MASS SPECTROMETRIC STRATEGIES FOR THE STUDY OF PLANT EXTRACTS BIOAVAILABILITY, BIOACTIVITY AND MECHANISMS OF ACTION
Tesi di Dottorato
Data di Pubblicazione:
2018
Citazione:
MASS SPECTROMETRIC STRATEGIES FOR THE STUDY OF PLANT EXTRACTS BIOAVAILABILITY, BIOACTIVITY AND MECHANISMS OF ACTION / G. Baron ; tutor: G. Aldini ; coordinator: G. Aldini. DIPARTIMENTO DI SCIENZE FARMACEUTICHE, 2018 Jan 17. 30. ciclo, Anno Accademico 2017. [10.13130/g-baron_phd2018-01-17].
Abstract:
1. Introduction and aim of the work
Drug discovery in phytomedicine has in the past been mainly focused on the isolation and characterization of new bioactive compounds from natural products. Several NCE (new chemical entities) have been isolated from plants and they are now the active principles of many drugs able to treat and prevent different kinds of diseases. This drug discovery approach is aimed at the determination of the single "active principle" in plants, based on the assumption that a plant has one or more ingredients which determine its therapeutic effects. Beside NCE derived from plants and herbs, there is another important approach which assumes that a synergy of all ingredients of plants will bring about the maximum of therapeutic efficacy [1]. There are new forms of registered plant-derived medicines (phytomedicines) that are not single chemical entities but a complex mixture of active and inert ingredients derived form a crude extraction. However this approach has long been limited since adequate methods to standardize complex plant mixtures as well as to rationalize complex modes of actions were lacking. Moreover ADMET studies were limited due to the complexity of the phytomedicines. Hence most of the information that is usually retrieved for NCE during the drug discovery stage, such as the ADME profile and the mechanism of action was often not obtained for such complex natural derivatives, limiting their efficacy and application in therapy.
Recently, thanks to the advent of novel MS techniques and to the commercial availability of high resolution MS analysers, the opportunity to determine the ADME profiles of plant extracts and to explore their mode of action has become possible. Advanced analytical techniques play an increasingly important role in the characterization, identification and quantification of plant extract compounds, not only in the context of their natural source but also in biological fluids to study their bioavailability and to discover the active compounds. Mass spectrometry has become one of the main standard techniques in this field because of the high sensitivity and specificity of the available mass analyzers.
Based on these premises, the aim of my PhD work has been to set-up and apply state of the art MS strategies to better understand the mechanisms of action of some crude plant extracts and in particular tannins and rice extracts as well as to define the absorption and PK profile of cranberry and bilberry standardized extracts which are widely used as therapeutic agents.
2. Set-up and application of MS methods to elucidate biological activities and mechanisms of action of plant extracts
During the first part of my Ph.D program, I have used MS strategies to investigate the ability of plant extracts to act as i) sequestering agents of reactive carbonyl species, toxic lipid peroxidation products involved in the pathogenetic mechanisms of several inflammatory based disorders and ii) as protein precipitation agents (tannin effect) using bradykinin, a pro-inflammatory mediator, as protein target.
2.1 Set-up of an isotopic labelling procedure for the characterization of HNE-sequestering agents in natural extracts and its application for the identification of anthocyanidins in black rice giant germ
Reactive carbonyl species (RCS) are cytotoxic molecules deriving from the oxidation of sugars and lipids. When the human system undergoes stress condition, the physiological detoxification pathways are not efficient enough to inhibit these reactive molecules. RCS are electrophilic compounds that can easily react with the nucleophilic centers of proteins leading to the generation of Advanced Glycation End Products (AGEs) and Advanced Lipoxidation End Products (ALEs) [2]. These p
Tipologia IRIS:
Tesi di dottorato
Keywords:
Plant extract; ADME; mass spectrometry
Elenco autori:
G. Baron
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