Concentrations Of Resveratrol Research Articles

Combination of Methotrexate and Resveratrol Reduces Pro-Inflammatory Chemokines in Human THP-1 Cells.

Methotrexate (MTX) is a widely used anti-metabolite drug in cancer therapy, but its efficacy is often hindered by reactive oxygen species (ROS)-induced cellular toxicity. Resveratrol, a natural polyphenol, possesses antioxidant and anticancer properties. Therefore, this in vitro study aimed to investigate the synergistic anti-proliferative and anti-inflammatory effects of MTX and resveratrol in human THP-1 cells. THP-1 cells were differentiated into macrophage-like cells using phorbol 12-myristate 13-acetate. In vitro experiments assessed the impact of various concentrations of MTX and resveratrol on cell viability and proliferation using the MTT assay. Concentration-effect curves were generated to elucidate their relationship. Gene expression was analyzed by RT-qPCR, while chemokine expression was measured via ELISA. Phagocytic and migratory activities were also evaluated. Differentiated THP-1 cells were treated with MTX and resveratrol and stimulated with dimethyl sulfoxide (DMSO) and lipopolysaccharide (LPS) as inflammatory stimuli. The combination of MTX and resveratrol exhibited an anti-proliferative effect in THP-1 cells (p = 0.03). The concentration-effect curve revealed IC50 values of 49.15 µg at 24hours (R = 0.8236) and 2.029e-005 µg at 48hours (R = 0.97) for MTX, and 20.17 µg at 48hours (R = 1.000) and 55.38 µg at 96hours (R = 0.9666) for resveratrol. Co-treatment with MTX and resveratrol significantly reduced mRNA and chemokine expression of CCL2, CCL3, CCL4, CCL5, and CXCL10 (p < 0.05). Moreover, decreased phagocytic and migratory activities were confirmed by phagocytosis and migration assays (p < 0.05). The combination of MTX and resveratrol effectively attenuated pro-inflammatory activity in THP-1 cells, as evidenced by the downregulation of mRNA and chemokine expression. These findings suggest that the synergistic effects of MTX and resveratrol hold promise for enhancing cancer therapeutics.

Ultrasonic-Assisted Extraction and Antioxidant Evaluation of Resveratrol from Peanut Sprouts

The orthogonal array design method was used to optimize ultrasonic-assisted extraction of resveratrol from peanut sprouts. The results showed that the highest extraction yield of resveratrol using ultrasonic-assisted extraction could be up to 1.1%. The optimal extraction conditions were liquid to solid ratio of 30:1 (mL/g) and ethanol concentration of 80% (v/v) as solvent for 40 min at the temperature of 70 °C. AB-8 macroporous adsorption resin was used to purify the crude extract and the resveratrol content increased to 47.5% after one treatment run. The optimal adsorption parameters were initial concentrations in the sample solution of 2 mg/mL, a pH of 5.0, a flow rate of 2 mL/min, and a temperature of 25 °C. The optimal desorption parameters were 60% ethanol and a flow rate of 1 mL/min. The chemical composition of the peanut sprout’s resveratrol sample was investigated via HPLC, and the predominant constituents were found to be protocatechuic acid, catechins, caffeic acid, epicatechuic acid, resveratrol, and rutin. The antioxidant activities of the resveratrol were measured via the following different analytical methods: reducing power, 2,2-diphenyl-1-picrylhdrazyl (DPPH), hydroxyl radical-scavenger activity, superoxide radical-scavenger activity, the β-carotene bleaching test, and the scavenging nitrite test. The results indicated that the resveratrol in peanut sprouts have significant antioxidant activities and can be used as a source of potential antioxidant. And peanut sprout’s resveratrol has the potential and valuable application to be used as a new type of resveratrol resource. The finding of this study can provide some theoretical reference for the comprehensive utilization of peanut resources in the development of antioxidant health foods.

Resveratrol enhances sensitivity of renal cell carcinoma to tivozanib: An in-vitro study

BackgroundSince tivozanib has many side effects in the treatment of kidney cancer, we decided to use resveratrol as a bioactive molecule with anticancer and antioxidant properties to make tivozanib more effective and also reduce its side effects in kidney cancer cell line. MethodIn this in vitro study, we evaluated the effect of tivozanib, resveratrol and tivozanib- resveratrol combination therapy in ACHN cell line as representatives of human kidney cancer. The assessment includes Hoechst dye staining, scratch-wound assay, 3D spheroid, 2D colony formation assay, flow cytometric analysis of apoptosis and DNA cell cycle, real-time PCR (BAX/BCL2, E-cadherin, Snail, HIF1α, VEGFC and KLK3 genes). ResultTo determine IC50 levels, ACHN cells was exposed to different concentration of tivozanib and resveratrol. Our data indicated that IC50 values for tivozanib (0.5 μM) and resveratrol (30 μM) with MTT in a dose and time-dependent manner. Due to the efficacy of resveratrol in combination with tivozanib, we used 20 μM resveratrol, and 0.25 μM tivozanib instead of 30 μM and 0.25 μM respectively. This data was approved by flow cytometry for ACHN cell line with 38.39, 14.74 and 66.06 percent apoptosis and 8.25, 5.12 and 15.6 percent subG1 for tivozanib, resveratrol and tivozanib-resveratrol combination respectively which was as a consequence of cell cycle arrest at G1/S phase. The treatment also reduced cells’ migration, fragmented nuclei, 3D spheroid and colony formation potentials in analyses. Evaluation of gene expression presented that the effect of the tivozanib and resveratrol combination in ACHN cell lines is completely different during the evaluation of apoptosis genes, BAX, P53 genes and E-Cadherin had significantly increased expression compared to single treatment groups (P < 0.01). Meanwhile, a significant decrease was observed in the expression of VEGFC and HIF1α genes in the combination group compared to the monotherapy groups (P < 0.001). ConclusionConsidering that resveratrol can increase the apoptosis of cancer cells alone and in combination with tivozanib and prevent the proliferation of cancer cells and also reduce the side effects of tivozanib, we suggest that resveratrol as a potential bioactive molecule can be used in treatment of kidney cancer should be used in combination with tivozanib.

The Mechanism Involved in the Inhibition of Resveratrol and Genistein on the Contractility of Isolated Rat Uterus Smooth Muscle

Purpose: This study aimed to compare the effects of the phytoestrogens resveratrol (RES) and genistein (GEN) on the contractility of isolated uterine smooth muscle from rats, focusing on both spontaneous and stimulated contractions, and to investigate the underlying mechanisms. Methods: Uterine strips were suspended vertically in perfusion chambers containing Kreb’s solution, various concentrations of RES and GEN were added to the ex vivo uterine strips, and contractions were measured before and after incubation with RES or GEN. Results: (1) Both RES and GEN inhibited K+-induced contractions in a dose-dependent manner; the β/β2-adrenoceptor antagonist propranolol (PRO), ICI118551, the ATP-dependent K+ channel blocker glibenclamide (HB-419) and the NO synthase inhibitor N-nitro-L-arginine (L-NNA) diminished the inhibitory effects of RES and GEN on K+-induced contractions. (2) RES and GEN also dose-dependently inhibited PGF2α-induced uterine contractions. (3) The inhibitory effects of RES and GEN were observed in spontaneous contractile activities as well; PRO, ICI118551, HB-419 and L-NNA attenuated the inhibitory effects of RES and GEN on the spontaneous contractions of isolated uterine muscle strips. (4) RES and GEN significantly decreased the cumulative concentration response of Ca2+ and shifted the Ca2+ cumulative concentration–response curves to the right in high-K+ Ca2+-free Kreb’s solution. (5) RES and GEN markedly reduced the first phasic contraction induced by oxytocin, acetylcholine, and prostaglandin F2α but did not alter the second phasic contraction caused by CaCl2 in Ca2+-free Kreb’s solution. Conclusions: RES and GEN can directly inhibit both spontaneous and activated contractions of isolated uterine smooth muscle. The mechanisms underlying the inhibitory effects of RES and GEN likely involve β adrenergic receptor activation, reduced Ca2+ influx and release, the activation of ATP-dependent K+ channels and increased NO production.

Shading Impairs Mycorrhizal Benefits on Plant Growth, Leaf Gas Exchange, and Active Ingredients in Polygonum cuspidatum

Polygonum cuspidatum, an important medicinal plant, often experiences shading from surrounding vegetation during its growth phase, raising questions about the impact of such conditions on the functionality of arbuscular mycorrhizal fungi. This study investigated the effects of an arbuscular mycorrhizal fungus (Funneliformis mosseae) on the growth, leaf gas exchange, and concentrations of active ingredient concentrations in leaves and roots of P. cuspidatum under shading (with a 72% shading rate) conditions. A nine-week shading intervention significantly suppressed root colonization by F. mosseae and the formation of soil mycorrhizal mycelium. Shading significantly inhibited the above-ground growth performance, biomass production, leaf photosynthetic rate, transpiration rate, stomatal conductance, and intercellular CO2 concentration, while F. mosseae significantly increased these variables in the absence of shading. Plant height, leaf biomass, stem biomass, leaf photosynthetic rate, transpiration rate, and stomatal conductance were all decreased by F. mosseae when the plants were shaded. The shading treatment also significantly diminished the concentrations of active components measured in both leaves and roots. Under no-shading conditions, F. mosseae significantly boosted the concentrations of polydatin, resveratrol, aloe-emodin, emodin, chrysophanol, and physcion in roots, as well as the concentrations of polydatin and chrysophanol in leaves. Conversely, in the presence of shading, F. mosseae distinctly reduced these active ingredient levels in roots, followed by an increase in leaf polydatin and chrysophanol concentrations. In summary, shading substantially impaired the mycorrhizal benefits on plant growth, leaf gas exchange, and root active ingredients in P. cuspidatum, highlighting the importance of sufficient light to maximize mycorrhizal contributions.

Anti-Cancer Activity and Mechanism of Resveratrol Against Triple-Negative Breast Cancer

This research analyzed the antitumor of resveratrol in triple negative breast cancer (TNBC). TNBC were divided into control group and resveratrol group. Tnbc-associated TNBC cells were stimulated by different concentrations of resveratrol, and the proliferation, apoptosis, migration of the cells were analyzed. The amount of migration was measured by Transwell method. The PI3K, Akt, and mTOR were detected. Results showed that the cell apoptosis was obvious and the invasion ability was decreased in resveratrol group, and the effect was more obvious with the increase of dosage, and there was a statistical difference between groups (P &lt; 0.05). Resveratrol significantly decreased the expression of Akt, PI3K and mTOR, and there were statistical differences between groups (P &lt; 0.05). In summary, resveratrol reduces cell migration, promotes cell apoptosis, inhibits cell proliferation, and its mechanism is closely related to the blocking of PI3K/Akt/mTOR.

Investigation on the in vitro effects of resveratrol on peripheral blood mononuclear cells harvested from healthy and atopic dogs

Canine atopic dermatitis (AD) is a common skin disease. Many therapeutic options are available to decrease inflammation and ameliorate pruritus. However, those treatments are associated with side effects, a long lag phase for efficacy, or high expense. Natural plant extracts have been identified as possible, safer alternatives to traditional anti-inflammatory and antipruritic drugs. Resveratrol has been revisited as a new, possible alternative for its numerous beneficial properties. The purpose of this study was to evaluate the in vitro effects of resveratrol on peripheral blood mononuclear cells (PBMC) harvested from healthy and atopic privately-owned dogs.The PBMC harvested from nine healthy and 11 atopic dogs were isolated and exposed to four concentrations (1.5-9 μg/mL) of resveratrol both with or without phytohemagglutinin stimulation. After 24 h cytotoxicity, host defense peptides (HDPs), as well as oxidative stress (catalase and superoxide dismutase), and pro-inflammatory cytokines were assessed. Cytotoxicity was not observed in either group under any experimental conditions. An increase in catalase was only seen in healthy PBMC after exposure to low concentrations of resveratrol (p ≤ 0.03). Resveratrol did not show any effect on canine HDPs. Compared to baseline, there was a significant reduction in monocyte chemotactic protein-1 and interleukin-6 after exposure to 9 μg/mL of resveratrol in unstimulated healthy (p = 0.029) and stimulated atopic (p = 0.0075) PBMC. In conclusion, these data confirm the overall lack of cytotoxicity of resveratrol on healthy and atopic PBMC at the tested concentrations. However, at the concentrations tested, there was only a minimal effect of resveratrol on the secretion of HDPs and pro-inflammatory cytokines.

Revealing the synergistic antibacterial mechanisms of resveratrol (RES) and pulsed electric field (PEF) against Acetobacter sp

In the wine industry, Acetobacter sp. is a typical spoilage microorganism responsible for increased volatile acids and wine spoilage. This study investigated the impact of combined treatment using varying concentrations of resveratrol (RES) and pulsed electric field (PEF) on the bactericidal efficacy, intracellular enzyme activities, and cellular metabolism of Acetobacter sp. The results from the Weibull mathematical model revealed a notable enhancement in the bactericidal effectiveness of the RES and PEF treatments with increasing RES concentration. In addition, the synergies between RES and PEF might not only resulted in the deactivation of Alcohol dehydrogenase (ADH) and Aldehyde dehydrogenase (ALDH) of Acetobacter sp., but also induced modifications in the secondary and tertiary structures of intracellular enzymes as evidenced by fluorescence, ultraviolet, fourier transform infrared, and circular dichroism spectra. Furthermore, metabolomics results showed that 1,910 metabolites exhibited differential expression, with 1,118 metabolites being down-regulated and 792 metabolites being up-regulated. After the synergies between RES and PEF, 17 biochemical pathways were significantly changed, mainly involving amino acid metabolism, carbohydrate metabolism, cofactor and vitamin metabolism, nucleotide metabolism, etc. These findings demonstrated that the combined treatment of RES and PEF can effectively suppress the growth of Acetobacter sp. and the inactivation mechanism of Acetobacter sp. by PEF in conjunction with RES was revealed.

The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: The Interplay between Nrf2, HO-1, and BACH1 Genes.

The association between oxidative stress and prostate cancer (PC) has been demonstrated both epidemiologically and experimentally. Balance in reactive oxygen species (ROS) levels depends on multiple factors, such as the expression of Nrf2, HO-1, and BACH1 genes. Natural polyphenols, such as resveratrol (RSV) and gallic acid (GA), affect cellular oxidative profiles. The present study investigated the possible effects of GA and RSV on the oxidative profiles of PC3 and DU145 cells, as well as Nrf2, HO-1, and BACH1 gene expression to achieve an understanding of the mechanisms involved. PC3 and DU145 cells were treated with ascending concentrations of RSV and GA for 72 h. Then cell growth and mRNA expression of Nrf2, HO-1, and BACH1 genes were analyzed by real-time PCR. Various spectrophotometric analyses were performed to measure oxidative stress markers. RSV and GA significantly decreased the growth of PC3 and DU145 cells compared to the control group in a concentration-dependent manner. RSV and GA also decreased ROS production in PC3 cells, but in DU145 cells, only the latter polyphenol significantly decreased ROS content. In addition, RSV and GA had ameliorating effects on SOD, GR, GPX, and CAT activities and GSH levels in both cell lines. Also, RSV and GA induced HO- 1 and Nrf2 gene expression in both cell lines. BACH1 gene expression was induced by RSV only at lower concentrations, in contrast to GA in both cell lines. Our data suggest that RSV and GA can prevent the growth of prostate cancer cells by disrupting oxidative stress-related pathways, such as changes in Nrf2, HO-1, and BACH1 gene expression.

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

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

Monitoring the interfacial release rate of resveratrol in Pickering emulsions stabilized by cellulose nanocrystals through the control of the surface coverage

Pickering emulsions (PE) are emulsions stabilized by particles, rather than surfactants like conventional emulsions. This gives them numerous advantages, such as greater stability, reduced toxicity and a tighter drop size distribution. These are just some of the reasons why PEs are booming, particularly in the field of drug delivery. Controlling the release of the active ingredient is thought to depend on the coverage of the emulsion surface by the particles (C). This work first shows how to control C in the case of hexadecane-in-water emulsions stabilized by cellulose nanocrystals (CNCs). It decreases linearly with the salt (NaCl) concentration of the aqueous medium. When resveratrol (RSV), a hydrophobic model molecule, is incorporated into the hexadecane, with an uptake up to 98 ± 3 %, this dependence is lost in favour of a dependence, again linear with RSV concentration. By modelling the release of RSV incorporated into PE of different C, we have demonstrated that k1, the interfacial rate constant of RSV, is controlled by C. CNCs on the droplet surface slow down the release of encapsulated RSV, the higher the droplet surface coverage.

Effects of Resveratrol-Loaded Cyclodextrin on the Quality Characteristics of Ram Spermatozoa Following Cryopreservation.

This study investigated the effects of pure and methyl-β-cyclodextrin loaded forms of resveratrol (10 µg/mL, 20 µg/mL, and 40 µg/mL) on ram sperm functions post-thawing. Semen samples were pooled and divided into ten groups: Control, RES10, RES20, RES40, CD10, CD20, CD40, RLC10, RLC20, and RLC40. The groups were pre-diluted with media containing the group-specific chemicals, followed by 15 min of incubation, dilution, and freezing. To assess the effects of the chemicals, a post-thaw sperm quality assessment was conducted. Motility and other velocity parameters were evaluated using computer-assisted semen analysis. The functional integrity of spermatozoa membranes was assessed with the hypo-osmotic swelling test, and the capacitation status of spermatozoa was determined through fluorescent microscopic evaluation. Additionally, flow cytometry was used to evaluate mitochondrial activity, oxidative stress, and the integrity of the sperm membrane and acrosome. The results indicated that cyclodextrin adversely affected sperm functions following freezing-thawing, notably increasing the rate of spermatozoa exhibiting pre-capacitation and mitochondrial activity by approximately 34% and 16%, respectively (p < 0.05). It was found that 20 µg/mL resveratrol prevented pre-capacitation (p < 0.05). Both resveratrol and resveratrol-loaded cyclodextrin groups improved post-thaw sperm qualities overall, demonstrating their utility for freezing ram semen. However, higher concentrations of resveratrol were found to negatively impact sperm functions.

RNA-Seq Analysis Revealed circRNAs Associated with Resveratrol-Induced Apoptosis of Porcine Ovarian Granulosa Cells.

Circular RNAs (circRNAs) are a class of circular non-coding RNAs that play essential roles in the intricate and dynamic networks governing cell growth, development, and apoptosis. Resveratrol (RSV), a non-flavonoid polyphenol, is known to participate in follicular development and ovulation. In our previous research, we established a model using porcine ovarian granulosa cells (POGCs) treated with resveratrol, which confirmed its regulatory effects on long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) within these cells. However, the influence of resveratrol on circRNA expression has not been thoroughly investigated. To explore how resveratrol affects circRNA levels in POGCs, we designed an experiment with three groups: a control group (CON, n = 3, 0 μM RSV), a low-dose RSV group (LOW, n = 3, 50 μM RSV), and a high-dose RSV group (HIGH, n = 3, 100 μM RSV) for circRNA sequencing. We identified a total of 10,045 candidate circRNAs from POGCs treated with different concentrations of resveratrol (0, 50, and 100 μM). Differential expression analysis indicated that 96 circRNAs were significantly altered in the LOW vs. CON group, while 109 circRNAs showed significant changes in the HIGH vs. CON group. These circRNAs were notably enriched in biological processes associated with cell metabolism, apoptosis, and oxidative stress. Functional enrichment analysis of the host genes revealed their involvement in critical signaling pathways, including mTOR, AMPK, and apoptosis pathways. Additionally, we identified potential miRNA sponge candidates among the differentially expressed circRNAs, particularly novel_circ_0012954 and novel_circ_0004762, which exhibited strong connectivity within miRNA-target networks. Our findings provide valuable insights into the regulatory mechanisms of circRNAs in the context of resveratrol-induced apoptosis in POGCs, highlighting their potential as innovative therapeutic targets in reproductive biology.

The effect of resveratrol on the developmental competence of feline oocytes vitrified at the metaphase II stage

The objective of this research was to assess the viability and developmental potential of feline oocytes following in vitro maturation (IVM), vitrification, and post-warming incubation with resveratrol. In the first experiment, warmed oocytes were incubated with 0.2 μM, 2 μM, or 20 μM resveratrol for 2 h. Oocytes treated with 0.2 μM resveratrol had the highest viability (68.89 %), as assessed by fluorescein diacetate and ethidium bromide staining, while higher concentrations were associated with diminished oocyte viability. In the second experiment, the warmed oocytes were inseminated following the 2-h incubation with the three concentrations of resveratrol. The presumptive zygotes were then maintained in culture and their development evaluated. The highest cleavage rate was observed when the oocytes had been incubated with 0.2 μM resveratrol (88.34 %), which was higher than for the control group (without resveratrol (75 %)). Moreover, this concentration of resveratrol also augmented the blastocyst formation rate. While the vitrification of oocytes often results in diminished developmental potential in the ensuing embryos, attributed to cryopreservation-induced injury, the utilization of low concentrations of resveratrol enhances the procedure's efficacy.

Transcriptome analysis reveals high concentration of resveratrol promotes lipid synthesis and induces apoptosis in Siberian sturgeon (Acipenser baerii)

Resveratrol has been reported to promote immunity and decrease oxidative stress, but which demonstrates biphasic effects relied on the use concentration. In this study, the effects of diet supplement with a relative high concentration of resveratrol (0.32 mg/kg) on metabolism, antioxidation and apoptosis of liver were investigated in Siberian sturgeon. The results showed that resveratrol significantly increased the lipid synthesis and the apoptosis, but did not either activate the antioxidant NRF2/KEAP1 pathway or enhance the antioxidant enzyme activity. Transcriptome analysis revealed significant changes in regulatory pathways related to glycolipid, including PPAR signaling pathway, Insulin signaling pathway, Fatty acid biosynthesis, and Glycolysis/Gluconeogenesis. In addition, resveratrol significantly increased the lipid synthesis genes (accα and fas), fatty acid transport gene (fatp 6) and gluconeogenesis gene (gck), but decreased the survival-promoting genes (gadd45β and igf 1). These findings highlight a significant effect of resveratrol on glycolipid metabolism in Siberian sturgeon. Moreover, this study also demonstrated that 0.32 mg/kg resveratrol has physiological toxicity to the liver of Siberian sturgeon, indicating that this dose is too high for Siberian sturgeon. Thus, our study provides a valuable insight for future research and application of resveratrol in fish.

Investigating the effect of resveratrol on the survival rate of 4T1 breast cancer cells by MTT method

Cancer is known as an incurable, deadly and deadly disease with pain and disability. During recent decades, changes in people's lifestyles have increased the incidence and prevalence of breast cancer worldwide. With the wide spread of this disease, research has also increased on this issue. Resveratrol is known as a natural polyphenol found in red grapes and some other foods, and with its important anti-cancer properties, it can be effective in reducing the risk of breast cancer and its treatment. Research has shown that resveratrol can have positive effects on breast cancer by reducing DNA methylation, reducing cell proliferation, and reducing cancer growth factors. In this research, resveratrol has been used against 4T1 cancer cells, which were treated with different concentrations of resveratrol after cultivation in 96-well plates and measured by the MTT method. The obtained results showed that resveratrol in all concentrations and at different times significantly reduces the survival of 4T1 cancer cells. By increasing the concentration and treatment time, the decrease in cell viability increases. This indicates strong, dose- and time-dependent effects of resveratrol on breast cancer cells.

Resveratrol attenuates doxorubicin-induced toxicity during in vitro culture of mouse-isolated preantral follicles.

The aims of this study were to evaluate the doxorubicin concentration that induces toxic effects on in vitro culture of isolated mouse secondary follicles and to investigate whether resveratrol can inhibit or reduce this toxicity. Secondary follicles were isolated and cultured for 12 days in control medium (α-MEM+) or in α-MEM+ supplemented with doxorubicin (0.1 µg/ml) or different concentrations of resveratrol (0.5, 2, or 5 µM) associated with doxorubicin (0.1 µg/ml) (experiment 1). For experiment 2, follicles were cultured in α-MEM+ alone or supplemented with doxorubicin (0.3 µg/ml) or different concentrations of resveratrol (5 or 10 µM) associated or not with doxorubicin (0.3 µg/ml) (experiment 2). The endpoints analyzed were morphology (survival), antrum formation, follicular diameter, mitochondrial activity, glutathione (GSH) levels and DNA fragmentation. In the first experiment, doxorubicin (0.1 µg/ml) maintained survival and antrum formation similar to the control, while 5 µM resveratrol showed increased parameters, maintained mitochondrial activity and increased GSH levels compared to the control. In the second experiment, doxorubicin (0.3 µg/ml) reduced survival, antrum formation and follicular diameter compared to the control. Resveratrol at a concentration of 10 µM attenuated the damage caused by doxorubicin by improving follicular survival and did not present DNA fragmentation. In conclusion, supplementation of the in vitro culture medium with 0.3 µg/ml doxorubicin reduced the survival and impaired the development of mouse-isolated preantral follicles. Resveratrol at 10 µM reduced doxorubicin-induced follicular atresia, without DNA fragmentation in the follicles.

Denovo Production of Resveratrol by Engineered Rice Wine Strain Saccharomyces cerevisiae HJ08 and Its Application in Rice Wine Brewing.

Resveratrol is a plant-derived polyphenolic compound with numerous biological activities and health-promoting properties. Rice wine is a popular traditional alcoholic beverage made from fermented rice grains, and widely consumed in Asia. To develop resveratrol-enriched rice wine, a heterologous resveratrol biosynthesis pathway was established by integrating the 4-coumaroyl-CoA ligase (Pc4CL) and the stilbene synthase (VvSTS) from Petroselinum crispum and Vitis vinifera at the δ locus sites of industrial rice wine strains Saccharomyces cerevisiae HJ. The resulting S. cerevisiae HJ01 produced a level of 0.6 ± 0.01 mg/L resveratrol. Next, the resveratrol production was increased 16.25-fold through employing the fused protein Pc4CL::VvSTS with a rigidly linked peptide (TPTP, EAAAK). Then, the strains were further modified by removing feedback inhibition of tyrosine through point mutation of ARO4 and ARO7, which integrated at the rDNA region of strain HJ03, and generated strain HJ06, HJ07, and HJ08. Subsequently, the highest resveratrol titer (34.22 ± 3.62 mg/L) was obtained by optimizing fermentation time and precursor addition amount. Finally, resveratrol content of rice wine fermented with strain HJ08 was 2.04 ± 0.08 mg/L and 1.45 ± 0.06 mg/L with or without the addition of 400 mg/L tyrosine after 7 days fermentation.

Resveratrol suppresses liver cancer progression by downregulating AKR1C3: targeting HCC with HSA nanomaterial as a carrier to enhance therapeutic efficacy.

The enzyme AKR1C3 plays a crucial role in hormone and drug metabolism and is associated with abnormal expression in liver cancer, leading to tumor progression and poor prognosis. Nanoparticles modified with HSA can modulate the tumor microenvironment by enhancing photodynamic therapy to induce apoptosis in tumor cells and alleviate hypoxia. Therefore, exploring the potential regulatory mechanisms of resveratrol on AKR1C3 through the construction of HSA-RSV NPs carriers holds significant theoretical and clinical implications for the treatment of liver cancer. The aim of this study is to investigate the targeted regulation of AKR1C3 expression through the loading of resveratrol (RSV) on nanomaterials HSA-RSV NPs (Nanoparticles) in order to alleviate tumor hypoxia and inhibit the progression of hepatocellular carcinoma (HCC), and to explore its molecular mechanism. PubChem database and PharmMapper server were used to screen the target genes of RSV. HCC-related differentially expressed genes (DEGs) were analyzed through the GEO dataset, and relevant genes were retrieved from the GeneCards database, resulting in the intersection of the three to obtain candidate DEGs. GO and KEGG enrichment analyses were performed on the candidate DEGs to analyze the potential cellular functions and molecular signaling pathways affected by the main target genes. The cytohubba plugin was used to screen the top 10 target genes ranked by Degree and further intersected the results of LASSO and Random Forest (RF) to obtain hub genes. The expression analysis of hub genes and the prediction of malignant tumor prognosis were conducted. Furthermore, a pharmacophore model was constructed using PharmMapper. Molecular docking simulations were performed using AutoDockTools 1.5.6 software, and ROC curve analysis was performed to determine the core target. In vitro cell experiments were carried out by selecting appropriate HCC cell lines, treating HCC cells with different concentrations of RSV, or silencing or overexpressing AKR1C3 using lentivirus. CCK-8, clone formation, flow cytometry, scratch experiment, and Transwell were used to measure cancer cell viability, proliferation, migration, invasion, and apoptosis, respectively. Cellular oxygen consumption rate was analyzed using the Seahorse XF24 analyzer. HSA-RSV NPs were prepared, and their characterization and cytotoxicity were evaluated. The biological functional changes of HCC cells after treatment were detected. An HCC subcutaneous xenograft model was established in mice using HepG2 cell lines. HSA-RSV NPs were injected via the tail vein, with a control group set, to observe changes in tumor growth, tumor targeting of NPs, and biological safety. TUNEL, Ki67, and APC-hypoxia probe staining were performed on excised tumor tissue to detect tumor cell proliferation, apoptosis, and hypoxia. Lentivirus was used to silence or overexpress AKR1C3 simultaneously with the injection of HSA-RSV NPs via the tail vein to assess the impact of AKR1C3 on the regulation of HSA-RSV NPs in HCC progression. Bioinformatics analysis revealed that AKR1C3 is an important target gene involved in the regulation of HCC by RSV, which is associated with the prognosis of HCC patients and upregulated in expression. In vitro cell experiments showed that RSV significantly inhibits the respiratory metabolism of HCC cells, suppressing their proliferation, migration, and invasion and promoting apoptosis. Silencing AKR1C3 further enhances the toxicity of RSV towards HCC cells. The characterization and cytotoxicity experiments of nanomaterials demonstrated the successful construction of HSA-RSV NPs, which exhibited stronger inhibitory effects on HCC cells. In vivo, animal experiments further confirmed that targeted downregulation of AKR1C3 by HSA-RSV NPs suppresses the progression of HCC and tumor hypoxia while exhibiting tumor targeting and biological safety. Targeted downregulation of AKR1C3 by HSA-RSV NPs can alleviate HCC tumor hypoxia and inhibit the progression of HCC.

Effect of Magnetic Field and UV-C Radiation on Postharvest Fruit Properties

This review focuses on the recent information on the effect of different types of magnetic fields (MFs) and ultraviolet radiation (UV-C) on the processes that may finally affect fruit quality and its storage potential. Firstly, the biological effect of MFs on every plant’s growth and development level is described. The magnetic field interacts with a plant’s metabolism and changes the permeability of membranes affecting cells’ homeostasis. It also could affect early seedling development, stimulating enzyme activity and protein synthesis, and later on nutrient and water uptake of adult plants. In some cases, it makes plants more resilient, increasing their tolerance to environmental stresses. Also, MF treatment could lower the disease index of plants, thus improving the internal and external fruit quality indices. The second part of this review focuses on interesting perspectives of using UV-C radiation to reduce postharvest fruit diseases, but also to delay fruit ripening and senescence. The application of UV-C light to combat postharvest infections is associated with two mechanisms of action, such as direct elimination of microorganisms located on the fruit surface and indirect triggering of the plant’s defense reaction. Moreover, the use of hormetic doses of UV-C can additionally increase the nutritional properties of fresh fruit, lead to the accumulation of desired phytochemicals such as polyphenols, for example, to increase anthocyanin or resveratrol content, or elevate antioxidant activity.