Etude des effets neuroprotecteurs des stilbènes de la vigne sur la maladie de Parkinson

Parkinson’s disease is one of the most spread neurodegenerative diseases in the world. Post mortem analyses have put in evidence small inclusion bodies in patient’s brain, composed of α-synuclein fibrils. Several studies attempted then to identify compounds that could inhibit α-synuclein aggregation, as its aggregation is linked to its toxicity. Still, numerous active compounds need to be identified in order to put on relief shared active structures that could lead to a potent drug design. Stilbenes are phenolic compounds that often display interesting health-related biological activities. In this study, the anti-aggregative behavior of stilbenes monomers (resveratrol, piceatannol) and oligomers such as ampelopsin and isohopeaphenol was assessed. The results put on evidence stilbene propensity to inhibit α-synuclein aggregation and provide an insight into their inhibition mechanisms.La maladie de Parkinson est l’une des plus répandue dans le monde. Des analyses post mortem ont mis en évidences des inclusions dans les cerveaux des patients, composées d’α-synucléine. Plusieurs études ont visé à identifier des composés capables d’inhiber l’agrégation de cette protéine, étant donné que cette agrégation est liée à sa toxicité. Néanmoins, de nombreux composés restent encore à être identifiés afin de mettre en évidence des structures moléculaires actives partagées qui pourrait mener à la synthèse d’un principe actif. Les stilbènes sont des composés phénoliques démontrant régulièrement des activités biologiques intéressantes pour la santé. Dans cette étude, nous étudions le comportement anti-agrégatif des stilbènes monomériques (resvératrol, picéatannol) et oligomèriques (ampélopsine, viniférine, et isohopeaphénol). Les résultats présentés mettent en évidence la capacité des stilbènes à inhiber l’agrégation de l’α-synucléine et fournissent des éléments pour comprendre ce mécanisme

Study of vine stilbenes neuroprotective effects on Parkinson’s disease

La maladie de Parkinson est l’une des plus répandue dans le monde. Des analyses post mortem ont mis en évidences des inclusions dans les cerveaux des patients, composées d’α-synucléine. Plusieurs études ont visé à identifier des composés capables d’inhiber l’agrégation de cette protéine, étant donné que cette agrégation est liée à sa toxicité. Néanmoins, de nombreux composés restent encore à être identifiés afin de mettre en évidence des structures moléculaires actives partagées qui pourrait mener à la synthèse d’un principe actif. Les stilbènes sont des composés phénoliques démontrant régulièrement des activités biologiques intéressantes pour la santé. Dans cette étude, nous étudions le comportement anti-agrégatif des stilbènes monomériques (resvératrol, picéatannol) et oligomèriques (ampélopsine, viniférine, et isohopeaphénol). Les résultats présentés mettent en évidence la capacité des stilbènes à inhiber l’agrégation de l’α-synucléine et fournissent des éléments pour comprendre ce mécanisme.Parkinson’s disease is one of the most spread neurodegenerative diseases in the world. Post mortem analyses have put in evidence small inclusion bodies in patient’s brain, composed of α-synuclein fibrils. Several studies attempted then to identify compounds that could inhibit α-synuclein aggregation, as its aggregation is linked to its toxicity. Still, numerous active compounds need to be identified in order to put on relief shared active structures that could lead to a potent drug design. Stilbenes are phenolic compounds that often display interesting health-related biological activities. In this study, the anti-aggregative behavior of stilbenes monomers (resveratrol, piceatannol) and oligomers such as ampelopsin and isohopeaphenol was assessed. The results put on evidence stilbene propensity to inhibit α-synuclein aggregation and provide an insight into their inhibition mechanisms

Study of vine stilbenes neuroprotective effects on Parkinson’s disease

La maladie de Parkinson est l’une des plus répandue dans le monde. Des analyses post mortem ont mis en évidences des inclusions dans les cerveaux des patients, composées d’α-synucléine. Plusieurs études ont visé à identifier des composés capables d’inhiber l’agrégation de cette protéine, étant donné que cette agrégation est liée à sa toxicité. Néanmoins, de nombreux composés restent encore à être identifiés afin de mettre en évidence des structures moléculaires actives partagées qui pourrait mener à la synthèse d’un principe actif. Les stilbènes sont des composés phénoliques démontrant régulièrement des activités biologiques intéressantes pour la santé. Dans cette étude, nous étudions le comportement anti-agrégatif des stilbènes monomériques (resvératrol, picéatannol) et oligomèriques (ampélopsine, viniférine, et isohopeaphénol). Les résultats présentés mettent en évidence la capacité des stilbènes à inhiber l’agrégation de l’α-synucléine et fournissent des éléments pour comprendre ce mécanisme.Parkinson’s disease is one of the most spread neurodegenerative diseases in the world. Post mortem analyses have put in evidence small inclusion bodies in patient’s brain, composed of α-synuclein fibrils. Several studies attempted then to identify compounds that could inhibit α-synuclein aggregation, as its aggregation is linked to its toxicity. Still, numerous active compounds need to be identified in order to put on relief shared active structures that could lead to a potent drug design. Stilbenes are phenolic compounds that often display interesting health-related biological activities. In this study, the anti-aggregative behavior of stilbenes monomers (resveratrol, piceatannol) and oligomers such as ampelopsin and isohopeaphenol was assessed. The results put on evidence stilbene propensity to inhibit α-synuclein aggregation and provide an insight into their inhibition mechanisms

Piceatannol and other wine stilbenes: a pool of inhibitors against α-synuclein aggregation and cytotoxicity

The aggregation of alpha-synuclein is one on the key pathogenic events in Parkinson's disease. In the present study, we investigated the inhibitory capacities of stilbenes against alpha-synuclein aggregation and toxicity. Thioflavin T fluorescence, transmission electronic microscopy, and SDS-PAGE analysis were performed to investigate the inhibitory effects of three stilbenes against alpha-synuclein aggregation: piceatannol, ampelopsin A, and isohopeaphenol. Lipid vesicle permeabilization assays were performed to screen stilbenes for protection against membrane damage induced by aggregated alpha-synuclein. The viability of PC12 cells was examined using an MTT assay to assess the preventive effects of stilbenes against alpha-synuclein-induced toxicity. Piceatannol inhibited the formation of alpha synuclein fibrils and was able to destabilize preformed filaments. It seems to induce the formation of small soluble complexes protecting membranes against alpha-synuclein-induced damage. Finally, piceatannol protected cells against alpha-synuclein-induced toxicity. The oligomers tested (ampelopsin A and hopeaphenol) were less active

New E-miyabenol isomer isolated from grapevine cane using centrifugal partition chromatography guided by mass spectrometry

Stilbenoids have received increasing attention over the last two decades since the discovery of resveratrol in wine. With an ever-growing rhythm, a multitude of biological activities of naturally occurring stilbenes are being reported. In this work, we investigated minor stilbenoid compounds from Vitis vinifera stalks. The compounds were purified by means of centrifugal partition chromatography (CPC), a countercurrent-separation technique. Electrospray ionization–ion trap mass spectrometry (ESI–IT-MS) after optimization proved to be extremely efficient for the detection of these new molecules, providing both structural information for structure elucidation and a means to achieve identification even with minute amounts. Here a new stereoisomer of E-miyabenol C, E-cis-cis-miyabenol C (2), along with the already reported E-trans-cis-miyabenol C (1) and E-cis-trans-miyabenol C (3), was purified from a complex Vitis vinifera cane extract, using adapted solvent systems K and L from the ‘Arizona’ solvent system range, without the need for any solid support. Moreover, compounds 1–3 showed an inhibitory activity on α-synuclein filament formation

Food Chem

Several cultivars of peach fruit (Prunus persica L.) were investigated. Their phenolic composition and concentration were assessed by LC-MS. Concentrations were calculated in mg per g of dry weight extract. Their antioxidant capacity (Folin-Ciocalteu, ORAC, DPPH, ABTS, PFRAP and ICA), inhibitory property against β-amyloid and α-synuclein fibril formation and protective capacity against Aβ-induced toxicity on PC12 cell lines (viability assessed by MTT assay and intracellular ROS production by DCFH-DA assay) were evaluated. Fifteen different phenolic compounds were identified and quantified. In particular, new isorhamnetin derivatives were identified. Phenolic contents were ranged between 19 and 82mg/g. Spring Belle extract had the highest content and Romea the lowest. Except for the ICA assay, a good correlation between phenolic content and the antioxidant capacities of peach fruit extracts was found, indicating that phenolic compounds are major contributors to their antioxidant capacity. Results indicate that the phenolic extract of peach cultivars inhibits Aβ and αS fibril formation and protects PC12 cell lines against Aβ-induced toxicity

Flavonol profiles in berries of wild Vitis accessions using liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectrometry

The flavonol profiles of grape berry skins were analysed in order to assess phenotypic variation between six grapevines belonging to six different species: Vitis vinifera, Vitiscandicans, Vitischampinii, Vitisamurensis, Vitiscinerea and Vitisdoaniana. High-performance liquid chromatography coupled to mass spectrometry (LC-MS) and NMR spectrometry (LC-NMR) were used to separate and identify the flavonols present in these species. The combination of LC-MS and LC-NMR data resulted in the identification of eighteen flavonols. In particular, the new flavonol diglycoside and pentoside derivatives were determined. In addition, the antioxidant capacities of flavonol grape skin extracts were evaluated by using an oxygen radical absorbance capacity method (ORAC)

Bioactive stilbenes from Vitis vinifera grapevine shoots extracts.

Vitis vinifera grapevine shoots are potentially interesting as a source of new bioactive stilbenes, such as vitisinol C. © 2013 Society of Chemical Industry

The enhanced membrane interaction and perturbation of a cell penetrating peptide in the presence of anionic lipids: Toward an understanding of its selectivity for cancer cells

Cell penetrating peptides (CPPs) are usually short, highly cationic peptides that are capable of crossing the cell membrane and transport cargos of varied size and nature in cells by energy- and receptor-independent mechanisms. An additional potential is the newly discovered anti-tumor activity of certain CPPs, including RW16 (RRWRRWWRRWWRRWRR) which is derived frompenetratin and is investigated here. The use of CPPs in therapeutics, diagnosis and potential application as anti-tumor agents increases the necessity of understanding their mode of action, a subject yet not totally understood. With this in mind, the membrane interaction and perturbation mechanisms of RW16 with both zwitterionic and anionic lipid model systems (used as representative models of healthy vs tumor cells) were investigated using a large panoply of biophysical techniques. It was shown that RW16 autoassociates and that its oligomerization state highly influences its membrane interaction. Overall a stronger association and perturbation of anionic membranes was observed, especially in the presence of oligomeric peptide, when compared to zwitterionic ones. This might explain, at least in part, the anti-tumor activity and so the selective interaction with cancer cells whose membranes have been shown to be especially anionic. Hydrophobic contacts between the peptide and lipids were also shown to play an important role in the interaction. That probably results from the tryptophan insertion into the fatty acid lipid area following a peptide flip after the first electrostatic recognition. A model is presented that reflects the ensemble of results