Stilbene Compounds Research Articles

Dual Mode of Action of Grape Cane Extracts against Botrytis cinerea.

Crude extracts of Vitis vinifera canes represent a natural source of stilbene compounds with well characterized antifungals properties. In our trials, exogenous application of a stilbene extract (SE) obtained from grape canes on grapevine leaves reduces the necrotic lesions caused by Botrytis cinerea. The SE showed to possess a direct antifungal activity by inhibiting the mycelium growth. The activation of some grapevine defense mechanism was also investigated. H2O2 production and activation of mitogen-activated protein kinase (MAPK) phosphorylation cascades as well as accumulation of stilbenoid phytoalexins were explored on grapevine cell suspension. Moreover, the transcription of genes encoding for proteins affecting defense responses was analyzed on grapevine plants. The SE induced some grapevine defense mechanisms including MAPK activation, and the expression of pathogenesis-related (PR) genes and of a gene encoding the glutathione-S-transferase 1 ( GST1) . By contrast, treatment of grapevine leaves with SE negatively regulates de novo stilbene production.

Resveratrol analogues surprisingly effective against triple‑negative breast cancer, independent of ERα.

Resveratrol, a plant‑derived stilbene compound, has exhibited anticancerous properties, including breast cancer. Stilbenes have a molecular structure highly similar to estrogen and have the ability to bind estrogen receptors and regulate activity. Numerous studies have demonstrated the effectiveness of resveratrol in estrogen receptor‑positive (ER‑positive) subtypes of breast cancer, yet the effects in ER‑negative subtypes, including triple‑negative breast cancer (TNBC), have been limited. In the present study, resveratrol and 28analogues were tested on a panel of ER‑positive and TNBC cell lines to determine effects on cell viability. Several compoundsexhibited significant impacts on cell viability and suggested changes in cell morphology, with high potency of select compoundscompared to resveratrol observed in a dose‑dependent manner. Due to the lack of estrogen receptors in TNBC and the estrogenic nature of stilbenes, regulation of breast cancer‑associated cellular pathways was assessed for five analogues shown to significantly inhibit cell viability. Top regulated pathways included apoptosis (confirmed by caspase assay) and DNA damage repair. Overall, our results indicated several resveratrol analogues to be active in ER‑negative phenotypes, acting through an ER receptor‑independent manner, supporting further investigation into their mechanism of action and use as potential chemotherapeutics in higher‑risk breast cancer cases.

Methyl jasmonate and cyclodextrin-mediated defense mechanism and protective effect in response to paraquat-induced stress in peanut hairy root

Plant cells have a variety of defense mechanisms to alleviate the deleterious effects of oxidative stress. The present work elucidated a schematic diagram of the proposed pathway of peanut hairy root tissue treated with different elicitors; paraquat (PQ), methyl jasmonate (MeJA), and cyclodextrin (CD). The different elicitation approaches could provoke intrinsic stress in plant cells and might activate a distinct response pathway, allowing plants to overcome the deleterious effects of oxidative stress. Among all strategies, hairy root culture pretreated with PQ followed by application of MeJA plus CD showed an extensive induction of antioxidant defense mechanisms. The expression of the antioxidant enzyme genes and stilbene-synthesized enzyme genes were up-regulated in accordance with the dramatic increase in the production of stilbene compounds. The non-enzymatic antioxidant substances exhibited a highly enhanced capability. The pathogenesis-related protein (PR) genes were also highly up-regulated. In summary, we demonstrated that the interplay among MeJA plus CD and PQ may activate a complex signaling network to regulate plant defense mechanisms involving the up-regulation of detoxifying enzymes, induction of free-radical scavengers and overexpression of genes associated with plant defense pathways.

Sirtuin 1 (SIRT1) Content and Angiotensin II Receptor Type I (AT1) Expression in Human Umbilical Vein Endothelial Cells (HUVECs) in Response to Resveratrol: Pregnancy Induced Hypertension (PIH) vs Normotensive pregnancy (NTP)

Oxidative stress and endothelial dysfunction within uteroplacental unit are inherent components initiating PIH. The normal decrease of vascular angiotensin II sensitivity is lost in PIH. The polyphenol stilbene compound resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) boosts endothelium‐dependent vasorelaxation enhancing endothelial nitrix oxide synthase (eNOS) production. In fact, resveratrol acts as a secondary regulator influencing more complex biological response that includes the sirtuin system. SIRT1 is highly expressed in endothelial cells and activated/modulated by resveratrol has been shown to target eNOS for deacetylation resulting in enhanced NO‐dependent vascular relaxation. Moreover, anti‐hypertensive effects of resveratrol may be a consequence of the angiotensin II receptor type I (AT1) modulation by SIRT1. The aim of the study was to examine comparatively the effect of resveratrol on SIRT level in HUVECs isolated after PIH vs. NTP. In addition, AT1 expressions were compared. HUVECs were isolated immediately after cesarean section delivery from PIH (N = 24) and NTP (N = 24) patients (group I and group II, respectively). The umbilical cord segments was subjected to collagenase digestion and the HUVECs were cultured in vitro under normoxia. After achieving the confluence, HUVECs were exposed to resveratrol (50, 100 and 250 μM) administered into the culture media in the respective subgroups A, B and C during the 7 day period. SIRT1 levels were determined in HUVECs culture lysates obtained in the days 1,3 and 7, using ELISA. After termination of the cultures AT1 were immunostained in formalin fixed and paraffin embedded sections. To estimate the mean expression of AT1, quantitative immunohostochemistry was applied. The initial AT1 expression was estimated in the respective controls. After 3 and 7 days of the culture, in both groups the mean SIRT1 levels were significantly (p < 0.05) higher in the subgroups B and C, compared to the initial levels at day 1. However, the mean SIRT1 levels in group I were 4.6‐fold and 2.4‐fold lower (the subgroups B and C, respectively) than observed in normotensive group II. The initial expression of AT1 was significantly higher in group I and amounted to 170% of the average value in the normotensive group II. The mean expression of AT1 was significantly (p < 0.05) downregulated in group I (the subgroups B and C), while in group II was nearly unaffected. These results may suggest potential beneficial effect of SIRT1 activation by resveratrol with regard to antihypertensive therapy in PIH.Support or Funding InformationWUM grant: 2M2‐W1‐17This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Substituent effects on the ultraviolet absorption properties of stilbene compounds-Models for molecular cores of absorbents.

The effects of substituent X and Y on ultraviolet (UV) absorption properties of stilbene compounds XPhCHCHPhY (XSBY) were studied both experimentally and computationally from the viewpoint of UV maximum absorption wavelength (λmax) and the corresponding energy (υmax). In the studies, the contribution of substituents on υmax shift was explored. The results show that with increase of electron withdrawing or electron donating ability of X or Y, there is an enhanced electron delocalization of XSBY that leads to bathochromic shift. Computational analyses based on density functional theory were conducted to elucidate the phenomena. It is disclosed that the υmax values are significantly affected by the excited state, though the electronic effect of ground state cannot be ignored. Finally, on the basis of the respective influences of X and Y, a quantitative model, which was proved reliable by the leave-one-out method, was developed to scale the effects of terminal substituents on υmax. According to the model, the effects of substituents X or Y exhibit almost the same action on υmax owing to the symmetric skeleton of the XSBY compounds. The findings provide deep insight into the effects of terminal substituents on UV absorption properties of stilbene compounds, and the derived model enables practical expression of the relationship between substituents and UV absorption.

Dynamic translocation of stilbene synthase VpSTS29 from a Chinese wild Vitis species upon UV irradiation

Stilbene phytoalexins derived from grapevine can be rapidly accumulated when exposed to an artificial UV-C treatment. However, the underlying mechanisms involved in this accumulation and translocation are unclear. Here, we describe an investigation of the influence of UV-C treatment on the dynamic subcellular distribution of a member of a stilbene synthase family VpSTS29 derived from Chinese wild Vitis pseudoreticulata W.T. Wang when over-expressed in V. vinifera L. cv. Thompson Seedless. Our results show that VpSTS29-GFP was accumulated at a relatively high level in roots and mature leaves of transgenic grape lines, and was predominantly distributed in the cytoplasm. When exposed to UV-C irradiation, VpSTS29 displayed UV-induced feature coupled with the accumulation of stilbene compounds. Notably, VpSTS29-GFP can be translocated from the cytoplasm into chloroplasts upon UV-irradiation. Leaves from the two VpSTS29-GFP-expressing lines displayed more serious UV damage, showing withering and marginal scorching phenotype, and decreased content of H2O2, compared to the untransformed plant. Also, overexpression of VpSTS29 altered the expression of genes related to redox regulation, stilbene biosynthesis and light stimulus. Co-expression of VpSTS29-GFP with Glycolate oxidase 1 (myc-VpGLO1) confirmed the ability of stilbenes to decrease the content of H2O2 in Arabidopsis mesophyll protoplasts. These results provide new insight into the biological functions and properties of stilbene synthase and its product in response to environmental stimulus.

Synthesis and optical properties of bipolar quinoxaline-triphenylamine based stilbene compounds

Four new donor–acceptor based stilbene derivatives were synthesized via Heck coupling reaction. These materials are green light emitters with good fluorescence quantum yield. Furthermore, the emitters show well matched HOMO/LUMO value as bipolar molecule. In addition, they are highly thermally stable. Optimized structures and electronic distribution in ground state are also studied to understand photophysical properties using DFT calculation.

Plasma pharmacokinetics of isorhapontigenin, a novel derivative of stilbenes, in mice by LC-MS/MS method

Isorhapontigenin (ISO), a novel derivative of stilbene compound, possessess good pharmacological activities such as antiviral, antioxidant, and anticancer. The purpose of this study is to investigate the pharmacokinetic of ISO in mice plasma, after oral administration of three doses (40, 80, and 160 mg/kg). Isorhapontigenin was detected by liquid chromatography–tandem mass spectrometry (LC-MS/MS), and a reliable LC-MS/MS assay for ISO in mice plasma was developed. The method was linear over a concentration range of 5–2000 ng/ml, and the lower limit of quantification was 5 ng/ml. The results indicated that there was a linear relationship between AUC(0–t), AUC(0–∞), and Cmax of ISO and dosages. ISO underwent quick absorption and elimination in mice.

Evaluation of the DNA damage protective activity of the germinated peanut (Arachis hypogaea) in relation to antioxidant and anti-inflammatory activity

This study evaluated the increase in antioxidant activity, total phenolic content, in vitro anti-inflammatory activity, and DNA damage protective activity in the germinated peanut. The highest trans-resveratrol content, expressed as 8.8 ± 0.1 μg/g of peanut crude extract, was detected on the first day of germination. LC-MS/MS analysis shows the presence of stilbene compounds, namely trans-arachidin-3, trans-3′-Isopentadienyl-3, 5, 4′-trihydroxystilbene, trans-arachidin-1, trans-resveratrol, and 1,4-Isopentadienyl-3, 5, 3’, 4′-tetrahydroxystilbene, in the first germinated sprout. The in vitro anti-inflammatory activity was significantly increased in all peanut sprout crude extracts compared to the ungerminated peanut. The germinated peanut exhibited dose-dependent DNA damage protective activity in a concentration range of 5–5000 μg/ml. In addition, the germinated peanut at a concentration of 1000 μg/ml showed stronger DNA damage protective activity compared to trans-resveratrol. This might be due to the effect of the stilbene and other antioxidant compounds resulting from the germination process. Thus, germination is a promising process for improving the content of bioactive stilbene and potential antioxidant compounds in peanuts, which could be applicable for use in the functional food and nutraceutical industry.

Resveratrol suppresses colon cancer growth by targeting the AKT/STAT3 signaling pathway.

Colon cancer is a common type of cancer worldwide and accounts for a significant number of cancer‑related deaths. Although surgical techniques and treatment strategies for colon cancer have advanced over the past two decades, the prognosis has not improved considerably. Resveratrol, a natural stilbene compound, possesses antioxidant, cardioprotective and anticancer properties. However, the role of resveratrol in colon cancer has not been fully elucidated. The present study demonstrated that resveratrol inhibited cell proliferation and colony growth in DLD1 and HCT15 colon cancer cells, but did not affect normal colon epithelial cells. The resveratrol‑mediated inhibition of cell proliferation correlated with an induction of apoptosis and with G1 phase cell cycle arrest in colon cancer cells. Additionally, resveratrol treatment decreased the protein expression levels of cyclinD1, cyclinE2 and BCL2 apoptosis regulator, while it increased BCL2 associated X and tumor protein p53, all of which are involved in the regulation of cell cycle and apoptosis. Notably, the results obtained from insilico computational screening identified AKT serine/threonine kinase1(AKT1) and AKT2 as novel targets of resveratrol. Computational docking suggested that there are three or four possible hydrogen bonds in the active pocket of AKT1 and AKT2 that contribute to the mode of action of resveratrol. The present study confirmed that resveratrol bound to AKT1 and AKT2 with a pull‑down assay. Furthermore, knockdown of AKT1 and AKT2 inhibited cell proliferation and colony growth, by attenuating cell cycle progression and increasing apoptosis in colon cancer cells, effects that were similar to those caused by resveratrol treatment. Taken together, the present results suggest that the targeting effects of resveratrol to AKT1 and AKT2 may be a potent strategy for chemoprevention or therapy for colon cancer.

Using the relative abundance of characteristic product ions in UHPLC-ESI-QTOF-MS2 methods to identify isomers of resveratrol oligomers in extracts of Xinjiang winegrape stems

Stilbenoids, particularly resveratrol and its oligomer, are abundantly present in grapes, and their antioxidant activities have been widely reported. A quick and simple method based on UHPLC-ESI-QTOF-MS2 was established for the fragmentation pathways analysis of trans-ε-Viniferin, cis-ε-Viniferin, trans-δ-Viniferin and (−)-Hopeaphenol. MS/MS experiments on the [M-H]− ions provided abundant structural information, especially regarding the relative abundance of the key product ion at m/z 347. The product ion was used to further identify structures in isomers of resveratrol dimers and its analogues. Based on the fragmentation pathways, we tentatively determined two compounds from the crude extracts of Xinjiang winegrape stems as Gnetin C and cis-Scirpusin A. Results from these experiments contribute to a more complete understanding of the stilbene compounds found in grape stems. The UHPLC-QTOF-MS2 method can be used for the rapid analysis of stilbenes compounds in plant materials, foods and wine.

Production of Bioactive 3'-Hydroxystilbene Compounds Using the Flavin-Dependent Monooxygenase Sam5.

The flavin-dependent monooxygenase Sam5 was previously reported to be a bifunctional hydroxylase with a coumarte 3-hydroxylase and a resveratrol 3'-hydroxylase activity. In this article, we showed the Sam5 enzyme has 3'-hydroxylation activities for methylated resveratrol (pinostilbene and pterostilbene), hydroxylated resveratrol (oxyresveratrol) and glycosylated resveratrol (piceid) as substrates. However, the use of piceid, a glycone type stilbene, as a substrate for bioconversion experiments with the Sam5 enzyme expressed in, Escherichia coli does not convert to the hydroxylated compound astringin, but it has converted in vitro enzyme reactions. Finally, we report a novel catalytic activity of Sam5 monooxygenase for the synthesis of piceatannol derivatives, 3'-hydroxylated stilbene compounds. Development of this bioproduction method for the hydroxylation of stilbenes is challenging because of the difficulty in expressing P450-type hydroxylase in E. coli and regionspecific chemical synthesis.

Desoxyrhapontigenin inhibits RANKL‑induced osteoclast formation and prevents inflammation‑mediated bone loss.

Desoxyrhapontigenin (DRG), a stilbene compound from Rheum undulatum, has been found to exhibit various pharmacological activities, however, its impact on osteoclast formation has not been investigated. The present study investigated the effect of DRG on receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and inflammation‑induced bone loss invivo. BMMs or RAW264.7 cells were treated with DRG, followed by an evaluation of cell viability, RANKL‑induced osteoclast differentiation, actin‑ring formation and resorption pits activity. The effects of DRG on the RANKL‑induced phosphorylation of MAPK and the expression of nuclear factor of activated T cells cytoplasmic1 (NFATc1) and c‑Fos were evaluated using western blot analysis once the BMMs were exposed to RANKL and DRG. The expression levels of osteoclast marker genes were also evaluated using western blot analysis and reverse transcription‑quantitative polymerase chain reaction A lipopolysaccharide (LPS)‑induced murine bone loss model was used to evaluate the protective effect of DRG on inflammation‑induced bone‑loss. The results demonstrated that DRG suppressed the RANKL‑induced differentiation of BMMs into osteoclasts, osteoclast actin‑ring formation and bone resorption activity in a dose‑dependent manner. Furthermore, DRG significantly inhibited LPS‑induced bone loss in a mouse model. At the molecular level, DRG inhibited the RANKL‑induced activation of extracellular signal‑regulated kinase, the expression of c‑Fos, and the induction of NFATc1, a crucial transcription factor for osteoclast formation. DRG decreased the expression levels of osteoclast marker genes, including matrix metalloproteinase‑9, tartrate‑resistant acid phosphatase and cathepsin K. In conclusion, these findings suggested that DRG inhibited the differentiation of BMMs into mature osteoclasts by suppressing the RANKL‑induced activator protein‑1 and NFATc1 signaling pathways, and may be a potential candidate for treating and/or preventing osteoclast‑associated diseases, including osteoporosis.

The Switching from Cis-to-trans One-way Photoisomerization to Mutual Photoisomerization of a Stilbene–Urea Compound Triggered by Proton Transfer Reaction

We have developed a new photochromic material containing a stilbene moiety and a urea moiety based on cooperative effect of photoisomerization and proton transfer. An anthracene–urea–stilbene compound (stAn) exhibited cis-to-trans one-way photoisomerization via the excited triplet state. Furthermore, we succeeded in the switching from one-way to mutual photoisomerizations by the addition of a fluoride ion, which causes the ground state intermolecular proton transfer of stAn leading to negligible intersystem crossing from the excited singlet state.

Pterostilbene inhibited advanced glycation end products (AGEs)-induced oxidative stress and inflammation by regulation of RAGE/MAPK/NF-κB in RAW264.7 cells

Pterostilbene is a natural stilbene compound found in blueberries. It has been found to show anticancer, anti-inflammatory and anti-oxidative effects. However, little is known about its relationship with AGEs-induced oxidative stress and inflammation. In this study, we examined the inhibitory effect of pterostilbene on AGEs-induced damage using RAW264.7 cells. Pterostilbene was found to significantly suppress ROS production, mRNA expression of NADPH oxidase, and carbonyl levels of proteins and AOPP, which are related to oxidative stress. In addition, pterostilbene significantly reduced gene expression of inflammatory mediators, including TNF-α, IL-1β and IL-6. Further analysis showed that pterostilbene inhibited AGEs-induced RAGE up-regulation, but showed no effect on CD36. Moreover, it reduced NF-κB phosphorylation and MAPKs activation, including p38 and ERK1/2 induced by AGEs. Thus our results indicated that pterostilbene might act as a promising agent to alleviate AGEs-induced oxidative stress and inflammation via RAGE/MAPK/NF-κB pathway.

Enhancement of stilbene compounds and anti-inflammatory activity of methyl jasmonate and cyclodextrin elicited peanut hairy root culture

A highly stable and productive hairy root culture from peanut cultivar Tainan9 (T9-K599) was established using Agrobacterium rhizogenes strain K599 (NCPPB 2659)-mediated transformation. Valuable phenolic compounds with antioxidant activity and stilbene compounds were produced and secreted into the culture medium after elicitation with 100 µM methyl jasmonate (MeJA) and 6.87 mM cyclodextrin (CD). The antioxidant activity of the culture medium was increased to the highest Trolox equivalent antioxidant capacity (TEAC) value (28.30 ± 2.70 mM Trolox/g DW) in the group treated with CD. The group co-treated with MeJA and CD exhibited the highest phenolic content, with a gallic acid equivalent (GAE) value of 10.80 ± 1.00 µg gallic acid/g DW. The CuZn-SOD (CuZn superoxide dismutase) and APX (ascorbate peroxidase) antioxidant enzyme gene were up-regulated in the treatment with CD alone while the CuZn-SOD, GPX (glutathione peroxidase) and APX gene expression were down-regulated in the co-treatment with MeJA plus CD. The stilbene compounds resveratrol, trans-arachidin-1 and trans-arachidin-3 were detected by analysing the culture medium treated with CD alone and after co-treatment with MeJA and CD via HPLC. The LC-MS/MS results confirmed the presence of resveratrol, trans-arachidin-1, trans-arachidin-3, 4-Isopentadienyl-3,5,3′,4′-tetrahydroxystilbene (IPP), trans-3′-Isopentadienyl-3,5,4′-trihydroxystilbene (IPD) and arahypin-7. The results indicate that elicited peanut hairy roots can produce beneficial stilbene compounds that have antioxidant properties and anti-inflammatory activity. This peanut hairy root system could be applied as an experimental model to enhance the production of stilbene and other polyphenolic bioactive compounds.

A-π-D-π-A type oligomer based on carbazole and benzothiadiazole for organic solar cells

ABSTRACTAn acceptor-donor-acceptor (A-p-D-p-A) type oligomer based on benzothiadiazole and 2,7 carbazole, 2,7-Bis(5-{7–2[-(4-decyloxy-phenyl)-vinyl]-benzo[1,2,5]thiadiazol-4-yl}-thiophen-2-yl)-9-(2-octyl-dodecyl)-9 H-carbazole (CzBT-DP), is synthesized by the Suzuki Coupling reaction. In addition, to extend the effective of conjugated length, we introduce thiophene (T) ring as a p-bridge and stilbene in the end of the conjugated chain. Optical, electrical and thermal properties and photovoltaic performances of CzBT-DP is systematically investigated. UV-vis absorption spectra and cyclic voltammograms (CV) reveal that HOMO/LUMO level of CzBT-DP is −5.37 eV/−3.38eV with an optical band gap of 1.99 eV, respectively, due to the addition of conjugated chain using stilbene compound system. The HOMO energies of CzBT-DP were calculated from the measured onset potential of oxidation by assuming the energy level of ferrocene (Fc) as −4.8 eV by CV. Addition of thiophene affects the HOMO level which makes CzBT-DP has high-lying HOMO level. Due to higher LUMO energy values above 0.3 eV than PC71 BM, CzBT-DP could be applied to BHJ OSCs as the donor [1]. Inverted type organic solar cells (OSCs) with a configuration of ITO/ZnO/CzBT-DP:PC71BM/MoO3/Al are fabricated. Figure 1 shows the current density-voltage (J-V) characteristics of the optimized BHJ OSCs based on CzBT-DP:PC71BM blend ratios from 3:2 to 3:6 (w/w). Maximum power conversion efficiency (PCE) is 0.64% with a short-circuit current density (Jsc) of 1.78 mA/cm2, Voc of 0.94 V, and fill factor (FF) of 38.3%. The best blend ratio between CzBT-DP and PC71BM having the best PCE appeared at 3:3 (w/w).

Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray.

The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated S. aureus. Fourteen genes were upregulated and 38 genes downregulated by SK-03-92 treatment. Genes involved in sortase A production, protein metabolism, and transcriptional regulation were upregulated, whereas genes encoding transporters, purine synthesis proteins, and a putative two-component system (SACOL2360 (MW2284) and SACOL2361 (MW2285)) were downregulated by SK-03-92 treatment. Quantitative real-time polymerase chain reaction analyses validated upregulation of srtA and tdk as well as downregulation of the MW2284/MW2285 and purine biosynthesis genes in the drug-treated population. A quantitative real-time polymerase chain reaction analysis of MW2284 and MW2285 mutants compared to wild-type cells demonstrated that the srtA gene was upregulated by both putative two-component regulatory gene mutants compared to the wild-type strain. Using a transcription profiling technique, we have identified several cellular pathways regulated by SK-03-92 treatment, including a putative two-component system that may regulate srtA and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.

Selective opioid growth factor receptor antagonists based on a stilbene isostere

As part of an ongoing drug development effort aimed at selective opioid receptor ligands based on the pawhuskin natural products we have synthesized a small set of amide isosteres. These amides were centered on lead compounds which are selective antagonists for the delta and kappa opioid receptors. The amide isomers revealed here show dramatically different activity from the parent stilbene compounds. Three of the isomers synthesized showed antagonist activity for the opioid growth factor (OGF)/opioid growth factor receptor (OGFR) axis which is involved in cellular and organ growth control. This cellular signaling mechanism is targeted by “low-dose” naltrexone therapy which is being tested clinically for multiple sclerosis, Crohn’s disease, cancer, and wound healing disorders. The compounds described here are the first selective small molecule ligands for the OGF/OGFR system and will serve as important leads and probes for further study.

Expression patterns and promoter characteristics of the Vitis quinquangularis VqSTS36 gene involved in abiotic and biotic stress response.

Resveratrol is a stilbene compound that is synthesized by plants in response to biotic stress and has been linked to health benefits associated with the consumption of certain foods and food products, such as grapes and wine. The final step in the biosynthesis of resveratrol is catalyzed by the enzyme stilbene synthase (STS). Here, we assessed the expression of two STS genes (VqSTS36 and VpSTS36) from the wild grape species Vitis quinquangularis (accession 'Shang-24'; powdery mildew (PM) resistant) and Vitis pseudoreticulata (accession 'Hunan-1'; PM susceptible) following infection by Uncinula necator (Schw.) Burr, the causal agent of PM disease. Some correlation was observed between the relative levels of STS36 transcript and disease resistance. We also cloned the 5' upstream sequence of both VpSTS36 and VqSTS36 and generated a series of 5' VqSTS36 promoter deletions fused to the GUS reporter gene in order to analyze expression in response to wounding, the application of exogenous stress-associated hormones, and biotic stress in tobacco leaves. The promoter was shown to be induced by the hormone salicylic acid (SA), inoculation with the fungal pathogen Erysiphe cichoracearum, and by wounding. These results suggest that VqSTS36 is regulated by biotic stresses and that it plays an important role in mediating disease resistance in grape.