stilbenes and hopeaphenol

Grapevine co-products, as canes, represent a source of compounds of interest to control vineyard diseases with a sustainable approach. We chose to study an extract that we produced from grapevine trunk and roots. This extract, enriched in complex stilbenes, strongly reduced mycelial growth and spore germination of

Topics: Antifungal Agents; Plant Extracts; Resveratrol; Stilbenes; Vitis

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production. In contrast, it does not substantially inhibit the early PKC-mediated T-cell activation marker CD69 production of IL-6 or NF-κB signaling induced by tumor necrosis factor alpha (TNF-α). We further show that hopeaphenol can inhibit cyclin-dependent kinase 9 (CDK9) enzymatic activity required for HIV transcription. Finally, it inhibits HIV replication in peripheral blood mononuclear cells (PBMCs) infected

Topics: Cyclin-Dependent Kinase 9; HIV Infections; Humans; Leukocytes, Mononuclear; NF-kappa B; Protein Kinase C; RNA; Stilbenes; Virus Latency; Virus Replication

Drug development for regulating the innate immune system is important for the prevention and treatment of autoinflammatory and autoimmune diseases. In this context, we investigated the effect of resveratrol derivatives on the inflammatory reactions in the brain. Resveratrol, which can be found in Vitis plants in the form of oligomers, exhibits neuroprotective effects; however, its regulatory effects on innate immunity are still unclear. We examined the effects of (+)-hopeaphenol, a resveratrol tetramer, and its derivatives on the polyinosinic-polycytidylic acid (poly IC)-induced production of interferon (IFN)-β and C-X-C motif chemokine 10 (CXCL10) in the cultured human cerebral microvascular endothelial cell line hCMEC/D3. (+)-Hopeaphenol (1-10 μM) inhibited the poly IC-induced production of not only CXCL10 but also retinoic acid-inducible gene-I in a dose-dependent manner and significantly reduced the poly IC-induced IFN-β gene expression and protein release from hCMEC/D3 cells by inhibiting the phosphorylation of p65 but not that of the interferon regulatory transcription factor IRF3. A docking study indicated a high affinity of (+)-hopeaphenol for p65. These results suggest that (+)-hopeaphenol can regulate the innate immune system by inhibiting the poly IC/IFN-β/CXCL10 signaling axis via suppression of the phosphorylation of the transcription factor NF-ĸB.

Topics: Chemokine CXCL10; Endothelial Cells; Humans; Immunity, Innate; Interferon-beta; Phenols; Poly I-C; Resveratrol; Stilbenes

Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.

Topics: Anti-Bacterial Agents; Benzofurans; Drug Discovery; Flavonoids; Genes, Reporter; Green Fluorescent Proteins; Phenols; Pseudomonas aeruginosa; Resveratrol; Stilbenes; Type III Secretion Systems; Virulence; Yersinia pseudotuberculosis

Human sirtuin 1 (hSIRT1) is a NAD

Topics: Humans; Phenols; Polyphenols; Protein Binding; Resveratrol; Sirtuin 1; Stilbenes

Evidence suggests that the dietary consumption of plant extracts containing polyphenols might help prevent the onset of cancers of the gastrointestinal tract. In the present study, the chemopreventive and antiproliferative efficacy of a grapevine shoot extract (Vineatrol®30) containing resveratrol and resveratrol oligomers is investigated in vivo and in vitro.. The in vivo study is performed using Apc. Vineatrol®30 may merit further investigation as a potential dietary gastrointestinal cancer chemopreventive agent in humans.

Topics: Adenoma; Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Caspases; Cell Proliferation; Female; Intestinal Neoplasms; Male; Mice, Mutant Strains; Phenols; Resveratrol; Stilbenes

Two new sucrose derivatives, namely, belamcanosides A (

Topics: Adaptor Proteins, Vesicular Transport; Cell Survival; Cholesterol; Furans; Gene Expression Regulation; Hep G2 Cells; Humans; Hydroxymethylglutaryl CoA Reductases; Iris Plant; Lignans; Phenols; Plant Extracts; Quercetin; Receptors, LDL; Seeds; Squalene Monooxygenase; Stilbenes

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.

Topics: alpha-Synuclein; Animals; Benzothiazoles; Cell Survival; Electrophoresis, Polyacrylamide Gel; Flavonoids; Microscopy, Electron, Transmission; Parkinson Disease; PC12 Cells; Phenols; Rats; Stilbenes; Thiazoles; Wine

Ethanol extracts (Et) from the stem (S) and leaf (L) of Vitis thunbergii var. taiwaniana (VTT) were used to investigate yeast α-glucosidase and porcine kidney dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Both VTT-Et showed complete α-glucosidase inhibition at 0.1 mg/mL; VTT-S-Et and VTT-L-Et showed 26 and 11% DPP-IV inhibition, respectively, at 0.5 mg/mL. The VTT-Et interventions (20 and 50 mg/kg) resulted in improvements in impaired glucose tolerance of diet-induced obese rats. (+)-Hopeaphenol, (+)-vitisin A, and (-)-vitisin B were isolated from the ethyl acetate fractions of S-Et and showed yeast α-glucosidase inhibition (IC50 = 18.30, 1.22, and 1.02 μM) and porcine kidney DPP-IV inhibition (IC50 = 401, 90.75, and 15.3 μM) compared to acarbose (6.39 mM) and sitagliptin (47.35 nM), respectively. Both (+)-vitisin A and (-)-vitisin B showed mixed noncompetitive inhibition against yeast α-glucosidase and porcine kidney DPP-IV, respectively. These results proposed that VTT extracts might through inhibitions against α-glucosidase and DPP-IV improve the impaired glucose tolerance in diet-induced obese rats.

Topics: alpha-Glucosidases; Animals; Benzofurans; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Kinetics; Male; Obesity; Phenols; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Saccharomyces cerevisiae; Stilbenes; Swine; Vitis

The supply of (-)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screening of a prefractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A. thurifera, and similarly A. polyandra, resulted in three known resveratrol tetramers, (-)-hopeaphenol (1), vatalbinoside A (2), and vaticanol B (3). Compounds 1-3 displayed IC50 values of 8.8, 12.5, and 9.9 μM in a luminescent reporter-gene assay (YopE) and IC50 values of 2.9, 4.5, and 3.3 μM in an enzyme-based YopH assay, respectively, which suggested that they could potentially act against the T3SS in Yersinia. The structures of 1-3 were confirmed through a combination of spectrometric, chemical methods, and single-crystal X-ray structure determinations of the natural product 1 and the permethyl ether analogue of 3. The enzymatic hydrolysis of the β-glycoside 2 to the aglycone 1 was achieved through biotransformation using the endogenous leaf enzymes. This significantly enhanced the yield of the target bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (-)-hopeaphenol (1).

Topics: Animals; Anti-Bacterial Agents; Benzofurans; Dipterocarpaceae; Heterocyclic Compounds, 4 or More Rings; Inhibitory Concentration 50; Microbial Sensitivity Tests; Odonata; Papua New Guinea; Phenols; Rainforest; Resveratrol; Stilbenes; Yersinia pseudotuberculosis

Vineatrol(®) 30 is a grapevine-shoot extract, which contains resveratrol as well as considerable amounts of so-called resveratrol oligomers such as hopeaphenol and r2-viniferin. In this study, we analysed whether the two above-mentioned resveratrol oligomers were able to inhibit the growth of the canine glioblastoma cell line D-GBM and the canine histiocytic sarcoma cell line DH82, compared their potency to inhibit tumour cell growth with that of resveratrol and determined whether the induction of apoptosis via caspase 9 and 3/7 activation underlies the tumour cell growth-inhibiting effect of hopeaphenol and r2-viniferin. Vineatrol(®) 30, resveratrol, hopeaphenol and r2-viniferin inhibited the growth of D-GBM and DH82 cells in a concentration-dependent manner, whereby hopeaphenol and r2-viniferin were more potent than resveratrol itself in inhibiting the growth of the canine tumour cell lines. Moreover, the anti-proliferative effect of both resveratrol oligomers in D-GBM cells is based on their capacity to induce caspase 9 and 3/7 activation.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Dogs; Glioblastoma; Histiocytic Sarcoma; Molecular Structure; Phenols; Polyphenols; Resveratrol; Stilbenes

Grapevine canes are rich in resveratrol and its complex derivatives. These compounds have many biological activities and are needed mainly for health purposes. Canes, which are often wasted, can be used to produce these high-value compounds at low cost. We studied sixteen Vitis vinifera L. cultivars among the most widely cultivated ones worldwide. Polyphenols were extracted from their canes and identified by liquid chromatography-nuclear magnetic resonance spectroscopy. We accurately determined the content of E-ε-viniferin, E-resveratrol, E-piceatannol, and vitisin B and, for the first time, that of hopeaphenol and miyabenol C. The canes did not contain these major stilbene compounds in similar proportions, and their abundance and order of abundance varied according to the cultivar. For instance, Pinot noir has very high levels of E-resveratrol and E-ε-viniferin; Gewurztraminer has very high levels of vitisin B, and Carignan and Riesling have very high levels of hopeaphenol. These findings suggest that the right cultivar should be used to obtain the highest yield of a polyphenol of interest.

Topics: Benzofurans; Chromatography, Liquid; Phenols; Plant Stems; Polyphenols; Resveratrol; Species Specificity; Stilbenes; Vitis

Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)-Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

Topics: Bacterial Proteins; Bacterial Secretion Systems; Blotting, Western; Chlamydia trachomatis; HeLa Cells; Humans; Phenols; Protein Transport; Pseudomonas aeruginosa; Resveratrol; Stilbenes; Virulence; Yersinia pseudotuberculosis

Resveratrol, piceatannol, ε-viniferin, r-viniferin, r2-viniferin, and hopeaphenol are naturally occurring polyphenols, associated with potentially beneficial health effects. We developed a rapid liquid chromatography-ultraviolet detection (LC-UV) method, allowing for the simultaneous determination of these six compounds in biological samples in less than 2.5 min with standard LC equipment. Using this method for the assessment of the stability of the six analytes, we demonstrated that all stilbene polyphenols disappear rapidly in Dulbecco's modified Eagle's medium (e.g., half-life of resveratrol of 1 h). In contrast, the tetramer hopeaphenol was stable over the maximum incubation time of 72 h. In incubations with liver microsomes, ε-viniferin was rapidly glucuronidated, although to a lower extent than resveratrol. Hopeaphenol was not glucuronidated at all. Given that glucuronidation is the major metabolic pathway for polyphenols, hopeaphenol might exhibit significantly different pharmacokinetic properties than other polyphenols. When chemical and metabolic stability as well as biological activity of hopeaphenol are taken together, these findings warrant further investigation of this polyphenol.

Topics: Benzofurans; Chromatography, Liquid; Drug Stability; Glucuronides; Humans; Microsomes, Liver; Molecular Structure; Phenols; Polyphenols; Resveratrol; Stilbenes

An activity-guided isolation of bioactive stilbenes has been carried out with the grapevine-shoot extract Vineatrol 30. After hexane precipitation of the polymeric constituents, the stilbene mixture was separated on a preparative scale using low-speed rotary countercurrent chromatography (LSRCCC). The antiproliferative activity of the separated LSRCCC fractions was then screened in the human cancer cell line A-431, and trans-resveratrol, trans-ε-viniferin, r-2-viniferin, hopeaphenol, and miyabenol C were identified as active principles. In addition, a new class of stilbene derivatives, which exhibit a γ-lactam ring structure and exert a weak growth-inhibiting activity in A-431 cells, has been identified.

Topics: Antineoplastic Agents, Phytogenic; Benzofurans; Cell Line, Tumor; Chemical Fractionation; Countercurrent Distribution; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Phenols; Plant Shoots; Resveratrol; Stilbenes; Vitis

Five new stilbenoids, vatalbinosides A-E (1-5), and 13 known compounds (6-18) were isolated from the stem of Vatica albiramis. The effects of these new compounds on interleukin-1β-induced production of matrix metalloproteinase-1 (MMP-1) in human dermal fibroblasts were examined. Three resveratrol tetramers, (-)-hopeaphenol (6), vaticanol C (13), and stenophyllol C (14), were identified as strong inhibitors of MMP-1 production.

Topics: Dipterocarpaceae; Fibroblasts; Humans; Interleukin-1beta; Malaysia; Matrix Metalloproteinase 1; Molecular Structure; Phenols; Plant Stems; Plants, Medicinal; Resveratrol; Skin; Stereoisomerism; Stilbenes

It has been reported that resveratrol (trans-3,5,4'-trihydroxystilbene) from Vitis plants has various cardioprotective effects. Vitis plants also include various resveratrol tetramers. The aim of our study is to clarify the pharmacological properties of resveratrol tetramers. We isolated two resveratrol tetramers as major products of Vitis plants. One is vitisin A, a complex of two resveratrol dimers, (+)-epsilon-viniferin and ampelopsin B, and the other is hopeaphenol, composed of 2 mol ampelopsin B. Vitisin A (30-300 nM) unexpectedly dose-dependently facilitated swelling and depolarization of mitochondria and cytochrome c release from mitochondria, which are indices of cardiomyocyte apoptosis. Furthermore, vitisin A induced apoptosis in the primary culture of adult rat ventricular myocytes. On the other hand, hopeaphenol (1-10 microM) dose-dependently inhibited Ca(2+) (30 microM)-induced mitochondrial depolarization and cytochrome c release from mitochondria but had not affected mitochondrial swelling. Moreover, hopeaphenol inhibited vitisin A-induced apoptosis. In structural and functional studies, we further confirmed that vitisin B, one of the resveratrol tetramers having (+)-epsilon-viniferin unit, induces mitochondrial swelling and cytochrome c release from mitochondria like vitisin A and that vitisifuran A, one of the resveratrol tetramers having the ampelopsin B unit, inhibits Ca(2+)-induced cytochrome c release from mitochondria like hopeaphenol. These results show that resveratrol tetramers have at least two opposite effects on cardiomyocytes; the one having the (+)-epsilon-viniferin unit induces cardiomyocyte apoptosis, and the other having ampelopsin B but not (+)-epsilon-viniferin unit inhibits it.

Topics: Animals; Antioxidants; Apoptosis; Benzofurans; Calcium; Cytochromes c; Heart; Intracellular Membranes; Membrane Potentials; Mitochondria, Heart; Mitochondrial Swelling; Myocardium; Myocytes, Cardiac; Phenols; Rats; Rats, Wistar; Resveratrol; Stilbenes

A new oligostilbenoid, diptoindonesin C, has been isolated from the tree bark of Shorea pinanga Scheff., along with the two known oligostilbenoids gnetin H and hopeaphenol, and a known coumarin scopoletin. The new oligostilbenoid was moderately active against brine shrimps Artemia salina.

Topics: Dipterocarpaceae; Molecular Structure; Phenols; Plant Bark; Plant Extracts; Stilbenes

Grapes and wines are now known to constitute a rich source of phenolics such as stilbenes and flavonoids. These compounds have been shown to have cancer chemopreventive activity and potential beneficial effects on cardiovascular diseases thanks to their antioxidant and antiplatelet properties. However, because little is known about African wines and their phenolic compositions, we investigated wine samples from North Africa. A three-step method was used for the fractionation of the Merlot variety wine: column chromatography followed by centrifugal partition chromatography and reversed-phase semipreparative high-performance liquid chromatography (HPLC). Six polyphenolic compounds of the Merlot variety (from Algeria) were isolated and identified by NMR spectroscopy, five of which are known (trans-resveratrol, trans-piceid, trans-epsilon-viniferin, pallidol, and astilbin) and one that is reported for the first time in wine, (+)-hopeaphenol, a stilbene tetramer. Furthermore, these molecules were quantified in 10 commercial wines from North Africa by means of an analytical HPLC system coupled with diode array detection. Differences in concentrations were found ranging in mg/L from 4.6 to 45 (trans-piceid), 0.66 to 3.45 (trans-resveratrol), 0.2 to 1.2 (trans-epsilon-viniferin), 0.2 to 9.2 (pallidol), 0.3 to 3.8 (hopeaphenol), and 10.8 to 24.22 (astilbin). Such a high level of pallidol and astilbin has never been recorded in wine. North African wines may contribute to a significant proportion of dietary intake of stilbene and astilbin, which may have health benefits.

Topics: Africa, Northern; Algeria; Chromatography, High Pressure Liquid; Flavonoids; Flavonols; Magnetic Resonance Spectroscopy; Phenols; Polyphenols; Resveratrol; Stilbenes; Wine