Activity Of Resveratrol Research Articles

IMPACTO DOS COMPOSTOS BIOATIVOS DA UVA, COM ÊNFASE NO RESVERATROL, NA REDUÇÃO DA PRESSÃO ARTERIAL: UMA REVISÃO DE LITERATURA

The study aimed to analyze the main studies that address the impacts of grape bioactive compounds, with an emphasis on resveratrol, on reducing blood pressure. This is a literature review, which was carried out based on the definition of the research question, inclusion and exclusion criteria, search strategies, and selection of studies. 40 articles were selected from 230 identified, after assessing their methodological quality. Data analysis focused on the mechanisms of action of resveratrol, the effectiveness of supplementation methods, and its clinical perspectives. The study highlighted the potential of resveratrol, a grape bioactive compound, in reducing blood pressure, acting as an adjuvant in the treatment of hypertension. It promotes vasodilation, reduces oxidative stress, and improves cardiovascular health. Its effectiveness, however, depends on dosage and bioavailability. Despite advances, more clinical studies are needed to standardize its use and investigate interactions with medications. Continued research can consolidate resveratrol in integrative health strategies.

The Neuroprotective Action of Resveratrol Against Cognitive Impairments Induced by Lorazepam in Male Rats.

The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems. Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2-deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase. Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8- HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level (p < 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests. Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells.

Lin28A is an oncoprotein overexpressed in several cancer types such as testicular, ovarian, colon, breast and lung cancers. As a pluripotency factor that promotes tumorigenesis, Lin28A is associated with more undifferentiated and aggressive tumors phenotypes. Moreover, Lin28A is a highly stable protein that is difficult to downregulate. The compound resveratrol (RSV) has anticancer effects. The present study aimed to elucidate the mechanisms underlying the downregulation of Lin28A protein expression by RSV in the NCCIT cell line. NCCIT cells were treated with different concentrations of RSV to investigate its effects on Lin28A expression. The mRNA expression levels of Lin28A and ubiquitin-specific protease 28 (USP28) were assessed using reverse transcription-quantitative PCR. Western blot analysis was employed to evaluate the protein levels of Lin28A, USP28 and phosphorylated Lin28A. In addition, in some experiments, cells were treated with a MAPK/ERK pathway inhibitor, and other experiments involved transfecting cells with small interfering RNAs targeting USP28. The results demonstrated that RSV significantly reduced Lin28A expression by destabilizing the protein; this effect was mediated by the ability of RSV to suppress the expression of USP28, a deubiquitinase that normally protects Lin28A from ubiquitination and degradation. Additionally, RSV inhibited phosphorylation of Lin28A via the MAPK/ERK pathway; this phosphorylation event has previously been shown to enhance the stability of Lin28A by increasing its half-life. This resulted in Lin28A degradation through the proteasomal pathway in NCCIT cells. The results provide further evidence of the anticancer activity of RSV, and identified Lin28A and USP28 as promising therapeutic targets. As a stable oncoprotein, downregulating Lin28A expression is challenging. However, the present study demonstrated that RSV can overcome this hurdle by inhibiting USP28 expression and MAPK/ERK signaling to promote Lin28A degradation. Furthermore, elucidating these mechanisms provides avenues for developing targeted cancer therapies.

Potential of Resveratrol to Combine with Hydrogel for Photodynamic Therapy against Bacteria and Cancer-A Review.

Nine electronic databases, namely WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), were searched to conduct this literature review, without any regard to language constraints. Studies focusing on the photodynamic actions of hydrogel and Resveratrol were included that evaluated the effect of PDT against bacteria and cancer. All eligible studies were analyzed and summarized in this review. Resveratrol has antibacterial and anticancer effects. It can also act as PS in PDT or adjuvant but has some limitations. This is much better when combined with a hydrogel to enhance the effectiveness of PDT in the fight against bacteria and cancer. Resveratrol combined with hydrogel is possible for PDT treatment in bacteria and cancer. They are compatible and reinforce each other to increase the effectiveness of PDT. However, much more work is required, such as cytotoxicity safety assessments of the human body and further enhancing the effectiveness of PDT in different environments for future investigations.

Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments

Sarcopenic obesity (SO) is a metabolic disorder with increasing prevalence. It is characterized by a reduction in skeletal muscle mass and strength. Resveratrol (RSV) is one of the most frequently used herbs in the treatment of skeletal muscle atrophy. However, the precise mechanism of the action of RSV in SO remains unclear. The objective of this study was to examine the pharmacological mechanism of RSV in the context of SO through the lens of network pharmacology, to validate these findings through in vivo experimentation. A list of potential RSV targets was compiled by retrieving the data from multiple databases. This list was then cross-referenced with a list of potential targets related to SO. The intersections of RSV- and SO-related targets were analyzed using Venn diagrams. To identify the core genes, a protein-protein interaction (PPI) network of the intersection targets was constructed and subsequently analyzed. Molecular docking was used to predict RSV binding to its core targets. A high-fat diet was used to induce SO in mice. These findings indicated that RSV may prevent SO by acting on 11 targets. Among these, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF) are considered core targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the anti-SO effect of RSV was predominantly linked to metabolic disease-related pathways, including those associated with nonalcoholic fatty liver disease. The anti-inflammatory effects of RSV were confirmed in vivo in an SO mouse model. This study contributes to a more comprehensive understanding of the key mechanisms of the action of RSV against SO and provides new possibilities for drug development in the pathological process of SO.

Abstract 31: Deacetylation Mimetic Mutation of Mitochondrial Superoxide Dismutase Attenuates Angiotensin II-Induced Hypertension by Protecting Against Oxidative Stress

Almost one-half of adults have hypertension, and blood pressure is poorly controlled in a third of patients despite the use of multiple drugs, likely due to mechanisms that are not affected by current treatments. Hypertension is linked to oxidative stress; however, common antioxidants are ineffective. Hypertension is associated with inactivation of key intrinsic mitochondrial antioxidant, superoxide dismutase 2 (SOD2), due to hyperacetylation but the role of specific SOD2 lysine residues has not been defined. Hypertension is associated with SOD2 acetylation at Lysine 68 (Circ Res. 2020;126(4):439-452) and we suggested that deacetylation mimetic mutation of K68 to Arginine in SOD2 inhibits vascular oxidative stress and attenuates hypertension. To test this hypothesis, we have developed a new deacetylation mimic SOD2-K68R mice. We performed in vivo studies in SOD2-K68R mice using angiotensin II (AngII) model of vascular dysfunction and hypertension. AngII infusion in wild-type mice induced vascular inflammation and oxidative stress, and increased blood pressure to 160 mm Hg. SOD2-K68R mutation completely prevented increase in mitochondrial superoxide, abrogated vascular oxidative stress, preserved endothelial nitric oxide production, protected vasorelaxation, and attenuated AngII-induced hypertension. AngII and cytokines contribute to vascular oxidative stress and hypertension. Treatment of wild-type aortas with AngII and cytokines in organoid culture increased mitochondrial superoxide by 2-fold which was completely prevented in aortas isolated from SOD2-K68R mice. Interestingly, ex vivo treatment of aortas isolated from hypertensive mice with Sirtuin activator resveratrol reduces SOD2 acetylation, inhibits mitochondrial superoxide, and rescues endothelial nitric oxide. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and pathogenesis of hypertension. We conclude that strategies to reduce SOD2 acetylation may have therapeutic potential in the treatment of vascular dysfunction and hypertension.

Therapeutic Potential of Resveratrol and Lignans in the Management of Tuberculosis.

This study aims to investigate the therapeutic potential of herbal remedies, specifically resveratrol and lignans, as alternative treatments for tuberculosis (TB), given the challenges posed by drug-resistant strains and adverse effects of conventional therapies. A comprehensive review of the literature was conducted to analyze the mechanisms of action, safety profiles, and efficacy of resveratrol and lignans in the context of TB management. This review focused on the bactericidal and bacteriostatic effects of these compounds, examining their interaction with Mycobacterium tuberculosis within macrophages. Resveratrol and lignans were found to exhibit significant antibacterial properties through mechanisms such as SIRT1 modulation, coenzyme A transferase inhibition, suppression of intracellular bacterial proliferation in macrophages, and induction of autophagy. These mechanisms contribute to their effectiveness in combating TB and highlight their potential as alternative therapeutic agents.

Resveratrol alleviates endoplasmic reticulum stress-induced cell death and improves functional prognosis after traumatic brain injury in mice.

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1β were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.

Research progress of SIRTs activator resveratrol and its derivatives in autoimmune diseases.

Autoimmune diseases (AID) have emerged as prominent contributors to disability and mortality worldwide, characterized by intricate pathogenic mechanisms involving genetic, environmental, and autoimmune factors. In response to this challenge, a growing body of research in recent years has delved into genetic modifications, yielding valuable insights into AID prevention and treatment. Sirtuins (SIRTs) constitute a class of NAD-dependent histone deacetylases that orchestrate deacetylation processes, wielding significant regulatory influence over cellular metabolism, oxidative stress, immune response, apoptosis, and aging through epigenetic modifications. Resveratrol, the pioneering activator of the SIRTs family, and its derivatives have captured global scholarly interest. In the context of AID, these compounds hold promise for therapeutic intervention by modulating the SIRTs pathway, impacting immune cell functionality, suppressing the release of inflammatory mediators, and mitigating tissue damage. This review endeavors to explore the potential of resveratrol and its derivatives in AID treatment, elucidating their mechanisms of action and providing a comprehensive analysis of current research advancements and obstacles. Through a thorough examination of existing literature, our objective is to advocate for the utilization of resveratrol and its derivatives in AID treatment while offering crucial insights for the formulation of innovative therapeutic approaches.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

Sleep deprivation induced fat accumulation in the visceral white adipose tissue by suppressing SIRT1/FOXO1/ATGL pathway activation.

Sleep is critical for maintaining overall health. Insufficient sleep duration and poor sleep quality are associated with various physical and mental health risks and chronic diseases. To date, plenty of epidemiological research has shown that sleep disorders are associated with the risk of obesity, which is usually featured by the expansion of adipose tissue. However, the underlying mechanism of increased fat accumulation upon sleep disorders remains unclear. Here we demonstrated that sleep deprivation (SD) caused triglycerides (TG) accumulation in the visceral white adipose tissue (vWAT), accompanied by a remarkable decrease in the expression of adipose triglyceride lipase (ATGL) and other two rate-limiting lipolytic enzymes. Due to the key role of ATGL in initiating and controlling lipolysis, we focused on investigating the signaling pathway leading to attenuated ATGL expression in vWAT upon SD in the following study. We observed that ATGL downregulation resulted from the suppression of ATGL transcription, which was mediated by the reduction of the transcriptional factor FOXO1 and its upstream regulator SIRT1 expression in vWAT after SD. Furthermore, impairment of SIRT1/FOXO1/ATGL pathway activation and lipolysis induced by SIRT1 inhibitor EX527 in the 3 T3-L1 adipocytes were efficiently rescued by the SIRT1 activator resveratrol. Most notably, resveratrol administration in SD mice revitalized the SIRT1/FOXO1/ATGL pathway activation and lipid mobilization in vWAT. These findings suggest that targeting the SIRT1/FOXO1/ATGL pathway may offer a promising strategy to mitigate fat accumulation in vWAT and reduce obesity risk associated with sleep disorders.

A Single Terminal [NiII-OH] Catalyst for Direct Julia-Type Olefination and α-Alkylation Involving Sulfones and Alcohols.

A terminal [NiII-OH] complex 1, supported by triflamide-functionalized NHC ligands, showed divergent reactivity for the reaction of sulfone with alcohol, contingent on base concentration, temperature, and time. Julia-type olefination of alcohols with sulfones was achieved using one equiv. of base, whereas lowering base loading to 0.5 equiv. afforded α-alkylated sulfones. Besides excellent substrate scope and selectivity, biologically active stilbene derivatives DMU-212, pinosylvin, resveratrol, and piceatannol were synthesized in high yield under Julia-type olefination conditions. An extensive array of controlled experiments and DFT calculations provide valuable insight on the reaction pathway.

Preparation of Eudragit S100-pullulan/hydroxypropyl-β-cyclodextrin complex-Eudragit S100 multilayer nanofiber film for resveratrol colon delivery

Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-β-cyclodextrin (HPβCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPβCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability, and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD+ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside.

Resveratrol activates autophagy and protects from UVA-induced photoaging in human skin fibroblasts and the skin of male mice by regulating the AMPK pathway

Skin photoaging is mostly caused by ultraviolet A (UVA), although active medications to effectively counteract UVA-induced photoaging have not yet been created. Resveratrol, a naturally occurring polyphenol found in the skin of grapes, has been shown to have various biological functions such as anti-inflammatory and antioxidant characteristics. However, the role of resveratrol in UVA-induced photoaging has not been clarified. We investigated the mechanism of action of resveratrol by UVA irradiation of human skin fibroblasts (HSF) and innovatively modified a mouse model of photoaging. The results demonstrated that resveratrol promoted AMP-activated protein kinase (AMPK) phosphorylation to activate autophagy, reduce reactive oxygen species (ROS) production, inhibit apoptosis, and restore normal cell cycle to alleviate UVA-induced photoaging. In addition, subcutaneous injection of resveratrol not only improved the symptoms of roughness, erythema, and increased wrinkles in the skin of UVA photodamaged mice, but also alleviated epidermal hyperkeratosis and hyperpigmentation, reduced inflammatory responses, and inhibited collagen fiber degradation. In conclusion, our studies proved that resveratrol can treat UVA-induced photoaging and elucidated the possible molecular mechanisms involved, providing a new therapeutic strategy for future anti-aging.

A systematic review and meta-analysis of the impact of resveratrol on oral cancer: potential therapeutic implications

The present study aimed to investigate the impact of resveratrol on oral neoplastic parameters through a systematic review and meta-analysis. Resveratrol, a naturally occurring polyphenol, has shown promising potential as a therapeutic agent in various cancer types, including oral neoplasms. Understanding the collective findings from existing studies can shed light on the efficacy and mechanisms of resveratrol in oral cancer management. The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed to identify relevant studies from various databases, registers, websites, and citation searches. The inclusion criteria encompassed in-vivo studies investigating the impact of resveratrol on oral neoplastic parameters in animal models. After screening and assessment, a total of five eligible studies were included in the meta-analysis. The meta-analysis of the selected studies revealed that resveratrol treatment exhibited a potential impact on reducing oral neoplastic proliferation and promoting neoplastic apoptosis. The combined analysis showed a statistically significant decrease in neoplastic parameters with an overall effect size (ES) of 0.85 (95% CI: [0.74, 0.98]). Subgroup analyses were conducted to explore potential variations among different cellular types and exposure compounds, providing further insights into the efficacy of resveratrol in specific contexts. This systematic review and meta-analysis support the potential of resveratrol as a promising therapeutic agent in oral cancer management. The findings indicate that resveratrol may effectively modulate neoplastic proliferation and apoptosis in various cellular types within animal models of oral cancer. However, further well-controlled studies and clinical trials are warranted to validate these observations and elucidate the underlying mechanisms of resveratrol's actions. Resveratrol holds promise as a complementary therapeutic approach in the prevention and treatment of oral neoplastic conditions.

Anti-Inflammatory Action of Resveratrol in the Central Nervous System in Relation to Glucose Concentration-An In Vitro Study on a Blood-Brain Barrier Model.

Unbalanced blood glucose levels may cause inflammation within the central nervous system (CNS). This effect can be reversed by the action of a natural neuroprotective compound, resveratrol (RSV). The study aimed to investigate the anti-inflammatory effect of RSV on astrocyte cytokine profiles within an in vitro model of the blood-brain barrier (BBB) under varying glucose concentrations (2.2, 5.0, and 25.0 mmol/L), corresponding to hypo-, normo-, and hyperglycemia. The model included co-cultures of astrocytes (brain compartment, BC) and endothelial cells (microvascular compartment, MC), separated by 0.4 µm wide pores. Subsequent exposure to 0.2 μM LPS in the brain compartment (BC) and 50 μM RSV in the microvascular compartment (MC) of each well was carried out. Cytokine levels (IL-1 α, IL-1 β, IL-2, IL-4, IL-6, IL-8) in the BC were assessed using a Multi-Analyte ELISArray Kit before and after the addition of LPS and RSV. Statistical analysis was performed to determine significance levels. The results demonstrated that RSV reduced the concentration of all studied cytokines in the BC, regardless of glucose levels, with the most substantial decrease observed under normoglycemic conditions. Additionally, the concentration of RSV in the BC was highest under normoglycemic conditions compared to hypo- and hyperglycemia. These findings confirm that administration of RSV in the MC exerts anti-inflammatory effects within the BC, particularly under normoglycemia-simulating conditions. Further in vivo studies, including animal and human research, are warranted to elucidate the bioavailability of RSV within the central nervous system (CNS).

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation.

Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified. To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms. Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a "Resveratrol-Target-GC" network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A "Target-Pathway" network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments. A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc. FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression. The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

Synergistic inhibitory actions of resveratrol, epigallocatechin-3-gallate, and diallyl trisulfide against skin cancer cell line A431 through mitochondrial caspase dependent pathway: a combinational drug approach.

The harmful effect of chemotherapeutic side effects has paid a way to discover a novel with curative way for skin cancer treatment. Skin cancer prevention is more viable with the use of combination of bioactive agents than using of single bioactive compounds. Present work was demonstrated to evaluate the interaction of Resveratrol (Res), Epigallocatechin-3-gallate (EGCG), and diallyl trisulfide (DATS) with each other as a binary combination on A431 cells. Nuclear fragmentation analysis of combination of bioactive agents using DAPI analysis, detection of apoptosis, analysis of cell cycle, ROS assay, antimigration assays, and western blotting were implemented to study the combination of bioactive compounds on A431 cell line. Among the selected combination EGCG + DATS had a synergetic effect reducing cellular migration, increased intercellular reactive oxygen species generation, condensation, cell phagocytosis induced by phosphatidylserine externalization, rise in sub-G1 DNA content, and S-phase were cell cycle arrest. The combinations EGCG + DATS induced apoptotic proteins in A431 cells by upregulation of proapoptotic Bax and Bad proteins, a downmodulation of anti-apoptotic proteins Bcl2 and caspases (caspase-3, and -9) activity got triggered by intrinsic pathway. The combination of EGCG + DATS showed good anticancer potential against A431 skin cancer cell line via the mitochondrial caspase dependent pathway with very strong synergism. This finding will help to produce a novel combination/chemoprevention using dietary bioactive agents (EGCG + DATS) for the treatment of skin cancer after clinical trial.

Photosensitized isomerization of resveratrol: Evaluation of energy and electron transfer pathways

Resveratrol (3,5,4′-trihydroxystilbene, RSV) is a natural stilbene synthetized as trans-isomer in plants exposed to oxidative stress. In order to understand the mechanism involved during photosensitized degradation of trans-resveratrol, steady-state and time-resolved experiments were performed and compared with quantum-chemical calculations using density functional theory (DFT). Pterin (Ptr), a well-known photosensitizer, under UV-A radiation induces the oxidation of several biomolecules mainly through electron-transfer mechanisms.On the one hand, it was observed that trans-RSV participates in an energy-transfer pathway with Ptr triplet excited state (3Ptr*) forming 3trans-RSV*, which dissipates the energy by isomerization to cis-RSV. On the other hand, RSV neutral radical (trans-RSV(-H)•) was detected in laser flash photolysis experiments, evidencing an electron-transfer mechanism. The electron-transfer from 3Ptr* to trans-RSV is a barely feasible reaction, however, more favorable is the formation of trans-RSV(-H)• in a reaction between trans-RSV and Ptr radical cation (Ptr•+), which is produced during irradiation.The combination of experimental and theoretical approaches evidences the capability of trans-RSV to undergo energy-transfer (feasible by DFT calculations) and/or one-electron transfer pathways with 3Ptr*. These findings reveal the mechanisms involved in the interaction of trans-RSV and pterin excited states and provide information on the antioxidant action of resveratrol during photosensitized oxidation of biomolecules.