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Evaluation of pollen secondary metabolites in exacerbation of nonallergic asthma, and development of computer-assisted LC-MS batch processing, clustering, and visualization

Bozicevic, Alen. Evaluation of pollen secondary metabolites in exacerbation of nonallergic asthma, and development of computer-assisted LC-MS batch processing, clustering, and visualization. 2017, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12569

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Abstract

Pollen project
Asthma accounts for one of the many forms of chronic pulmonary diseases. Rather than a single disease, asthma includes a multitude of clinical symptoms related to gas
exchange limitation, airway hyper-responsiveness resulting in wheezing and coughing, and airway inflammation. This variety of symptoms depicts very well the complexity of asthma and suggests the involvement of a multitude of triggers and mechanisms. On one side, the allergic asthma is characterized by the inflammation of the airway tissue in response to a load of allergic triggers. Non-allergic triggers are organic and inorganic airway irritants, which modulate neuro-muscular macromolecular targets (receptors, channels) generating airways hyper-responsiveness and smooth muscle contraction. The Transient Receptor Potential cation channel A1 (TRPA1) is a ubiquitous Ca2+-selective
protein highly expressed on somatosensory neurons and is activated by environmental irritants inducing pain, cold and itchiness. Its expression on afferent neurons in the airways makes this channel a target for small chemical irritants, resulting in airway hyper-responsiveness to
contractile stimuli. Differently, the type I PhosphatidylInositol 4-Phosphate 5-Kinase (PIP5K)
gamma isoform is a lipid kinase involved in the regulation of intracellular Ca2+ in smooth muscle cells. The polyamines spermidine and spermine are crucial cofactors for
PIP5Kγ activation. The aim of this work was to investigate the potential role of plant pollen secondary metabolites in
the non-allergic exacerbation of asthma symptoms. We performed the phytochemical study of pollen from 30 plant species, including the highly allergenic Ambrosia artemisiifolia and Ambrosia psilostachya from the family Asteraceae, and the highly allergic Betula pendula and
Corylus avellana from the non-Asteraceae.
The spectrophotometric quantification of electrophiles in extracts revealed surprising results. Finally, extracts and pure compounds were tested in murine afferent neurons
for their effect on Ca2+ influx measured via calcium imaging, and for constriction of murine tracheal rings in organ bath experiments.
Ziziphus project
Glycosylated triterpenes are organic molecules belonging to the secondary metabolism of plants and other organisms such as marine invertebrates. The genus Zizyphus (Rhamnaceae)
comprises a variety of spiny shrubs and small trees, which leaves are commonly used in the oriental and Middle-East folk medicine for the treatment of various diseases but also to produce natural detergents and shampoos. Phytochemical characterization of glycosylated triterpenes in the hydroalcoholic extract from Ziziphus spina-christi leaves resulted in the identification of ten saponins, of which three were found to be novel dammarane-type aglycones.
ACD/Labs project
The technological development of LC-MS instrumentation has led to significant improvements in automation, performance, and sensitivity. Complex samples, such as plant extracts can now be analyzed routinely and in high-throughput mode. Software tools allow efficient deconvolution of LC-MS chromatograms to obtain comprehensive information on single
constituents. However, the systematic and unbiased comparison of large numbers of complex LC-MS chromatograms remains a challenge. Existing software tools for comparative processing are widely used in scientific fields like systems biology, including disciplines like genomics,
proteomic, and metabolomics. Nevertheless, still little application is observed in phytochemistry and drug discovery research. ACD/Labs
(Advanced Chemistry Development, Inc., Toronto, Canada) is a commercial analytical platform
integrated with a wide range of analytical and predictive functionalities such as LC-MS and NMR data processing and analysis, metabolite identification, and in silico drug likeliness predictions. In this work we focused on creating a two-step protocol comprising a parallel comparative
processing integrated in ACD/Labs, and a web platform developed in R language designed for clustering and visualization of chromatographic data.
Advisors:Hamburger, Matthias and Wolfender, Jean-Luc
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)
UniBasel Contributors:Bozicevic, Alen and Hamburger, Matthias
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12569
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (vi, 192 Seiten)
Language:English
Identification Number:
Last Modified:18 Apr 2018 13:44
Deposited On:16 Apr 2018 14:34

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