ellagitannin and vescalagin

The identification of unstable metabolites of ellagitannins having ortho-quinone structures or reactive carbonyl groups is important to clarify the biosynthesis and degradation of ellagitannins. Our previous studies on the degradation of vescalagin, a major ellagitannin of oak young leaves, suggested that the initial step of the degradation is regioselective oxidation to generate a putative quinone intermediate. However, this intermediate has not been identified yet. In this study, young leaves of

Topics: Hydrolyzable Tannins; Quercus; Quinones

Investigation on tannins having antitumor properties led to the isolation of two new C-glycosidic ellagitannins (1 and 2) along with seven known ellagitannins (3-9) and a related polyphenolic constituent (10) from Lawsonia inermis leaves. Our intensive HRESIMS, 1D and 2D NMR, and ECD spectroscopic studies of new tannins have shown that one (1) has a monomer structure of C-glycosidic tannin, and the other (2) has a dimeric structure of 2,3-O-hexahydroxydiphenoyl glucopyranose and a C-glycosidic tannin. Among the known compounds, one (3) is a C-glycosidic tannin that was isolated first of all from nature, five were C-glycosidic tannins, vescalagin (4), 1-O-methylvescalagin (5), castalagin (6), stachyurin (7), and casuarinin (8), and one was an O-glycosidic ellagitannin, tellimagrandin II (9). The remaining phenolic constituent from the leaves was identified as valoneic acid dilactone (10). The ellagitannins 1, and 3-9 demonstrated noticeable cytotoxicity on human oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22), and lower effects on human oral normal cells (HGF, HPC, and HPLF). Tellimagrandin II (9) had the highest tumor-specific cytotoxicity, and also cleaved poly (ADP-ribose) polymerase 1 in HSC-2 cells. These findings showed that L. inermis ellagitannins may be a candidate for the production of anti-oral cancer materials.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Squamous Cell; Cell Line, Tumor; Egypt; Gallic Acid; Glucosides; Glycosides; Humans; Hydrolyzable Tannins; Lawsonia Plant; Molecular Structure; Mouth Neoplasms; Phytochemicals; Plant Leaves

Vescalagin (

Topics: Biflavonoids; Catechin; Hydrolyzable Tannins; Molecular Structure; Oxidation-Reduction; Proanthocyanidins; Quercus; Wood

Actin subunits assemble into actin filaments whose dynamics and three-dimensional architectures are further regulated by a variety of cellular factors to establish the functional actin cytoskeleton. The C-glucosidic ellagitannin vescalagin and its simpler analogue vescalin, affect both the dynamics and the ultrastructure of the actin cytoskeleton by directly binding to F-actin. Herein, we show that in vitro, the two compounds induce the formation of distinct F-actin networks characterized by different superstructures and dynamics. In living mature osteoclasts, highly specialized bone-degrading cells that constantly remodel their cytoskeleton, vescalagin and vescalin alter actin dynamics at podosomes and compromise the integrity of the podosome belt that forms the bone-degrading apparatus. Both compounds target the bone-resorbing activity at concentrations that preserve osteoclastic maturation and survival and with no detectable impact on the behaviour of bone-forming osteoblastic cells. This anti-osteoclastic activity of vescalagin and vescalin reveals the potential of targeting actin dynamics as a new therapeutic opportunity and, in this case, as a plausible approach for the local treatment of osteoporosis.

Topics: Actin Cytoskeleton; Actins; Animals; Bone Resorption; Cell Adhesion; Cell Differentiation; Cell Survival; Cytoskeleton; Extracellular Matrix; Glucosides; Hydrolyzable Tannins; Mice, Inbred C57BL; Osteoclasts; Podosomes; Polymerization

Polyphenolic ellagitannins are natural compounds that are often associated with the therapeutic activity of plant extracts used in traditional medicine. They display cancer-preventing activity in animal models by a mechanism that remains unclear. Potential targets have been proposed, including DNA topoisomerases II (Top2). Top2α and Top2β, the two isoforms of the human Top2, play a crucial role in the regulation of replication, transcription, and chromosome segregation. They are the target of anticancer agents used in the clinic such as anthracyclines (e.g., doxorubicin) or the epipodophyllotoxin etoposide. It was recently shown that the antitumor activity of etoposide was due primarily to the inhibition of Top2α, whereas inhibition of Top2β was responsible for the development of secondary malignancies, pointing to the need for more selective Top2α inhibitors. Here, we show that the polyphenolic ellagitannin vescalagin preferentially inhibits the decatenation activity of Top2α in vitro, by a redox-independent mechanism. In CEM cells, we also show that transient small interfering RNA-mediated down-regulation of Top2α but not of Top2β conferred a resistance to vescalagin, indicating that the α isoform is a preferential target. We further confirmed that Top2α inhibition was due to a catalytic inhibition of the enzyme because it did not induce DNA double-strand breaks in CEM-treated cells but prevented the formation of Top2α- rather than Top2β-DNA covalent complexes induced by etoposide. To our knowledge, vescalagin is the first example of a catalytic inhibitor for which cytotoxicity is due, at least in part, to the preferential inhibition of Top2α.

Topics: Antigens, Neoplasm; Antineoplastic Agents; Catalysis; Cell Proliferation; DNA Breaks, Double-Stranded; DNA Topoisomerases, Type II; DNA-Binding Proteins; DNA, Kinetoplast; Down-Regulation; Etoposide; Humans; Hydrolyzable Tannins; Oxidation-Reduction; Poly-ADP-Ribose Binding Proteins; Protein Isoforms; Tumor Cells, Cultured

Topics: Actin Cytoskeleton; Actins; Animals; Cattle; Cells, Cultured; Endothelial Cells; Glucosides; Hydrolyzable Tannins; Protein Binding; Quercus; Surface Plasmon Resonance

Brandies, cognac, armagnac, whiskeys, and rums are aged in oak barrels to improve their organoleptic properties. During this period, numerous compounds such as ellagitannins are extracted from the wood and can subsequently be transformed into new derivatives by chemical reactions. Model solutions of castalagin and vescalagin have been studied to determine the behavior of polyphenols in ethanol-water. Upon prolonged exposure to 40 and 70% (v/v) ethanol at room temperature, hemiketal derivatives containing ethoxy groups have been characterized by LC/MS and NMR. These compounds further evolve to afford the corresponding ketals. They have also been detected in the extracts of oak wood stored under similar conditions.

Topics: Alcoholic Beverages; Antihypertensive Agents; Biphenyl Compounds; Catechols; Chromatography, High Pressure Liquid; Ethanol; Food Handling; Hydrolyzable Tannins; Molecular Conformation; Molecular Structure; Solutions; Tannins; Wood

The ellagitannins 2,3-(S)-hexahydroxydiphenoyl-glucose, pedunculagin, vescalagin, and castalagin; the flavanoellagitannins acutissimin A, acutissimin B, eugenigrandin A, guajavin B, and stenophyllanin C; and the procyanidinoellagitannin mongolicanin have been isolated from the bark of Quercus petraea. The ellagitannin fraction had a weak antisecretory effect.

Topics: Anthelmintics; Biphenyl Compounds; Catechols; Hydrolyzable Tannins; Magnetic Resonance Spectroscopy; Tannins; Trees