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In the present study, nanoliposome coated with gelatin containing resveratrol (RV) was prepared to maintain its antioxidant and anticancer properties in laboratory conditions. Thin-layer method for the synthesis of nanoliposomes containing RV coated with gelatin (RGNL) and nanoliposome RV carriers was used. Fourier transform infrared spectroscopy confirmed the formation of the RGNL inclusion complex. The formulation of RV-loaded nanoliposomes showed size (79 nm). The size of the coated nanoparticles was 91 nm increased, and also, the zeta potential became more positive with increasing gelatin concentration. The encapsulation efficiency of the coated NLPs was measured to be 76.16%. The results showed that the gelatin coating stabilizes the nanoliposome and RV and reduces the release rate of RV. The cititoxicity of the nanoparticles was evaluated, the biocompatibility of the constructed system was excellent, and its cytotoxicity in breast cancer cells was significantly increased. In the present study, liposome thin film hydration method was used to synthesize gelatin-coated liposome containing RV. [ABSTRACT FROM AUTHOR]

The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 μM). The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, mitochondrial swelling, mitochondrial cytochrome c release, and mitochondrial membrane potential (MMP) in HCM cells were investigated. Also, the expression of Bax and Bcl-2, caspace-3 activity, and apoptosis were assessed. The present investigation revealed that AlP substantially increased the level of ROS and decreased SOD activation, which were significantly modulated by resveratrol in a dose-dependent manner. Moreover, AlP induced an elevation of mitochondrial swelling, cytochrome c release, and MMP collapse. Co-administration of resveratrol significantly reduced above mitochondrial markers. AlP also significantly upregulated BAX and downregulated Bcl-2 expression, elevated caspace-3 activity, and apoptosis. Resveratrol co-administration was able to meaningfully modulate the mentioned parameters and finally reduce apoptosis. In conclusion, resveratrol, via its pleotropic properties, significantly demonstrated cytoprotective effects on HCM cytotoxicity induced by AlP. [ABSTRACT FROM AUTHOR]

With recent advances in neonatal intensive care, preterm infants are surviving into adulthood. Nonetheless, epidemiological data on the health status of these preterm infants have begun to reveal a worrying theme; prematurity and the supplemental oxygen therapy these infants receive after birth appear to be risk factors for kidney disease in adulthood, affecting their quality of life. As the incidence of chronic kidney disease and the survival time of preterm infants both increase, the management of the hyperoxia-induced renal disease is becoming increasingly relevant to neonatologists. The mechanism of this increased risk is currently unknown, but prematurity itself and hyperoxia exposure after birth may predispose to disease by altering the normal trajectory of kidney maturation. This article reviews altered renal reactivity due to hyperoxia, the possible mechanisms of renal injury due to hyperoxia, and the role of resveratrol in renal injury. Key Points Premature infants commonly receive supplementary oxygen. Hyperoxia can cause kidney damage via signal pathways. We should reduce the occurrence of late sequelae. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies scrutinize how NETosis (a unique cell death mechanism of neutrophil), impacts thrombosis patients with essential thrombocythemia (ET). This research evaluates the susceptibility of ET neutrophils to form NETs and tests two potential inhibitors, resveratrol (RSV) and tetrahydroisoquinoline (THIQ), in vitro. Methods: Platelet‐rich plasma from low‐risk ET patients was used, along with neutrophils from both patients and controls. NET formation assays, with or without RSV and THIQ treatment after LPS stimulation, were conducted in a CO2 incubator. Evaluation included flow cytometry and fluorescence microscopy for NET formation and ELISA for TNFα, IL8, and vWF:Ag levels in patient and control plasma. Results: Neutrophils from ET patients released more NETs than controls, confirmed by flow cytometry and fluorescence microscopy. Additionally, patients had significantly higher plasma levels of IL8 and TNFα compared to controls, while RSV was more effective than THIQ in reducing NETosis rates in these patients. Conclusions: In ET patients, a platelet counts over 1 million indicates the need for preventive treatment against thrombotic events. Similarly, in this study, RSV and THIQ significantly reduced the rate of NETosis in ET patients with higher platelet counts, and this role was more prominent in the case of the second inhibitor (RSV). [ABSTRACT FROM AUTHOR]

Resveratrol is a bioactive polyphenolic compound mainly present in grapes and red wine. It is known to exert beneficial effects in various experimental settings, such as antioxidant, anti-inflammatory, anti-proliferative, and immunoregulatory. Accumulating evidence suggests these health benefits might be, at least partially, attributed to resveratrol's role in protecting the intestinal barrier, regulating the gut microbiome, and inhibiting intestinal inflammation. The purpose of this review is to examine the bioactivities of resveratrol in disease prevention and health promotion from the standpoint of regulating the gut microbiome. The article aims to provide additional insight into the potential applications of resveratrol in the food and nutraceutical industry. [ABSTRACT FROM AUTHOR]

BACKGROUND METHODS RESULTS CONCLUSION Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non‐flavonoid polyphenol, possesses anti‐cancer properties. It has been shown to inhibit arecoline‐induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline‐induced oral cancer.Data mining identified common targets and hub targets of resveratrol in arecoline‐induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments.Sixty‐one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial‐mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down‐regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis.Resveratrol inhibits the arecoline‐induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Resveratrol is a polyphenol known to have metabolic as well as circadian effects. However, there is little information regarding the metabolic and circadian effect of resveratrol on muscle cells. We sought to investigate the metabolic impact of resveratrol throughout the circadian cycle to clarify the associated signaling pathways. C2C12 myotubes were incubated with resveratrol in the presence of increasing concentrations of glucose, and metabolic and clock proteins were measured for 24 h. Resveratrol led to SIRT1, AMPK and PP2A activation. Myotubes treated with increasing glucose concentrations showed higher activation of the mTOR signaling pathway. However, resveratrol did not activate the mTOR signaling pathway, except for P70S6K and S6. In accordance with the reduced mTOR activity, resveratrol led to advanced circadian rhythms and reduced levels of pBMAL1 and CRY1. Resveratrol increased myogenin expression and advanced its rhythms. In conclusion, resveratrol activates the SIRT1-AMPK-PP2A axis, advances circadian rhythms and induces muscle development. [ABSTRACT FROM AUTHOR]

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 μmol) and catechol (100 μmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that resveratrol can relieve exercise-induced fatigue and protect the heart, but its action mechanism needs further study. OBJECTIVE: To explore the protective effect and regulatory mechanism of resveratrol on ventricular remodeling in exercise-induced fatigue rats. METHODS: Totally 48 male Sprague-Dawley rats were randomly divided into four groups, with 12 rats in each group. Rats in the blank control group were fedconventionally. After one week of adaptive training, rats in the exercise-related fatigue group and exercise-related fatigue with resveratrol supplement group were trained by 6-week weight-bearing swimming (5% body mass lead block fixed in the tail, 70%-80% maximal oxygen uptake intensity), 6 days a week, 60 minutes a day. Rats in the resveratrol supplement group and exercise-related fatigue with resveratrol supplement group were given resveratrol (50 mg/kg per day) by gavage one hour after exercise intervention. Blank control group and exercise-related fatigue group were given the same volume of 2% dimethyl sulfoxide, 6 days a week, once a day for 6 weeks. The body mass and heart mass of the rats were measured 24 hours after the last intervention. Plasma creatine kinase isoenzyme, cardiac troponin 1, pyruvate dehydrogenase and uncoupling protein 1 levels in myocardial tissue were determined by ELISA. The mRNA expression levels of ventricular remodeling-related factor Foxp1, transforming growth factor β1 and endothelin 1 were detected by RT-PCR. RESULTS AND CONCLUSION: Compared with the blank control group, the body mass of rats decreased and the heart mass increased in the exercise-related fatigue group (P < 0.05). Compared with the exercise-related fatigue group, the body mass and heart mass of the rats reduced in the exercise-related fatigue with resveratrol supplement group (P < 0.05). Compared with the blank control group, the levels of creatine kinase isoenzyme, cardiac troponin 1 and uncoupling protein 1 increased (P < 0.01), and the level of pyruvate dehydrogenase decreased (P < 0.01) in the exercise-related fatigue group. Compared with the exercise-related fatigue group, the levels of creatine kinase isoenzyme, myocardial troponin 1 and uncoupling protein 1 decreased (P < 0.05), and the level of pyruvate dehydrogenase increased (P < 0.05) in the exercise-related fatigue with resveratrol supplement group. Compared with the blank control group, the expression of the Foxp1 gene decreased (P < 0.01), and the expression of transforming growth factor β1 and endothelin 1 gene increased (P < 0.01) in the myocardium of the exercise-related fatigue group. Compared with the exercise-related fatigue group, the expression of the Foxp1 gene in the myocardium of the exercise-related fatigue with resveratrol supplement group increased (P < 0.01), while the expression of the transforming growth factor β1 and endothelin 1 gene decreased (P < 0.05). It is suggested that exercise-induced fatigue can promote myocardial adaptability and cause compensatory hypertrophy. Resveratrol can improve myocardial injury and energy metabolism and delay ventricular energy remodeling in rats. This effect may be related to the regulation of Foxp1/ transforming growth factor β1/endothelin 1 signaling pathway. [ABSTRACT FROM AUTHOR]

Piceatannol is a natural compound found in plants and can be derived from resveratrol. While resveratrol has been extensively researched for its effects and how the body processes it, there are concerns about its use. These concerns include its limited absorption in the body, the need for specific dosages, potential interactions with other drugs, lack of standardization, and limited clinical evidence to support its benefits. Interestingly, Piceatannol, another compound derived from resveratrol, has received less attention from researchers but appears to offer advantages. It has better bioavailability and seems to have a more favorable therapeutic profile compared to resveratrol. Surprisingly, no previous attempts have been made to explore or predict the metabolites of piceatannol when it interacts with the enzyme cytochrome P450. This study aims to fill that gap by predicting how piceatannol is metabolized by cytochrome P450 and assessing any potential toxicity associated with its metabolites. This research is interesting because it's the first of its kind to investigate the metabolic fate of piceatannol, especially in the context of cytochrome P450. The findings have the potential to significantly contribute to the field of piceatannol research, particularly in the food industry where this compound has applications and implications. [ABSTRACT FROM AUTHOR]

Resveratrol is a natural polyphenol with important anti-inflammatory and antioxidant properties for treating cardiometabolic disorders. Therefore, the present meta-analysis aimed to review and investigate the oral resveratrol supplementation effects on metabolic syndrome (MetS) components. The bibliographic search was carried out in 2023 in the following databases: PubMed, Web of Science, and Scopus. Studies that investigated the oral resveratrol effects on the MetS parameters were included. Statistical analyses were performed using RevMan Software V.5.3. The main findings showed that resveratrol significantly decreased systolic and diastolic blood pressure while having no significant effects on waist circumference and high-density lipoprotein levels. In addition, glucose level was significantly decreased in the subgroup of studies reporting change from baseline means, although the overall effect was not statistically significant (p = 0.81), while triglyceride levels were increased after the treatment period. In conclusion, the present meta-analysis evidenced the potential therapeutic effect of resveratrol on improving some MetS features, especially regarding systolic blood pressure, diastolic blood pressure, and glucose reduction; however, the results are still borderline and sometimes controversial, which might be justified by the methodological and statistical heterogeneity of the studies, with the latter varying from 17 to 57%. [ABSTRACT FROM AUTHOR]

Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the demand for resveratrol exceeds the capacity of plant extraction methods, necessitating alternative production strategies. Microbial synthesis offers several advantages over plant-based approaches and presents a promising alternative. Yarrowia lipolytica stands out among microbial hosts due to its safe nature, abundant acetyl-CoA and malonyl-CoA availability, and robust pentose phosphate pathway. This study aimed to engineer Y. lipolytica for resveratrol production. The resveratrol biosynthetic pathway was integrated into Y. lipolytica by adding genes encoding tyrosine ammonia lyase from Rhodotorula glutinis, 4-coumarate CoA ligase from Nicotiana tabacum, and stilbene synthase from Vitis vinifera. This resulted in the production of 14.3 mg/L resveratrol. A combination of endogenous and exogenous malonyl-CoA biosynthetic modules was introduced to enhance malonyl-CoA availability. This included genes encoding acetyl-CoA carboxylase 2 from Arabidopsis thaliana, malonyl-CoA synthase, and a malonate transporter protein from Bradyrhizobium diazoefficiens. These strategies increased resveratrol production to 51.8 mg/L. The further optimization of fermentation conditions and the utilization of sucrose as an effective carbon source in YP media enhanced the resveratrol concentration to 141 mg/L in flask fermentation. By combining these strategies, we achieved a titer of 400 mg/L resveratrol in a controlled fed-batch bioreactor. These findings demonstrate the efficacy of Y. lipolytica as a platform for the de novo production of resveratrol and highlight the importance of metabolic engineering, enhancing malonyl-CoA availability, and media optimization for improved resveratrol production. [ABSTRACT FROM AUTHOR]

Simple Summary: We have made the first finding of resveratrol in the leaves of C. sumatranum and identified that all Cratoxylum extracts are toxic to cancer cell lines but are only slightly toxic to PBMCs at the cell level and are not harmful to DNA levels. All the studied extracts induced both apoptosis and necrosis in cancer cell lines, as evidenced by a significant decrease in DNA quantity in the S and G2-M phases. C. sumatranum extracts did not induce apoptosis and necrosis in PBMCs and showed a high percentage of cell viability, but the ethanolic extracts of the two subspecies of C. formosum induced apoptosis and necrosis in PBMCs. These data confirmed that the three studied Cratoxylum samples have inhibition activity on the growth of cancer cells and low toxicity to PBMCs. C. sumatranum showed better biological activity than C. formosum leaf extracts, which may be due to the combined activity of substances such as α-amyrin and resveratrol, which are proposed to be of a high quantity and similar function as anti-inflammatory substances. All studied samples deserve clinical trials for further application to plant-derived products, especially C. sumatranum. This knowledge renders the plants more useful for human health than commonly used as vegetables, cooking and traditional medicines. The plants can be used in other modified forms such as functional foods, supplements, drugs and nutraceuticals. Cratoxylum formosum ssp. formosum (Cff), C. formosum ssp. pruniflorum (Cfp), and C. sumatranum (Cs) were investigated for phytochemical analysis. Toxicity testing, programmed cell death, and cell cycle arrest were tested on CHL-1, HCT-116, and HepG2 cancer cell lines, and human normal PBMCs. The results are revealed in the following order. The phytochemical percentages varied in each species, the quantity and concentration of α-amyrin and resveratrol were 0.038 mg/g and 0.955 mg/mL, and 0.064 mg/g and 0.640 mg/mL. The most studied Cratoxylum extracts showed IC50 values in PBMCs and cancer cell lines except for the hexane Cff and ethanol Cfp extracts. All studied extracts did not induce DNA breaks in PBMCs but caused significant DNA breaks in the cancer cell lines. All studied extracts induced both apoptosis and necrosis in cancer cell lines, and the DNA quantity in the S and G2-M phases decreased significantly but did not induce apoptosis and necrosis in PBMCs. Except for the ethanolic extracts of Cff and Cfp that induced PBMCs apoptosis and necrosis, these data confirmed that the three studied Cratoxylum samples have inhibiting properties for the growth of cancer cells and low toxicity to PBMCs. Cs showed more toxicity to cancer cell lines than Cf and cisplatin. [ABSTRACT FROM AUTHOR]

Simple Summary: Excessive synthesis of liver lipids can lead to various diseases, such as fatty liver disease and hyperlipidaemia. This study investigated the effects of resveratrol (Res) and (-)-Epigallocatechin-3-gallate (EGCG) on lipid synthesis in liver cells. The results showed that both resveratrol and EGCG can inhibit cholesterol synthesis in liver cells by activating Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK). Therefore, this study can provide a reference for the study of lipid metabolism. The purpose of this study was to explore the effects of Res and EGCG on cell growth, cellular antioxidant levels, and cellular lipid metabolism in hepatocytes. In this experiment, leghorn male hepatoma (LMH) cells were used as hepatocytes. The results showed that 6.25–25 μM Res and EGCG had no adverse effects on cell viability and growth. Meanwhile, with the increasing dosage of Res and EGCG, the contents of total cholesterol (TC), total glyceride (TG), and malondialdehyde (MDA) in hepatocytes decreased significantly (p < 0.05), while the contents of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT) increased significantly (p < 0.05). In addition, western blot results showed that Res and EGCG could significantly increase the expression of p-AMPK protein and reduce the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) protein in hepatocytes (p < 0.05). Moreover, q-PCR results showed that with the increase in Res and EGCG, the expression of cholesterol- and fatty acid synthesis-related genes decreased significantly (p < 0.05). In conclusion, Res and EGCG can increase the antioxidant capacity of hepatocytes and reduce the synthesis of TC and TG in hepatocytes by activating AMPK, thereby regulating lipid metabolism in hepatocytes. [ABSTRACT FROM AUTHOR]

Resveratrol butyrate esters (RBEs) are novel resveratrol (RSV) derivatives synthesized by esterification with butyric acid. In addition, ED2 (3,4′‐di‐O‐butanoylresveratrol) and ED4 (3‐O‐butanoylresveratrol) in different structural monomers of RBEs have been shown as abundant cellular antioxidants. Therefore, this study was performed to apply RSV and its esterified derivatives in the manufacturing and preservation of Chinese sausage, investigated these ingredients' impact on the sausage's physicochemical properties and changes during storage, and evaluated the feasibility of minimizing sodium nitrite's use in sausage production. This study showed that a high dose (500 ppm) of ED2 and ED4 (with the added 25 mg/kg of sodium nitrite) were effective in maintaining the color of sausages and extending the shelf‐life for at least 30 days in refrigerated storage, which was consistent with 150 mg/kg sodium nitrite. Altogether, ED2 or ED4 can potentially reduce sodium nitrite usage by 83% while preventing lipid oxidation and antimicrobial effects, thereby effectively maintaining sausage product stability. Hence, RBEs facilitate the development of natural functional food additives that provide antioxidant benefits products for all ages of people, namely widely used in any processed food that requires antioxidant functionality or as dietary supplements. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterised by the progressive loss of specific neuronal cell populations due to multifactorial factors, including neurochemical and immunological disturbances. Consequently, patients can develop cognitive, motor and behavioural dysfunctions, which lead to impairments in their quality of life. Over the years, studies have reported on the neuroprotective properties inherent in phenolic compounds. Therefore, this review highlights the most recent scientific findings regarding phenolic compounds as promising neuroprotective molecules against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This study evaluated if miR-34a/SIRT1 signalling mediates the anti-hepatosteatotic effect of resveratrol (RSV) in high-fat-diet (HFD)-fed rats. Rats were divided into seven groups (n = 6/each) as control, control + miR-34a agomir negative control, HFD, HFD + miR-34a, HFD + RSV, HFD + RSV + Ex-527 (a SIRT1 inhibitor), and HFD + RSV + miR-34a agomir. After 8 weeks, RSV suppressed dyslipidemia, lowered fasting glucose and insulin levels, improved insulin sensitivity, and prevented hepatic lipid accumulation. These effects were associated with hepatic downregulation of SREBP1 and SREBP2, upregulation of PPARα, and acetylation of Nrf2 (activation) and NF-κβ p65 (inhibition). Also, RSV reduced the transcription of miR-34a and increased the nuclear localisation of SIRT1 in the livers, muscles, and adipose tissues of HFD-fed rats. All these effects were prevented by EX-527 and miR-34a agmir. In conclusion, RSV prevents HFD-induced insulin resistance and hepatic steatosis by suppressing miR-34a-induced activation of SIRT1. [ABSTRACT FROM AUTHOR]

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to investigate the therapeutic effects of astaxanthin (AST) and resveratrol (RVT) on multiorgan damage in an animal model of the supraceliac aortic ischemia-reperfusion (I/R). Methods In this study, 28 rats (n = 7/group), 200 to 250 g in weight, were randomized to four groups (1: Sham, 2: Control + I/R, 3: AST + I/R, and 4: RVT + I/R). Following the abdominal incision, aortic dissection was performed in the sham group without injury. Other groups underwent I/R injury via supraceliac aortic clamping (20 minutes) and reperfusion. The rats were administered olive oil (3 mL/kg) orally for 2 weeks before and 1 week after the laparotomy. Additionally, oral AST (10 mg/kg) or RVT (50 mg/kg) was given to the study groups. All rats were sacrificed on the 3rd week of the experiment after blood samples were taken for analysis. Multiple rat tissues were removed. Results We found that RVT increased total antioxidant status (TAS) and superoxide dismutase (SOD) levels, and decreased total oxidant status (TOS), oxidative stress index (OSI), myeloperoxidase (MPO), and malondialdehyde (MDA) levels, while AST increased the levels of TAS, decreased TNF-α, MDA, TOS, and OSI (p <0.05). Pathological investigations of the rat tissues revealed that both AST and RVT ameliorated tissue damage and apoptosis. Conclusion Our study suggests that AST and RVT might show therapeutic effects against oxidative tissue damage and apoptosis in an animal model of aortic I/R. Further studies are required. Key Points Major congenital heart diseases are at high risk of multiorgan damage. Re-establishment of blood flow may result in ischemia-reperfusion (I/R) injury. Astaxanthin and resveratrol may have therapeutic effects against I/R injury. [ABSTRACT FROM AUTHOR]

Objectives Our previous study showed that resveratrol (Res) attenuates apoptosis and mitochondrial dysfunction in alveolar epithelial cell injury induced by hyperoxia by activating the SIRT1/PGC-1α signaling pathway. In the present study, we investigated whether Res protects against hyperoxia-induced lung injury in neonatal rats by activating SIRT1/PGC-1α signaling pathway. Methods Naturally delivered neonatal rats were randomly divided into six groups: normoxia + normal saline, normoxia + dimethyl sulfoxide (DMSO), normoxia + Res, hyperoxia + normal saline, hyperoxia + DMSO, and hyperoxia + Res. Lung tissue samples were collected on postnatal days 1, 7, and 14. Hematoxylin and eosin staining was used to evaluate lung development. Dual-immunofluorescence staining, real-time polymerase chain reaction, and western blotting were used to evaluate the levels of silencing information regulator 2-related enzyme 1 (SIRT1), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), nuclear respiratory factor 1 (Nrf1), Nrf2, transcription factor A (TFAM) and citrate synthase, the number of mitochondrial DNA (mtDNA) and mitochondria, the integrity of mtDNA, and the expression of TFAM in mitochondria. Results We found that hyperoxia insulted lung development, whereas Res attenuated the hyperoxia lung injury. Res significantly upregulated the levels of SIRT1, PGC-1α, Nrf1, Nrf2, TFAM, and citrate synthase; promoted TFAM expression in the mitochondria; and increased the copy number of ND1 and the ratio of ND4/ND1. Conclusion Our data suggest that Res attenuates hyperoxia-induced lung injury in neonatal rats, and this was achieved, in part, by activating the SIRT1/PGC-1α signaling pathway to promote mitochondrial biogenesis. Key Points Hyperoxia insulted lung development in neonatal rats. Resveratrol promoted mitochondrial biogenesis to attenuate hyperoxia lung injury in neonatal rats. Resveratrol, at least in part, promoted mitochondrial biogenesis by activating the SIRT1/PGC-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Mammary gland tumors are prevalent in canines, posing significant threats to their health and survival. With the limited efficacy of traditional treatments due to the high heterogeneity of these tumors, there is a growing focus on exploring new therapeutic avenues. Natural Killer cell-based immunotherapy has emerged as a promising approach in anti-tumor treatment, prompting research into optimization strategies. Resveratrol, a natural polyphenol compound, shows potential in regulating Natural Killer cell immune activity. However, the specific impact of Resveratrol-activated Natural Killer cells on canine mammary tumors and their therapeutic potential remain unclear. This study investigated the therapeutic potential of Resveratrol-activated Natural Killer cells in treating canine mammary tumors. Using various assays, including wound healing and flow cytometry, the study examined the impact of Resveratrol-pretreated Natural Killer cells on tumor cells in vitro and in a mouse model. The results demonstrate that Resveratrol enhances Natural Killer cells' ability to induce tumor cell death and inhibit tumor growth, migration, and invasion. Moreover, Resveratrol boosts Natural Killer cell recruitment to other immune cells in the body. Overall, Resveratrol shows promise in enhancing Natural Killer cell-mediated anti-tumor effects, suggesting a potential avenue for optimizing immunotherapy for canine mammary tumors and improving treatment efficacy. In order to explore the therapeutic effect of Resveratrol (Res)-activated Natural Killer (NK) cells on canine mammary tumors, this study employed a range of assays, including wound healing, colony formation, Transwell, flow cytometry, and Western blot experiments, to investigate the impact of Res-pretreated NK cells on canine mammary tumor cells in vitro. Additionally, a tumor-bearing mouse model was utilized to further analyze the therapeutic effects of Res-pretreated NK cells in vivo. The results showed that Res enhances the capacity of NK cells to induce apoptosis, pyroptosis, and ferroptosis in canine breast tumor cells, while also augmenting their influence on the migration, invasion, and epithelial-mesenchymal transition of these cells. Furthermore, pretreatment of NK cells with Res significantly amplified their inhibitory effect on breast tumor growth in vivo and promoted tumor tissue apoptosis. Additionally, Res enhanced the recruitment of NK cells to other immune cells in the body. In summary, Res has been shown to enhance the anti-breast-tumor effect of NK cells both in vitro and in vivo, offering a new avenue for optimizing immunotherapy for canine breast tumors. [ABSTRACT FROM AUTHOR]

One aspect of ovarian tumorigenesis which is still poorly understood is the tumor–stroma interaction, which plays a major role in chemoresistance and tumor progression. Cancer-associated fibroblasts (CAFs), the most abundant stromal cell type in the tumor microenvironment, influence tumor growth, metabolism, metastasis, and response to therapy, making them attractive targets for anti-cancer treatment. Unraveling the mechanisms involved in CAFs activation and maintenance is therefore crucial for the improvement of therapy efficacy. Here, we report that CAFs phenoconversion relies on the glucose-dependent inhibition of autophagy. We show that ovarian cancer cell-conditioning medium induces a metabolic reprogramming towards the CAF-phenotype that requires the autophagy-dependent glycolytic shift. In fact, 2-deoxy-D-glucose (2DG) strongly hampers such phenoconversion and, most importantly, induces the phenoreversion of CAFs into quiescent fibroblasts. Moreover, pharmacological inhibition (by proline) or autophagy gene knockdown (by siBECN1 or siATG7) promotes, while autophagy induction (by either 2DG or rapamycin) counteracts, the metabolic rewiring induced by the ovarian cancer cell secretome. Notably, the nutraceutical resveratrol (RV), known to inhibit glucose metabolism and to induce autophagy, promotes the phenoreversion of CAFs into normal fibroblasts even in the presence of ovarian cancer cell-conditioning medium. Overall, our data support the view of testing autophagy inducers for targeting the tumor-promoting stroma as an adjuvant strategy to improve therapy success rates, especially for tumors with a highly desmoplastic stroma, like ovarian cancer. [ABSTRACT FROM AUTHOR]

Background and Purpose: Because of cervical cancer (CC) metastasis, the prognosis of diagnosed patients is poor. However, the molecular mechanisms and therapeutic approach for metastatic CC remain elusive. Experimental Approach: In this study, we first evaluated the effect of resveratrol (RSV) on CC cell migration and metastasis. Via an activity‐based protein profiling (ABPP) approach, a photoaffinity probe of RSV (RSV‐P) was synthesized, and the protein targets of RSV in HeLa cells were identified. Based on target information and subsequent in vivo and in vitro validation experiments, we finally elucidated the mechanism of RSV corresponding to its antimetastatic activity. Key Results: The results showed that RSV concentration‐dependently suppressed CC cell migration and metastasis. A list of proteins was identified as the targets of RSV, through the ABPP approach with RSV‐P, among which fatty acid binding protein 5 (FABP5) attracted our attention based on The Cancer Genome Atlas (TCGA) database analysis. Subsequent knockout and overexpression experiments confirmed that RSV directly interacted with FABP5 to inhibit fatty acid transport into the nucleus, thereby suppressing downstream matrix metalloproteinase‐2 (MMP2) and matrix metalloproteinase‐9 (MMP9) expression, thus inhibiting CC metastasis. Conclusions and Implications: Our study confirmed the key role of FABP5 in CC metastasis and provided important target information for the design of therapeutic lead compounds for metastatic CC. [ABSTRACT FROM AUTHOR]

Background: The evidence for resveratrol's anti-obesity and anti-inflammatory qualities is accumulating, though meta-analyses have reported mixed results. The current umbrella meta-analysis aimed to assess the present evidence and provide an accurate estimate of the overall effects of resveratrol on the anthropometric indices and inflammatory markers. Method: The Web of Science, PubMed, Scopus, and Google Scholar databases were searched till March 2023. The meta-analysis was performed utilizing a random-effects model. Moreover, the overall strength and quality of the evidence were assessed using the GRADE tool. Results: The results from 19 meta-analyses investigating 81 unique randomized controlled trials with 4088 participants revealed that resveratrol supplementation reduced the body mass index (ES = − 0.119, 95% CI (− 0.192, − 0.047), p = 0.001), waist circumference (ES = − 0.405, 95% CI [− 0.664, − 0.147], p = 0.002), serum levels of C-reactive protein (ES = − 0.390, 95% CI [− 0.474, − 0.306], p < 0.001), and tumor necrosis factor-α (ES = − 0.455, 95% CI [− 0.592, − 0.318], p < 0.001) in comparison to the control group. The effects of resveratrol on body weight and Interleukin-6 levels of participants were not significant. However, resveratrol administration significantly decreased body weight in trials with intervention duration ≥ 12 weeks [ES = − 0.160, 95% CI (− 0.268, − 0.052)] and supplement dosage ≥ 500 mg/day [ES = − 0.130, 95% CI (− 0.238, − 0.022)]. Conclusion: The findings suggest the beneficial effects of resveratrol supplementation on reducing general and central obesity, as well as decreasing some inflammatory markers. Nevertheless, further high-quality research is required to prove these achievements and also evaluate resveratrol's effects on other inflammatory markers. [ABSTRACT FROM AUTHOR]

A phytoalexin polyphenolic chemical, resveratrol, can be found in a variety of foods, including cereals, peanuts, grapes, strawberries, and raspberries. It is also known that resveratrol protects the body against cardiovascular diseases as well as various types of cancer. In addition to these health issues, resveratrol is currently the subject of research since it helps treat and prevent a number of illnesses. More clinical research is needed to validate resveratrol's potential as a therapeutic agent, despite the plethora of in vitro and in vivo evidence to support this. When the literature data are evaluated, the fact that resveratrol has a therapeutic effect in these studies, but it is known to be subject to rapid metabolism despite its low bioavailability and oral absorption of approximately 75%, has directed the studies to resveratrol derivatives, especially piceatannol. Based on recent studies, 4 types of resveratrol derivatives were assessed in this work: hydroxylated compounds, methoxylated compounds, glycosides, and oligomers. Because of their advantageous bioactivities, methoxylated, hydroxylated, and halogenated derivatives have drawn the most interest among these classes. However, as a result of these studies, more studies should be conducted to better understand whether resveratrol derivatives can be recommended as therapeutic agents. [ABSTRACT FROM AUTHOR]

Resveratrol has a protective effect on sepsis-induced acute kidney injury (AKI). Circ_0074371 has been confirmed to inhibit sepsis-induced AKI process, but whether resveratrol inhibits sepsis-induced AKI by regulating circ_0074371-related pathway remains unclear. In this study, lipopolysaccharide (LPS)-induced renal tubular epithelial cells (HK2) were used to mimic AKI cell models. Quantitative real-time PCR was used to detect relative expression of circ_0074371, microRNA (miR)-145-5p and inositol polyphosphate multikinase (IPMK). Cell proliferation and apoptosis were detected by cell counting kit 8 assay, EdU assay and flow cytometry. The levels of inflammation factors were measured by ELISA assay, and MDA level and SOD activity were examined to assess oxidative stress. Protein expression of IPMK was evaluated by western bolt analysis. The relationship between miR-145-5p and circ_0074371 or IPMK was confirmed by dual-luciferase reporter assay. It was showed that circ_0074371 was upregulated in AKI patients and LPS-induced HK2 cells, and silencing of circ_0074371 promoted proliferation and inhibited apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In terms of mechanism, circ_0074371 sponged miR-145-5p to positively regulate IPMK. IPMK overexpression could reverse the relieving effect of circ_0074371 knockdown on LPS-induced HK2 cell injury. Moreover, resveratrol suppressed LPS-induced apoptosis, inflammation and oxidative stress in HK2 cells, and circ_0074371 overexpression also reversed the protective effect of resveratrol against LPS-induced cell injury. Our data suggested that resveratrol alleviated LPS-induced HK2 cell injury by inactivating the circ_0074371/miR-145-5p/IPMK axis. Highlights: Circ_0074371 knockdown alleviates LPS-induced HK2 cell injury; Circ_0074371 sponges miR-145-5p to regulate IPMK. Resveratrol relieves LPS-induced HK2 cell injury via circ_0074371-related pathway. [ABSTRACT FROM AUTHOR]

Objective and design: Ulcerative colitis (UC) is a multi-faceted, recurrent immune disorder caused by dextran sulfate sodium (DSS). The intestinal microbiota has multiple functions in the host, so UC requires long-term potent medication. The effect of resveratrol (RSV) has seldom been reported, and this study researched that. Herein, the effect of RSV and Grape seed oil that anti-inflammatory ability in experimental mice was explored, also why RSV altered Gut Microbiota has been researched. Materials and methods: In this experiment, the effects of experimental drugs on colon length in mice with DSS-induced colitis were compared. H&E Staining was performed on serial sections of colon tissues and histological scores were determined for all groups. The expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the colon tissue of mice was detected by immunohistochemical staining. In the end, the α-diversity index, sobs index, and rarefaction curve of the cecal and colon microbiota of different groups of mice were measured. Bray–Curtis-based Venn diagram of PCoA (principal coordinate analysis) and OTUs distribution in mouse gut microbiota were obtained. Results: The results showed that the use of 40 mg/kg RSV (high dose) significantly reduced the severity of UC. The use of 10 mg/kg RSV (low dose) significantly reduced the effect of shortened colon length in DSS mice. Compared with the DSS-treated group, the levels of COX-2 and TNF-α in the colon tissues of RSV + DSS-treated mice were significantly decreased. According to this experiment, 19 mouse gut microbiota species had a relative abundance greater than 0.1%, with Beerella, Bacteroides, Helicobacter, Oscillator, and cecum pylori being more abundant in the colon than in the colon. A higher relative abundance of Lachnospira NK4A136 was observed in DSS and RSV groups compared with the control group, whereas the opposite was observed for Alloprevotella. This proves that resveratrol increases the uniformity and diversity of gut microbes to a certain extent, and has a protective effect on the gut. [ABSTRACT FROM AUTHOR]

The aims of this research were to investigate the usability of black grape pomace in the production of shalgam juice, which is a traditional fermented Turkish beverage, to transform the pomace into the high value‐added product and to enrich the shalgam juice with phenolic compounds. Black grape pomace and black carrot were used as the sources of polyphenols and five different formulations were obtained according to the amounts of black carrot and black grape pomace. During the fermentation, the samples were taken at different periods and analyzed for anthocyanins, phenolic compounds, antioxidant activity, and tannin content. Gentisic, caffeic, ferulic, coumaric, and chlorogenic acids, catechin, glucosides of kaemferol and isorhamnetin, resveratrol, rutin, cyanidin‐3‐xylosylglucosylgalactoside, cyanidin‐3‐xylosylgalactoside, cyanidin‐3‐xylosylglucosylgalactoside acylated with sinapic acid, ferulic acid, or coumaric acid, and glucosides of cyanidin, petunidin, and malvidin were identified in the shalgam juices that contained both black grape pomace and black carrot in their formulation. Some of these polyphenols were not detected detect in the shalgam juices that were produced from only the black carrot or black grape pomace. During the fermentation, a decrease in the amount of anthocyanins originated from black carrots and an increase in the amount of anthocyanins orginated from black grape pomace were determined. Black grape pomace addition to the formulation before the fermentation caused an increase in the amount of tannin in the shalgam juice samples. Consequently, it is thought that black grape pomace can be fruitfully evaluated in shalgam juice production and can be enhanced by polyphenolic profile of shalgam juice. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionChronic kidney disease (CKD) is a global health problem and it is stated that the use of resveratrol supplement contributes to the protection of kidney health. In this study, it was aimed to evaluate the effect of resveratrol supplementation on kidney function, inflammation and histopathological findings in rats with experimental adenine-induced kidney damage.Three different groups of 10 randomly selected rats were formed. The first group was the negative control group, the second group was the uremic control group (KDG), and the third group was the group in which uremia was created and resveratrol was applied (RG). Kidney damage was induced by administration of 200 mg/kg adenine. Resveratrol supplementation was administered at 20 mg/kg after kidney damage. Serum urea, creatinine, indoxyl sulfate (IS), p-cresol, glomerular filtration rate, C-reactive protein (CRP); interleukin (IL)-6 and tumor necrosis factor (TNF)-α gene expression levels and histopathological findings were evaluated.It was determined that resveratrol supplement applied after the formation of connective tissue in renal failure didn’t have an improvement effect on the urine amount, kidney function and inflammatory parameters and histopathological changes (p > 0.05). Just, the increase in the CRP value of KDG (p < 0.05) was not observed in RG.The findings suggest that resveratrol administered after kidney damage with adenine has no effect on kidney disease. [ABSTRACT FROM AUTHOR]

Background: In aquaculture, sturgeons are generally maintained in the confined spaces, which not only hinders sturgeon movement, but also threatens their flesh quality that seriously concerned by aquaculture industry. As a typical antioxidant, resveratrol can improve the flesh quality of livestock and poultry. However, the mechanism of resveratrol's effect on the muscle of Siberian sturgeon is still unclear. Results: In this study, the dietary resveratrol increased the myofiber diameter, the content of the amino acids, antioxidant capacity markers (CAT, LDH and SOD) levels and the expression levels of mTORC1 and MYH9 in muscle of Siberian sturgeon. Further transcriptome analysis displayed that ROS production-related pathways ("Oxidative phosphorylation" and "Chemical carcinogenes-reactive oxygen species") were enriched in KEGG analysis, and the expression levels of genes related to the production of ROS (COX4, COX6A, ATPeF1A, etc.) in mitochondria were significantly down-regulated, while the expression levels of genes related to scavenging ROS (SOD1) were up-regulated. Conclusions: In summary, this study reveals that resveratrol may promote the flesh quality of Siberian sturgeon probably by enhancing myofiber growth, nutritional value and the antioxidant capacity of muscle, which has certain reference significance for the development of a new type of feed for Siberian sturgeon. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Growing incidences of chronic wounds recommend the development of optimal therapeutic wound dressings. Electrospun nanofibers have been considered to show potential wound healing properties when accompanied by other wound dressing materials. This study aimed to explore the potential role of Chitosan (CS) nanofibrous mats coated with resveratrol (RS) as an antioxidant and pro‐angiogenic agent in rat models of skin wound healing.Electrospun chitosan/polyethylene oxide (PEO) nanofibers were prepared using electrospinning technology and coated by 0.05 and 0.1 mg.ml resveratrol named as (CS/RS 0.05) and (CS/RS 0.1), respectively. The scaffolds were characterized physiochemically such as in vitro release study, TGA, FTIR spectroscopy analysis, biodegradability, and human dermal fibroblast seeding assay. The scaffold was subsequently used in vivo as a skin substitute on a rat skin wound model.In vitro tests revealed that all scaffolds promoted cell adhesion and proliferation. However, more cell viability was observed in CS/RS 0.1 scaffold. The biocompatibility of the scaffolds was validated by MTT assay, and the results did not show any toxic effects on human dermal fibroblasts. It was observed that RS‐coated scaffolds had the ability to release RS in a controlled manner. In in vivo tests CS/RS 0.1 scaffold had the greatest impact on the healing process by improving the neodermis formation and modulated inflammation in wound granulation tissue. Histological analysis revealed enhanced vascular endothelial growth factor expression, epithelialization and increased depth of wound granulation tissue.The RS‐coated CS/PEO nanofibrous scaffold accelerates wound healing and may be useful as a dressing for cell transfer and clinical skin regeneration. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a long-life disease with periods of recurrence and relief. Oxidative stress plays an important role in the pathogenesis of this disease. Recent years' studies in the field of IBD treatment mostly have focused on targeting cytokines and immune cell trafficking using antibodies and inhibitors, altering the composition of intestinal bacteria in the line of attenuation of inflammation using probiotics and prebiotics, and attenuating oxidative stress through antioxidant supplementation. Studies in animal models of IBD have shown that some polyphenolic compounds including curcumin, quercetin, resveratrol, naringenin, and epigallocatechin-3-gallate can affect almost all of the above aspects and are useful compounds in the treatment of IBD. Clinical studies performed on IBD patients have also confirmed the findings of animal model studies and have shown that supplementation with some of the above-mentioned polyphenolic compounds has positive effects in reducing disease clinical and endoscopic activity, inducing and maintaining remission, and improving quality of life. In this review article, in addition to a detailed reviewing the effects of the above-mentioned polyphenolic compounds on the events involved in the pathogenesis of IBD, the results of these clinical studies will also be reviewed. [ABSTRACT FROM AUTHOR]

Background: Varicocele still today represents a common cause of infertility in young men. The treatment strategy remains a surgical approach such as scleroembolization; however, the complete restoration of spermatic parameters afterward requires an average of six or more months to fully regain optimal seminal parameters. Recently, many studies have demonstrated the beneficial effects of Resveratrol in male fertility, given its potential anti-inflammatory, antiapoptotic, and mitochondrial effects. Therefore, Resveratrol-based nutraceuticals could be promising as an adjuvant to mitigate subfertility in patients with varicocele. Methods: In the present study, we retrospectively analyzed the effects of the administration of a Resveratrol-based nutraceutical after the scleroembolization procedure. The improvement of sperm quality in terms of number, motility, and morphology were considered to be the study's main endpoints. A spreadsheet program was used for data analysis, and a p-value of <0.05 was considered significant. Results: We found a statistically significant improvement in the spermatic parameters (sperm count and total motility) and an increase in normal sperm after only 4 months of treatment. The supplementation with a Resveratrol-based nutraceutical associated with the surgical procedure showed encouraging results if compared to data from a control group and the results reported in the literature linked to scleroembolization practice alone. In fact, there was a clear improvement in the seminal parameters at 4 months. Conclusions: This suggests the positive impact of the Resveratrol-based nutraceutical in synergizing with scleroembolization in reducing the time needed to fully recover sperm function. [ABSTRACT FROM AUTHOR]

Oocyte–cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus–oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells. [ABSTRACT FROM AUTHOR]

Mulberry is a rapidly growing plant that thrives in diverse climatic, topographical, and soil types, spanning temperature and temperate countries. Mulberry plants are valued as functional foods for their abundant chemical composition, serving as a significant reservoir of bioactive compounds like proteins, polysaccharides, phenolics, and flavonoids. Moreover, these compounds displayed potent antioxidant activity by scavenging free radicals, inhibiting reactive oxygen species generation, and restoring elevated nitric oxide production induced by LPS stimulation through the downregulation of inducible NO synthase expression. Active components like oxyresveratrol found in Morus demonstrated anti-inflammatory effects by inhibiting leukocyte migration through the MEK/ERK signaling pathway. Gallic and chlorogenic acids in mulberry leaves (ML) powder-modulated TNF, IL-6, and IRS1 proteins, improving various inflammatory conditions by immune system modulation. As we delve deeper into understanding its anti-inflammatory potential and how it works therapeutically, it is crucial to refine the extraction process to enhance the effectiveness of its bioactive elements. Recent advancements in extraction techniques, such as solid–liquid extraction, pressurized liquid extraction, superficial fluid extraction, microwave-assisted extraction, and ultrasonic-assisted extraction, are being explored. Among the extraction methods tested, including Soxhlet extraction, maceration, and ultrasound-assisted extraction (UAE), UAE demonstrated superior efficiency in extracting bioactive compounds from mulberry leaves. Overall, this comprehensive review sheds light on the potential of mulberry as a natural immunomodulatory agent and provides insights into its mechanisms of action for future research and therapeutic applications. [ABSTRACT FROM AUTHOR]

Background and purpose: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. Methods: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-β1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1β in combination with TGF-β1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. Results: Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-β1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. Conclusion: In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD. [ABSTRACT FROM AUTHOR]

Chagas disease (CD), or American trypanosomiasis, caused by the parasitic protozoa Trypanosoma cruzi, is a substantial global health burden. This comprehensive review explored the multifaceted landscape of CD treatment, providing a historical perspective on the development and discontinuation of benznidazole (BNZ) and nifurtimox (NF), the primary medications. Efforts towards a pediatric version of BZN in Brazil address demographic‐specific treatments, while concerns over drug resistance prompt the exploration of alternative medications like Amiodarone, Allopurinol, Posaconazole, Ravuconazole, and Fexinidazole, which were clinically tested as antichagasic drugs. In recent years, some of the synthesized derivative (1,3‐thiazoles, 4‐thiazolidinones, 2‐styrylquinolines, imidazole‐containing nitrophthalazine, and some others) were found to better activity as compared to standard drug. Traditional herbal alternatives (Resveratrol, curcumin, 1,8‐cineole, β‐pinene, and some others) rooted in traditional practices show promise, with various plant extracts exhibiting anti‐parasitic properties. The frontier of nanomedicine unfolds with studies on solid nanomedicines, PLA‐nanoparticles, ZIF‐8, BNZ carriers, and PLGA nanoparticles, showcasing improved drug delivery systems and controlled release mechanisms. The absence of a definitive vaccine accentuates ongoing research in recombinant antigens, peptide‐based vaccines, and nanoparticle formulations, with notable candidates like TcG1, TcG2, TcG4, MASPpep‐KLH, adenovirus vectors, Tc24 protein, and integrin activators. A novel strategy combining a recombinant protein vaccine with low dose BZN treatment presents promising results in a mouse model, emphasizing the urgency for further research and potential advancements in CD therapeutics. [ABSTRACT FROM AUTHOR]

Background: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells. Methods: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay. Results: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer. Conclusions: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells. [ABSTRACT FROM AUTHOR]

Purpose: Considering inhibition of pre-adipocyte cells differentiation in adipose tissue fibrosis, we aimed to explore whether Sirt1 and Hif-1α in pre-adipocytes have a significant effect on fibrotic gene expression. Methods: 3T3-L1 pre-adipocytes were transfected with SIRT1-specific siRNA, confirmed by real-time polymerase chain reaction (RT-PCR) and western blotting. Additionally, cells were treated with varying concentrations of resveratrol and sirtinol as the activator and inhibitor of Sirt1, respectively. Involvement of Hif-1α was evaluated by treatment with echinomycin. Subsequently, we assessed the gene and protein expressions related to fibrosis in the extracellular matrix of adipose tissue, including collagen VI (Col VI), lysyl oxidase (Lox), matrix metalloproteinase-2 (Mmp-2), Mmp-9, and osteopontin (Opn) in pre-adipocytes through RT-PCR and western blot. Results: The current study demonstrated that Sirt1 knockdown and reduced enzyme activity significantly increased the expression of Col VI, Lox, Mmp-2, Mmp-9, and Opn genes in the treated 3T3-L1 cells compared to the control group. Interestingly, resveratrol significantly decreased the gene expression related to the fibrosis pathway. Inhibition of Hif-1α by echinomycin led to a significant reduction in Col VI, Mmp-2, and Mmp-9 gene expression in the treated group compared to the control. Conclusion: This study highlights that down-regulation of Sirt1 might be a predisposing factor in the emergence of adipose tissue fibrosis by enhancing the expression of extracellular matrix (ECM) components. Activation of Sirt1, similar to suppressing of Hif-1α in pre-adipocytes may be a beneficial approach for attenuating fibrotic gene expression. [ABSTRACT FROM AUTHOR]

Curcumin and resveratrol are polyphenolic compounds that have been shown to exhibit synergistic therapeutic properties including anti-inflammatory, anticancer, and antiulcer activities, which may be exploited for the treatment of gastric diseases. However, both compounds have poor aqueous solubility and rapid metabolism, resulting in a low oral bioavailability. In situ gelling, liquid formulations were developed to produce a gastroretentive, raft-forming delivery vehicle to improve bioavailability. Solid dispersions containing a mixture of curcumin and resveratrol with Eudragit® EPO (Cur/Res-SD) were first prepared using solvent evaporation, to improve the solubility and dissolution of the compounds. Solid dispersions of a weight ratio of 1:10 curcumin/resveratrol to Eudragit® EPO were subsequently incorporated into in situ gelling, liquid formulations based on the gelling polymers, sodium alginate (low viscosity and medium viscosity), pectin, and gellan gum, respectively. Calcium carbonate and sodium bicarbonate were included to produce carbon dioxide bubbles in the gel matrix, on exposure to gastric fluid, and to achieve flotation. Moreover, the calcium ions acted as a crosslinking agent for the hydrogels. Optimized formulations floated rapidly (<60 s) in simulated gastric fluid (pH = 1.2) and remained buoyant, resulting in the gradual release of more than 80% of the curcumin and resveratrol content within 8 h. The optimized formulation based on medium-viscosity sodium alginate exhibited enhanced cytotoxic activity toward human gastric adenocarcinoma cell lines (AGS), compared with unformulated curcumin and resveratrol compounds, and increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate that in situ gelling, liquid formulations, loaded with a combination of curcumin and resveratrol in the form of solid dispersions, show potential as gastroretentive delivery systems for local and systemic effects. [ABSTRACT FROM AUTHOR]

In this study, the encapsulation of resveratrol (Res) in zein-rhamnolipid (RL) composite nanoparticles (NPs) by a pH-driven method and its relationship with the controlled release behavior of the NPs were investigated. The properties of the produced NPs were elucidated with different zein-RL mass ratios and encapsulation of different amounts of Res. The NPs had relatively high encapsulation efficiency, loading capacity, stability, and cumulative release percentages. The SEM analysis showed the spherical NPs obtained with and without Res incorporation and the FTIR study indicated the interactions of Res with zein-RL components. The NPs had relatively good stability over a wide range of pH (4–9), salt concentration (0–200 mM) (pH = 7), and Res amount (0–160 mg) (pH = 7.4). Ultrasonic and shaking water baths were used for release studies of Res from NPs with an optimum zein-RL mass ratio of 1.0:0.6 (w/w). In vitro release studies of Res under acidic (pH = 1.2) and neutral (pH = 7.4) conditions demonstrated initial rapid release followed by slow release. The highest cumulative release percentage was obtained at pH 1.2 and 7.4 with 120 mg Res encapsulated zein-RL NPs. The release of Res from the capsules was a pH-dependent process and the cumulative release profiles were considered to be slightly higher in acidic environments. Among the controlled release kinetic models, the Weibull model gave the best fit for optimum Res-loaded NPs. Release studies indicated that zein-RL NPs have the potential to be used as delivery systems for health-promoting bioactive molecules in functional foods, nutraceutical/dietary supplements, and pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood–brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering −3.31, −1.68, and −6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated. [ABSTRACT FROM AUTHOR]

Resveratrol, a polyphenolic compound found primarily in red grapes and pomegranates is known as an antioxidant but can act as a pro-oxidant when copper ions are present. Here, resveratrol is demonstrated to reduce cell growth (as evaluated by MTT assay) and promote apoptosis-like cell death (as measured by Histone/DNA ELISA) in prostate cancer cell lines PC3 and C42B. This effect is effectively inhibited by a copper chelator (neocuproine) and reactive oxygen species (ROS) scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide). These inhibitory effects provide evidence that intracellular copper reacts with resveratrol within cancer cells, resulting in DNA damage via the generation of reactive oxygen species. Additionally, it has been demonstrated that non-tumorigenic epithelial cell lines (MCF-10A) grown in media supplemented with copper are more susceptible to growth inhibition by resveratrol, as confirmed by the observed reduction in cell proliferation. Copper supplementation induces enhanced expression of the copper transporter CTR1 in MCF-10A cells, which is reduced by the addition of resveratrol to the media. The selective cell death of cancer cells generated by copper-mediated and ROS mechanisms may help to explain the anticancer properties of resveratrol. [ABSTRACT FROM AUTHOR]

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism. [ABSTRACT FROM AUTHOR]

Senescence is a heterogenous and dynamic process in which various cell types undergo cell‐cycle arrest due to cellular stressors. While senescence has been implicated in aging and many human pathologies, therapeutic interventions remain inadequate due to the absence of a comprehensive set of biomarkers in a context‐dependent manner. Polyphenols have been investigated as senotherapeutics in both preclinical and clinical settings. However, their use is hindered by limited stability, toxicity, modest bioavailability, and often inadequate concentration at target sites. To address these limitations, nanocarriers such as polymer nanoparticles and lipid vesicles can be utilized to enhance the efficacy of senolytic polyphenols. Focusing on widely studied senolytic agents—specifically fisetin, quercetin, and resveratrol—we provide concise summaries of their physical and chemical properties, along with an overview of preclinical and clinical findings. We also highlight common signaling pathways and potential toxicities associated with these agents. Addressing challenges linked to nanocarriers, we present examples of senotherapeutic delivery to various cell types, both with and without nanocarriers. Finally, continued research and development of senolytic agents and nanocarriers are encouraged to reduce the undesirable effects of senescence on different cell types and organs. This review underscores the need for establishing reliable sets of senescence biomarkers that could assist in evaluating the effectiveness of current and future senotherapeutic candidates and nanocarriers. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease is associated with the dysbiosis of the gut microbiota and its metabolites. db/db mice were fed chow diet with or without 0.4% resveratrol for 12 weeks, after which the gut microbiota, faecal short-chain fatty acids (SCFAs), and renal fibrosis were analysed. Resveratrol ameliorated the progression of diabetic kidney disease and alleviated tubulointerstitial fibrosis. Further studies showed that gut microbiota dysbiosis was modulated by resveratrol, characterised by the expansion of SCFAs-producing bacteria Faecalibaculum and Lactobacillus, which increased the concentrations of SCFAs (especially acetic acid) in the faeces. Moreover, microbiota transplantation experiments found that alteration of the gut microbiota contributed to the prevention of diabetic kidney disease. Acetate treatment ameliorated proteinuria, glomerulosclerosis and tubulointerstitial fibrosis in db/db mice. Overall, resveratrol improved the progression of diabetic kidney disease by suppressing tubulointerstitial fibrosis, which may be involved, at least in part, in the regulation of the gut microbiota-SCFAs axis. [ABSTRACT FROM AUTHOR]

Inflammation is an adaptive response that involves activation, and recruitment of cells of innate and adaptive immune cells for restoring homeostasis. To safeguard the host from the threat of inflammatory agents, microbial invasion, or damage, the immune system activates the transcription factor NF-κB and produces cytokines such as TNF-α, IL- 6, IL-1β, and α. Sirtuin 1 (SIRT1) controls the increased amounts of proinflammatory cytokines, which in turn controls inflammation. Three phytoconstituents resveratrol (RES), pterostilbene (PTE), and curcumin (CUR) which are SIRT1- activators and that have marked anti-inflammatory effects (in-vivo), were chosen for the current study. These compounds were compared for their anti-inflammatory potential by in-silico docking studies for IL-6, TNF-α, NF-κB, and SIRT1 and in-vitro THP-1 cell line studies for IL-6, TNF-α. PTE was found to be more effective than RES and CUR in lowering the concentrations of IL-6 and TNF-α in THP-1 cell line studies, and it also showed a favorable docking profile with cytokines and SIRT1. Thus, PTE appears to be a better choice for further research and development as a drug or functional food supplement with the ability to reduce inflammation in metabolic disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Resveratrol (Res) is promising food functional factor with favorable antioxidant and anti‐inflammatory properties, although its poor water solubility and low bioavailability limit extensive application. Therefore, in combination with another promising polysaccharide (Mesona chinensis polysaccharides, MCP), Res‐loaded food nanocarriers (ResNPs) were developed to increase its water solubility, bioactivity and targeting properties. ResNPs were then applied to alleviate dextran sulfate sodium (DSS)‐induced ulcerative colitis. RESULTS: Resveratrol can be well encapsulated in MCP‐based nanoparticles in an amorphous state, improving its water solubility. ResNPs showed pH‐response controlled release behavior in the gastrointestinal tract and increased the enrichment of Res in the colon. In vivo experiments of ResNPs against DSS‐induced ulcerative colitis (UC) revealed that ResNPs significantly improved UC symptoms, modulated intestinal inflammation and down‐regulated oxidative stress levels compared to free Res. ResNPs also play an positive role with respect to inhibiting the mitogen‐activated protein kinase pathway and promoting the expression of tight junction proteins. In addition, ResNPs improved the species composition and relative abundance of intestinal flora in UC mice, which effectively regulated the balance of intestinal flora and promoted the production of short‐chain fatty acids. CONCLUSION: These results suggest that MCP‐based nanoparticles can effectively improve the solubility of resveratrol and enhance its in vivo bioactivity. Moreover, the present study also provides a new strategy for the prevention and treatment of UC with food polyphenol. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Heterogous expression of lignin peroxidase (LiP) from Phanerochaete chrysosporium was performed in by E. coli prokaryotic expression system, and pure LiP was prepared by washing, refolding, and purification. The enzyme activity was measured by the resveratrol oxidation method. The effects of different chemicals on LiP activity were explored by adding different kinds of metal ions, acids/phenols, and surfactants. The optimal pH and temperature are 4.2 and 40 °C. The single-factor screening experiment showed that adding 1 mM Mn2+, 0.1 mM DL-lactic acid, and 2% PEG-4000 had the best promotion effect on the enzyme activity of recombinant LiP, which was 160.61%, 188.46%, and 247.83%, respectively. Further, the synergistic addition of Mn2+ and PEG-4000 achieved the best enzyme activity promotion effect of 277.51%. In addition, the addition of DL-lactic acid alone could promote LiP activity. However, the co-addition of lactic acid with Mn2+ and PEG-4000 contributed only 247.87%, which indicated that the addition of DL-lactic acid had an inhibitory effect when applied synergistically. For the first time, it was found that PEG-4000 increased LiP enzyme activity obviously and had a synergistic effect with Mn2+, serving as a reference for LiP in studies and applications pertaining to lignin breakdown. [ABSTRACT FROM AUTHOR]