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eNOS activity-guided isolation of active compounds with particular emphasis on Rosaceae fruits

Supervisor:Brigitte Kopp, Department of Pharmacognosy

Student: Katharina Waldbauer

Cardiovascular diseases, such as atheriosclerosis, are still the major cause of death in the western world. The consumption of fruits and vegetables seem to reduce the risk for cardiovascular disease. Nitric oxide (NO) is the major anti-atherogenic molecule produced by the endothelium. Under pathological conditions eNOS is dysregulated, which among other factors leads to endothelial dysfunctions, a phenomenon induced by many cardiovascular risk factors, including hypertension, obesity and dyslipidemia, and precedes atheriosclerosos.

Thus, compounds that promote eNOS function may help to prevent endothelial dysfunction and finally the development of atheriosclerosis. The aim of the project is the bioguided fractionation of fruits and fruit pomace using, as a biological activity read-out, NO release from endothelial cells and the activity of the human eNOS promoter.

Fruit or fruit pomace will be selected. First choices will be apple pomace, as well as fruits from Rosaceae and other families (such as blackberry, blackcurrent, blueberry or cranberry), and preparations thereof.
Natural products known from these materials will be evaluated by means of extensive search in literature and ranked according to chemical stability, non toxicity, drug likeness, accessibility, etc. It also includes the proper pharmacognostic identification and phytochemical characterization (metabolic profiling) of the plant material and dereplication.
Selected plant material will be extracted by automated solvent extraction (ASE) with solvents of different polarity for pharmacological screening in the in-vitro assays.

Potent extracts are phytochemically characterized by TLC and HPLC fingerprints, also using LC-MS/MS for dereplication. In some cases LC-NMR is used, too. Active extracts will be fractionated using the concept of activity guided isolation. Fractionation and isolation is achieved by applying column chromatography, medium pressure liquid chromatography, preparative HPLC and/or solvent partition chromatography.

The structures of the pure compounds are elucidated by spectroscopic means (UV, IR, MS, NMR).

Initiativkolleg Biopromotion

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Letzte Änderung: 06.10.2011 - 06:39