There was no evidence of systemic absorption or significant local absorption of intravaginally administered curcumin.
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Nanopartículas de curcumina: obtenção e caracterização / Nanoparticles of curcumin: preparation and characterizationMassimino, Lívia Contini 26 January 2016 (has links)
Curcumina é um composto natural presente na Curcuma longa, que apresenta diversas atividades medicinais, porém sua baixa solubilidade limita sua aplicação médica. Para solucionar esse problema e viabilizar seu uso, diversas pesquisas no campo da nanotecnologia estão sendo feitas. Neste estudo foram obtidas nanopartículas de curcumina utilizando como solventes o etanol (E) e o clorofórmio (C), e através dos procedimentos de agitação magnética e sonicação. As nanopartículas foram caracterizadas por espalhamento de luz dinâmico (DLS), potencial Zeta, microscopia de força atômica (AFM) e pelas espectroscopias no infravermelho (FTIR), no ultravioleta/visível (UV-Vis) e de fluorescência. Foram feitos ensaios de solubilidade, fotodegradação e citotoxicidade. As nanopartículas obtidas com o solvente E e pelos processos de agitação e sonicação foram denominadas de NEA e NES, e com o solvente C de NCA e NCS, respectivamente. Teste inicial de liberação in vitro foi feito para a amostra NCA dispersas em gelatina com posterior recobrimento com Eudragit S100®; esse teste foi feito em HCl (pH 2,0) e tampão fosfato (pH 7,5). A morfologia dessas membranas recobertas ou não com Eudragit S100® foram analisadas por microscopia eletrônica de varredura (MEV). As nanopartículas tiveram um rendimento entre 60 e 78%. O resultado de DLS mostrou a obtenção de partículas nanométricas entre 189 e 248 nm para as NEA, NES e NCS e de 591 nm para NCA, com potencial Zeta acima de |25| mV para todas as amostras. As nanopartículas apresentaram uma fotodegradação mais lenta do que o produto comercial. As espectroscopias de FTIR, UV-Vis e fluorescência apresentaram bandas características da curcumina comercial, indicando que as nanopartículas têm as mesmas características químicas e físicas do bioativo. As nanopartículas mostraram um aumento na solubilidade de 37 a 56 vezes em relação à curcumina comercial. Os ensaios de citotoxicidade indicam que as nanopartículas não apresentaram toxicidade para a linhagem VERO, enquanto que para a linhagem HEp-2 ocasionaram morte celular. Assim, os procedimentos utilizados para o preparo das nanopartículas de curcumina foram eficientes, sendo que uso do solvente E mostrou ser o mais indicado para se obter nanopartículas. A morfologia por MEV das membranas de gelatina/NCA mostra um recobrimento uniforme com Eudragit S100®. Os testes iniciais de liberação in vitro mostraram que as nanopartículas de curcumina são protegidas pelo sistema em pH ácido e liberadas apenas quando em pH 7,5. / Curcumin is a natural compound present in Curcuma longa, which has several medicinal effects but due to its low solubility, its medical application gets constrained. To solve this problem and make it feasible to use, several studies are being made in the nanotechnology field. In this study curcumin nanoparticles were obtained using different solvents, ethanol (E) and chloroform (C), with two procedures, magnetic stirring and sonication. The nanoparticles were characterized by dynamic light scattering (DLS), Zeta potential, atomic force microscopy (AFM) and by infrared spectroscopy (FTIR), ultraviolet/visible spectroscopy (UV-vis), fluorescence spectroscopy. Solubility, photodegradation and cytotoxicity trials were made. The nanoparticles were named NEA and NES when prepared with E solvent, by magnetic stirring and sonication processes, and named NCA and NCS with C solvent, respectively. A preliminary in vitro release test was made with the NCA sample. It was dispersed in gelatin with the Eudragit S100® coating; this release test was done in HCl (pH 2.0) and phosphate buffer (pH 7.5). The membranes with and without Eudragit S100® coating were morphologically analyzed by scanning electron microscopy (SEM). The nanoparticles yield between 60 and 78%. The DLS results showed nanometric particles between 189 and 248 nm for NEA, NES and NCS samples and 591 nm for NCA sample. Moreover, a Zeta potential superior to |25| mV was obtained for all samples. The nanoparticles showed a slower photodegradation compared to the commercial curcumin. The FTIR, UV-vis and fluorescence spectroscopy resulted in characteristic bands, indicating that these nanoparticles have the same chemical and physical characteristics of the commercial curcumin. Likewise, an increase in solubility of 37 to 56 times was observed in comparison with the commercial product. Furthermore, the cytotoxicity assays suggested no toxicity to VERO cell lineage, while death for HEp-2 cell lineage. The procedures used for the curcumin nanoparticles preparation were efficient; however, the most suitable nanoparticles were obtained with E solvent. The morphology by SEM of gelatin/NCA membranes indicates a uniform coating with Eudragit S100®. In vitro release tests showed that curcumin nanoparticles were protected by this system at acid pH and released at pH 7.5.
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Effects of Curcumin and Ursolic Acid on the Mitochondrial Coupling Efficiency and Hydrogen Peroxide Emission of Intact Skeletal MyoblastsTueller, Daniel J. 01 July 2017 (has links)
Curcumin is a natural compound that improves blood glucose management. While some evidence from isolated mitochondria indicates that curcumin uncouples electron transport from oxidative phosphorylation, the effects of curcumin on mitochondrial respiration and hydrogen peroxide emission in intact skeletal muscle cells are not known. By assessing rates of oxygen consumption, we demonstrated for the first time that curcumin (40 µM) reduced the mitochondrial coupling efficiency (percentage of oxygen consumption that supports ATP synthesis) of intact skeletal muscle cells. A 30-minute incubation with curcumin decreased mitochondrial coupling efficiency by 17.0 ± 0.4% relative to vehicle (p < 0.008). Curcumin also decreased the rate of hydrogen peroxide emission by 43 ± 13% compared to vehicle (p < 0.05). Analysis of cell respiration in the presence of curcumin revealed a 40 ± 4% increase in the rate of oxygen consumption upon curcumin administration (p < 0.05 compared to vehicle). In additional experiments, no difference in mitochondrial coupling efficiency was observed between vehicle- and curcumin-pretreated cells after permeabilization of cell membranes (p > 0.7). The possibility of synergistic effects between curcumin and ursolic acid, another natural compound that improves blood glucose management, was also examined. Interestingly, ursolic acid (0.12 µM) increased mitochondrial coupling efficiency by 4.1 ± 1.1% relative to vehicle (p < 0.008) and attenuated the effect of curcumin when the two compounds were used in combination (decreased mitochondrial coupling efficiency by 8.0 ± 0.9% compared to vehicle, p < 0.008). These results provide evidence for lower mitochondrial coupling efficiency and hydrogen peroxide emission as possible contributors to the increased glucose uptake and insulin sensitivity of subjects after treatment with curcumin but not ursolic acid. Unless cells are assessed in the intact condition, changes to mitochondrial coupling efficiency after curcumin treatment may go unnoticed.
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A HYBRID MOLECULE OF MELATONIN AND CURCUMIN FOR THERPEUTIC USE IN PULMONARY FIBROSISNair, Varsha V 01 January 2019 (has links)
Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms of action. Accordingly, this project hypothesized that a novel hybrid molecule of MEL and CUR, AM24, was a more potent inhibitor against oxidative stress and TGF-b1 induced PF pathobiologic events than MEL or CUR, so that its pulmonary delivery enabled therapeutic intervention in an animal model of PF. Free radical scavenging activity and various in vitro lung cell-based anti-fibrotic activities of AM24 were determined and compared with those of MEL and CUR as well as their admixture (MEL+CUR) and PIR. Pulmonary administration of AM24 was then examined for therapeutic intervention in a rat model of bleomycin (BLM)-induced experimental PF.
AM24 was equipotent to MEL, but less potent than CUR in the hydrogen peroxide-induced free radical (ABTS) scavenging assay, ranked with the half-maximal inhibitory concentration (IC50) of 25.7, 32.0 and 11.4 uM, respectively. However, in the in vitro human lung fibroblast systems, AM24 was shown to be more potent than MEL or CUR and notably than MEL+CUR or PIR in the TGF-b1 induced 1) collagen synthesis by the picrosirius red assay, 2) proliferation by the MTT assay; and 3) differentiation to myofibroblast by western blot analysis of a myofibroblast marker, a-smooth muscle actin (a-SMA). In detail, at 10 uM, AM24 inhibited TGF-b1 induced 1) collagen synthesis by 90 %; 2) proliferation by ~72 %; and 3) differentiation to myofibroblast completely, while MEL, CUR, MEL+CUR and PIR resulted in 30-55 % or insignificant inhibition. In addition, in the in vitro human lung alveolar epithelial cell system, AM24 at 10 uM almost completely inhibited TGF-b1 induced epithelial-mesenchymal transition (EMT), as measured with western blot expressions of an epithelial marker, E-cadherin, and a mesenchymal marker, vimentin. Again, MEL, CUR, MEL+CUR and PIR exerted much less inhibitory activities. Hence, all these results consistently suggested that AM24 was a unique hybrid molecule of MEL and CUR and possessed highly potent anti-fibrotic activities in addition to the free radical scavenging activity.
AM24 was then examined for therapeutic intervention in an in vivo rat model of BLM-induced PF. BLM was orotracheally spray-dosed to the lungs at 0.6 mg/kg on day 1 to develop experimental PF in 14 days. Lung administrations of AM24 at 0.1 mg/kg commenced at 6 hours of BLM induction on day 1 and continued thrice weekly over two weeks. Functional treadmill exercise endurance was measured on day 12 and 15; and lungs were harvested upon sacrifice on day 16. Overall, AM24 showed significant intervention activities as follows: 1) exercise endurance was reduced only ~20%, much lower than 78% of the untreated PF rats; 2) reduced fibrotic tissue area and alveolar structural destruction were seen by histological examinations; and 3) lung’s induced collagen deposition was inhibited by ~78 %. However, unlike the literature, the lung’s TGF-b1, PCNA (a cell proliferation marker), and a-SMA (a differentiation marker), were not largely induced in the BLM-induced PF model, so that the intervention activities of AM24 to these markers were not clearly shown. In contrast, induced EMT was seen in the BLM-induced model, represented by increased mesenchymal marker, vimentin, and by decreased epithelial marker, E-cadherin; and AM24 appeared to counter this induced EMT. Accordingly, while the BLM-induced PF model may need further optimizations for clearer pathogenic changes, AM24 exerted certain degree of in vivo efficacies with a lung dose of 0.1 mg/kg, which was much lower than the effective doses of MEL, CUR, PIR and nintedanib seen in the literature with BLM induced PF model.
In conclusion, this thesis study has provided an early proof-of-concept for AM24, a novel MEL-CUR hybrid molecule, being potently anti-oxidative and anti-fibrotic in the in vitro lung cell-based assessments. As a result, AM24 enabled therapeutic intervention just with a lung dose of 0.1 mg/kg in the BLM-induced rat model of experimental PF.
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n-3 PUFA and Curcumin Modulate the Resolution of Murine Intestinal InflammtionJia, Qian 1980- 16 December 2013 (has links)
Bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) and curcumin modulate multiple determinants that link inflammation to cancer initiation and progression. In this dissertation, both transgenic and dietary mouse models were used to elucidate the effect of n-3 PUFA and curcumin treatment on murine intestinal inflammation.
Specifically, fat-1 transgenic mice, which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues, exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 plus/minus 0.29 versus 2.12 plus/minus 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA–derived eicosanoids compared with wild-type (wt) mice in an azoxymethane (AOM) - dextran sodium sulfate (DSS) model.
Following a 2-week recovery period after 5 days of DSS exposure, colonic inflammation and ulceration scores returned to pretreatment levels only in fat-1 mice. In addition, fat-1 vs wt mice exhibited decreased (P < 0.05) levels of CD3 , CD4 T helper, and macrophage cell numbers in the colon. The ability of n-3 PUFA to favorably modulate the resolution of intestinal inflammation in fat-1 mice was linked to an enhancement (P < 0.05) in the percentage of colonic lamina propria (cLP) CD4 FoxP3 cells and a decrease in both splenic and cLP Th17 cells (0.8 vs 1.2 percent in spleen, 1.4 vs 1.7 percent in colon) (P < 0.05) in fat-1 mice compared to wt. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated via its anti-inflammatory properties.
The combined effect of n-3 PUFA and curcumin on DSS induced colitis was assessed in C57BL/6 mice. Addition of fish oil (FO) and/or curcumin to a corn oil (CO) based diet increased animal mortality compared to CO alone (P < 0.05). Consistently, following 1 or 2 cycles of DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared to CO. However, compared to other diets, FO and curcumin combined feeding enhanced the resolution of chronic inflammation and suppressed (p < 0.05) a key inflammatory mediator, NF-kB, in colon mucosa. Mucosal microarray analysis revealed that dietary FO and curcumin differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.
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INVESTIGATING THE MASS SPECTROMETRIC BEHAVIOR OF NOVEL ANTINEOPLASTIC CURCUMIN ANALOGUES2015 January 1900 (has links)
Curcumin analogues are novel antineoplastic agents designed by structural modifications of the natural product curcumin to enhance its therapeutic effects. Various curcumin analogues displayed a significant cytotoxic effect towards different cancer cell lines including leukemia, melanoma, and colon cancer. In order to evaluate the safety, efficiency and metabolism of the new anticancer candidates, sensitive and high throughput analytical methods are needed. Thirteen curcumin analogues with the backbone structure of 3,5-bis(benzylidene)-4-piperidone were tested. The ionization behavior of curcumin analogues was investigated to reveal the possible mechanisms for the unusual formation of the positively charged [M-H]+ ions during single stage positive ion mode MALDI-MS analysis. Different ionization techniques (i.e., ESI, APCI, APPI, and MALDI) were used to evaluate this phenomenon. The results showed that curcumin analogues ionize into [M-H]+ along with the expected [M+H]+ species during MALDI and dopant free APPI-MS. In contrast, ESI, APCI and the dopant mediated APPI showed only the expected [M+H]+ peak. Our experiments revealed that photon energy triggers the ionization of the curcumin analogues even in the absence of any ionization enhancer such as matrix, solvent or dopant. Three proposed mechanisms for the formation of [M-H]+ were evaluated, two of them are probably involved in the [M-H]+ formation: (i) hydrogen transfer from the analyte radical cation and (ii) hydride abstraction.
In addition to the ionization behavior, the collision induced dissociation-tandem mass spectrometric (CID-MS/MS) fragmentation behavior of curcumin analogues was evaluated showing similar dissociation pathways that centered on the piperidone ring of the 3,5-bis(benzylidene)-4-piperidone moiety. The presence of different substitutes on that moiety resulted in specific product ions for each curcumin analogue. The fragmentation patterns were established to confirm the chemical structure of the tested compounds and identify the diagnostic product ions of each compound. Twelve common product ions were identified resulting from the breakage of various bonds within the piperidone moiety. There was a tendency for the formation of highly conjugated product ions that are stabilized via resonance. Common product ions were identified allowing for the establishment of a general MS/MS behavior for any curcumin analogue that belongs to the 3,5-bis(benzylidene)-4-piperidone structural family. The fragmentation routes and the genesis of the product ions were confirmed via MS3 and neutral loss analysis.
In summary, the ionization of curcumin analogues provided insights into the formation of unique [M-H]+ ions which were linked to photo ionization of such compounds without the need for additives, such as matrix, dopant or solvent. As such, curcumin analogues should be evaluated as MALDI matrices in the future. The CID-MS/MS analysis of curcumin analogues revealed a common fragmentation behavior of the tested compounds. It will be applied, in the future to determine metabolic by-products of the tested compounds as well as to develop targeted liquid chromatography (LC)-MS/MS methods.
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Wirkung von Curcumin und Licht auf Haut- und TumorzellenDujić, Jadranka Unknown Date (has links) (PDF)
Frankfurt (Main), Univ., Diss., 2009 / Erscheinungsjahr an der Haupttitelstelle: 2008
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Solubility and Stability of Natural Food Colorants in MicroemulsionsAbd-el-Galeel, Mohamed Awad Saad. Unknown Date (has links) (PDF)
Universiẗat, Diss., 2002--Bonn.
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