Medicinal Plants from Ancient Tradition as a Source for Matrix Proteases Inhibitors. Study of Correlation between Biological Activity and Phytochemical Profile

Mandrone, Manuela (2016) Medicinal Plants from Ancient Tradition as a Source for Matrix Proteases Inhibitors. Study of Correlation between Biological Activity and Phytochemical Profile, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze farmacologiche e tossicologiche, dello sviluppo e del movimento umano, 28 Ciclo. DOI 10.6092/unibo/amsdottorato/7613.
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Considering the crucial involvement of matrix metalloproteinases’ (MMPs) misregulated activity in the pathogenesis of several degenerative diseases, this class of enzymes has been considered a highly active set of targets for the design of new therapeutic agents. However, the scant success of synthetic MMP inhibitors, largely due to the disappointing results obtained in both clinical and preclinical studies, makes medicinal plants a valuable source of new active compounds able to modulate MMPs activity. In this work, a consistent number of plants, selected on the base of an ethnobotanical research, were tested as inhibitors of collagenase, the founding member of the MMPs family. 1H-NMR-based metabolomic analysis combined with multivariate data treatment (PLS and OPLS) was used to correlate the biological activity to the phytochemical profiles, suggesting tannins as an important class of collagenase inhibitors. Thus, a tannin-removal procedure was developed, which allowed to prove this hypothesis and to identify another class of active metabolites, the glucuronide-conjugated flavonoids (especially quercetin-3-O-β-glucoronide), whose the plant Alchemilla vulgaris was found to be a good source. In another stage of the project, different varieties of tea were investigated as collagenase inhibitors, finding black tea samples particularly potent. Then, an OPLS model was developed with the aim of correlating the biological activity to the UV-Vis spectra of teas, showing that a high activity was related to absorption values in the range 350-440 nm. A subsequent fractionation of the most active tea sample was carried out, and this approach allowed to corroborate the results obtained by the metabolomic analysis. Considering that the absorbance measurement of an extract represents a cheap and simple procedure, the proposed method can be suitable, for instance, to select the best tea variety to be developed as an anti-wrinkles cosmetic or food supplement.

Tipologia del documento
Tesi di dottorato
Mandrone, Manuela
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Settore disciplinare
Settore concorsuale
Parole chiave
MMPs inhibitors, traditional medicine, collagenase, natural products, tannins, flavonoids, NMR-based metabolomics, Uv-Vis-based metabolomics, Tea, Alchemilla vulgaris
Data di discussione
19 Aprile 2016

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