Resveratrol: Challenges and prospects in extraction and hybridization with nanoparticles, polymers, and bio-ceramics.

Resveratrol (RSV), a bioactive natural phenolic compound found in plants, fruits, and vegetables, has garnered significant attention in pharmaceutical, food, and cosmetic industries due to its remarkable biological and pharmacological activities. Despite its potential in treating various diseases, its poor pharmacokinetic properties, such as low solubility, stability, bioavailability, and susceptibility to rapid oxidation, limit its biomedical applications. Recent advancements focus on incorporating resveratrol into innovative materials like nanoparticles, polymers, and bio-ceramics to enhance its properties and bioavailability. In this review, an exhaustive literature search was conducted from PubMed, Google Scholar, Science Direct, Scopus, and Web of Science databases to explore these advancements, to compares conventional and innovative extraction methods, and to highlights resveratrol's therapeutic potential, including its anti-inflammatory, anti-oxidative, anti-cancerogenic, antidiabetic, neuroprotective, and cardio-protective properties. Additionally, we discuss the challenges and prospects of hybrid materials combining resveratrol with nanoparticles, polymers, and bio-ceramics for therapeutic applications. Rigorous studies are still needed to confirm their clinical efficacy.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers.

Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1ß, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV's immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.

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

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

Antimicrobial efficiency and cytocompatibility of resveratrol and naringin as chemical decontaminants on SLA surface.

Bacterial biofilms are the major etiology agent of peri-implant disease. Chemical decontamination is a promising treatment strategy against bacterial biofilms; however, its applications are limited by its low efficiency and poor biocompatibility. In contrast to three conventional cleaners (sterile saline, hydrogen peroxide, and chlorhexidine), this study used resveratrol and naringin solutions to remove mature Staphylococcus aureus and Porphyromonas gingivalis biofilm on sandblasted (with large grit and acid-etched (SLA) titanium surface. To determine changes in surface characteristics, the surface wettability and roughness were measured, and micromorphology was observed by scanning electron microscopy. With crystal violet (CV) and live/dead bacterial staining, residual plaque quantity and composition were measured. The biocompatibility was tested using pH and cytotoxicity, as well as by osteoblasts (MC3T3-E1) adhesion, proliferation, and differentiation, and fibroblasts (L-929) proliferation were also analyzed. It was found that resveratrol and naringin solutions were more effective in restoring surface characteristics and also showed that less plaque and viable bacteria were left. Naringin removed S. aureus biofilms better than chlorhexidine. Alkaline resveratrol and naringin solutions increased cell adhesion, proliferation, and osteogenic differentiation without any cytotoxicity. Resveratrol increased the expression of mRNA and protein associated with osteogenesis. In conclusion, resveratrol and naringin effectively restored SLA titanium surface characteristics and decontaminated the biofilm with good biocompatibility, suggesting their therapeutic potential as chemical decontaminants. IMPORTANCE: Bacterial biofilms are considered the primary etiology of peri-implant disease. Physical cleaning is the most common way to remove bacterial biofilm, but it can cause grooving, melting, and deposition of chemicals that alter the surface of implants, which may hamper biocompatibility and re-osseointegration. Chemical decontamination is one of the most promising treatments but is limited by low efficiency and poor biocompatibility. Our study aims to develop safer, more effective chemical decontaminants for peri-implant disease prevention and treatment. We focus on resveratrol and naringin, two natural compounds, which have shown to be more effective in decontaminating biofilms on dental implant surfaces and exerting better biocompatibility. This research is groundbreaking as it is the first exploration of natural plant extracts' impact on mature bacterial biofilms on rough titanium surfaces. By advancing this knowledge, we seek to contribute to more effective and biocompatible strategies for combating peri-implant diseases, enhancing oral health, and prolonging implant lifespan.

Suppression of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by cyclophosphamide toxicity using resveratrol in rat models.

Cyclophosphamide (CP) is a chemotherapy drug that can be used to treat different types of cancers, but its nephrotoxicity effects restrict its usage in clinical settings. Currently, we examined whether the polyphenolic antioxidant and anti-inflammatory compound, resveratrol (RES), can protect against CP-induced nephrotoxicity. Twenty male mature Sprague-Dawley rats were divided into 4 groups of equal size: control group, RES group which received RES (20 mg/kg) for 15 consecutive days, CP group which received CP as a single dose (150 mg/kg) on day 16, and CP+RES group which was similar of the RES and CP groups. Tissue samples were obtained for the stereological, immunohistochemical, biochemical, and molecular evaluations. Findings showed that the numerical density of glomerulus, total volumes and interstitial tissue volumes of kidney, antioxidative biomarkers concentrations (CAT, GSH, SOD), and expression levels of OCT2 gene were notably greater in the CP+RES group than the CP group (P<0.05). During treatment, there was a significant decrease in the serum levels of the urea and creatinine, the densities of apoptotic and inflammatory cells, as well as levels of MDA and proinflammatory cytokines (IL-1ß, TNF-α, and PFN1) in the CP+RES group than the CP group (P<0.05). We deduce that giving RES can suppress of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by CP toxicity.

Trans-resveratrol mitigates miR-204-3p mediated progression of allergic rhinitis by regulating the EGLN3/HIF-1α/IL33/ST2 signalling pathway.

BACKGROUND: Allergic rhinitis (AR) is a multifactorial disease triggered by interactions between genes and the environment. Clinical evidence has shown that trans-resveratrol, a widely used drug, significantly ameliorates AR pathology. However, the precise mechanisms underlying this effect remain unclear. PURPOSE: This study aimed to elucidate the pharmacological mechanisms of action of trans-resveratrol in patients with AR who exhibit hypoxic symptoms. This will be achieved through microRNA sequencing and signaling pathway screening combined with basic experiments to determine the effects of Trans-resveratrol intervention in this patient population. METHODS: Network pharmacology was used to determine the therapeutic value of trans-resveratrol in AR. The micro-RNA miR-204-3p was pinpointed by sequencing. Quantitative reverse transcription polymerase chain reaction was used to quantify the expression levels. Haematoxylin and eosin, alcian blue-periodic acid-Schiff, and Masson's trichrome staining were used to assess the effects of hypoxia on nasal mucosa immunohistochemistry and immunofluorescence-localised target proteins. Egl nine homolog 3 (EGLN3) was screened using bioinformatics software. Protein expression was detected by western blotting. Cell growth and death were gauged via Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining, respectively. Cell migration was observed using a transwell assay. Enzyme-linked immunosorbent assay was used to measure interleukin (IL)33 levels in the cell supernatants. Flow cytometry was used to verify cell cycle and antigen levels. Electron microscopy was used to visualise the status of the nasal mucosa prior to in vivo expression analysis. RESULTS: Patients with hypoxic AR demonstrated more pronounced nasal mucosal remodelling than that in patients with common AR. Sequencing results indicated that these patients had a reduced expression of miR-204-3p. Through a combination utilizing of bioinformatics analysis and experimental validation, EGLN3 has been identified as a direct target of HIF-1α. The low expression level of miR-204-3p represses EGLN3, resulting in the accumulation of HIF-1α and the activation of the IL33/ST2 signaling pathway. These stimulate the proliferation, survival, and migration of HNEpCs, ultimately contributing to mucosa remodeling and AR progression. Trans-resveratrol notably downregulated the levels of HIF-1α and IL33/ST2, while simultaneously increasing the expression of EGLN3. CONCLUSIONS: Downregulation of miR-204-3p initiated a vicious cycle of hypoxic AR via EGLN3/HIF-1α/IL33/ST2. Trans-resveratrol reversed the pathological process of nasal mucosa remodeling of hypoxic AR by exhibiting anti-inflammatory and anti-angiogenic functions via the above signaling pathway. Our study uncovers the underlying mechanism by which hypoxia drives the progression of AR. It presents innovative strategies for addressing inflammatory and hypoxia-related diseases, bridging traditional and modern medicine, and highlighting the potential of natural compounds in clinical practice.

Resveratrol Alleviated T-2 Toxin-Induced Liver Injury via Preservation of Nrf2 Pathway and GSH Synthesis.

T-2 toxin is a trichothecene mycotoxin and is considered as an extremely inevitable pollutant with potent hepatotoxicity. However, the approach to alleviation of T-2 toxin-triggered hepatotoxicity has been recognized as a serious challenge. Resveratrol (Res) is a polyphenol natural product isolated from various plant species, but its protective effect against T-2 toxin hepatotoxicity and detailed mechanism remains obscure. In the present study, the effect of Res against the hepatotoxicity was evaluated, and the underlying mechanisms were further revealed in mice. Functionally, Res inhibited liver injury, oxidative damage, and mitochondrial dysfunction induced by T-2 toxin. Mechanistically, Res modulated Nrf2-mediated antioxidant pathway and glutathione synthesis inhibition. Collectively, our findings first showed beyond doubt that Res ameliorated T-2 toxin-triggered liver injury by regulating Nrf2 pathways in mice.

Outcome of resveratrol and resveratrol with donepezil combination on the ß-amyloid plaques and neurofibrillary tangles in Alzheimer's disease.

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

Rapid Synthesis and Evaluation of Resveratrol-Piperazine Cocrystals by Ultrasound and Microwave Methods.

OBJECTIVE: Resveratrol-piperazine cocrystals have been obtained by ultrasound (US) and microwave-assisted (MW) techniques, using the solution and slurry-based methods, to study the influence of the synthesis method on the resulting cocrystal properties, and scalability of the processes. The potential of these cocrystals is represented by the unique properties of their components, resveratrol, and piperazine, which could be also used in veterinary practice. Resveratrol has antimicrobial, antiviral and anticarcinogenic properties, while piperazine can be used in the treatment of parasitic infections. METHODS: The influence of ultrasound and microwave-assisted treatment was studied by varying synthesis parameters such as reaction time, temperature, and US or MW power. The main advantage of using these methods is represented by shorter synthesis time compared to conventional methods, resulting in the direct formation of the cocrystals. RESULTS: All samples were obtained in high purity, above 97%. Cocrystal yield correlated positively with ultrasound reaction time, while temperature was not found to influence the microwave synthesis yield up to 50°C, in the case of solution-based methods. MW and US-assisted solution-based methods lead to yields between 52.9 and 68.1%. In the case of the slurry-based method, a minimum reaction time of 5 min leads to the formation of cocrystals with high purity. The resveratrol-piperazine cocrystal's solubility and in vitro antibacterial activity were also evaluated, showing promising results. CONCLUSIONS: Ultrasound and microwave-assisted techniques offer a viable alternative for synthesizing resveratrol-piperazine cocrystals with short reaction times, high yield, and purity, suitable for scalable resveratrol-piperazine cocrystals.

Combinatorial effect of Apigenin-resveratrol on white adipocyte plasticity and trans-differentiation for activating lipid metabolism.

Inducing browning in white adipocytes has emerged as a promising therapeutic approach for addressing obesity. Bioactive that modulate the WAT microenvironment to induce trans browning in white adipocytes have been explored as a strategy to control unregulated lipid storage. However, relying on a single bioactive for modulating lipid metabolism has proven insufficient in obese individuals during human trials, because these compounds primarily activate a single biochemical pathway in promoting browning. Consequently, there is a growing emphasis on targeting multiple pathways to ensure a safe and effective browning process. The present study investigated the combinatorial effect of bioactives namely Apigenin and Resveratrol for activating multiple pathways for effective trans-browning of white adipocytes. The combination was seen to promote the browning more effectively than the single bioactive, as the combination simultaneously activated multiple signaling pathways to induce angiogenesis-mediated browning in primary white adipocytes isolated from obese mice. Activation of PI3K signaling via estrogen receptor-α-dependent pathway resulted in simultaneous activation of angiogenesis and trans browning in white adipocytes. The study provides valuable insights into the potential use of bioactives in combination with therapeutic intervention to improve the overall health of obese subjects by enhancing lipid metabolism by activating trans-differentiation of white adipocytes.

Resveratrol Enhances Antioxidant and Anti-Apoptotic Capacities in Chicken Primordial Germ Cells through m6A Methylation: A Preliminary Investigation.

Avian primordial germ cells (PGCs) are essential in avian transgenic research, germplasm conservation, and disease resistance breeding. However, cultured PGCs are prone to fragmentation and apoptosis, regulated at transcriptional and translational levels, with N6-methyladenosine (m6A) being the most common mRNA modification. Resveratrol (RSV) is known for its antioxidant and anti-apoptotic properties, but its effects on PGCs and the underlying mechanisms are not well understood. This study shows that RSV supplementation in cultured PGCs improves cell morphology, significantly enhances total antioxidant capacity (p < 0.01), reduces malondialdehyde levels (p < 0.05), increases anti-apoptotic BCL2 expression, and decreases Caspase-9 expression (p < 0.05). Additionally, RSV upregulates the expression of m6A reader proteins YTHDF1 and YTHDF3 (p < 0.05). m6A methylation sequencing revealed changes in mRNA m6A levels after RSV treatment, identifying 6245 methylation sites, with 1223 unique to the control group and 798 unique to the RSV group. Combined analysis of m6A peaks and mRNA expression identified 65 mRNAs with significantly altered methylation and expression levels. Sixteen candidate genes were selected, and four were randomly chosen for RT-qPCR validation, showing results consistent with the transcriptome data. Notably, FAM129A and SFRP1 are closely related to apoptosis, indicating potential research value. Overall, our study reveals the protective effects and potential mechanisms of RSV on chicken PGCs, providing new insight into its use as a supplement in reproductive stem cell culture.

Nrf2 cell signaling pathway is responsible for the antioxidant effect of resveratrol in aging.

INTRODUCTION: One of the markers of aging is oxidative stress, a condition characterized by an increase in free radicals concomitant with a reduction in antioxidant defenses. Within this, resveratrol is a compound that has been shown to act as a potent antioxidant. However, few studies highlight the cellular signaling pathways that are activated or inhibited during aging and that are responsible for this biological effect. AIM: To verify the antioxidant profile of resveratrol (5 µM) in leukocytes from donors in different age groups. METHODS: The project was approved by the Ethics Committee. Individuals were divided into three groups: 20-39, 40-59, and 60-80 years old. After separating the leukocytes, assays were performed to evaluate the AMPK (AMP-activated protein kinase) and Nrf2 (erythroid nuclear factor 2-related factor 2) pathways. In addition, luciferase assay and enzyme-linked immunosorbent assay were performed to evaluate transcription factor activation and Nrf2 expression, respectively. The analysis between age and treatment was performed using Pearson correlation (*P < 0.05). RESULTS: There was a reduction in the antioxidant effect of resveratrol during the aging process. In leukocytes from donors over 60 years of age, the AMPK pathway was silenced. Nrf2 was active at all ages. There was an increase in the activation of the transcription factor and phosphorylated protein in all age groups. CONCLUSIONS: Nrf2 is an important biochemical mechanism responsible for the antioxidant effect of resveratrol. This effect diminishes with aging but is still observed. Geriatr Gerontol Int 2024; ••: ••-••.

Effect of resveratrol on spermatogenesis in breeding boars and the proteomic analysis for testes.

Effect of resveratrol (RSV) on spermatogenesis and the mechanism of resveratrol in promoting spermatogenesis of breeding boars was explored by feeding sexually mature Duroc boars with normal diet and 20 mg/kg resveratrol diet for 14 days to the control group and experimental group, respectively. Semen volume, sperm density, motility, viability and abnormality rate were analyzed on day 0, 7, and 14. Blood samples were collected, and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) in serum were analyzed. On day 14, the testis tissue was collected for antioxidant and proteomics analysis etc. The semen volume, sperm density, motility, and viability of the experimental group and the contents of serum FSH, LH, T and plasma SOD activity were significantly higher than those in the control group. However, the serum IL-6, TNF-α and plasma MDA were remarkably lower in experimental group. The above results showed that resveratrol can simulate spermatogenesis in breeding boars. Proteomic results demonstrated that three differentially expressed proteins (DEPs) were up-regulated and 12 DEPs were down-regulated; ODF1, calmodulin, Cabs1, and Hp were involved in spermatogenesis; and the main enriched metabolic pathway is steroid hormone synthesis pathway. Therefore, the improvement in sperm quality by resveratrol may be achieved by regulating the changes in outer dense fiber 1, calmodulin, spermatid specific 1, and haptoglobin expression and steroid synthesis pathway.

[Resveratrol enhances the local antioxidant ability of the ovary in rats with polycystic ovary syndrome].

OBJECTIVE: To investigate the effects of resveratrol (RSV) on ovarian morphology, plasma anti-Müllerian hormone (AMH) and insulin-like growth factor 1 levels (IGF-1), and oxidative stress parameters in rats with polycystic ovary syndrome (PCOS). METHODS: Forty-six rats were randomly divided into a normal control (n = 12), a PCOS model control (n = 12), a rosiglitazone (RSG, n = 11), and an RSV group (n = 11). The PCOS model was established in the latter three groups by rejection of epidehydroandrosterone. The rats in the normal control and PCOS model control groups were treated by gavage of normal saline and those in the RSG and RSV groups by intragastric administration of RSG at 10 mg/(kg·d) and RSV at 3.0 mg/(kg·d), respectively. After 4 weeks of treatment, the ovarian histology was observed under the light microscope, the levels of plasma AMH and IGF-1 measured by ELISA, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the ovarian tissue detected using the Ellman, Sun and AEBI methods, respectively. RESULTS: After a 4-week treatment, statistically significant differences were observed in the above indicators between the normal control and PCOS model control groups (P<0.05). The rats treated with RSG and RSV also showed significant differences in these parameters from the model controls (P<0.05). CONCLUSION: RSV can enhance the local antioxidant capacity of the ovary, reduce the levels of AMH and IGF-1, and improve the morphology of the ovarian tissue in rats with PCOS, indicating its potential value in the treatment of PCOS.

Herbal nanoparticles: a targeted approach for neurodegenerative disorder treatment.

Nanotechnology has significantly impacted human life, particularly in overcoming the limitations associated with neurodegenerative diseases (NDs). Various nanostructures and vehicle systems, such as polymer nanoparticles, carbon nanotubes (CNTs), nanoliposomes, nano-micelles, lipid nanoparticles, lactoferrin, polybutylcyanoacrylate, and poly lactic-co-glycolic acid, have been shown to enhance drug efficacy, reduce side effects, and improve pharmacokinetics. NDs affect millions worldwide and are challenging to treat due to the blood-brain barrier (BBB), which hinders drug delivery to the central nervous system (CNS). Research suggests that natural ingredients can be formulated into nanoparticles, offering a promising approach for ND treatment. This review examines the advantages and disadvantages of herbal-based nanoformulations, highlighting their potential effectiveness when used alone or in combination with other medications. Herbal nanoparticles provide benefits over synthetic ones due to their biocompatibility, reduced toxicity, and potential for synergistic effects. The study's findings can be applied to develop more efficient drug delivery systems, improving the treatment of NDs by enhancing drug penetration across the BBB and targeting affected CNS areas more precisely.

A one-dimensional bacterial cellulose nano-whiskers-based binary-drug delivery system for the cancer treatment.

It's currently a challenge to design a drug delivery system for chemotherapy with high drug contents and minimal side effects. Herein, we constructed a novel one-dimensional binary-drug delivery system for cancer treatment. In this drug delivery system, drugs (doxorubicin (DOX) and resveratrol (RES)) self-assemble on bacterial cellulose nano-whiskers (BCW) and are subsequently encapsulated by polydopamine (PDA) with high encapsulation efficiencies (DOX: 81.53 %, RES: 70.32 %) and high drug loading efficiencies (DOX: 51.54 %, RES: 36.93 %). The cumulative release efficiencies can reach 89.27 % for DOX and 80.05 % for RES in acidic medium within 96 h. The BCW/(DOX + RES)/PDA can enter tumor cells easily through endocytosis and presents significant anti-cancer effects. Furthermore, the released-RES plays a protective role in normal cells through up-regulation of antioxidant enzymes activities and scavenging of reactive oxygen species. Taken together, the one-dimensional BCW/(DOX + RES)/PDA binary-drug delivery system can be used for the anticancer treatment along with slight side effects.

Dietary resveratrol supplementation alleviates cold exposure-induced pyroptosis and inflammation in broiler heart by modulating oxidative stress and endoplasmic reticulum stress.

To explore the potential protective effect of resveratrol (RES) on cold-exposed broilers, 360 21-day-old broilers were equally divided into 5 groups with 6 replicates. A control (CON) group was reared at the normal feeding temperature and received a basal diet, and 4 cold exposure (8 ± 1°C for 10 h/d from d 29 to 42) groups were fed the basal diet with 0 (CE), 250 (CE + RES250), 500 (CE + RES500), and 750 (CE + RES750) mg/kg RES from d 22 to 42. Broilers were slaughtered on d 42 and heart tissues were collected to measure the relevant indexes. The results showed that heart tissues of all CE-broilers had inflammatory cell infiltrations, and dietary RES supplementation reduced this phenomenon. Compared to CON group, the concentrations of MDA and H2O2 were increased and activities of SOD and CAT were decreased in all CE-broilers (P < 0.05). mRNA expression of genes related to endoplasmic reticulum (ER) stress (GRP78, IRE1, PERK, EIF-2α, ATF4, ATF6, and CHOP), pyroptosis (NLRP3, ASC, Caspase1, GSDME, IL-18, and IL-1ß), and proinflammation (TNF-α, IFN-γ, IL-2, and IL-6) was upregulated and that of ant-inflammatory cytokines (IL-4 and IL-10) was downregulated in CE and all CE + RES groups compared to CON group (P < 0.05). Compared to CE group, the activities of SOD and CAT and mRNA expression of anti-inflammatory genes were increased (P < 0.05), and concentrations of MDA and H2O2 and mRNA expression of ER stress, pyroptosis and proinflammatory genes were reduced (P < 0.05) in 3 CE + RES groups. Additionally, protein levels of PERK, ATF4, CHOP, NLRP3, Caspase1, GSDMD, IL-18, IL-1ß, TNF-α, and IL-10 were similar in their mRNA expression. Overall, cold exposure caused oxidative stress and ER stress, and induced pyroptosis and inflammatory response, resulting in heart injury in broilers, and dietary RES addition reduced heart damage by enhancing antioxidant defense function. This study indicates that RES can be a feed additive to alleviate cold exposure-induced heart injury in broilers, and a 500 mg RES/kg diet is the optimal supplemental level.

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

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

A comparison of different cleaning approaches for blood contamination after curing universal adhesives on the dentine surface.

OBJECTIVE: This study compared the effectiveness of various cleaning approaches, including spray rinsing, repreparing with diamond burs, and using phosphoric acid or sodium hypochlorite alone or with polyphenols (resveratrol or myricetin), in removing blood contamination from the dentine after adhesive light-curing. METHODS: The contact angles of the treated surfaces were measured and scanning electron microscopy/ energy dispersive X-ray spectroscopy observation was performed. The bond strength and nanoleakage were assessed, and in situ zymography was performed before and after aging. Interactions between matrix metalloproteinase (MMP)-9 and polyphenols were evaluated using molecular dynamics and rhMMP-9 inhibition analyses. The destruction of sodium hypochlorite on collagen and the resistance of polyphenols-treated dentine collagen to enzymolysis were evaluated using the hydroxyproline (HYP) assay. The effect of polyphenols on dentine collagen crosslinking was assessed by Fourier Transform Infrared Spectroscopy. RESULTS: The repreparation group had the lowest contact angle compared to the other groups. The spray rinsing group had the lowest bond strength and highest amounts of nanoleakage. Cleaning with phosphoric acid or sodium hypochlorite alone removed the blood contaminants and parts of the adhesive; moreover, applying polyphenols further improved the bond strength and decreased nanoleakage and MMP activity after aging. Both polyphenols inhibited rhMMP-9 activity and promoted collagen crosslinking. Sodium hypochlorite showed the maximum HYP release when used alone, which was decreased after adding polyphenols. SIGNIFICANCE: Phosphoric acid or sodium hypochlorite cleaning can remove blood contamination from the dentine surface after adhesive curing, and the addition of polyphenols can improve the durability of dentine bonding.

Dual combination of resveratrol and pterostilbene aqueous core nanocapsules for integrated prostate cancer targeting.

ABSTARCTAim: Development and evaluation of aqueous core nanocapsules (ACNs) of BCS-II-class drug like resveratrol (RSV) and pterostilbene (PTE) for prostate cancer. Materials & methods: Identify synergistic effects of molar ratios of RSV and PTE against PC-3 cell. Selected ratio of drugs was added to ACNs by double-emulsification-method using Box-Behnken design. Further, assessed for physicochemical characterization, release kinetics, compatibility, in vitro cytotoxicity, in vivo pharmacokinetic and biodistribution studies. Results: Selected 1:1 ratio of RSV and PTE had greatest synergy potential have smaller particle-size (128.1 ± 3.21 nm), zeta-potential (-22.12 ± 0.2 mV), 0.53 PDI, improved encapsulation (87% for RSV, 72% for PTE), stable, no systemic toxicity, high biodistributed/accumulated in prostate cells. Conclusion: ACNs exhibited high t1/2 (12.42 ± 1.92 hs) and 8.20 ± 8.21 hs Mean Residence Time and lower clearance, proving the high effectiveness for prostate cancer.

[Box: see text].