Effects Of Resveratrol Research Articles

Inhibition Effect of Resveratrol on Spontaneous Senescence of Human Bone Marrow Derived Mesenchymal Stem Cells

To explore whether Resveratrol (RSV) can inhibit the spontaneous senescence of human bone marrow-derived mesenchymal stem cells (MSC). MSC were serially cultured to passage 13 and passage 15 to establish model groups exhibiting spontaneous senescence, respectively. MSC at passage 13 and passage 15 were treated with 5 nmol/L RSV for 48 h to establish the RSV-treated groups. SA-β-Gal staining was used to detect cell senescence. MTT assay was used to detect cell proliferation. RT-PCR method was used to detect senescenceassociated telomerase activity. Western blot was used to detect the senescence-associated protein level of the phosphorylated-mTOR. SA-β-Gal staining showed that the senescent cells of MSC in RSV-treated group was significantly less than those in the model group (RSV group compared with model group at passage 13, P < 0.05; RSV group compared with model group at passage 15, P < 0.01). The cell proliferation ability of MSC in RSV-treated group was significantly higher than those in model group, at 72 h in passage 13, there was significant difference between RSV-treated group and model group (P < 0.05). RT-PCR results showed that the hTERT mRNA expression of MSC in RSV-treated group was higher than that in model group, which was significantly different between RSV-treated group and model group at passage 13 (P < 0.05). Western blot results showed that the phosphorylated (Ser2448)-mTOR level of MSC in RSV-treated group was lower than that in model group, which was significantly different between RSV-treated group and model group at passage 13 (P < 0.05). RSV can inhibit the spontaneous senescence of human MSC by mediating mTOR activity.

Outcome of resveratrol and resveratrol with donepezil combination on the β-amyloid plaques and neurofibrillary tangles in Alzheimer’s disease

The goal of this research was to study the effect of different doses of resveratrol (RS) and RS with donepezil (DPZ) on the deposition of amyloid beta (Aβ) and neurofibrillary tangles (NFTs) in colchicine-induced Alzheimer’s disease (AD) brain. The study included three months old male Albino Wistar rats and consisted of six animal groups: AD model (group 1), treatment groups, RS 10 mg/kg body weight (group 2), RS 20 mg/kg body weight (group 3), RS 10 mg/kg body weight along with DPZ 1 mg/kg body weight (group 6), prophylaxis groups, RS 10 mg/kg body weight (group 4) and RS 20 mg/kg body weight (group 5). In the treatment groups, RS was given for 7 consecutive days from the day of induction of AD, and in the prophylaxis groups, we started RS 7 days even before the induction of AD and continued for seven days after the induction. The number of Aβs and NFTs at the frontal region, cornu ammonis (CA) 1,2,3,4 and dentate gyrus regions of hippocampus were evaluated. The immunohistochemical analysis was performed by using mouse anti-β-amyloid antibody for the Aβ plaques and polyclonal rabbit anti-human tau for the tau-positive neurons. The present study observed the accumulation of Aβ plaques and tau-positive neurons in the AD model. However, their numbers were significantly decreased in the treatment groups (p < 0.001). The best results were observed when RS 10 mg was given prophylactically (p < 0.01) and RS along with DPZ (p < 0.001), suggesting the neuroprotective effect of RS and its synergistic effect with the DPZ.

Investigating the Molecular Mechanisms of Resveratrol in Treating Cardiometabolic Multimorbidity: A Network Pharmacology and Bioinformatics Approach with Molecular Docking Validation.

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. 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. 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. 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.

Preparation and characterization of agarose-sodium alginate hydrogel beads for the co-encapsulation of lycopene and resveratrol nanoemulsion

In the study, lycopene and resveratrol nanoemulsion hydrogel beads were prepared by using agarose‑sodium alginate as a carrier and the semi-interpenetrating polymer network technique, characteristics and morphologies were evaluated by scanning electron microscopy, fluorescence microscopy, rheological measurement. The synergistic antioxidant effect of lycopene and resveratrol was confirmed, the best synergistic antioxidant performance is achieved when the ratio of 1:1. To increase the solubility and improve the stability, the lycopene was prepared as solid dispersion added to the nanoemulsion. The encapsulation rate of lycopene and resveratrol reached 93.60 ± 2.94 % and 89.30 ± 1.75 %, respectively, and the cumulative release showed that the addition of agarose slowed down the release rate of the compound, which improves the applicability of lycopene and resveratrol and development of carriers for the delivery of different bioactive ingredients.

Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus

Rosiglitazone (RSG), as an insulin-sensitizing drug to treat type 2 diabetes mellitus (T2DM) is reported to decrease bone quality and increase bone fracture risk. The multiple off-target effects of Resveratrol (RSV), a natural specific agonist of Sirtuin1 (Sirt1) with pro-osteoblastogenesis and anti-adipogenesis effects, on bone loss in T2DM are still under discussion. In this study, successfully ovariectomized rats were fed with high-fat diet and STZ (HFD/STZ) to induced T2DM mice. RSV alone, RSG alone or co-administration of RSV and RSG were given orally to T2DM rats for 8 weeks to determine whether RSV administration had any prevention effect on T2DM osteoporosis. Bone mesenchymal stem cells (BMSCs) and bone marrow‑derived macrophages (BMMs) were cultured under high glucose condition and were induced to osteoblasts or adipocytes and osteoclasts, respectively. μCT and HE staining showed that in T2DM osteoporotic rats, RSV co-administration prevents RSG induced-bone loss. ELISA results confirmed that RSV suppressed osteoclast activity and promoted osteoblast activity in diabetic osteoporosis rats and RSG-administrated diabetic osteoporosis rats. In vitro study showed that RSV significantly reversed RSG induced inhibition on osteogenesis and promotion on adiopogenesis of BMSC under high glucose (HG). Moreover, RSV significantly reverse RSG induced osteoclast formation and mature under HG. Taken together, these findings uncover a previously unappreciated anti-osteoporosis effect of concomitant treatment with RSV in RSG-administrated diabetic rats, suggesting the clinical use of RSV as an adjuvant in the treatment of T2DM for preventing or reversing RSG administration-associated bone loss.

In silico investigation of lipid-based compounds implicated in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, currently incurable neurodegenerative disease that progressively affects the upper motor neurons in the brain and lower motor neurons in the spinal cord. A significant portion of patients exhibit abnormalities in lipid metabolism, which appear to contribute to denervation and subsequent motor neuron degeneration. This study aimed to computationally identify lipid-based compounds associated with ALS and elucidate their pathological and therapeutic roles to facilitate effective ALS diagnosis and treatment. The methodologies employed encompassed rational database searches, pharmacokinetic and target predictions, as well as docking and molecular dynamics simulations (MDS). The findings from the disease-to-lipids analysis identified 20 lipid compounds correlated with ALS, primarily categorized as potential inhibitors within the functional classes of vitamins, antibiotics, organic acids, and phytochemicals. Pharmacokinetic predictions revealed that only four compounds exhibited permeability across the blood&amp;ndash;brain barrier, namely 4-hydroxynonenal, resveratrol, rotenone, and valproic acid. Docking simulations indicated the highest binding affinity for 4-hydroxynonenal with alkaline ceramidase 2 (&amp;minus;4.516 kcal/mol), resveratrol with carbonic anhydrase 6 (&amp;minus;7.070 kcal/mol), rotenone with cytochrome P450 2C19 (&amp;minus;7.378 kcal/mol), and valproic acid with glutamate carboxypeptidase 2 (&amp;minus;5.629 kcal/mol). Furthermore, MDS and molecular mechanics/generalized born surface area calculations demonstrated the stability and binding energies of the complexes under simulated physiological conditions. In summary, further investigation is warranted to explore the synergistic effects of resveratrol and valproic acid in ALS, the mechanisms underlying 4-hydroxynonenal adduct-assisted aggregate formation of certain enzymes in ALS, and the impact of prolonged human exposure to rotenone from marine food sources (such as fish) on the development of ALS.

Anti-proliferative impact of resveratrol on gingival fibroblasts from juvenile hyaline fibromatosis

AimResveratrol is a natural polyphenolic compound with biological activities such as anti-inflammation and antioxidation. Its anti-fibrotic effect has been experimentally demonstrated in the pancreas and liver. This study aims to determine the anti-proliferative effect of resveratrol on fibroblasts obtained from hyperplastic gingival tissues from a patient diagnosed with Juvenile Hyaline Fibromatosis (JHF).Materials and methodsPrimary gingival fibroblast cell lines were obtained from gingival growth tissues by the gingivectomy of a patient with JHF. Gingival fibroblasts were treated with or without 3 different doses of resveratrol (50, 100, 200 µM). Cytotoxicity and cell proliferation were evaluated after 24, 48, and 72 h. Collagen, TGF, and CTGF were analyzed by ELISA in the 48-hour supernatants.ResultsAll three doses of resveratrol suppressed the proliferation of JHF gingival fibroblasts at 24 and 48 h without showing any cytotoxic effect compared to the control group (p < 0.0001). At 72 h, 100 and 200 µM resveratrol showed significantly less proliferation (p < 0.0001), less collagen, CTGF, and TGF- β (p < 0.001) than the control group.ConclusionResveratrol had a profound anti-proliferative effect on gingival fibroblasts obtained from gingival enlargements with JHF, suggesting that it can be used as a therapeutic to prevent excessive cell growth by suppressing collagen, CTGF, and TGF- β synthesis in the pathogenesis of hyperplasia.

Small Intestinal Toxicity Induced by Imidacloprid in Rats and The Protective Role of Berberine and Resveratrol

Imidacloprid is one of the insecticides in the neonicotinoid group. Resveratrol and berberine are powerful antioxidants known to alleviate the adverse effects of toxicity caused by oxidative stress. The aim of this study was to investigate the potential toxic effects of imidacloprid in the small intestinal tissues of rats and the protective effects of berberine and resveratrol against these effects. In the study, rats were divided into 7 groups. The groups were as follows: control group, resveratrol (20 mg/kg), berberine (100 mg/kg), imidacloprid (9 mg/kg.), imidacloprid plus resveratrol, imidacloprid plus berberine, imidacloprid plus resveratrol plus berberine. Test compounds were administered to rats by gavage for 28 days. At the end of the experimental period, antioxidant enzyme activities (SOD, CAT, GST, and GPx) and MDA levels were evaluated in small intestinal tissues obtained from rats. At the end of the 28-day treatment period, it was determined that MDA level increased and antioxidant enzyme activities decreased in the intestinal tissue of rats treated with imidacloprid. However, when imidacloprid plus resveratrol plus berberberine treated group, imidacloprid plus resveratrol treated group and imidacloprid plus berberine treated group were compared with imidocloprid group, a significant decrease in MDA level and a significant increase in antioxidant enzyme activities were observed. Histological findings support the protective properties of resveratrol and berberine. The results of this study showed that berberine and resveratrol, which were administered to prevent damage caused by imidacloprid in the small intestine tissue of rats, showed a positive effect and improved the studied parameters.

Evaluation of the Effects of Locally Applied Resveratrol and Cigarette Smoking on Bone Healing

Background: Bone healing is a complex process controlled by various mechanisms. It is known that cigarette smoking (CS) negatively affects bone healing by disrupting many of these mechanisms. In an effort to find ways to eliminate these negative effects caused by CS, studies have been conducted on various vitamins, antioxidants, and medications. Since high doses and repeated injections are required to increase the therapeutic effect of conventional drug applications, controlled drug delivery systems have been developed to avoid such problems. This study aimed to investigate the effects of resveratrol (RES), which has been made into a controlled drug delivery system, on bone healing in rats that were experimentally exposed to cigarette smoke to create a chronic smoking model. Methods: After establishing a chronic CS model by exposing the subjects to cigarette smoke of six cigarettes/day for four weeks, monocortical critical size defects of 3 mm (SD ± 0.02 mm) in diameter were created in the femur using a trephine bur. During the operation, the defects in RES groups were filled locally with a gel-formed solution of RES (50 µM) and Pluronic F-127 (14 µL). CS exposure was continued during the bone healing period after surgery. All groups were sacrificed one month after the operation, and femur samples were taken. Results: The obtained samples were examined by histomorphometric and immunohistochemical techniques; osteoblast count, new bone area, macroscopic filling score, vascularization, and proliferation were evaluated. Conclusion: The results of this study indicate that CS negatively affects bone healing and that local application of RES reduces this effect.

Identification and Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Networks in A2780 Cells Treated with Resveratrol.

Ovarian cancer (OC) is one of the most commonplace gynecological malignancies. This study explored the effects of resveratrol (RES) on OC cell proliferation and apoptosis. Proliferation activity was measured for A2780 cells treated with RES for 24 h and 48 h at concentrations of 0, 10, 25, 50, 75, 100, 150, 200, and 300 μM. RNA sequencing (RNA-seq) was performed to analyze the circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) expression spectrum. The differentially expressed genes included 460 circRNAs, 1988 miRNAs, and 1671 mRNAs, and they were subjected to analyses including Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment. We selected signaling pathways enriched in the cell processes by mRNA KEGG, comprehensively analyzed the circRNA-miRNA-mRNA regulatory network, and verified several miRNAs expressed in the regulatory network diagram using the quantitative real-time polymerase chain reaction. The data showed that the cell proliferation of A2780 cells treated with RES for 24 h or 48 h decreased with increasing concentrations of RES. The circRNA-miRNA-mRNA regulatory network that we constructed provides new insights into the ability of RES to inhibit cell proliferation and promote apoptosis in A2780 cells.

Resveratrol ameliorates pathological fibrosis of the myodural bridge by regulating the SIRT3/TGF-β1/Smad pathway

PurposePathological fibrosis of the myodural bridge (MDB) affects cerebrospinal fluid circulation. However, no optimal drug treatments are available. We aimed to explore the antifibrotic effect of resveratrol on bleomycin-induced pathological fibrosis of the MDB and its underlying mechanisms. MethodsGenes common to the potential targets of resveratrol were determined using network pharmacology, genes related to muscle and tendon fibrosis were acquired from the GeneCards database, and genes related to MDB development were determined using Venny. These genes were considered potential resveratrol treatment targets in bleomycin-induced pathological fibrosis of the MDB and were annotated using bioinformatics methods. We validated the intersected genes using quantitative real-time polymerase chain reaction (qRT-PCR) and performed molecular docking analysis to calculate the binding activity between the target gene and resveratrol. Hematoxylin and eosin and Masson staining were used to detect the morphological changes in bleomycin-induced fibrosis of the MDB following resveratrol treatment. We used qRT-PCR and immunohistochemistry to evaluate the expression of the sirtuin 3 (SIRT3)/transforming growth factor-β1 (TGF-β1)/Smad pathway and the profibrotic markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ. ResultsThrough network pharmacology and bioinformatics analyses, we identified four core intersected genes, and SIRT3 expression was validated using qRT-PCR. Molecular docking analysis revealed that resveratrol had good binding affinity for SIRT3. Resveratrol ameliorated morphological abnormalities in bleomycin-induced pathological fibrosis of the MDB by inhibiting fibroblast activation and excessive collagen fiber deposition. Resveratrol exerted its antifibrotic effect by regulating the SIRT3/TGF-β1/Smad pathway. ConclusionResveratrol has an antifibrotic effect in bleomycin-induced pathological fibrosis of the MDB in vivo and may be considered a novel therapeutic strategy.

Effect and mechanism of resveratrol on ferroptosis mediated by p53/SLC7A11 in oral squamous cell carcinoma

ObjectiveResveratrol (Res) is a natural phytoestrogen with antitumor activity. This study sought to investigate the role of Res in ferroptosis in oral squamous cell carcinoma (OSCC).MethodsNormal human oral keratinocyte (HOK)/oral OSCC (CAL-27/SCC-9) cell lines were treated with different doses of Res. Res toxicity was determined by MTT assay, with half maximal inhibitory concentration values of Res on CAL-27 and SCC-9 cells calculated. Cell viability/colony formation efficiency/migration/invasion/cycle were assessed by CCK-8/colony formation assay/transwell assay/flow cytometry. The expression of p53 protein in the nucleus and cytoplasm, glutathione peroxidase 4 (GPX4) expression, and SLC7A11 messenger RNA (mRNA) and protein expression levels were determined by Western blot and RT-qPCR. Fe2+ content, reactive oxygen species (ROS) level, reduced glutathione (GSH), and lactate dehydrogenase (LDH) release were assessed.ResultsMedium- to low-dose Res had no toxic effect on HOK cells, while high-dose Res markedly reduced HOK cell viability. Res significantly suppressed the viability of OSCC cells (CAL-27 and SCC-9). Res inhibited OSCC cell colony formation/migration/invasion, and induced G1 phase arrest. Res caused the translocation of p53 protein to the nucleus, obviously increased Fe2+ content, ROS level and LDH release, decreased GSH content and GPX4 protein expression, and induced ferroptosis. Down-regulation of p53 partially reversed the inhibitory effects of Res on CAL-27 cell malignant behaviors. Res inhibited SLC7A11 transcription by promoting p53 entry into the nucleus. SLC7A11 overexpression negated the the regulatory effects of p53 knockout on the role of Res in OSCC cell malignant behaviors and ferroptosis.ConclusionRes accelerated ferroptosis and inhibited malignant behaviors in OSCC cells by regulating p53/SLC7A11.

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial

BackgroundThis study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS).MethodsFifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial.ResultsResveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05).ConclusionsThese findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction.Trial registration numberhttp://www.irct.ir; IRCT20221106056417N1; 2023 February 09.

Effects of Nasal Solution Incorporating Resveratrol and Carboxymethyl-Β-Glucan in Preschool Non-Atopic Children with Wheezing.

Upper respiratory tract infections (URTI) account for more than 80% of wheezing episodes in children with a high incidence of hospitalization in preschool age. Most children with symptoms of wheezing during an URTI are usually non-atopic. As the majority of wheezing episodes resulting from URTI are attributed to viral triggers, several studies have suggested the potential anti-inflammatory and antiviral properties of resveratrol. This study aims to identify the effect of resveratrol for pediatric non-atopic patients with recurrent wheezing triggered by URTIs. We conducted a prospective single-blind study to assess the effectiveness of a short course of nasal solutions incorporating resveratrol and carboxymethyl-β-glucan, administered for 7 days at the onset of URTIs, compared to standard nasal lavage with 0.9% saline solution. A total of 19 patients entered the active group, 20 patients were assigned to the placebo group. The comparison of overall wheezing days (p < 0.001), mean wheezing days per month (p < 0.01), and wheezing episodes per patient (p < 0.001) in the two groups showed a significant reduction in the group receiving resveratrol compared with the placebo group, with less hospital access (p < 0.001) and oral corticosteroid administration (p < 0.01). Our findings seem to suggest that, in non-atopic children with recurrent wheezing secondary to URTIs, nasal resveratrol could be effective to prevent or reduce the occurrence of wheezing, when started from the onset of upper airway symptoms.

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats

ObjectiveThe hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. MethodsThirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Resultsα-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. ConclusionResveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

Antitumor Effects of Resveratrol Opposing Mechanisms of Helicobacter pylori in Gastric Cancer.

Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer.

Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression.

Resveratrol is a non-flavonoid polyphenol that shows promise in reducing pro-inflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events. To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease (CAD). A thorough search was conducted in databases (Cochrane Library, ProQuest, PubMed, LILACS, ScienceDirect, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane RoB 2.0. Heterogeneity of results was explored by meta-regression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis. Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction (95% CI: -0.73 to -0.20; P=0.0005) in tumor necrosis factor-α (TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6 (IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase (eNOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and eNOS elevation was deemed low. Resveratrol reduces TNF-α in individuals at risk for CAD, specifically 15 mg per day. However, its usefulness in patients with confirmed CAD is limited due to factors such as age, high blood pressure, and insufficient dosage. Due to the small sample size, the reduction of IL-6 is inconclusive. Animal studies suggest that resveratrol enhances endothelial function by increasing eNOS. (PROSPERO registration No. CRD42023465234).

Expression of Concern: The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation.

Expression of Concern: The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation.

Microbiota and Resveratrol: How Are They Linked to Osteoporosis?

Osteoporosis (OP), which is characterized by a decrease in bone density and increased susceptibility to fractures, is closely linked to the gut microbiota (GM). It is increasingly realized that the GM plays a key role in the maintenance of the functioning of multiple organs, including bone, by producing bioactive metabolites such as short-chain fatty acids (SCFA). Consequently, imbalances in the GM, referred to as dysbiosis, have been identified with a significant reduction in beneficial metabolites, such as decreased SCFA associated with increased chronic inflammatory processes, including the activation of NF-κB at the epigenetic level, which is recognized as the main cause of many chronic diseases, including OP. Furthermore, regular or long-term medications such as antibiotics and many non-antibiotics such as proton pump inhibitors, chemotherapy, and NSAIDs, have been found to contribute to the development of dysbiosis, highlighting an urgent need for new treatment approaches. A promising preventive and adjuvant approach is to combat dysbiosis with natural polyphenols such as resveratrol, which have prebiotic functions and ensure an optimal microenvironment for beneficial GM. Resveratrol offers a range of benefits, including anti-inflammatory, anti-oxidant, analgesic, and prebiotic effects. In particular, the GM has been shown to convert resveratrol, into highly metabolically active molecules with even more potent beneficial properties, supporting a synergistic polyphenol-GM axis. This review addresses the question of how the GM can enhance the effects of resveratrol and how resveratrol, as an epigenetic modulator, can promote the growth and diversity of beneficial GM, thus providing important insights for the prevention and co-treatment of OP.

Effects of resveratrol on biochemical and structural outcomes in osteoarthritis: A systematic review and meta-analysis of preclinical studies

Background and objectiveOsteoarthritis (OA) is the most common age-related disease of joints with increasing global prevalence. Persistent inflammation within the joint space is speculated to be the cause of OA. Resveratrol is an anti-inflammatory and antioxidant compound which can influence cartilage metabolism through multiple signalling pathways. This systematic review and meta-analysis aimed to summarize the therapeutic effects of resveratrol in animal models of OA. MethodsA comprehensive literature search was performed using PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Wanfang and VIP databases in May 2023. Studies on the effects of resveratrol in animal models of OA written in English or Mandarin, published from the inception of databases until the date of the search were considered. ResultsFifteen eligibility studies were included and analysed. Resveratrol was shown to inhibit the secretion of interleukin-1β, tumour necrosis factor-α, interleukin-6, nitric oxide, and apoptosis of articular chondrocytes. Joint structure as indicated by Mankin scores was restored with resveratrol in animal OA models. ConclusionResveratrol is a potential therapeutic agent for OA based on animal studies. Further evidence from well-planned human studies would be required to validate its clinical efficacies.