trans-Stilbene

The role of resveratrol as a natural modulator in glia activation in experimental models of stroke.[Pubmed:33299813]

Avicenna J Phytomed. 2020 Nov-Dec;10(6):557-573.

Objective: Stroke is one of the most important causes of death and disability in modern and developing societies. In a stroke, both the glial cells and neurons develop apoptosis due to decreased cellular access to glucose and oxygen. Resveratrol (3, 5, 4'-trihydroxy-trans-Stilbene) as a herbal compound shows neuroprotective and glioprotective effects. This article reviews how resveratrol can alleviate symptoms after stroke to help neurons to survive by modulating some signaling pathways in glia. Materials and Methods: Various databases such as ISI Web of Knowledge, Scopus, Medline, PubMed, and Google Scholar, were searched from 2000 to February 2020 to gather the required articles using appropriate keywords. Results: Resveratrol enhances anti-inflammatory and decreases inflammatory cytokines by affecting the signaling pathways in microglia such as AMP-activated protein kinase (5' adenosine monophosphate-activated protein kinase, AMPK), SIRT1 (sirtuin 1) and SOCS1 (suppressor of cytokine signaling 1). Furthermore, through miR-155 overexpressing in microglia, resveratrol promotes M2 phenotype polarization. Resveratrol also increases AMPK and inhibits GSK-3beta (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces reactive oxygen species (ROS). Besides, resveratrol increases oligodendrocyte survival, which can lead to maintaining post-stroke brain homeostasis. Conclusion: These results suggest that resveratrol can be considered a novel therapeutic agent for the reduction of stroke symptoms that can not only affect neuronal function but also play an important role in reducing neurotoxicity by altering glial activity and signaling.

Synthesis and Biological Evaluation of Halogenated E-Stilbenols as Promising Antiaging Agents.[Pubmed:33297520]

Molecules. 2020 Dec 7;25(23). pii: molecules25235770.

The increased risk of illness and disability is related to the age inevitable biological changes. Oxidative stress is a proposed mechanism for many age-related diseases. The crucial importance of polyphenol pharmacophore for aging process is largely described thanks to its effects on concentrations of reactive oxygen species. Resveratrol (3,5,4'-trihydroxy-trans-Stilbene, RSV) plays a critical role in slowing the aging process but has a poor bioavailabity after oral intake. In this present work, a series of RSV derivatives was designed, synthesized, and evaluated as potential antioxidant agents. These derivatives contain substituents with different electronic and steric properties in different positions of aromatic rings. This kind of substituents affects the activity and the bioavailability of these compounds compared with RSV used as reference compound. Studies of Log P values demonstrated that the introduction of halogens gives the optimum lipophilicity to be considered promising active agents. Among them, compound 6 showed the higher antioxidant activity than RSV. The presence of trifluoromethyl group together with a chlorine atom increased the antioxidant activity compared to RSV.

Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.[Pubmed:33239684]

Sci Rep. 2020 Nov 25;10(1):20585.

Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-Stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

Machaerium acutifolium compounds with larvicidal activity against Aedes aegypti.[Pubmed:33128432]

Pest Manag Sci. 2020 Oct 31.

BACKGROUND: Plant extracts and isolated compounds are known for their insecticidal activity. The Aedes aegypti mosquito has a significant medical impact as it transmits a number of arboviruses and is able to develop resistance to the commercially available insecticides. This study investigates larvicidal compounds isolated from Machaerium acutifolium, designated by the Brazilian Forest Service as a sustainable species. RESULTS: A M. acutifolium trunk ethyl acetate extract was fractionated using chromatographic methods with full structural elucidation by mass spectrometry (MS), nuclear magnetic resonance and specific rotation analyses revealing: one new 3-arylcoumarin derivative 1; two flavonoids 2 and 3; a trans-Stilbene 4, and an unprecedented natural indene 5. The larvicidal activity against Ae. aegypti after 24 h exposure was: crude extract (median lethal dose, LC50 205 mg L(-1) ), fraction C (LC50 27 mg L(-1) ) and 5 (LC50 24 mg L(-1) ). CONCLUSION: A M. acutifolium extract showed larvicidal activity, which increased with prolonged exposure, demonstrating LC50 75 mg L(-1) after 72 h. Although the flavonoids 2 and 3 and trans-Stilbene 4 were deemed inactive according to the adopted mortality limit, additional tests revealed their ability to cause 65% Ae. aegypti larvae mortality, suggesting they could contribute to the larvicidal activity. Compound 5, identified by liquid chromatography-MS, was over eight-fold more toxic to larvae than the crude extract after 24 h. Therefore, 5 constitutes a structural model for new prototypes to control Ae. aegypti. These data reinforce the potential of natural products as a source of commercial alternatives for vector control strategies, respecting both sustainability and eco-friendly principles.

Two resveratrol analogs, pinosylvin and 4,4'-dihydroxystilbene, improve oligoasthenospermia in a mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.[Pubmed:32987309]

Bioorg Chem. 2020 Nov;104:104295.

Two synthesized resveratrol analogs from our laboratory, namely pinosylvin (3,5-dihydroxy-trans-Stilbene, PIN) and 4,4'-dihydroxystilbene (DHS), have been carefully evaluated for treatment of oligoasthenospermia. Recent studies have demonstrated that PIN and DHS improved sperm quality in the mouse. However, the mechanism of action of PIN and DHS on oligoasthenospermia remains unknown. Herein, we investigated the mechanistic basis for improvements in sperm parameters by PIN and DHS in a mouse model of oligoasthenospermia induced by treatment with busulfan (BUS) at 6 mg/kg b.w.. Two weeks following busulfan treatment, mice were administered different concentrations of PIN or DHS daily for 2 consecutive weeks. Thereafter, epididymal sperm concentration and motility were determined, and histopathology of the testes was performed. Serum hormone levels including testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured using corresponding specific enzyme-linked immunosorbent assay (ELISA) kits. Testicular mRNA expression profiles were determined by RNA sequencing analysis. These findings were validated by quantitative real-time PCR, western blotting and ELISA. Both PIN and DHS improved the epididymal sperm concentration and motility, enhanced testosterone levels, and promoted testicular morphological recovery following BUS treatment. PIN treatment was found to significantly reduce oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE)-dependent antioxidant, glutathione peroxidase 3. DHS treatment significantly reduced oxidative stress via the Nrf2-ARE-dependent antioxidants glutathione S-transferase theta 2 and glutathione S-transferase omega 2. In summary, PIN and DHS ameliorated oligoasthenospermia in this mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.

Resveratrol and Resveratrol-Aspirin Hybrid Compounds as Potent Intestinal Anti-Inflammatory and Anti-Tumor Drugs.[Pubmed:32847114]

Molecules. 2020 Aug 24;25(17). pii: molecules25173849.

Resveratrol (3,4,5-Trihydroxy-trans-Stilbene) is a naturally occurring polyphenol that exhibits beneficial pleiotropic health effects. It is one of the most promising natural molecules in the prevention and treatment of chronic diseases and autoimmune disorders. One of the key limitations in the clinical use of resveratrol is its extensive metabolic processing to its glucuronides and sulfates. It has been estimated that around 75% of this polyphenol is excreted via feces and urine. To possibly alleviate the extensive metabolic processing and improve bioavailability, we have added segments of acetylsalicylic acid to resveratrol in an attempt to maintain the functional properties of both. We initially characterized resveratrol-aspirin derivatives as products that can inhibit cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) activity, DNA methyltransferase (DNMT) activity, and cyclooxygenase (COX) activity. In this study, we provide a detailed analysis of how resveratrol and its aspirin derivatives can inhibit nuclear factor kappa B (NFkappaB) activation, cytokine production, the growth rate of cancer cells, and in vivo alleviate intestinal inflammation and tumor growth. We identified resveratrol derivatives C3 and C11 as closely preserving resveratrol bioactivities of growth inhibition of cancer cells, inhibition of NFkappaB activation, activation of sirtuin, and 5' adenosine monophosphate-activated protein kinase (AMPK) activity. We speculate that the aspirin derivatives of resveratrol would be more metabolically stable, resulting in increased efficacy for treating immune disorders and as an anti-cancer agent.

A Highly Fluorescent Nucleobase Molecular Rotor.[Pubmed:32786749]

J Am Chem Soc. 2020 Aug 26;142(34):14422-14426.

Fluorescent base analogs (FBAs) are powerful probes of nucleic acids' structures and dynamics. However, previously reported FBAs exhibit relatively low brightness and therefore limited sensitivity of detection. Here we report the hitherto brightest FBA that has ideal molecular rotor properties for detecting local dynamic motions associated with base pair mismatches. The new trans-Stilbene annulated uracil derivative "(ts)T" exhibits bright fluorescence emissions in various solvents (epsilon x Phi = 3400-29700 cm(-1) M(-1)) and is highly sensitive to mechanical motions in duplex DNA (epsilon x Phi = 150-4250 cm(-1) M(-1)). (ts)T is thereby a "smart" thymidine analog, exhibiting a 28-fold brighter fluorescence intensity when base paired with A as compared to T or C. Time-correlated single photon counting revealed that the fluorescence lifetime of (ts)T (tau = 4-11 ns) was shorter than its anisotropy decay in well-matched duplex DNA (theta = 20 ns), yet longer than the dynamic motions of base pair mismatches (0.1-10 ns). These properties enable unprecedented sensitivity in detecting local dynamics of nucleic acids.

A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo.[Pubmed:32780460]

Drug Dev Res. 2020 Aug 11.

E-DRS is a novel salvianolic acid A (SAA) analog, which was synthesized from resveratrol (RES) and methyldopate. Its structure is similar to that of SAA, but the 3',4'-dihydroxy-trans-Stilbene group and the ester structure in SAA were replaced by the RES structure and an amine group, respectively. E-DRS scavenged free oxygen radicals effectively, including superoxide anion (ascorbic acid > E-DRS > SAA >/= rutin > RES) and DPPH radical (rutin > E-DRS >/= ascorbic acid > SAA > RES), and exhibited powerful total antioxidant capacity (ascorbic acid > E-DRS > SAA >/= rutin > RES) in vitro. Furthermore, oral administration of E-DRS dose-dependently and significantly decreased CCl4 -induced oxidative stress in mice as indicated by the decreased content of hepatic malondialdehyde (MDA). In addition, oral administration of E-DRS also increased the content of nonenzymatic antioxidant glutathione (GSH) and the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) in the liver of mice. All these results demonstrated that E-DRS had good antioxidant activities both in vitro and in vivo, and could be a potential antioxidant agent after further optimization and evaluation.

The big effect of a small change: formation of CuO nanoparticles instead of covalently bound Cu(ii) over functionalized mesoporous silica and its impact on catalytic efficiency.[Pubmed:32662469]

Dalton Trans. 2020 Aug 7;49(29):10138-10155.

Two different heterogeneous catalysts, one with Cu(ii) covalently bonded to functionalized mesoporous silica (FMS-Cu(II)) and another with CuO nanoparticles immobilized over the same silica (FMS-CuO-np), have been synthesized by a common route but with a minor alteration in the sequence of addition of reagents. It is interesting to find that by merely changing the order of the addition of reagents Cu(ii) can be incorporated into the framework in two different forms. In one case Cu(ii) binds to the N and O donor centers present in the functionalized material whereas in the other case CuO nanoparticles are generated in situ. The materials have been thoroughly characterized by powder X-ray diffraction, nitrogen adsorption/desorption, transmission electron microscopy, thermal analysis, FT-IR spectroscopy, solid state MAS-NMR spectroscopy and atomic absorption spectrophotometric studies. The synthesized products have been examined for their catalytic efficiencies in the oxidation of olefins, as a model case. Styrene, alpha-methyl styrene, cyclohexene, trans-Stilbene and cyclooctene have been used as substrates in the presence of tert-butyl hydroperoxide as the oxidant in acetonitrile medium under mild conditions. The products of the catalytic reactions have been identified and estimated by gas chromatography and gas chromatography-mass spectrometry. The rate of conversion of the substrates for both the catalysts is high and the selectivity is also good. But from comparative studies, it is found that FMS-CuO-np which contains CuO nanoparticles shows better efficiency than FMS-Cu(II). The catalysts have been recycled for five catalytic cycles without showing much decrease in their catalytic activity.

Mechanisms of resveratrol in the prevention and treatment of gastrointestinal cancer.[Pubmed:32607320]

World J Clin Cases. 2020 Jun 26;8(12):2425-2437.

Gastrointestinal (GI) cancer is one of the leading causes of cancer-related deaths worldwide. According to the Global Cancer Statistics, colorectal cancer is the second leading cause of cancer-related mortality, closely followed by gastric cancer (GC). Environmental, dietary, and lifestyle factors including cigarette smoking, alcohol intake, and genetics are the most important risk factors for GI cancer. Furthermore, infections caused by Helicobacter pylori are a major cause of GC initiation. Despite improvements in conventional therapies, including surgery, chemotherapy, and radiotherapy, the length or quality of life of patients with advanced GI cancer is still poor because of delayed diagnosis, recurrence and side effect. Resveratrol (3, 4, 5-trihydroxy-trans-Stilbene; Res), a natural polyphenolic compound, reportedly has various pharmacologic functions including anti-oxidant, anti-inflammatory, anti-cancer, and cardioprotective functions. Many studies have demonstrated that Res also exerts a chemopreventive effect on GI cancer. Research investigating the anti-cancer mechanism of Res for the prevention and treatment of GI cancer has implicated multiple pathways including oxidative stress, cell proliferation, and apoptosis. Therefore, this paper provides a review of the function and molecular mechanisms of Res in the prevention and treatment of GI cancer.

Strong, Nonresonant Radiation Enhances Cis-Trans Photoisomerization of Stilbene in Solution.[Pubmed:32585098]

J Phys Chem A. 2020 Jul 23;124(29):5999-6008.

Previously, it has been demonstrated that external electric fields may be used to exert control over chemical reactivity. In this study, the impact of a strong, nonresonant IR field (1064 nm) on the photoisomerization of cis-stilbene is investigated in cyclohexane solution. The design of a suitable reaction vessel for characterization of this effect is presented. The electric field supplied by the pulsed, near-IR radiation (epsilonl = 4.5 x 10(7) V/cm) enhances the cis --> trans photoisomerization yield at the red edge of the absorption spectrum (wavelengths between 337 and 340 nm). Within the microliter focal volume, up to 75% of all cis-stilbene molecules undergo isomerization to trans-Stilbene in the strong electric-field environment, indicating a significant increase relative to the 35% yield of trans-Stilbene under field-free conditions. This result correlates with a 1-3% enhancement in the trans-Stilbene concentration throughout the bulk solution. Theoretical analysis suggests that the observed change is the result of dynamic Stark shifting of the ground and first excited states, leading to a significant redshift in cis-stilbene's absorption spectrum. The predicted increase in the absorption cross section in this range of excitation wavelengths is qualitatively consistent with the experimental increase in trans-Stilbene production.

Potassium channels on smooth muscle as a molecular target for plant-derived Resveratrol.[Pubmed:32583792]

Cell Mol Biol (Noisy-le-grand). 2020 Jun 25;66(4):133-144.

Resveratrol (3,5,4'-trihydroxy-trans-Stilbene) is a phytoalexin present in a variety of plant species. Resveratrol has a wide spectrum of pharmacologic properties, and it exhibits versatile biological effects on different human and animal models. The studies have shown that potassium (K) channels can be potential targets in the mechanism of resveratrol action. K channels play a crucial role in maintaining membrane potential. Inhibition of K channels causes membrane depolarization and then contraction of smooth muscles, while the activation leads to membrane hyperpolarization and subsequently, relaxation. Five diverse types of K channels have been identi fi ed in smooth muscle cells in different tissue: ATP-sensitive K channels (KATP), voltage-dependent K channels (Kv), Ca2+ - and voltage-dependent K channels (BKCa), inward recti fi er K channels (Kir), and tandem two-pore K channels (K2P). The expression and activity of K channels altered in many types of diseases. Aberrant function or expression of K channels can be underlying in pathologies such as cardiac arrhythmia, diabetes mellitus, hypertension, preterm birth, preeclampsia, and various types of cancer. Modulation of K channel activity by molecular approaches and selective drug development may be a novel treatment modality for these dysfunctions in the future. The plant-derived non-toxic polyphenols, such as resveratrol, can alter K channel activity and lead to the desired outcome. This review presents the basic properties, physiological, pathophysiological functions of K channels, and pharmacological roles of resveratrol on the major types of K channels that have been determined in smooth muscle cells.

Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential.[Pubmed:32520230]

Arq Neuropsiquiatr. 2020 Jun 8;78(8):501-511.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible loss of cognitive function. The presence of senile plaques is one of the pathological markers of the disease and is associated with the onset of neuroinflammatory mechanisms. The exact pathophysiology of AD has not been completely understood, and there are no curative therapies yet. Resveratrol (3,5,4'-trihydroxy-trans-Stilbene) is a polyphenol that is noted for its antioxidant and anti-inflammatory properties. OBJECTIVE: To review the role of resveratrol in the pathophysiological aspects of AD. METHODS: This study carried out a literature review using PubMed/Medline, Virtual Health Library (VHL), Web of Sciences, SCOPUS and the Cochrane Library databases. Original research articles, describing both in vitro and in vivo experiments, published between 2008 and 2018, were included. RESULTS: We identified 667 articles, of which 619 were excluded because they were repeated or did not follow the inclusion criteria. The present study includes the remaining 48 articles. DISCUSSION: Resveratrol demonstrates beneficial and protective effects in AD models and seems to provide a promising therapeutic alternative. CONCLUSION: Although resveratrol appears to mitigate some pathophysiological aspects of AD, further studies are needed to prove the safety and efficacy of this compound in humans.

General Method for Determining Redox Potentials without Electrolyte.[Pubmed:32437607]

J Phys Chem A. 2020 Jul 2;124(26):5487-5495.

A novel method to determine redox potentials without electrolyte is presented. The method is based on a new ability to determine the dissociation constant, K degrees d, for ion pairs formed between any radical anion and any inert electrolyte counterion. These dissociation constants can be used to determine relative shifts of redox potential as a function of electrolyte concentration, connecting referenced potentials determined with electrochemistry (with 0.1 M electrolyte) to electrolyte-free values. Pulse radiolysis created radical anions enabling determination of equilibrium constants for electron transfer between anions of donor and acceptor molecules as a function of electrolyte concentration in THF. The measurements determined "composite equilibrium constants", KeqC, which contain information about the dissociation constant for the electrolyte cations, X(+), with the radical anions of both the donor, K degrees d(D(-*),X(+)) and the acceptor, K degrees d(A(-*),X(+)). Dissociation constants were obtained for a selection of radical anions with tetrabutylammonium (TBA(+)). The electrolyte was found to shift the reduction potentials of small molecules 1-methylpyrene and trans-Stilbene by close to +130 mV whereas oligo-fluorenes and polyfluorenes experienced shifts of only (+25 +/- 6) mV due to charge delocalization weakening the ion pair. These shifts for reduction of aromatic hydrocarbon molecules are smaller than shifts of +232 and +451 mV seen previously for benzophenone radical anion with TBA(+) and Na(+) respectively where the charge on the radical anion is localized largely on one C horizontal lineO bond, thus forming a more tightly bound ion pair.

Nonadiabatic Dynamics of Photoexcited cis-Stilbene Using Ab Initio Multiple Spawning.[Pubmed:32428407]

J Phys Chem B. 2020 Jul 2;124(26):5476-5487.

The photochemistry of cis-stilbene proceeds through two pathways: cis-trans isomerization and ring closure to 4a,4b-dihydrophenanthrene (DHP). Despite serving for many decades as a model system for photoisomerization, the photodynamics of cis-stilbene is still not fully understood. We use ab initio multiple spawning on a SA-2-CASSCF(2,2) potential energy surface to simulate the nonadiabatic dynamics of isolated cis-stilbene. We find the cyclization (to DHP and cis-stilbene) and isomerization (to trans- and cis-stilbene) reaction coordinates to be orthogonal; branching between the two pathways is determined on the S1 excited state within 150 fs of photoexcitation. Trajectory basis functions (TBFs) undergoing cyclization decay rapidly to the ground state in 250 fs, while TBFs moving along the isomerization coordinate remain on the excited state longer, with the majority decaying between 300 and 500 fs. We observe three avoided crossing regions in the dynamics: two along the isomerization coordinate (displaying pyramidalization and migration of an ethylenic hydrogen or phenyl group), and one DHP-like conical intersection along the cyclization coordinate. The isomeric form of the vibrationally hot photoproducts (as determined by measurement 2 ps after photoexcitation) is determined within less than 50 fs of decay to the ground state mediated by passage through a conical intersection. Excess vibrational energy of ground state cis- and trans-Stilbene is channelled into phenyl torsions (with mostly opposing directionality). Our simulations are validated by direct comparison to experiment for the absorption spectrum, branching ratio of the three photoproducts (44:52:4 cis-stilbene:trans-Stilbene:DHP), and excited state lifetime (520 +/- 40 fs).