stilbenes and alpha-viniferin

Resveratrol has well-known anticancer properties; however, its oligomers, including α-viniferin, ε-viniferin, and kobophenol A, have not yet been well investigated. This is the first study examining the anti-epithelial-mesenchymal transition (EMT) effects of α-viniferin and ε-viniferin on A549, NCI-H460, NCI-H520, MCF-7, HOS, and U2OS cells. The results showed that α-viniferin and ε-viniferin significantly inhibited EMT, invasion and migration in TGF-β1- or IL-1β-induced non-small cell lung cancer. α-Viniferin and ε-viniferin also reversed TGF-β1-induced reactive oxygen species (ROS), MMP2, vimentin, Zeb1, Snail,

Topics: Animals; Benzofurans; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Down-Regulation; Epithelial-Mesenchymal Transition; Humans; Lung Neoplasms; Mice; Stilbenes; Transforming Growth Factor beta1; Vimentin

This study investigated the effects and molecular mechanisms of ε-viniferin and α-viniferin in non-small cell lung cancer cell line A549, melanoma cell line A2058, and osteosarcoma cell lines HOS and U2OS. Results showed ε-viniferin having antiproliferative effects on HOS, U2OS, and A549 cells. Compared with ε-viniferin at the same concentration, α-viniferin had higher antiproliferative effects on HOS cells, but not the same effect on U2OS and A549 cells. Lower dose combination of α-viniferin and ε-viniferin had more synergistic effects on A549 cells than either drug alone. α-Viniferin induced apoptosis in HOS cells by decreasing expression of phospho-c-Jun-N-terminal kinase 1/2 (p-JNK1/2) and increasing expression of cleaved Poly (ADP-ribose) polymerase (PARP), whereas α-viniferin in combination with ε-viniferin induced apoptosis in A549 cells by decreasing expression of phospho-protein kinase B (p-AKT) and increasing expression of cleaved PARP and cleaved caspase-3. ε-Viniferin and α-viniferin have not been studied using in vivo tumor models for cancer. This research is the first showing that ε-viniferin treatment resulted in significant inhibition of tumor growth in A549-cell xenograft-bearing nude mice compared with the control group. Consequently, ε-viniferin and α-viniferin may prove to be new approaches and effective therapeutic agents for osteosarcoma and lung cancer treatment.

Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Benzofurans; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Necrosis; Osteosarcoma; Stilbenes

α-Viniferin (AVF) and its monomer resveratrol (RESV) are natural phytostilbenes produced by several plants in response to injury or under the influence of pathogens such as bacteria or fungi. Our earlier studies have revealed that both the compounds exert anthelmintic activity through alterations of cestode tegument and its associated enzymes. The present study investigates the effects of these phytochemicals on some energy metabolism related enzymes in the fowl tapeworm, Raillietina echinobothrida. The phytostilbenes AVF, RESV and the reference drug praziquantel (PZQ) were tested against some selected enzymes i.e., phosphoenolpyruvate carboxykinase (PEPCK), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) of R. echinobothrida. Exposure of the tapeworm to AVF, RESV and PZQ causes reduction in activity of PEPCK to the extent of 40.57/41.96, 24.58/23.75 and 41.11/13.47%, respectively, and LDH up to 48.95/16.25, 38.31/38.42 and 45.67/41.87%, respectively, at the time of paralysis. Whereas activity of MDH decreased by 34.22/37.7, 39.1/35.24 and 28.83/19.26%, respectively. Decrease in activities of LDH and MDH was also visible through histochemical observations. The results suggest that both the phytochemicals interfere with the energy transducing pathways by inhibiting the studied energy metabolism related enzymes of the parasite.

Topics: Animals; Anthelmintics; Benzofurans; Cestoda; Energy Metabolism; Enzyme Inhibitors; L-Lactate Dehydrogenase; Malate Dehydrogenase; Phosphoenolpyruvate Carboxykinase (ATP); Praziquantel; Resveratrol; Stilbenes

Phytostilbenes, like resveratrol and α-viniferin, which occur mainly in the plants and belong to the families Cyperaceae, Vitaceae, and Gnetaceae are extensively popular for their medicinal and nutritional properties. In Northeast India, the Jaintia tribes consume these phytochemicals through aqueous extract of the medicinal plant Carex baccans to control helminthiasis. The present study aimed to investigate the inhibitory effect of the phytochemicals on neurotransmitters and its related enzymes in helminth parasite Raillietina echinobothrida. Viability of the parasites exposed to the phytostilbenes and extent of inhibition of cholinergic and nitrergic enzymes were evaluated in comparison to reference anthelmintic drug praziquantel and two known enzyme inhibitors, namely Nω-nitro-L-arginine and pyridostigmine. On exposure to resveratrol, α-viniferin, and reference drug praziquantel, the parasites ceased movement at 9.37, 11.38, and 0.24 h followed by death at 23.65, 34.13, and 1.87 h, respectively. Exposed parasites also showed a significant decrease in the activity of acetylcholinesterase (46.101, 65.935, and 63.645%) and nitric oxide synthase (61.241, 55.046, and 29.618%) in comparison to the controls. In addition, a decreased trend in nitric oxide (NO) level was also detected in the tissue of different phytochemical-exposed parasites compared to control. The present study suggests that anthelmintic potential of both the phytochemicals is mediated through inhibition of two vital enzymes which play diverse role in intracellular communications through neuromuscular system.

Topics: Acetylcholinesterase; Animals; Anthelmintics; Benzofurans; Cestoda; Cholinesterase Inhibitors; India; Nitric Oxide; Nitric Oxide Synthase; Plant Extracts; Praziquantel; Resveratrol; Stilbenes

The aim of this work was to evaluate the effect of stilbenes from different cultivars of Vitis vinifera on tumour proliferation. Extracts were obtained from elicited V. vinifera cell cultures and characterised by HPLC/DAD/MS. Cell growth was evaluated in four human cancer cell lines and in normal human fibroblasts. The cells were exposed to the extracts or to trans-resveratrol, used as reference molecule, for 48 h, at 1-10 μM concentrations of total stilbenoids. All the extracts exhibited antiproliferative activity, mediated by modulation of the cell cycle and induction of cytotoxicity in cancer but not in normal cell lines, and positively correlated with the content in dimeric stilbenoids. The Alphonse Lavallée extract was the most active, and the obtained stilbenoid fraction resulted 8-10 times more active than trans-resveratrol. Extracts from V. vinifera cell cultures could represent new sources of active stilbenoid compounds to be further assayed in in vivo studies for their antitumoural properties.

Topics: Antineoplastic Agents, Phytogenic; Benzofurans; Cell Culture Techniques; Cell Proliferation; Chromatography, High Pressure Liquid; Chromatography, Liquid; Fibroblasts; Humans; Mass Spectrometry; Plant Extracts; Resveratrol; Stereoisomerism; Stilbenes; Vitis

Phytochemical investigation on the stem bark of Shorea maxwelliana yielded five oligostilbenoids identified as α-viniferin (1), maximol A (2), vaticanol A (3), suffruticosol A (4) and vaticanol G (5). Chemotaxonomy of isolated compounds was discussed briefly. Major compounds were tested for neurotoxic and cytotoxic activities. Neurotoxicity for all tested compounds did not pose any toxic effect against cultured cell (cell viability range ±100-94%). Compounds 2-5 possessed active cyctotoxic activity against HL60 cell line with IC50 values range of 2.7-78 µg mL(-1).

Topics: Benzofurans; Cell Survival; Dipterocarpaceae; HL-60 Cells; Humans; Plant Bark; Plant Extracts; Stilbenes

Bioassay-guided investigation of the stem bark of Hopea chinensis led to the isolation of two new polyphenols, hopeachinols C(1) and D(2), together with ten known compounds (3-12). Compounds 1 and 2 were determined by extensive analysis of spectroscopic data and computational methods. All of these phytochemicals were tested for acetylcholinesterase inhibitory activity, and five resveratrol-derived compounds (1 and 7-10) exhibited significant activity with their IC₅₀ values ranging from 4.81 to 11.71 µM.

Topics: Benzofurans; Chemical Fractionation; Cholinesterase Inhibitors; Computational Biology; Dipterocarpaceae; Enzyme Assays; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Conformation; Plant Bark; Plant Stems; Polyphenols; Resveratrol; Stilbenes

The objectives of this research were to determine simultaneously the contents of two stilbene tetramers, carasinol B (1) and kobophenol A (2), and one stilbene trimer, (+)-alpha-viniferin (3), in the roots, tubers, and leaves of Caragana sinica in various seasons. A HPLC method has been developed for efficiently quantifying the three analytes in the plant. Using this method, different samples of Caragana sinica were evaluated. The results showed that the contents of 1, 2, and 3 in the roots were much higher than those in the tubers, and the contents of stilbene tetramers were maximal in winter while the contents of the stilbene trimer were maximal in summer. Compounds 1, 2, and 3 could not be detected in the flowers of Caragana sinica in our detection ranges.

Topics: Benzofurans; Caragana; Chromatography, High Pressure Liquid; Plant Extracts; Plant Leaves; Plant Roots; Reference Standards; Reproducibility of Results; Seasons; Solvents; Stilbenes

The objectives of this research were to determine simultaneously the contents of two stilbene tetramers, carasinol B (1) and kobophenol A (2), and one stilbene trimer, (+)-alpha-viniferin (3), in Jin Que-gen in different regions. A HPLC method has been developed for efficiently quantifying the three analytes in the plant. Using this method, different samples of Jin Que-gen were evaluated. The results showed that contents of the three analytes varied significantly among different samples, and the contents of the three analytes in commercial Jin Que-gen were markedly lower than those in the plants collected directly from growing regions. And for the three analytes, the longer the cultivation time, the higher the contents.

Topics: Benzofurans; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Plant Extracts; Plants, Medicinal; Stilbenes

We present the results of an in vitro investigation of the inhibitory effects of sophorastilbene A and (+)-alpha-viniferin isolated from Sophora moorcroftiana BENTH ex BAKER on copper ion-induced protein oxidative modification. They inhibited copper-induced protein oxidative modification. The order of these stilbenes and mannitol as a hydroxyl radical scavenger was sophorastilbene A > (+)-alpha-viniferin > mannitol.

Topics: Animals; Benzofurans; Brain; Copper; Dose-Response Relationship, Drug; Male; Mannitol; Mice; Mice, Inbred Strains; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Roots; Sophora; Stilbenes

The anti-inflammatory activity of alpha-viniferin, a trimer of resveratrol, has been demonstrated in an animal model of carrageenin-induced paw edema, and inhibitory effects of the compound on cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) have been investigated in order to understand the mode of the observed action. alpha-Viniferin at doses > 30 mg/kg ( p. o.) or > 3 mg/kg ( i. v.) showed significant anti-inflammatory activity on carrageenin-induced paw edema in mice. alpha-Viniferin showed an inhibitory effect with an IC (50) value of 4.9 microM on COX-2 activity but a very weak inhibitory effect with 55.2 +/- 2.1 % of the control (100 %) at 100 microM on COX-1 activity. alpha-Viniferin at doses of 3 microM to 10 microM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. alpha-Viniferin showed an IC50 value of 2.7 microM on nitric oxide (NO) production in LPS-activated Raw264.7 cells when alpha-viniferin and LPS were treated simultaneously, but did not inhibit the NO production when alpha-viniferin was treated at 12 h after LPS stimulation. alpha-Viniferin inhibited synthesis of iNOS transcript with an IC50 value of 4.7 microM. Consequently, the inhibitory effect of alpha-viniferin on the release of prostanoids and NO could play an important role to show anti-inflammatory action.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Caragana; Carrageenan; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; DNA Primers; Dose-Response Relationship, Drug; Edema; Inhibitory Concentration 50; Injections, Intravenous; Isoenzymes; Macrophages; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phytotherapy; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes

In the course of screening natural products for anti-acetylcholinesterase (AChE) activity, we found that a total methanolic extract of the underground parts of Caragana chamlague (Leguminosae) had significant inhibition towards AChE. Bioactivity-guided fractionation of the total methanolic extract resulted in the isolation and identification of two active stilbene oligomers, (+)-alpha-viniferin (1) and kobophenol A (2). Both 1 and 2 inhibited AChE activity in a dose-dependent manner, and the IC50 values of 1 and 2 were 2.0 and 115.8 microM, respectively. The AChE inhibitory activity of 1 was specific, reversible and noncompetitive.

Topics: Acetylcholinesterase; Benzofurans; Butyrylcholinesterase; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Fabaceae; Kinetics; Plant Extracts; Plant Roots; Spectrophotometry, Infrared; Stilbenes

Bioassay-guided high-performance liquid chromatography analysis of a MeOH extract of Iris clarkei seeds yielded the resveratrol-type oligomeric stilbenes, ampelopsin B and alpha-viniferin, which antagonize the action of 20-hydroxyecdysone; with a 20-hydroxyecdysone concentration of 50 nM, the ED50 values were 33 microM and 10 microM, respectively. The structures of these compounds were determined by spectroscopic analysis, notably ultraviolet, liquid secondary ion mass spectrometry and modern one- and two-dimensional nuclear magnetic resonance techniques.

Topics: Animals; Benzofurans; Cell Line; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drosophila melanogaster; Ecdysterone; Flavonoids; Magnetic Resonance Spectroscopy; Mass Spectrometry; Plants; Radioimmunoassay; Resveratrol; Seeds; Stilbenes