68 research outputs found
Analysis of a caffeic acid derivative by ESI-MS/MS: unexpected product ions formed by ‘internal residue loss’
Comparative cytotoxicity of artemisinin and cisplatin and their interactions with chlorogenic acids in MCF7 breast cancer cells.
In parts of Africa and Asia, self-medication with a hot water infusion of Artemisia annua (Artemisia tea) is a common practice for a number of ailments including malaria and cancer. In our earlier work, such an extract showed better potency than artemisinin alone against both chloroquine-sensitive and -resistant parasites. In this study, in vitro tests of the infusion in MCF7 cells showed high IC50 values (>200 μM). The combination of artemisinin and 3-caffeoylquinic acid (3CA), two major components in the extract, was strongly antagonistic and gave a near total loss of cytotoxicity for artemisinin. We observed that the interaction of 3CAs with another cytotoxic compound, cisplatin, showed potentiation of activity by 2.5-fold. The chelation of cellular iron by 3CA is hypothesized as a possible explanation for the loss of artemisinin activity.This study was funded by the Engineering and Physical Sciences
Research Council (EPSRC, UK) and SensaPharm Ltd. via an Industrial
CASE PhD studentship. The award was allocated competitively
by the Chemistry Innovation Knowledge Transfer Network
(CIKTN, UK).This is the final published version. It was originally published by Wiley at http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201402285/abstract
Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms
Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin
A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL
Lipidome profile of fluids and tissues is a growing field as the role of lipids as signaling molecules is increasingly understood, relying on an effective and representative extraction of the lipids present. A number of solvent systems suitable for lipid extraction are commonly in use, though no comprehensive investigation of their effectiveness across multiple lipid classes has been carried out. To address this, human LDL from normolipidemic volunteers was used to evaluate five different solvent extraction protocols [Folch, Bligh and Dyer, acidified Bligh and Dyer, methanol (MeOH)-tert-butyl methyl ether (TBME), and hexane-isopropanol] and the extracted lipids were analyzed by LC-MS in a high-resolution instrument equipped with polarity switching. Overall, more than 350 different lipid species from 19 lipid subclasses were identified. Solvent composition had a small effect on the extraction of predominant lipid classes (triacylglycerides, cholesterol esters, and phosphatidylcholines). In contrast, extraction of less abundant lipids (phosphatidylinositols, lyso-lipids, ceramides, and cholesterol sulfates) was greatly influenced by the solvent system used. Overall, the Folch method was most effective for the extraction of a broad range of lipid classes in LDL, although the hexane-isopropanol method was best for apolar lipids and the MeOH-TBME method was suitable for lactosyl ceramides
Cognitive consequences and central nervous system injury following treatment for childhood leukemia
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Mass spectrometry of compounds of biological interest
Mass spectrometric methods, including EI, CI, FAB and ESI LC/MS have been surveyed as tools for identification and characterization of compounds of natural origin exhibiting biological activity. Bioactive catechins isolated from green tea were analyzed by mass spectral methods: EI spectra provided both molecular weight and structural information, including epimer differentiation. FAB mass spectrometry gave both molecular weight and structural information on all compounds. ESI LC/MS provided unambiguous MW information on all compounds and some additional structural data on compounds ECG and EGCG. ESI LC/MS provided a means for separation of all compounds in a mixture and is an appropriate method for analysis of a crude extract of this plant material. Based on the result from biological testing, showing that quinic acid derivatives possess considerable anti-HIV activity, four analogs of dicaffeoylquinic acid were characterized by mass spectral methods. An attempt was made to design a mass spectral method allowing the differentiation between the analogs. FAB mass spectral analysis provided good MW information for all compounds. In addition, ions representing the elimination of water from MH+ ion of the 3,5-DCQA-OAc clearly differentiated this isomer from the 3,4-DCQA-OAc. MIKES analysis of the MH+ ions of the acetate derivative confirmed the isomer specific water loss. ESI provided unambiguous MW information on all compounds, confirming that loss of water is specific for the 3,5-DCQA-OAc. The extract of the CSF in patients with ALL was surveyed for a suitable biomarker which would indicate brain tissue damage following therapy. Phospholipid levels in CSF in three groups of patients receiving different CNS propylaxis were monitored during the course of treatment and the elevated levels were correlated to the cognitive impairment evaluation results. As a result of the CNS propylaxis, the levels of phospholipids in CSF are significantly elevated, indicating disruption of brain cell membranes. Two major classes of phospholipid were identified by FAB mass spectral analysis, PC and SM. Their elevated levels were inversely correlated with the decreased scores from cognitive testing. A close correlation was found between the PC levels and some test scores
Tandem mass spectrometry of the B-type procyanidins in wine and B-type dehydrodicatechins in an autoxidation mixture of (+)-catechin and (?)-epicatechin
Analysis of theaflavins in biological fluids using liquid chromatography–electrospray mass spectrometry
Cognitive consequences and central nervous system injury following treatment for childhood leukemia
OBJECTIVES: To determine the relationship between membrane damage and intellectual and academic abilities in children with acute lymphoblastic leukemia (ALL) and pilot test a math intervention for children with ALL who were affected. DATA SOURCES: Research studies and review articles. CONCLUSIONS: Despite the prophylactic central nervous system (CNS) treatment for long-term disease-free survival, many children with ALL subsequently experience declines in intellectual and academic skills. IMPLICATIONS FOR NURSING PRACTICE: Improving academic abilities in children who have received CNS treatment is of high priority and may have longlasting implications on quality of life
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