The characterization of bioactive resveratrol oligomers extracted from Vitis vinifera canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, trans-ε-viniferin, hopeaphenol, isohopeaphenol, R2-viniferin, and R-viniferin) for their cytotoxic activity to human hepatocellular carcinoma (HCC) cell lines p53 wild-type HepG2 and p53-null Hep3B. The cytotoxic efficacy depended on the cell line. R2-viniferin was the most toxic stilbene in HepG2, with inhibitory concentration 50 (IC₅₀) of 9.7 ± 0.4 µM at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC₅₀ of 47.8 ± 2.8 µM). By contrast, hopeaphenol (IC₅₀ of 13.1 ± 4.1 µM) and isohopeaphenol (IC₅₀ of 26.0 ± 3.0 µM) were more toxic to Hep3B. Due to these results, and because it did not exert a large cytotoxicity in HH4 non-transformed hepatocytes, R2-viniferin was selected to investigate its mechanism of action in HepG2. The stilbene tended to arrest cell cycle at G2/M, and it also increased intracellular reactive oxygen species (ROS), caspase 3 activity, and the ratio of Bax/Bcl-2 proteins, indicative of apoptosis. The distinctive toxicity of R2-viniferin on HepG2 encourages research into the underlying mechanism to develop the oligostilbene as a therapeutic agent against HCC with a particular genetic background.

Polyphenols are widely acknowledged for their health benefits, especially for the prevention of inflammatory and age-related diseases. We previously demonstrated that hydroxytyrosol (HT) and procyanidins (PCy), alone or in combination, drive preventive anti-osteoathritic effects in vivo. However, the lack of sufficient clinical evidences on the relationship between dietary phytochemicals and osteoarthritis remains. In this light, we investigated in humans the potential osteoarticular benefit of a grapeseed and olive extract (OPCO) characterized for its hydroxytyrosol (HT) and procyanidins (PCy) content. We first validated, in vitro, the anti-inflammatory and chondroprotective properties of the extract on primary cultured human articular chondrocytes stimulated by interleukin-1 beta (IL-1 β). The sparing effect involved a molecular mechanism dependent on the nuclear transcription factor-kappa B (NF-κB) pathway. To confirm the clinical relevance of such a nutritional strategy, we designed an innovative clinical approach taking into account the metabolites that are formed during the digestion process and that appear in circulation after the ingestion of the OPCO extract. Blood samples from volunteers were collected following ingestion, absorption, and metabolization of the extract and then were processed and applied on human primary chondrocyte cultures. This original ex vivo methodology confirmed at a clinical level the chondroprotective properties previously observed in vitro and in vivo.

The aggregation of α-synuclein is one on the key pathogenic events in Parkinson’s disease. In the present study, we investigated the inhibitory capacities of stilbenes against α-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 α-synuclein aggregation: piceatannol, ampelopsin A, and isohopeaphenol. Lipid vesicle permeabilization assays were performed to screen stilbenes for protection against membrane damage induced by aggregated α-synuclein. The viability of PC12 cells was examined using an MTT assay to assess the preventive effects of stilbenes against α-synuclein-induced toxicity. Piceatannol inhibited the formation of α synuclein fibrils and was able to destabilize preformed filaments. It seems to induce the formation of small soluble complexes protecting membranes against α-synuclein-induced damage. Finally, piceatannol protected cells against α-synuclein-induced toxicity. The oligomers tested (ampelopsin A and hopeaphenol) were less active.

Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (4–10) were isolated from the aerial parts of the Asian orchid Arundina graminifolia. The structures of the isolated compounds were elucidated by spectroscopic methods, including extensive 1D, 2D NMR (heteronuclear single quantum coherence (HSQC), heteronuclear multiple-bond correlation spectroscopy (HMBC), and HR-ESI-MS techniques, as well as comparison with respective literature reports. The cytoprotective activity of the isolated compounds were evaluated for their ability to reduce beta amyloid induced toxicity on undifferentiated PC12 cells. Compound 8 showed moderate cytoprotective activity at 0.5 µmol/L (71% of cell viability) while the other compounds showed no significant activity at the highest concentration tested.

The structure of a new procyanidin tetramer, which we call a crown procyanidin tetramer, with an unprecedented macrocyclic structure has been characterized for the first time. Its comprehensive spectroscopic analysis revealed that it is a symmetric procyanidin tetramer composed of four (−)-epicatechin sub-units linked alternatively via 4β→8 or 4β→6 B-type interflavanyl linkages to form the macrocyclic structure. This NMR-characterized carbon skeleton has never been reported before for procyanidins in grape or in wine, neither in the plant kingdom. Surprisingly, the crown procyanidin tetramer appeared to be specifically localized in grape skin, contrasting with the oligomeric and polymeric procyanidins present in seed, skin, and bunch stem. Moreover, this crown procyanidin tetramer showed promising protective effects against amyloid-β induced toxicity.