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Zhong, Zixing, Xin Guo e Yanmei Zheng. "Network Pharmacology-based and Molecular Docking Analysis of Resveratrol’s Pharmacological Effects on Type I Endometrial Cancer". Anti-Cancer Agents in Medicinal Chemistry 22, n.º 10 (junho de 2022): 1933–44. http://dx.doi.org/10.2174/1871520621666211015140455.
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Background: Resveratrol is a natural polyphenol commonly seen in foods. It has demonstrated an inhibitive effect on endometrial cancer, but the molecular action is still not known. Objective: We aimed to use network pharmacology to systematically study the possible mechanisms of resveratrol’s pharmacological effects on type I endometrial cancer. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to predict resveratrol’s possible target genes. They were then converted to UniProt gene symbols. Simultaneously, type I endometrial cancer-related target genes were collected from GeneCards. All data were pooled to identify common target genes. The protein-protein interaction (PPI) network was constructed and further analyzed via STRING Online Database. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were also performed afterward. To visualise resveratrol's overall pharmacological effects on type I endometrial cancer, a network of drug components-target gene-disease (CTD) was constructed. Then, we performed in silico molecular docking study to validate the possible binding conformation between resveratrol and candidate targets. Results: There are 150 target genes of resveratrol retrieved after UniProt conversion; 122 of them shared interaction with type I endometrial cancer. Some important oncogenes and signaling pathways are involved in the process of resveratrol’s pharmacological effects on endometrioid cancer. Molecular docking analysis confirmed that hydrogen bonding and hydrophobic interaction are the main interaction between resveratrol and its targets. Conclusion: We have explored the possible underlying mechanism of resveratrol in antagonising type I endometrial cancer through a network pharmacology-based approach and in-silico verification. However, further experiments are necessary to add to the evidence identifying resveratrol as a promising anti-type I endometrial cancer agent.
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Jang, Ae-Ra, Jun-Sang Ham, Dong-Wook Kim, Kuk-Hwan Seol, Mi-Hwa Oh, Hyun-Seok Chae, Sang-Ho Kim e Dong-Hun Kim. "Dietary Supplementation of Resveratrol and Methoxylated Resveratrol Affects on Chicken Thigh Meat Quality". Korean Journal of Poultry Science 38, n.º 4 (31 de dezembro de 2011): 315–22. http://dx.doi.org/10.5536/kjps.2011.38.4.315.
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Peng, Han, e Fereidoon Shahidi. "The Effects of Acyl Chain Length on Antioxidant Efficacy of Mono- and Multi-Acylated Resveratrol: A Comparative Assessment". Molecules 27, n.º 3 (2 de fevereiro de 2022): 1001. http://dx.doi.org/10.3390/molecules27031001.
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Acylated derivatives of the dietary phenolic, resveratrol, were prepared via enzymatic and chemical transesterification modification with selected vinyl fatty acids to expand the potential application of resveratrol and its acylated derivatives in functional supplement, cosmetic/skincare, and pharmaceutical fields. The acylation was implemented using eight vinyl fatty acids with varying chain lengths (C2:0-C18:0). Eight monoesters enzymatically prepared, eight diesters and four triesters, chemically prepared, were isolated and purified and identified via MS (mass spectra) or/and NMR (nuclear magnetic resonance). The lipophilicity of resveratrol and its acylated derivatives was calculated using ALOGPS 2.1. Compared with related acylated products, resveratrol itself rendered higher antioxidant efficacy in all the antioxidant assays, namely DPPH, ABTS, FRAP, and ferrous chelation tests. Within various ester derivatives of resveratrol, short-chain fatty acid mono- and di-substituted resveratrols, especially the resveratrol monoacetate/diacetate, exhibited higher antioxidant efficacy in DPPH and ABTS assays than the rest of resveratrol derivatives, but the medium-chain monoesters of resveratrol, including caproate, caprylate, caprate, and laurate, showed a higher metal ion chelation ability compared to other acylated resveratrols. These results imply that resveratrol derivatives may be used in lipidic media as health-beneficial antioxidants.
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Yanagi, Masayoshi, Noriyuki Uchida e Hiroki Hamada. "Versatile Synthetic Route for Resveratrol Modification via Amine Functionalization". Natural Product Communications 14, n.º 9 (setembro de 2019): 1934578X1987621. http://dx.doi.org/10.1177/1934578x19876210.
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Resveratrol derivatives containing a primary amine functional group were synthesized by an introduction of N-Boc-bromoethylamine to resveratrol using Williamson ether synthesis and subsequent deprotection of the Boc group with trifluoroacetic acid. After conjugation of fluorescent NBD-F or rhodamine B with isothiocyanate (Rhd B-ITC) using the amine group, resveratrols modified with NBD or Rhd B (Resveratrol-NBD and Resveratrol-Rhd B, respectively) were successfully obtained.
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Andreato, Camilla Cavasin, Adriana Kulpe, Waleria Christiane Rezende Fett e Carlos Alexandre Fett. "The use of resveratrol in the fight against Cancer in women: a review". Brazilian Journal of Health Review 7, n.º 4 (26 de agosto de 2024): e72231. http://dx.doi.org/10.34119/bjhrv7n4-391.
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Cancer continues to be a major global health challenge, especially among women. Recent scientific studies have focused on resveratrol (RSV), a natural polyphenol found in various foods, as a potential supplementary therapy for cancer. This review assesses the existing evidence on resveratrol's effects on cancer cells, examining its mechanisms, potential benefits, and clinical implications. Research involved analyzing articles sourced from PUBMED with keywords: "(resveratrol) AND (cancer) AND (women)" (197 articles), "(resveratrol) AND (ovarian cancer)" (149 articles), and "(resveratrol) AND (endometrial cancer)" (21 articles). The selection was based on the specificity of results concerning resveratrol’s role in combating women’s cancer, with the most recent articles chosen in cases of redundancy. RSV has demonstrated capabilities to inhibit cancer cell viability and proliferation, including in breast cancer. It influences cell signaling, enhancing apoptosis and reducing tumor growth, and regulates cyclins and kinases to arrest the cell cycle, curbing uncontrolled cell division. RSV’s anti-inflammatory properties potentially suppress tumor progression, and its antioxidant activity activates enzymes to shield cells from oxidative harm, lowering cancer risks. Despite RSV’s promising potential, more research is needed to determine the ideal dosages, safety, and long-term impacts. Maintaining a diet rich in fruits, vegetables, and RSV-containing foods is vital for cancer prevention. RSV supplementation emerges as a promising support in combating cancer.
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Alquisiras-Burgos, Iván, Irma Gabriela González-Herrera, Sergio Alcalá-Alcalá e Penélope Aguilera. "Nose-to Brain Delivery of Resveratrol, a Non-Invasive Method for the Treatment of Cerebral Ischemia". Drugs and Drug Candidates 3, n.º 1 (26 de janeiro de 2024): 102–25. http://dx.doi.org/10.3390/ddc3010007.
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Cerebral ischemia represents a particular condition among neurological diseases due to its high frequency, high associated mortality, and the permanent disability in patients that survive it. Numerous studies in animal models have demonstrated the protective properties of resveratrol against cerebral ischemia. Resveratrol is a soluble molecule in polar solvents with high membrane permeability; however, it is rapidly metabolized at the liver and is also a substrate of the ATP binding cassette transporters located at the blood–brain barrier. These circumstances reduced bioavailability of resveratrol to the brain. In this review, we examined nasal resveratrol’s formulations including nanocarriers such as nanostructured lipid carriers, nanoemulsions, nanoparticles, bilosomes, cubosomal, and transferosomes that are directly transported to the brain. An intranasal administration route evades resveratrol transformation due to liver metabolism. Components of nanoformulations increased resveratrol absorption to the brain by enhancing permeation through specific approaches and also maintaining stability during storage. Both characteristics improved the delivery of resveratrol with conserved antioxidant capacity and protective properties for neurological models. Although demonstration that the nanoformulations prevents resveratrol’s blood–brain barrier retention is missing, properties of resveratrol’s nanoformulation encourage testing in clinical trials; however, regulatory approval for a novel nanocarrier in nasal drug delivery is complicated and needs approval.
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Novakovic, Radmila, Nebojsa Radunovic, Jovana Rajkovic, Vladimir Djokic, Aleksandar Petrovic, Branka Ivkovic, Vitomir Cupic, Vladimir Kanjuh, Helmut Heinlev e Ljiljana Gojkovic-Bukarica. "Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels". Veterinarski glasnik 70, n.º 3-4 (2016): 121–29. http://dx.doi.org/10.2298/vetgl1604121n.
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Resveratrol is a phytoalexin produced in a number of plant species including grapes. The benefit of resveratrol to health is widely reported. Resveratrol has been found to promote relaxation of non-pregnant and pregnant uterus, but its mechanism of action is unclear. The aims of our study were to investigate the involvement of inwardly rectifying potassium channels (Kir) in inhibitory effects of resveratrol on three models of contractions of non-pregnant rat uterus: the spontaneous rhythmic contractions (SRC), oxytocin-elicited phasic contractions and tonic oxytocin-elicited contractions.Uterine strips were obtained from virgin female Wistar rats in oestrus. Strips were mounted into organ bath for recording isometric tension in Krebs-Ringer solution. Experiments followed a multiple curve design. In order to test the involvement of Kirchannels in a mechanism of action of resveratrol(1-100 ?M),BaCl2 (1 mM),a antagonist of inwardly rectifying pota?ssium channels was used. Resveratrol induced a concentration-dependent relaxation of all models of contractions. BaCl2 antagonized the response to resveratrolon SRC and oxytocin-elicited phasic contractions. Relaxation achieved by resveratrolon tonic oxytocin-elicited concentrations was insensitive to BaCl2.The antagonism of resveratrol effects by inwardly rectifying potassium channels antagonist suggests that Kir channels are involved in resveratrol action on phasic contractions of rat uterus. Inhibitory effect of resveratrol on tonic contractions did not include Kir channels.
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Luís, Ângelo, Helena Marcelino, Fernanda Domingues, Luísa Pereira e José Francisco Cascalheira. "Therapeutic Potential of Resveratrol for Glioma: A Systematic Review and Meta-Analysis of Animal Model Studies". International Journal of Molecular Sciences 24, n.º 23 (22 de novembro de 2023): 16597. http://dx.doi.org/10.3390/ijms242316597.
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Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol’s anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol’s effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect’s weighted standardized difference in means was −2.046 (95%CI: −3.156 to −0.936; p-value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models.
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Boo, Yong Chool. "Human Skin Lightening Efficacy of Resveratrol and Its Analogs: From in Vitro Studies to Cosmetic Applications". Antioxidants 8, n.º 9 (22 de agosto de 2019): 332. http://dx.doi.org/10.3390/antiox8090332.
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Antioxidants are deemed useful in controlling oxidative stress associated with extrinsic skin aging and pigmentation disorders. Resveratrol is a polyphenol compound found in many edible plants such as Vitis vinifera, and its inhibitory effects on the catalytic activity, gene expression, and posttranslational modifications of tyrosinase, a key enzyme in the melanin biosynthetic pathway, provide a mechanistic basis for its antimelanogenic effects seen in melanocytic cells, three-dimensionally reconstituted skin models, and in vivo animal models. As a potent antioxidant and a modulator of nuclear factor erythroid 2-related factor 2 (Nrf2), and sirtuin 1, resveratrol can also regulate multiple signaling pathways associated with inflammation and premature aging. Recent clinical studies have supported the efficacy of resveratrol and its analogs, such as resveratryl triacetate (RTA) and resveratryl triglycolate (RTG), in human skin lightening and antiaging. These findings suggest that resveratrol and its analogs are potentially useful as skin lightening and antiaging agents in cosmetics.
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Farhan, Mohd, e Asim Rizvi. "The Pharmacological Properties of Red Grape Polyphenol Resveratrol: Clinical Trials and Obstacles in Drug Development". Nutrients 15, n.º 20 (23 de outubro de 2023): 4486. http://dx.doi.org/10.3390/nu15204486.
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Resveratrol is a stilbenoid from red grapes that possesses a strong antioxidant activity. Resveratrol has been shown to have anticancer activity, making it a promising drug for the treatment and prevention of numerous cancers. Several in vitro and in vivo investigations have validated resveratrol’s anticancer capabilities, demonstrating its ability to block all steps of carcinogenesis (such as initiation, promotion, and progression). Additionally, resveratrol has been found to have auxiliary pharmacological effects such as anti-inflammatory, cardioprotective, and neuroprotective activity. Despite its pharmacological properties, several obstacles, such as resveratrol’s poor solubility and bioavailability, as well as its adverse effects, continue to be key obstacles to drug development. This review critically evaluates the clinical trials to date and aims to develop a framework to develop resveratrol into a clinically viable drug.
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Chen, Xiangxiu, Xu Song, Xinghong Zhao, Yu Zhang, Yiming Wang, Renyong Jia, Yuanfeng Zou, Lixia Li e Zhongqiong Yin. "Insights into the Anti-inflammatory and Antiviral Mechanisms of Resveratrol". Mediators of Inflammation 2022 (12 de agosto de 2022): 1–11. http://dx.doi.org/10.1155/2022/7138756.
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Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound, which has been extensively studied on its biological activity. It has been widely accepted that resveratrol possesses anti-inflammatory and antiviral activities. In this review, we summarize the anti-inflammatory dosages and mechanism and antiviral mechanism of resveratrol. Since viral infections are often accompanied by inflammation, we propose that the NF-κB signaling pathway is a key and common molecular mechanism of resveratrol to exert anti-inflammatory and antiviral effects. For future studies, we believe that resveratrol’s anti-inflammatory and antiviral mechanisms can consider the upstream signaling molecules of the NF-κB signaling pathway. For resveratrol antivirus, future studies can be conducted on the interaction of resveratrol with key proteins or important enzymes of the virus. In addition, we also think that the clinical application of resveratrol is very important. In short, resveratrol is a promising anti-inflammatory and antiviral drug, and research on it needs to be expanded.
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Wang, Nasui, Seung-Hyun Ko, Weidong Chai, Guolian Li, Eugene J. Barrett, Lijian Tao, Wenhong Cao e Zhenqi Liu. "Resveratrol recruits rat muscle microvasculature via a nitric oxide-dependent mechanism that is blocked by TNFα". American Journal of Physiology-Endocrinology and Metabolism 300, n.º 1 (janeiro de 2011): E195—E201. http://dx.doi.org/10.1152/ajpendo.00414.2010.
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Resveratrol, a polyphenol found in many plants, has antioxidant and anti-inflammatory actions. It also improves endothelial function and may be cardioprotective. Tumor necrosis factor-α (TNFα) causes oxidative stress and microvascular endothelial dysfunction. Whether resveratrol affects microvascular function in vivo and, if so, whether inflammatory cytokines antagonize its microvascular action are not clear. In cultured bovine aortic endothelial cells (BAECs), reserveratrol (100 nM) increased the phosphorylation of protein kinase B (Akt), endothelial nitric oxide (NO) synthase (eNOS), and ERK1/2 within 15 min by more than twofold, and this effect lasted for at least 2 h. Treatment of BAECs with TNFα (10 ng/ml) significantly increased the NADPH oxidase activity and the production of hydrogen peroxide and superoxide. Pretreatment of cells with resveratrol (100 nM) prevented each of these. Injection (ip) of resveratrol in rats potently increased muscle microvascular blood volume (MBV; P = 0.007) and flow (MBF; P < 0.02) within 30 min, and this was sustained for at least 2 h. The phosphorylation of Akt in liver or muscle was unchanged. Superimposed systemic infusion of l-NAME (NOS inhibitor) completely abolished resveratrol-induced increases in MBV and MBF. Similarly, systemic infusion of TNFα prevented resveratrol-induced muscle microvascular recruitment. In conclusion, resveratrol activates eNOS and increases muscle microvascular recruitment via an NO-dependent mechanism. Despite the potent antioxidant effect of resveratrol, TNFα at concentrations that block insulin-mediated muscle microvascular recruitment completely neutralized resveratrol's microvascular action. Thus, chronic inflammation, as seen in type 2 diabetes, may limit resveratrol's vasodilatory actions on muscle microvasculature.
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Lin, Jian, Xican Li, Ban Chen, Gang Wei e Dongfeng Chen. "E-Configuration Improves Antioxidant and Cytoprotective Capacities of Resveratrols". Molecules 23, n.º 7 (20 de julho de 2018): 1790. http://dx.doi.org/10.3390/molecules23071790.
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The antioxidant and cytoprotective capacities of E-resveratrol and Z-resveratrol were compared using chemical and cellular assays. Chemical assays revealed that the two isomers were dose-dependently active in •O2−-scavenging, ferric reducing antioxidant power (FRAP), Cu2+-reducing antioxidant capacity (CUPRAC), 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-scavenging (pH 7.4 and pH 4.5), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH•)-scavenging assays. The cellular assay indicated that the two isomers could also increase cell viabilities. However, quantitative analyses suggested that E-resveratrol exhibited stronger effects than Z-resveratrol in all chemical and cellular assays. Finally, the conformations of E-resveratrol and Z-resveratrol were analyzed. It can be concluded that both E-resveratrol and Z-resveratrol can promote redox-related pathways to exhibit antioxidant action and consequently protect bone marrow-derived mesenchymal stem cells (bmMSCs) from oxidative damage. These pathways include electron transfer (ET) and H+-transfer, and likely include hydrogen atom transfer (HAT). The E-configuration, however, improves antioxidant and cytoprotective capacities of resveratrols. The detrimental effect of the Z-configuration may be attributed to the non-planar preferential conformation, where two dihedral angles block the extension of the conjugative system.
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Pignet, Anna-Lisa, Marlies Schellnegger, Andrzej Hecker, Michael Kohlhauser, Petra Kotzbeck e Lars-Peter Kamolz. "Resveratrol-Induced Signal Transduction in Wound Healing". International Journal of Molecular Sciences 22, n.º 23 (23 de novembro de 2021): 12614. http://dx.doi.org/10.3390/ijms222312614.
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Resveratrol is a well-known polyphenol that harbors various health benefits. Besides its well-known anti-oxidative potential, resveratrol exerts anti-inflammatory, pro-angiogenic, and cell-protective effects. It seems to be a promising adjuvant for various medical indications, such as cancer, vascular, and neurodegenerative diseases. Additionally, resveratrol was shown to display beneficial effects on the human skin. The polyphenol is discussed to be a feasible treatment approach to accelerate wound healing and prevent the development of chronic wounds without the drawback of systemic side effects. Despite resveratrol’s increasing popularity, its molecular mechanisms of action are still poorly understood. To take full advantage of resveratrol’s therapeutic potential, a profound knowledge of its interactions with its targets is needed. Therefore, this review highlights the resveratrol-induced molecular pathways with particular focus on the most relevant variables in wound healing, namely inflammation, oxidative stress, autophagy, collagen proliferation and angiogenesis.
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Valenzuela, Hector F., Giovanni Samayoa, Kassandra Martinez e Samantha Salvador. "Resveratrol, Modafinil and Caffeine’s modulation of B cell’s CD19 activation receptor". Journal of Immunology 208, n.º 1_Supplement (1 de maio de 2022): 122.29. http://dx.doi.org/10.4049/jimmunol.208.supp.122.29.
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Abstract Resveratrol a natural compound with anti-oxidant properties shown to inhibit cell proliferation and induces cellular apoptosis in Jurkat cell lines. Mechanistically, it was observed that interleukin-2 expression was blocked in T cells, suggesting resveratrol’s anti-inflammatory mechanism may involve downregulation of activation molecules. In this study, we investigated the effects of resveratrol or in combination with Modafinil or caffeine on a B cell line, Nor20. Modafinil is a compound shown to directly act on enzymes in the brain’s free-radical scavenging system and therefore directly reduce free radical levels. Caffeine has been shown to abolish the anti-inflammatory effects of resveratrol in astrocytes. Here we show that Nor20 treated with resveratrol can have up to 47.3% reduction in viability, consistent with previous observations. To determine a mechanism to explain these results, we used flow cytometry to measure the expression of CD19, the dominant receptor for all forms of B cell activation and modulator of B cell activation threshold combined with Modafinil or caffeine. We observed that resveratrol reduced the expression of CD19 up to 51%, Modafinil, inhibited up to 65%, but when resveratrol and Modafinil were combined the effect was not additive remaining at 53% inhibition when compare to the controls. In contrast, caffeine did not affect CD19 expression but when combined with resveratrol, caffeine abolished the downregulation of CD19 by resveratrol returning to the same levels as the untreated controls. Taken together, these results may indicate that resveratrol’s anti-inflammatory effects may initiate at the lymphocyte’s early recognition signaling receptors as a mechanisms to control cell growth. Supported by RevGenetics and Whittier College's Faculty Research Grant.
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Chang, Huai-Chia, Tyng-Guey Chen, Yu-Ting Tai, Ta-Liang Chen, Wen-Ta Chiu e Ruei-Ming Chen. "Resveratrol Attenuates Oxidized LDL-Evoked Lox-1 Signaling and Consequently Protects against Apoptotic Insults to Cerebrovascular Endothelial Cells". Journal of Cerebral Blood Flow & Metabolism 31, n.º 3 (13 de outubro de 2010): 842–54. http://dx.doi.org/10.1038/jcbfm.2010.180.
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Cerebrovascular endothelial cells (CECs) are crucial components of the blood—brain barrier. Our previous study showed that oxidized low-density lipoprotein (oxLDL) induces apoptosis of CECs. This study was designed to further evaluate the effects of resveratrol on oxLDL-induced CEC insults and its possible molecular mechanisms. Resveratrol decreased the oxidation of LDL into oxLDL. Additionally, the oxLDL-caused oxidative stress and cell damage were attenuated by resveratrol. Exposure of CECs to oxLDL induced cell shrinkage, DNA fragmentation, and cell apoptosis, but resveratrol defended against such injuries. Application of Lox-1 small interference (si)RNA into CECs reduced the translation of this membrane receptor, and simultaneously increased resveratrol protection from oxLDL-induced cell apoptosis. By comparison, overexpression of Lox-1 attenuated resveratrol protection. Resveratrol inhibited oxLDL-induced Lox-1 mRNA and protein expressions. Both resveratrol and Lox-1 siRNA decreased oxLDL-enhanced translocation of proapoptotic Bcl-2-associated X protein (Bax) from the cytoplasm to mitochondria. Sequentially, oxLDL-induced alterations in the mitochondrial membrane potential, cytochrome c release, and activities of caspases-9, -3, and -6 were decreased by resveratrol. Pretreatment with Z-VEID-FMK (benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethyl ketone) synergistically promoted resveratrol's protection against DNA fragmentation and cell apoptosis. Therefore, this study shows that resveratrol can protect CECs from oxLDL-induced apoptotic insults via downregulating Lox-1-mediated activation of the Bax-mitochondria—cytochrome c—caspase protease pathway.
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Yalçın, Rıza, Asım Kart, Özlem Özmen e Esra Zeybek. "Protective effects of resveratrol against fumonisin B1-induced liver toxicity in mice". Archives of Industrial Hygiene and Toxicology 74, n.º 2 (1 de junho de 2023): 115–19. http://dx.doi.org/10.2478/aiht-2023-74-3648.
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Abstract The aim of this study was to investigate the effects of resveratrol against fumonisin B1 (FB1)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB1 and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB1, resveratrol, and FB1+resveratrol groups. Control received saline for 14 days. The FB1 group received 2.25 mg/kg FB1 every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB1+resveratrol group received 2.25 mg/kg FB1 every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB1 group than control. Resveratrol countered FB1 effects for all parameters, including TOS and TAS. Liver histology showed FB1-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB1+resveratrol group. Our findings confirm resveratrol’s protective effect against liver damage and oxidative stress caused by FB1. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB1-induced hepatotoxicity.
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Szymkowiak, Izabela, Malgorzata Kucinska e Marek Murias. "Between the Devil and the Deep Blue Sea—Resveratrol, Sulfotransferases and Sulfatases—A Long and Turbulent Journey from Intestinal Absorption to Target Cells". Molecules 28, n.º 8 (7 de abril de 2023): 3297. http://dx.doi.org/10.3390/molecules28083297.
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For nearly 30 years, resveratrol has attracted the scientific community’s interest. This has happened thanks to the so-called French paradox, that is, the paradoxically low mortality from cardiovascular causes in the French population despite a diet rich in saturated fat. This phenomenon has been linked to the consumption of red wine, which contains a relatively high level of resveratrol. Currently, resveratrol is valued for its versatile, beneficial properties. Apart from its anti-atherosclerotic activity, resveratrol’s antioxidant and antitumor properties deserve attention. It was shown that resveratrol inhibits tumour growth at all three stages: initiation, promotion, and progression. Moreover, resveratrol delays the ageing process and has anti-inflammatory, antiviral, antibacterial, and phytoestrogenic properties. These favorable biological properties have been demonstrated in vitro and in vivo in animal and human models. Since the beginning of the research on resveratrol, its low bioavailability, mainly due to its rapid metabolism, especially the first-pass effect that leaves almost no free resveratrol in the peripheral circulation, has been indicated as a drawback that has hindered its use. The elucidation of such issues as pharmacokinetics, stability, and the biological activity of resveratrol metabolites is therefore crucial for understanding the biological activity of resveratrol. Second-phase metabolism enzymes are mainly involved in RSV metabolism, e.g., UDP-glucuronyl transferases and sulfotransferases. In the present paper, we took a closer look at the available data on the activity of resveratrol sulfate metabolites and the role of sulfatases in releasing active resveratrol in target cells.
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Y. Mohammed, Zainab, Essam F. Al-Jumaily e Nahi Y. Yaseen. "In Vitro Cytotoxic Study for Purified Resveratrol Extracted from Grape Skin Fruit Vitis vinifera". Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512) 18, Suppl. (30 de março de 2017): 19–25. http://dx.doi.org/10.31351/vol18isssuppl.pp19-25.
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This study was conducted with the aim to extract and purify a polyphenolic compound “ Resveratrol†from the skin of black grapes Vitis vinifera cultivated in Iraq. The purified resveratrol is obtained after ethanolic extraction with 80% v/v solution for fresh grape skin, followed by acid hydrolysis with 10% HCl solution then the aglycon moiety was taken with organic solvent
( chloroform). Using silica gel G60 packed glass column chromatography with mobile phase benzene: methanol: acetic acid 20:4:1 a partial purified resveratrol was obtained then preperative thin layer chromatography technique yielded pure crystals identified as resveratrol (mixture of two isomers cis and trans) in relation to resveratrol standard (35 mg resveratrol crystals / 0.5 kg fresh grape skin was obtained as a result of these processes ). The study was also employed an in vitro evaluation the cytotoxic effect of pure resveratrol on some cell line including : the murine mammary adenocarcinoma AMN-3 cell line, the human laryngeal carcinoma (Hep-2) cell line and the Rat embryo fibroblast (Ref) cell line, at different concentrations and different expousure time. The cytotoxic effect of the pure resveratrol was studied in comparison with trans- resveratrol standard in concentrations of (12.5, 25, 50 and 100) µg/ml for both purified resveratrol and the standard, also the comparism included methotrexate drug in concentrations (0.05 , 0.1 , 0.2 and 0.4) µg/ml toward the growth effects of the three types of cell lines and at three exposure times (24, 48 and 72) hours. The cytotoxic inhibition effect for the purified extracted resveratrol revealed that the highest significant effect (P<0.01) was achieved after 24 hr of exposure on both AMN-3 and Ref cell lines. Hep-2 cell line responded to extracted resveratrol in different manners.
Keywords: Resveratrol , grape skin , polyphenols, cytotoxic study
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Xiao, Zijian, Qing Ye, Xiaomei Duan e Tao Xiang. "Network Pharmacology Reveals That Resveratrol Can Alleviate COVID-19-Related Hyperinflammation". Disease Markers 2021 (22 de setembro de 2021): 1–12. http://dx.doi.org/10.1155/2021/4129993.
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Hyperinflammation is related to the development of COVID-19. Resveratrol is considered an anti-inflammatory and antiviral agent. Herein, we used a network pharmacological approach and bioinformatic gene analysis to explore the pharmacological mechanism of Resveratrol in COVID-19 therapy. Potential targets of Resveratrol were obtained from public databases. SARS-CoV-2 differentially expressed genes (DEGs) were screened out via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE147507, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; then, protein-protein interaction network was constructed. The common targets, GO terms, and KEGG pathways of Resveratrol targets and SARS-CoV-2 DEGs were confirmed. KEGG Mapper queried the location of common targets in the key pathways. A notable overlap of the GO terms and KEGG pathways between Resveratrol targets and SARS-CoV-2 DEGs was revealed. The shared targets between Resveratrol targets and SARS-CoV-2 mainly involved the IL-17 signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Our study uncovered that Resveratrol is a promising therapeutic candidate for COVID-19 and we also revealed the probable key targets and pathways involved. Ultimately, we bring forward new insights and encourage more studies on Resveratol to benefit COVID-19 patients.
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WM*, Dos Santos. "Resveratrol’s Action against Viral Infections". Advances in Pharmacology and Clinical Trials 9, n.º 2 (10 de maio de 2024): 1–3. http://dx.doi.org/10.23880/apct-16000236.
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The biological activity of resveratrol (3,5,4’-trihydroxy-trans-stilbene) has been the subject of extensive study in the treatment of various diseases due to its anti-inflammatory, antioxidant and anticancer activities, as well as its minimal toxicity and side effects. It has been widely accepted that resveratrol also has antiviral activities. In this mini-review, we summarize resveratrol’s antiviral mechanisms. Since viral infections are often accompanied by inflammation, the TLRs/NF-κB signaling pathways are key and common molecular mechanisms for resveratrol to exert anti-inflammatory and antiviral effects.
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Sebori, Rio, Atsushi Kuno, Ryusuke Hosoda, Takashi Hayashi e Yoshiyuki Horio. "Resveratrol Decreases Oxidative Stress by Restoring Mitophagy and Improves the Pathophysiology of Dystrophin-Deficient mdx Mice". Oxidative Medicine and Cellular Longevity 2018 (29 de outubro de 2018): 1–13. http://dx.doi.org/10.1155/2018/9179270.
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We previously showed that treatment with resveratrol (3,5,4′-trihydroxy-trans-stilbene), an activator of the NAD+-dependent deacetylase SIRT1 at 4 g/kg food for 32 weeks, significantly decreased the muscular reactive oxygen species (ROS) levels and ameliorated the pathology of mdx mice, an animal model of Duchenne muscular dystrophy (DMD). Here, we treated mdx mice with various doses of resveratrol (0.04, 0.4, and 4 g/kg food) for 56 weeks and examined the effects on serum creatine kinase levels and physical activities. Because resveratrol promotes autophagy, we also investigated whether autophagy including mitochondrial autophagy (mitophagy) is involved in resveratrol’s effects. Autophagy/mitophagy-related genes and autophagic flux were downregulated in the muscle of mdx mice, and these phenomena were reversed by resveratrol with significant ROS reduction. Resveratrol at 4 g/kg food reduced the number of immature myofibers containing central nuclei and fine fibers < 400 μm2 and increased that of thicker myofibers in the quadriceps, suggesting that resveratrol decreased myofiber wasting and promoted muscular maturation. Accordingly, resveratrol at 0.4 g/kg food reduced the creatine kinase levels to one-third of those in untreated mdx mice and significantly increased the animals’ physical activities. In C2C12 myoblast cells, resveratrol promoted mitophagy and eliminated mitochondria containing high superoxide levels. The clearance of damaged mitochondria and ROS reduction by resveratrol was completely suppressed by an autophagy inhibitor (chloroquine) and by knocking down Atg5 or Pink1, essential genes for autophagy and mitophagy, respectively. Thus, resveratrol is a potential therapeutic agent for DMD, and the clearance of damaged mitochondria probably contributes to its action.
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Bowers, Jennifer L., Valentyn V. Tyulmenkov, Sarah C. Jernigan e Carolyn M. Klinge. "Resveratrol Acts as a Mixed Agonist/Antagonist for Estrogen Receptors α and β*". Endocrinology 141, n.º 10 (1 de outubro de 2000): 3657–67. http://dx.doi.org/10.1210/endo.141.10.7721.
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Abstract Epidemiological evidence indicates that phytoestrogens inhibit cancer formation and growth, reduce cholesterol levels, and show benefits in treating osteoporosis. At least some of these activities are mediated through the interaction of phytoestrogens with estrogen receptors α and β (ERα and ERβ). Resveratrol, trans-3,5,4′-trihydroxystilbene, is a phytoestrogen in grapes that is present in red wine. Resveratrol was shown to bind ER in cytosolic extracts from MCF-7 and rat uteri. However, the contribution of ERα vs. ERβ in this binding is unknown. Here we report that resveratrol binds ERβ and ERα with comparable affinity, but with 7,000-fold lower affinity than estradiol (E2). Thus, resveratrol differs from other phytoestrogens that bind ERβ with higher affinity than ERα. Resveratrol acts as an estrogen agonist and stimulates ERE-driven reporter gene activity in CHO-K1 cells expressing either ERα or ERβ. The estrogen agonist activity of resveratrol depends on the ERE sequence and the type of ER. Resveratrol-liganded ERβ has higher transcriptional activity than E2-liganded ERβ at a single palindromic ERE. This indicates that those tissues that uniquely express ERβ or that express higher levels of ERβ than ERα may be more sensitive to resveratrol’s estrogen agonist activity. For the natural, imperfect EREs from the human c-fos, pS2, and progesterone receptor (PR) genes, resveratrol shows activity comparable to that induced by E2. We report that resveratrol exhibits E2 antagonist activity for ERα with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERβ. These data indicate that resveratrol differentially affects the transcriptional activity of ERα and ERβ in an ERE sequence-dependent manner.
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Synowiec-Wojtarowicz, Agnieszka, Agata Krawczyk e Magdalena Kimsa-Dudek. "The Effect of Resveratrol and Static Magnetic Field Interactions on the Oxidation–Reduction Parameters of Melanoma Malignant Cells". Applied Sciences 13, n.º 14 (10 de julho de 2023): 8042. http://dx.doi.org/10.3390/app13148042.
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Background: Scientific research has confirmed the biological activity of resveratrol, which includes its antioxidant, anti-inflammatory, cardioprotective and anticancer properties. There is no known interaction between a static magnetic field and resveratrol that can modulate resveratrol’s effect on cells. Thus, the main aim of our research was to assess the effect of the co-exposure to resveratrol and a static magnetic field on the oxidation–reduction homeostasis of C32 and Colo829 melanoma cells. Methods: The studies consisted of determining the activity of the antioxidant enzymes that constitute the body’s first line of defense—SOD, GPx and CAT—and determining the lipid peroxidation product—MDA—and the value of the total antioxidant status of melanoma cells. Results and conclusions: Resveratrol was shown to exhibit anticancer properties, possibly through the ferroptosis of melanoma cells. A static magnetic field was also found to abolish the anticancer properties of resveratrol and to have a protective effect against melanoma cells by restoring the redox balance in the cells.
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Chai, Mei, Xuyan Tang, Jinzhong Zhang e Chenchen Huang. "Resveratrol in Periodontitis Treatment: Efficacy and Mechanism of Action in Rat Models and its Clinical Implications". Current Topics in Nutraceutical Research 22, n.º 2 (6 de janeiro de 2024): 452–58. http://dx.doi.org/10.37290/ctnr2641-452x.22:452-458.
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Periodontitis, a prevalent periodontal disease, serves as the foundation for numerous periodontal pathologies. The current study aimed to examine the adjunctive role of resveratrol in treating periodontitis. Our findings reveal that resveratrol significantly augments periodontal health of patients, indicating its substantial efficacy. Further experimentation involving the construction of a rat model of periodontitis demonstrated that resveratrol effectively mitigates periodontal tissue damage and inhibits apoptosis in periodontal cells. This confirms resveratrol's promising clinical applicability. Moreover, the Osteoclastogenesis inhibitory factor/Recombinant receptor activator of nuclear factor kappa B/Recombinant receptor activator of nuclear factor kappa B-Ligand pathway is pivotal in modulating the pathological progression of periodontitis. This pathway exhibited significant activation in rats afflicted with periodontitis, and resveratrol intervention effectively regulated its expression. These findings suggest that the therapeutic impact of resveratrol on periodontitis could be attributed to the inhibition of the Osteoclastogenesis inhibitory factor/Recombinant receptor activator of nuclear factor kappa B/Recombinant receptor activator of nuclear factor kappa B-Ligand pathway.
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Wu, Hong, Liang Chen, Feifei Zhu, Xu Han, Lindan Sun e Keping Chen. "The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells". Toxins 11, n.º 12 (13 de dezembro de 2019): 731. http://dx.doi.org/10.3390/toxins11120731.
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Resveratrol, a natural polyterpenoid, can scavenge reactive oxygen species in vivo to carry out the functions of antioxidation and antiaging. Resveratrol’s anti-cancer capability has attracted widespread attention, but its molecular mechanism has not been systematically explained. In this study, by comparing the activity of normal cell lines and cancer cell lines after treating with resveratrol, it was found that resveratrol has more significant cytotoxicity in cancer cell lines. Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. A total of 330 significantly differential genes were identified through large-scale transcriptome sequencing, among which 103 genes were upregulated and 227 genes were downregulated. Transcriptome and qRT-PCR data proved that a large number of genes related to cell cycle were differentially expressed after the treatment of resveratrol. The changes of cell cycle phases at different time points after treating with resveratrol were further detected, and it was found that the cells were arrested in the S phase because of the percentage of cells in S phase increased and cells in G1/G0 phase decreased. In conclusion, resveratrol can inhibit the proliferation of 4T1 cancer cells by inhibiting cell cycle and inducing apoptosis.
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Gowd, Vemana, Qingzheng Kang, Qi Wang, Qiang Wang, Feng Chen e Ka-Wing Cheng. "Resveratrol: Evidence for Its Nephroprotective Effect in Diabetic Nephropathy". Advances in Nutrition 11, n.º 6 (23 de junho de 2020): 1555–68. http://dx.doi.org/10.1093/advances/nmaa075.
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ABSTRACT Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Dietary habits play a major role in determining the onset and progression of DM-related disorders and a proper diet (rich in fruits and vegetables) can delay or prevent the process of DM pathogenesis. Thus, increasing attention has been paid to polyphenols and polyphenol-rich foods since their increased intake has been associated with a reduced incidence of DM and its associated complications. Resveratrol is a polyphenolic phytoalexin that is mainly found in grapevines and berries. It is available in various pharmaceutical dosages and is widely recommended as a dietary supplement due to its beneficial effects. Remarkably, resveratrol's capability to effectively lower blood glucose levels without any side effects has been amply demonstrated in many in vitro and in vivo studies. Herein, we comprehensively review and discuss the nephroprotective effect of resveratrol during DN and its associated mechanisms. Resveratrol exerts its nephroprotective effects via various mechanisms including reducing oxidative stress and advanced glycation end-product (AGE) production, stimulating autophagy, inhibiting endoplasmic reticulum (ER) stress and inflammation, ameliorating lipotoxicity, activating the AMP kinase (AMPK) pathway, and modulating angiogenesis. Moreover, the use of resveratrol as an adjuvant to conventional antidiabetic therapies could be an effective approach to manage DN in humans. However, evidence is scarce to support whether resveratrol has beneficial effects in humans during DN. Therefore, clinical studies are warranted to elucidate resveratrol's role against DN.
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Kobylka, Paulina, Malgorzata Kucinska, Jacek Kujawski, Dawid Lazewski, Marcin Wierzchowski e Marek Murias. "Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship". Molecules 27, n.º 20 (17 de outubro de 2022): 6973. http://dx.doi.org/10.3390/molecules27206973.
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Resveratrol is a plant-derived phytoalexin found in grapes, red wine and many other plants used in Asian folk medicine. It is extensively studied for pleiotropic biological activity. The most crucial are anticancer and chemopreventive properties. Resveratrol has also been reported to be an antioxidant and phytoestrogen. The phytoestrogenic activity of resveratrol was assayed in different in vitro and in vivo models. Although these works brought some, on the first look, conflicting results, it is commonly accepted that resveratrol interacts with estrogen receptors and functions as a mixed agonist/antagonist. It is widely accepted that the hydroxyl groups are crucial for resveratrol’s cytotoxic and antioxidative activity and are responsible for binding estrogen receptors. In this work, we assayed 11 resveratrol analogues, seven barring methoxy groups and six hydroxylated analogues in different combinations at positions 3, 4, 5 and 3′,4′,5′. For this purpose, recombined estrogen receptors and estrogen-dependent MCF-7 and Ishikawa cells were used. Our study was supported by in silico docking studies. We have shown that, resveratrol and 3,4,4′5′-tetrahydroxystilbene, 3,3′,4,5,5′-pentahydroxystilbene and 3,3′,4,4′,5,5′-hexahydroxystilbene may act as selective estrogen receptor modulators.
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Shin, Jung-Won, Hyun-Sun Lee, Jung-Im Na, Chang-Hun Huh, Kyung-Chan Park e Hye-Ryung Choi. "Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes". International Journal of Molecular Sciences 21, n.º 10 (13 de maio de 2020): 3446. http://dx.doi.org/10.3390/ijms21103446.
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Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol’s effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.
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NADERALI, Ebrahim K., Patrick J. DOYLE e Gareth WILLIAMS. "Resveratrol induces vasorelaxation of mesenteric and uterine arteries from female guinea-pigs". Clinical Science 98, n.º 5 (3 de abril de 2000): 537–43. http://dx.doi.org/10.1042/cs0980537.
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Naturally occurring hydroxystilbenes have been shown to induce vasorelaxation. Here, we studied the mechanism of resveratrol-induced vasorelaxation in different types of blood vessels, namely mesenteric (resistance) and main uterine (conductance) arteries, from female guinea-pigs on day 7 and day 15 of the oestrous cycle. Resveratrol (5–70 µmol/l) induced concentration-dependent relaxation of both mesenteric and uterine arteries preconstricted with either noradrenaline (NA; 10 µmol/l) or KCl (125 mmol/l). Resveratrol was 2-fold more potent in inducing relaxation of mesenteric arteries than of uterine arteries. Its effects on uterine arteries from both day-7 and day-15 guinea-pigs were similar, irrespective of the constrictor used, but it was significantly (P < 0.01) more potent in inducing relaxation of mesenteric arteries contracted with NA compared with those constricted with KCl. In day-7 arteries precontracted with NA, NG-nitro-l-arginine methyl ester (l-NAME; 10 µmol/l) had no effects on the time course of resveratrol-induced vasorelaxation in either mesenteric or uterine arteries. However, indomethacin (50 µmol/l) significantly (P < 0.05) potentiated resveratrol's effect on mesenteric, but not uterine, arteries. Indomethacin had no effect on resveratrol-induced vasorelaxation of arteries contracted with KCl, whereas l-NAME significantly (P < 0.05) reduced the effects of resveratrol on uterine, but not on mesenteric, arteries. In day-15 arteries, l-NAME significantly (P < 0.01) attenuated the effects of resveratrol on mesenteric arteries contracted with NA. Indomethacin had no effect on resveratrol activity. This study indicates that: (a) the effect of resveratrol on resistance arteries is greater than that on conductance arteries; (b) the effects of resveratrol are not mediated via prostanoids, but NO may play a role; and (c) the stage of the oestrous cycle has no influence on resveratrol-induced vasorelaxation.
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Feng, Zeming, Zhengrong Yang, Xiang Gao, Yuhua Xue e Xiaohui Wang. "Resveratrol Promotes HIV-1 Tat Accumulation via AKT/FOXO1 Signaling Axis and Potentiates Vorinostat to Antagonize HIV-1 Latency". Current HIV Research 19, n.º 3 (6 de maio de 2021): 238–47. http://dx.doi.org/10.2174/1570162x19666210118151249.
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Background: The latent reservoir of HIV-1 is a major barrier to achieving the eradication of HIV-1/AIDS. One strategy is termed “shock and kill”, which aims to awaken the latent HIV-1 using latency reversing agents (LRAs) to replicate and produce HIV-1 particles. Subsequently, the host cells containing HIV-1 can be recognized and eliminated by the immune response and anti-retroviral therapy. Although many LRAs have been found and tested, their clinical trials were dissatisfactory. Objective: To aim of the study was to investigate how resveratrol reactivates silent HIV-1 transcription and assess if resveratrol could be a candidate drug for the “shock” phase in “shock and kill” strategy. Method: We used established HIV-1 transcription cell models (HeLa-based NH1 and NH2 cells) and HIV-1 latent cell models (J-Lat A72 and Jurkat 2D10 cells). We performed resveratrol treatment on these cell lines and studied the mechanism of how resveratrol stimulates HIV-1 gene transcription. We also tested resveratrol’s bioactivity on primary cells isolated from HIV-1 latent infected patients. Results: Resveratrol promoted HIV-1 Tat protein levels, and resveratrol-induced Tat promotion was found to be dependent on the AKT/FOXO1 signaling axis. Resveratrol could partially dissociate P-TEFb (Positive Transcription Elongation Factor b) from 7SK snRNP (7SK small nuclear Ribonucleoprotein) and promote Tat-SEC (Super Elongation Complex) interaction. Preclinical studies showed that resveratrol potentiated Vorinostat to awaken HIV-1 latency in HIV-1 latent infected cells isolated from patients. Conclusion: We found a new mechanism of resveratrol stimulating the production of HIV-1. Resveratrol could be a promising candidate drug to eradicate HIV-1 reservoirs.
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Silva, Paula, María P. Portillo e Alfredo Fernández-Quintela. "Resveratrol and Wine: An Overview of Thirty Years in the Digital News". International Journal of Environmental Research and Public Health 19, n.º 23 (28 de novembro de 2022): 15815. http://dx.doi.org/10.3390/ijerph192315815.
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Background: Resveratrol’s health benefits have received wide media coverage. Since resveratrol is usually associated with wine, informative texts about it should be prepared very carefully, since inaccurate website content could easily change people’s wine consumption behavior. This study aimed to assess the quality of informative texts related to resveratrol on science journalism websites. Methods: We analyzed 125 resveratrol posts on Science Daily, WebMD, and EurekAlert! published between 1990 and 2020. Results: A higher number of posts was published in the years in which the number of people looking for information on the internet also increased. The increase can also be related to David Sinclair’s notoriety, a fact that we called the “Sinclair effect”. Most of the posts are replications of universities’ press releases, mainly reporting resveratrol’s health benefits, which resulted from preclinical studies and cannot be translated to humans. Most of them mention wine in the text and some in the title. Conclusions: Wine is usually mentioned in headline resveratrol news, which could potentially influence wine consumption behavior. Scientists must intensify their efforts to communicate with the public to increase people’s health literacy. Online news portals should have science journalists skilled in exploring scientific data and their translation into a simple and accurate language.
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Li, Yuexin. "A Systematic Review of Application of Resveratrol and the Recent Progress of the Drug Delivery System". BIO Web of Conferences 124 (2024): 02019. http://dx.doi.org/10.1051/bioconf/202412402019.
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Background: Resveratrol is a natural compound in plants like grapes and peanuts, it’s an antioxidant used in supplements and medicine. It’s a colorless crystal soluble in organic solvents, with poor water solubility but high cell membrane permeability. It exists in cis and trans forms. Objective: To explore the background of resveratrol, this review comprehensively summarizes the recent advances in resveratrol including its application in cancer, type-2 diabetes mellitus, vascular disease, and the delivery system. Data sources: We performed a narrative review, based on relevant articles written in English from a PubMed search, using the following search terms: “resveratrol”, and “bioavailability” and “bone health” or “cancer”, or “cardiovascular”, or “diabetes” or “estrogen” or “weight management” or “metabolism”. Results: Cancer’s aggressive nature requires multiple therapies, but they often cause side effects. Resveratrol (RSV) is a promising cancer treatment due to its fewer adverse effects. It inhibits cancer cell growth and promotes cell death by targeting specific pathways. Recent studies also examine the relationship between polyphenol intake and diabetes markers in overweight/obese individuals with metabolic syndrome. Increased polyphenol intake may reduce these markers, particularly in those with pre-diabetes. However, findings vary due to study heterogeneity. Vascular endothelial dysfunction is a critical factor in cardiovascular diseases. Phytochemical compounds, like resveratrol have antioxidative and anti-inflammatory properties that protect the cardiovascular system. Resveratrol prevents inflammation, reduces oxidative stress, and improves endothelial function, making it a promising therapy for cardiovascular diseases. To face the limitation like its low solubility and rapid metabolism, the drug delivery system has also been studied in this review. Various nanodelivery systems, including liposomes, polymeric nanoparticles, and inorganic nanoparticles, have shown promise in overcoming these challenges by improving solubility, biocompatibility, and therapeutic efficacy. Conclusions: While recent advancements in resveratrol’s application show promise, further research is needed to optimize nanoformulations, validate efficacy in vivo, and tackle challenges like scalability and toxicity. Overall, these developments offer a promising path to maximize resveratrol’s therapeutic potential in clinical settings.
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Chhabra, Gagan, Chandra K. Singh, Deeba Amiri, Neha Akula e Nihal Ahmad. "Recent Advancements on Immunomodulatory Mechanisms of Resveratrol in Tumor Microenvironment". Molecules 26, n.º 5 (3 de março de 2021): 1343. http://dx.doi.org/10.3390/molecules26051343.
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Immunomodulation of the tumor microenvironment is emerging as an important area of research for the treatment of cancer patients. Several synthetic and natural agents are being investigated for their ability to enhance the immunogenic responses of immune cells present in the tumor microenvironment to impede tumor cell growth and dissemination. Among them, resveratrol, a stilbenoid found in red grapes and many other natural sources, has been studied extensively. Importantly, resveratrol has been shown to possess activity against various human diseases, including cancer. Mechanistically, resveratrol has been shown to regulate an array of signaling pathways and processes involving oxidative stress, inflammation, apoptosis, and several anticancer effects. Furthermore, recent research suggests that resveratrol can regulate various cellular signaling events including immune cell regulation, cytokines/chemokines secretion, and the expression of several other immune-related genes. In this review, we have summarized recent findings on resveratrol’s effects on immune regulatory cells and associated signaling in various cancer types. Numerous immunomodulatory effects of resveratrol suggest it may be useful in combination with other cancer therapies including immunotherapy for effective cancer management.
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Angelov, George, Lubomir Boyadzhiev e Silviya Georgieva. "Useful Bioactive Substances from Wastes: Recovery of Trans-Resveratrol from Grapevine Stems". Open Chemical Engineering Journal 10, n.º 1 (8 de abril de 2016): 4–9. http://dx.doi.org/10.2174/1874123101610010004.
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The methods for producing natural resveratrol are of big interest because of the many health benefits of this substance and its increasing use in functional foods, food supplements and para-pharmaceutical preparations. Generally, resveratrol is extracted from different natural sources, most of them usually produced for consumption purposes (grapes, nuts). This paper presents a method for recovery of resveratrol from a widely available raw material - grapevine stems, a by-product of vine pruning. An efficient extraction-fractionation scheme is developed, based on shifting the phase equilibrium, by which more concentrated extracts of resveratrol are obtained. After a simple extraction, the initial extract is further separated into two fractions, containing either water or ethanol-soluble compounds. Using this approach, the resveratrol’s low water solubility helps isolate it from other water-soluble substances. The resulting product is almost ten times more concentrated in trans-resveratrol than the initial total extract. Additionally, a fraction containing water-soluble polyphenols is obtained, which could be used for water-based pharmaceutical and cosmetic preparations.
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Gong, Wei, Peng Sun, Xiujing Li, Xi Wang, Xinyu Zhang, Huimin Cui e Jianjun Yang. "Investigating the Molecular Mechanisms of Resveratrol in Treating Cardiometabolic Multimorbidity: A Network Pharmacology and Bioinformatics Approach with Molecular Docking Validation". Nutrients 16, n.º 15 (31 de julho de 2024): 2488. http://dx.doi.org/10.3390/nu16152488.
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Background: Resveratrol is a potent phytochemical known for its potential in treating cardiometabolic multimorbidity. However, its underlying mechanisms remain unclear. Our study systematically investigates the effects of resveratrol on cardiometabolic multimorbidity and elucidates its mechanisms using network pharmacology and molecular docking techniques. Methods: We screened cardiometabolic multimorbidity-related targets using the OMIM, GeneCards, and DisGeNET databases, and utilized the DSigDB drug characterization database to predict resveratrol’s effects on cardiometabolic multimorbidity. Target identification for resveratrol was conducted using the TCMSP, SymMap, DrugBank, Swiss Target Prediction, CTD, and UniProt databases. SwissADME and ADMETlab 2.0 simulations were used to predict drug similarity and toxicity profiles of resveratrol. Protein–protein interaction (PPI) networks were constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID online platform, and target-pathway networks were established. Molecular docking validated interactions between core targets and resveratrol, followed by molecular dynamics simulations on the optimal core proteins identified through docking. Differential analysis using the GEO dataset validated resveratrol as a core target in cardiometabolic multimorbidity. Results: A total of 585 cardiometabolic multimorbidity target genes were identified, and the predicted results indicated that the phytochemical resveratrol could be a major therapeutic agent for cardiometabolic multimorbidity. SwissADME simulations showed that resveratrol has potential drug-like activity with minimal toxicity. Additionally, 6703 targets of resveratrol were screened. GO and KEGG analyses revealed that the main biological processes involved included positive regulation of cell proliferation, positive regulation of gene expression, and response to estradiol. Significant pathways related to MAPK and PI3K-Akt signaling pathways were also identified. Molecular docking and molecular dynamics simulations demonstrated strong interactions between resveratrol and core targets such as MAPK and EGFR. Conclusions: This study predicts potential targets and pathways of resveratrol in treating cardiometabolic multimorbidity, offering a new research direction for understanding its molecular mechanisms. Additionally, it establishes a theoretical foundation for the clinical application of resveratrol.
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Brown, Karen, Despoina Theofanous, Robert G. Britton, Grandezza Aburido, Coral Pepper, Shanthi Sri Undru e Lynne Howells. "Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities". International Journal of Molecular Sciences 25, n.º 2 (6 de janeiro de 2024): 747. http://dx.doi.org/10.3390/ijms25020747.
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Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current ‘state-of-play’ and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol’s potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
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Tseilikman, Vadim E., Olga B. Tseilikman, Vadim A. Shevyrin, Oleg N. Yegorov, Alexandr A. Epitashvili, Maxim R. Aristov, Marina N. Karpenko et al. "Unraveling the Liver–Brain Axis: Resveratrol’s Modulation of Key Enzymes in Stress-Related Anxiety". Biomedicines 12, n.º 9 (10 de setembro de 2024): 2063. http://dx.doi.org/10.3390/biomedicines12092063.
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Stress-related anxiety disorders and anxiety-like behavior in post-traumatic stress disorder (PTSD) are associated with altered neurocircuitry pathways, neurotransmitter systems, and the activities of monoamine and glucocorticoid-metabolizing enzymes. Resveratrol, a natural polyphenol, is recognized for its antioxidant, anti-inflammatory, and antipsychiatric properties. Previous studies suggest that resveratrol reduces anxiety-like behavior in animal PTSD models by downregulating key enzymes such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and monoamine oxidases (MAOs). However, the underlying mechanisms remain unclear. In this study, we explored the efficacy of resveratrol in treating stress-induced anxiety using a chronic predator stress model in rats. Resveratrol was administered intraperitoneally at 100 mg/kg following a 10-day stress exposure, and anxiety behavior was assessed with an elevated plus maze. Our results indicated that stress-related anxiety correlated with increased activities of brain MAO-A, MAO-B, and hepatic 11β-HSD-1, alongside elevated oxidative stress markers in the brain and liver. Resveratrol treatment improved anxiety behavior and decreased enzyme activities, oxidative stress, and hepatic damage. We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol’s potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.
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Briskey, David, e Amanda Rao. "Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology". Pharmaceutics 12, n.º 12 (8 de dezembro de 2020): 1190. http://dx.doi.org/10.3390/pharmaceutics12121190.
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Resveratrol is a naturally produced compound that has been well researched for its potential health benefits. The primary hindrance towards resveratrol’s therapeutic efficacy is its traditionally poor oral bioavailability. LipiSperse® is a novel delivery system designed to increase the dispersion of lipophilic ingredients, like resveratrol, in aqueous environments. This single-dose, double-blind, randomized study compared the pharmacokinetics of a commercially available resveratrol with (Veri-Sperse®) and without (Veri-te) the LipiSperse® delivery complex. Healthy adults randomly received a single dose of either 150 Veri-te, 75 Veri-Sperse®, or 150 mg Veri-Sperse®. Venous blood samples were taken prior to dosing in a fasted state and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 h post supplementation. Plasma trans-resveratrol conjugates were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The area under the curve (AUC) (0–24 h), maximum concentration (Cmax), and time of maximum concentration (Tmax) of plasma conjugates were calculated. The 150 mg dose of Veri-Sperse® had a 2-fold increase in absorption (AUC) and a 3-fold increase in Cmax of trans-resveratrol conjugates compared to 150 mg Veri-te. There was no statistical difference between 75 Veri-Sperse and 150 mg Veri-te for AUC or Cmax of resveratrol conjugates. These findings provide support for the use of LipiSperse® to improve absorption of resveratrol.
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Zhang, Hanrui, Brandon Morgan, Barry J. Potter, Lixin Ma, Kevin C. Dellsperger, Zoltan Ungvari e Cuihua Zhang. "Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress: in vivo demonstration with magnetic resonance imaging". American Journal of Physiology-Heart and Circulatory Physiology 299, n.º 4 (outubro de 2010): H985—H994. http://dx.doi.org/10.1152/ajpheart.00489.2010.
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Resveratrol is a natural phytophenol that exhibits cardioprotective effects. This study was designed to elucidate the mechanisms by which resveratrol protects against diabetes-induced cardiac dysfunction. Normal control ( m-Lepr db) mice and type 2 diabetic ( Lepr db) mice were treated with resveratrol orally for 4 wk. In vivo MRI showed that resveratrol improved cardiac function by increasing the left ventricular diastolic peak filling rate in Lepr db mice. This protective role is partially explained by resveratrol's effects in improving nitric oxide (NO) production and inhibiting oxidative/nitrative stress in cardiac tissue. Resveratrol increased NO production by enhancing endothelial NO synthase (eNOS) expression and reduced O2·− production by inhibiting NAD(P)H oxidase activity and gp91phox mRNA and protein expression. The increased nitrotyrosine (N-Tyr) protein expression in Lepr db mice was prevented by the inducible NO synthase (iNOS) inhibitor 1400W. Resveratrol reduced both N-Tyr and iNOS expression in Lepr db mice. Furthermore, TNF-α mRNA and protein expression, as well as NF-κB activation, were reduced in resveratrol-treated Lepr db mice. Both Lepr db mice null for TNF-α ( dbTNF−/ dbTNF− mice) and Lepr db mice treated with the NF-κB inhibitor MG-132 showed decreased NAD(P)H oxidase activity and iNOS expression as well as elevated eNOS expression, whereas m-Lepr db mice treated with TNF-α showed the opposite effects. Thus, resveratrol protects against cardiac dysfunction by inhibiting oxidative/nitrative stress and improving NO availability. This improvement is due to the role of resveratrol in inhibiting TNF-α-induced NF-κB activation, therefore subsequently inhibiting the expression and activation of NAD(P)H oxidase and iNOS as well as increasing eNOS expression in type 2 diabetes.
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Woodman, Keryn G., Chantal A. Coles, Shireen R. Lamandé e Jason D. White. "Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice". Molecules 26, n.º 4 (6 de fevereiro de 2021): 853. http://dx.doi.org/10.3390/molecules26040853.
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Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100–400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol’s mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD.
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Herrera, Daniela P., Andrea M. Chánique, Ascensión Martínez-Márquez, Roque Bru-Martínez, Robert Kourist, Loreto P. Parra e Andreas Schüller. "Rational Design of Resveratrol O-methyltransferase for the Production of Pinostilbene". International Journal of Molecular Sciences 22, n.º 9 (21 de abril de 2021): 4345. http://dx.doi.org/10.3390/ijms22094345.
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Pinostilbene is a monomethyl ether analog of the well-known nutraceutical resveratrol. Both compounds have health-promoting properties, but the latter undergoes rapid metabolization and has low bioavailability. O-methylation improves the stability and bioavailability of resveratrol. In plants, these reactions are performed by O-methyltransferases (OMTs). Few efficient OMTs that monomethylate resveratrol to yield pinostilbene have been described so far. Here, we report the engineering of a resveratrol OMT from Vitis vinifera (VvROMT), which has the highest catalytic efficiency in di-methylating resveratrol to yield pterostilbene. In the absence of a crystal structure, we constructed a three-dimensional protein model of VvROMT and identified four critical binding site residues by applying different in silico approaches. We performed point mutations in these positions generating W20A, F24A, F311A, and F318A variants, which greatly reduced resveratrol’s enzymatic conversion. Then, we rationally designed eight variants through comparison of the binding site residues with other stilbene OMTs. We successfully modified the native substrate selectivity of VvROMT. Variant L117F/F311W showed the highest conversion to pinostilbene, and variant L117F presented an overall increase in enzymatic activity. Our results suggest that VvROMT has potential for the tailor-made production of stilbenes.
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Chin, Yu-Tang, Po-Li Wei, Yih Ho, André Wendindondé Nana, Chun A. Changou, Yi-Ru Chen, Yu-Chen SH Yang et al. "Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells". Endocrine-Related Cancer 25, n.º 5 (maio de 2018): 533–45. http://dx.doi.org/10.1530/erc-17-0376.
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Thyroid hormone,l-thyroxine (T4), has been shown to promote ovarian cancer cell proliferation via a receptor on plasma membrane integrin αvβ3 and to induce the activation of ERK1/2 and expression of programmed death-ligand 1 (PD-L1) in cancer cells. In contrast, resveratrol binds to integrin αvβ3 at a discrete site and induces p53-dependent antiproliferation in malignant neoplastic cells. The mechanism of resveratrol action requires nuclear accumulation of inducible cyclooxygenase (COX)-2 and its complexation with phosphorylated ERK1/2. In this study, we examined the mechanism by which T4impairs resveratrol-induced antiproliferation in human ovarian cancer cells and found that T4inhibited resveratrol-induced nuclear accumulation of COX-2. Furthermore, T4increased expression and cytoplasmic accumulation of PD-L1, which in turn acted to retain inducible COX-2 in the cytoplasm. Knockdown ofPD-L1by small hairpin RNA (shRNA) relieved the inhibitory effect of T4on resveratrol-induced nuclear accumulation of COX-2- and COX-2/p53-dependent gene expression. Thus, T4inhibits COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with PD-L1 in the cytoplasm. These findings provide new insights into the antagonizing effect of T4on resveratrol’s anticancer properties.
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Ardianto, Chrismawan, Aniek Setiya Budiatin, I. Nengah Budi Sumartha, Nurrahmi Nurrahmi, Mahardian Rahmadi e Junaidi Khotib. "Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior". Journal of Basic and Clinical Physiology and Pharmacology 32, n.º 4 (25 de junho de 2021): 335–40. http://dx.doi.org/10.1515/jbcpp-2020-0437.
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Abstract Objectives Depression is a mental disorder that profoundly affects all aspects of life, but currently, antidepressants have some problems with their effectiveness and side effects. Resveratrol is a compound that has the ability to regulate the hypothalamic-pituitary-adrenal axis. This study aimed to determine resveratrol’s effect on physical and psychological stress-induced depressive-like behavior. Methods Mice were divided into control, physical stress, psychological stress groups. Treatment was conducted with fluvoxamine 20 mg/kg and resveratrol 20, 40, and 80 mg/kg for seven days. The depressive-like state was evaluated using a forced swim test (FST), tail suspension test (TST), and open field test (OFT). Results Physical stress and psychological stress induction increase the immobility time on FST and TST. Besides, there is an increase in time in central on OFT, which indicates an anxiety or mental illness-like behavior. However, the OFT examination on sniffing, rearing, grooming, and crossing behavior did not show a significant difference. Resveratrol 80 mg/kg and fluvoxamine 20 mg/kg were significantly reduced immobility time at TST compared to the physical stress group. While in psychological stress, resveratrol 80 mg/kg tended to decrease immobility time but not significant. A significant increase in time in central duration was seen in the resveratrol 40 mg/kg compared to the psychological stress. Stress induction causes increased amygdala corticotrophin-releasing factor (CRF) mRNA expression. However, neither resveratrol nor fluvoxamine affected amygdala CRF mRNA expression. Conclusions Resveratrol ameliorates depressive-like behavior induced by physical and psychological stress.
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Clark, Paul A., Saswati Bhattacharya, Ardem Elmayan, Soesiawati R. Darjatmoko, Bradley A. Thuro, Michael B. Yan, Paul R. van Ginkel, Arthur S. Polans e John S. Kuo. "Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration". Journal of Neurosurgery 126, n.º 5 (maio de 2017): 1448–60. http://dx.doi.org/10.3171/2016.1.jns152077.
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OBJECTIVEGlioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than 2 years with current treatment. Glioblastomas exhibit extensive intratumoral and interpatient heterogeneity, suggesting that successful therapies should produce broad anticancer activities. Therefore, the natural nontoxic pleiotropic agent, resveratrol, was studied for antitumorigenic effects against GBM.METHODSResveratrol's effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed. Resveratrol was also tested in vivo against U87 glioma flank xenografts in mice by using multiple delivery methods, including direct tumor injection. Finally, resveratrol was delivered directly to brain tissue to determine toxicity and achievable drug concentrations in the brain parenchyma.RESULTSResveratrol significantly inhibited proliferation in U87 glioma and multiple patient-derived GSC lines, demonstrating similar inhibitory concentrations across these phenotypically heterogeneous lines. Resveratrol also inhibited the sphere-forming ability suggesting anti–stem cell effects. Additionally, resveratrol blocked U87 glioma and GSC invasion in an in vitro Matrigel Transwell assay at doses similar to those mediating antiproliferative effects. In U87 glioma cells and GSCs, resveratrol reduced AKT phosphorylation and induced p53 expression and activation that led to transcription of downstream p53 target genes. Resveratrol administration via oral gavage or ad libitum in the water supply significantly suppressed GBM xenograft growth; intratumoral or peritumoral resveratrol injection further suppressed growth and approximated tumor regression. Intracranial resveratrol injection resulted in 100-fold higher local drug concentration compared with intravenous delivery, and with no apparent toxicity.CONCLUSIONSResveratrol potently inhibited GBM and GSC growth and infiltration, acting partially via AKT deactivation and p53 induction, and suppressed glioblastoma growth in vivo. The ability of resveratrol to modulate AKT and p53, as well as reportedly many other antitumorigenic pathways, is attractive for therapy against a genetically heterogeneous tumor such as GBM. Although resveratrol exhibits low bioavailability when administered orally or intravenously, novel delivery methods such as direct injection (i.e., convection-enhanced delivery) could potentially be used to achieve and maintain therapeutic doses in the brain. Resveratrol's nontoxic nature and broad anti-GBM effects make it a compelling candidate to supplement current GBM therapies.
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Arslaner, Ayla, e Zehra Türkoğlu. "A potential antiviral and food-derived healthy ingredient: Resveratrol". Food and Health 7, n.º 1 (2021): 54–63. http://dx.doi.org/10.3153/fh21007.
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Polyphenols are the secondary metabolites of plants and has an important role in human nutrition as the leading antioxidants. According to the carbon number-based classification of polyphenols, resveratrol is a natural polyphenol in the stilbene group with antioxidant and anticarcinogenic effects. Its beneficial effects on cardiovascular diseases have also been reported. It was first identified in 1940 and has recently gained importance especially in medicine and pharmacy. Researchers have carried out various studies on resveratrol and its time-honored use in traditional eastern medicine has been reported. Resveratrol is a food ingredient that has the potential to be used in the treatment of various diseases, but also has antiviral effects. The study focuses on resveratrol’s physical and chemical properties, effects on health, antiviral effects and use in foods as a functional component.
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Mota-Lugo, Esmeralda, Mariana Dolores-Hernández, Elvia A. Morales-Hipólito, Iris A. Blanco-Alcántara, Hugo Cuatecontzi-Flores e Raquel López-Arellano. "Development and Validation of a Stability-Indicating HPLC Method for the Simultaneous Determination of trans-Resveratrol and cis-Resveratrol in an Injectable Solution". Journal of Analytical Methods in Chemistry 2021 (13 de novembro de 2021): 1–12. http://dx.doi.org/10.1155/2021/8402157.
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trans-Resveratrol, a phytochemical compound with antioxidant power and various therapeutic effects, such as cardioprotective, chemopreventive, and neuroprotective, among others, has disadvantages of poor solubility and limited stability, creating difficulties for the development of new strategies for its quantification. This study developed and validated an analytical stability method for trans-resveratrol by high-pressure liquid chromatography with photodiode-array detection (HPLC-PDA), which allowed its quantification in the presence of its degradation products. The quantification of trans-resveratrol occurred at a retention time of 2.6 min, with ammonium formate (10 mM, pH = 4)/acetonitrile, 70/30 v/v, as mobile phase. The validation met the ICH Q2 criteria of specificity, method linearity (2.8–4.2 μg/ml), precision and accuracy, robustness, quantification limit (0.176 μg/ml), and detection (0.058 μg/ml). As degradation products, cis-resveratrol was observed at 3.9 min, which could be resveratrone in 3.2 min and five unidentified products in 0.7, 1.0, 1.4, 1.8, and 5 min. Some solutions subjected to temperature stress of 40 and 60°C, UV light, and acidic and basic hydrolysis exhibited colour changes. An analytical method was obtained by HPLC-PDA, which allowed quantifying the stability of trans-resveratrol in a fast and specific manner in the presence of its degradation products.
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Blanke, Meik, Jan Balszuweit, Marco Saccone, Christoph Wölper, David Doblas Jiménez, Markus Mezger, Jens Voskuhl e Michael Giese. "Photo-switching and -cyclisation of hydrogen bonded liquid crystals based on resveratrol". Chemical Communications 56, n.º 7 (2020): 1105–8. http://dx.doi.org/10.1039/c9cc07721a.
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Liu, Qing, Xiuhua Gao, Cheng C. Yin, Chen Ling e M. James You. "Resveratrol Inhibits Proliferation and Induces Apoptosis of Mouse Pten Null T-Cell Acute Lymphocytic Leukemia Cells". Blood 112, n.º 11 (16 de novembro de 2008): 3967. http://dx.doi.org/10.1182/blood.v112.11.3967.3967.
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Abstract Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a plant antibiotic produced in a wide variety of plants (including grapes, peanuts, and mulberries) in response to stress, injury, UV irradiation, and fungal infection, has been shown to inhibit cell growth of several types of cancer. Here, we have investigated the effects of Resveratrol on the proliferation and apoptosis in T-cell lymphocytic leukemia (T-ALL) cells. These T-ALL cells were derived from T-ALL of mice with the T-cell specific deletion of the Pten tumor suppressor gene. Flow cytometric analysis demonstrated that the T-ALL cells are positive for CD4 and negative for CD8. Morphologically, the T-ALL cells strikingly mimic human counterparts. Western blot analysis confirmed the absence of Pten expression and high expression level of phosphorylated Akt of the T-ALL cells. A single dose treatment of the T-ALL cells with Resveratrol (ranging from 3 to 50 mM) resulted in significant decrease in cell growth. In addition, Resveratrol treatment with the above concentrations showed a remarkable increase in apoptosis. The vehicle treated T-ALL cells grew exponentially and had minimal apoptotic cell death. Further investigation of the mechanisms of the Resveratrol’s efforts on inhibiting T-ALL cell growth and inducing apoptosis is on-going. In addition, combination of Resveratrol with conventional chemotherapy reagents for treating T-ALL is also being evaluated.
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Bhattacharjee, Surajit, Debasree Lodh e Arijit Chakraborty. "Potentiality of Resveratrol in Mitigating Exercise-Induced Inflammation - A Bioinformatic Study on Interleukin-6 (IL-6) in Athletes". Open Access Journal of Kinesiology and Sports Medicine 2, n.º 1 (2024): 1–8. http://dx.doi.org/10.23880/oajksm-16000111.
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Background: Athletes, engaging in vigorous exercise, confront elevated reactive oxygen species (ROS) and inflammation. Dietary antioxidants, abundant in diverse foods, offer protection. Resveratrol, a potent polyphenol from grapes and berries, explores its anti-inflammatory potential and mechanism through in-silico analysis in athletes. Method: Initial steps involved IL-6 data retrieval (PDB ID 1alu), receptor preparation, and ligand selection (Resveratrol, CID 445154). IL-6 receptor binding site identification utilized literature and PyMol. Molecular docking was facilitated by AutoDock, validated through re-docking and overlay methods. Lead molecule selection in in silico virtual screening was based on binding energy (-5 to -15 kcal/mol). The evaluation concluded with interaction assessment and binding affinity calculation. Result and Discussion: The study utilized IL-6 from the Protein Data Bank. Resveratrol was prepared for molecular docking. Docking outcomes showed optimal fit and interaction of resveratrol with IL-6, forming three bonds and exhibiting a low binding energy of -5.2 kcal/mol. The research addressed exercise-induced inflammation, emphasizing IL-6's role. Bioinformatics and molecular docking provided insights into IL-6 binding. Resveratrol demonstrated a potential inhibitory effect on IL-6 action, presenting a promising avenue for anti-inflammatory intervention in athletes. Conclusion: Exploring resveratrol's anti-inflammatory potential on IL-6, our study used molecular docking, suggesting its protective effects in athletes. Ongoing research is vital for validation and broader implications