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Background: Resveratrol, a kind of polyphenolic phytoalexin, can be obtained from numerous natural foods. Although resveratrol is demonstrated to have various bioactivities, little is known about the regulation of intestinal barrier function under immunosuppression. The present study is aimed at investigating the regulatory effect of resveratrol on intestinal barrier function in immunosuppression in mice induced by cyclophosphamide., Results: The effects of resveratrol on intestinal biological barrier were evaluated by 16S rRNA and metagenome sequencing analysis. The results showed that resveratrol could improve diversity of the intestinal microbiota and intestinal flora structure by increasing the abundance of probiotics, and resveratrol regulated the function of gut microbiota to resist immunosuppression. Resveratrol could significantly upregulate the secretion of secretory immunoglobulin A and promote the transcriptional levels of test cytokines, including tumor necrosis factor α, interferon γ, interleukin 4 and interleukin 6 in jejunum and ileum mucosa, suggesting improved intestinal immune barrier by resveratrol. The mRNA and protein levels of tight junction proteins involved in intestinal physical barrier function, including zonula occludens 1 (ZO-1), claudin 1 and occludin, were increased after resveratrol treatment. The protein levels of toll-like receptor 4 (TLR4), phosphorylation nuclear factor kappa-B (NF-κB-p65) and inhibitor of nuclear factor kappa-B kinase α were decreased by resveratrol treatment when compared with the untreated group, indicating inhibition of the TLR4/NF-ĸB signaling pathway., Conclusion: These results provide new insights into regulation of the intestinal barrier function by resveratrol under immunosuppression and potential applications of resveratrol in recovering intestinal function. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Context: Resveratrol is a natural polyphenol compound. It exhibits antitumor, immunostimulatory, and antiviral activities. However, poor water solubility and structural instability limit its administration and storage. Objective: A resveratrol dry suspension (RDS) was prepared and immunomodulatory effect in immunosuppressive mice induced by cyclophosphamide and anti-inflammatory activities in mice were evaluated. Materials and methods: The preparation of RDS was optimized by the orthogonal design method. To evaluate the immunomodulatory effects, SPF Kunming mice were divided into seven groups comprising of nine males and nine females for each group. The RDS supplemented group was administrated doses of 3.33, 1.67, and 0.83 g/kg/d. Then visceral index, lymphocyte proliferation, the ratio of CD3 +  CD4 + /CD3 +  CD8 + , and the contents of cytokines in serum were tested. To ameliorate effects of acetic acid induced capillary permeability, xylene-based ear oedema, and cotton pellet granuloma, RDS as anti-inflammatory agent was administered at doses of 1, 0.33, and 0.1 g/kg/d as compared to indomethacin (IM) provided as a positive control at 10 mg/kg. Results: RDS inhibited the degradation of resveratrol and enhanced the CD3 +  CD4 + /CD3 +  CD8 + ratio, spleen index, IL-2 level, and splenic lymphocytes in immunosuppressive mice. RDS (0.1 g/kg/d) significantly inhibited the acetic acid-induced capillary permeability, and at doses of 0.33 and 1 g/kg/d repressed the ear swelling and granuloma formation in immunocompromised mice. Discussion and Conclusion: RDS is a stable, cheaper, and suitable preparation with potent immunoregulatory and anti-inflammatory activities. Keeping in view these remarkable properties, RDS could be an appropriate preparation for clinic use of resveratrol.

Resveratrol had shown various properties before, like immunomodulatory, anti-inflammatory and antiviral activities. Based on these properties, the present study was designed to evaluate the effects and mechanism of resveratrol as an immune-adjuvant for pseudorabies virus (PRV) vaccine. We found that oral administration of resveratrol to mice significantly increased the number of T lymphocytes in the spleen, and elevated the concentrations of antibodies and cytokines in the serum. Resveratrol (30 mg/kg) could enhance phagocytic capacity of peritoneal macrophage (PM) by boosting the percentage of phagocytosis, phagocytic index and the level of lysozyme. Resveratrol also enhanced antigen presentation function of PM by upregulating the expressions of CD86 and MHC-II. Further study revealed that resveratrol could increase the protein levels of TLR4, Ikk, IκBα, NF-κB and JNK when compared with non-adjuvant group. These results provide further insight into the mechanism of action in adjuvant activity of resveratrol, and also offer preclinical evidence for development as a PRV vaccine adjuvant., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pseudorabies virus (PRV) is one of the most important pathogens of swine, resulting in devastating disease and economic losses worldwide. Nevertheless, there are currently no antiviral drugs available for PRV infection. Resveratrol (Res) was identified to exert its antiviral activity by inhibiting the PRV replication in preliminary investigations. In our previous study, we found that Res has anti-PRV activity in vitro. Here, we show that Res can effectively reduce the mortality and increase the growth performance of PRV-infected piglets. After Res treatment, the viral loads significantly ( p < 0.001) decreased. Pathological symptoms, particularly inflammation in the brain caused by PRV infection, were significantly ( p < 0.001) relieved by the effects of Res. In Res-treated groups, higher levels of cytokines in serum, including interferon gama, interleukin 12, tumor necrosis factor-alpha and interferon alpha were observed at 7 days post infection. These results indicated that Res possesses potent inhibitory activity against PRV-infection through inhibiting viral reproduction, alleviating PRV-induced inflammation and enhancing animal immunity, suggesting that Res is expected to be a new alternative control measure for PRV infection.

Pseudorabies virus (PRV) is a pathogen of swine resulting in devastating disease and economic losses worldwide. Resveratrol (Res) exhibits inhibitory activity against a wide range of viruses. Despite these important advances, the molecular mechanism(s) by which Res exerts its broad biological effects have not yet been elucidated. In this paper, the antiviral activity of Res against PRV and its mechanism of action were investigated. The results showed that Res potently inhibited PRV replication in a dose-dependent manner, with a 50% inhibition concentration of 17.17 μM. The inhibition of virus multiplication in the presence of Res was not attributed to direct inactivation or inhibition of viral entry into the host cells but to the inhibition of viral multiplication in host cells. Further studies demonstrated that Res is a potent inhibitor of both NF-κB activation and NF-κB-dependent gene expression through its ability to inhibit IκB kinase activity, which is the key regulator in NF-κB activation. Thus, the inhibitory effect of Res on PRV-induced cell death and gene expression may be due to its ability to inhibit the degradation of IκB kinase. These results provided a new alternative control measure for PRV infection and new insights into the antiviral mechanism of Res.

Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound, which has been extensively studied on its biological activity. It has been widely accepted that resveratrol possesses anti-inflammatory and antiviral activities. In this review, we summarize the anti-inflammatory dosages and mechanism and antiviral mechanism of resveratrol. Since viral infections are often accompanied by inflammation, we propose that the NF-κB signaling pathway is a key and common molecular mechanism of resveratrol to exert anti-inflammatory and antiviral effects. For future studies, we believe that resveratrol's anti-inflammatory and antiviral mechanisms can consider the upstream signaling molecules of the NF-κB signaling pathway. For resveratrol antivirus, future studies can be conducted on the interaction of resveratrol with key proteins or important enzymes of the virus. In addition, we also think that the clinical application of resveratrol is very important. In short, resveratrol is a promising anti-inflammatory and antiviral drug, and research on it needs to be expanded. [ABSTRACT FROM AUTHOR]

Resveratrol is a natural polyphenolic product in red wine and peanuts and has many pharmacological activities in humans. Our previous studies showed that resveratrol has good antiviral activity against the pseudorabies virus (PRV). However, little is known about the antiviral mechanism of resveratrol against PRV. In this study, we found that resveratrol inhibited the nuclear localization of IE180 protein, which is an important step for activating early/late genes transcription. Interestingly, the results show that resveratrol inhibited the activity of IE180 protein by dual-luciferase assay. Furthermore, molecular docking analysis shows that resveratrol could bind to the Thr601, Ser603, and Pro606 of IE180 protein. Point mutation assay confirmed that resveratrol lost its inhibition activity against the mutant IE180 protein. The results demonstrate that resveratrol exerts its antiviral activity against PRV by targeting the Thr601/Ser603/Pro606 sites of IE180 protein and inhibiting the transcriptional activation activity of IE180 protein. This study provides a novel insight into the antiviral mechanism of resveratrol against herpes viruses. [ABSTRACT FROM AUTHOR]

Resveratrol (Res) is a natural compound that possesses anti-inflammatory properties. However, the protective molecular mechanisms of Res against lipopolysaccharide (LPS)-induced inflammation have not been fully studied. In the present study, RAW264.7 cells were stimulated with LPS in the presence or absence of Res, and the subsequent modifications to the LPS-induced signaling pathways caused by Res treatment were examined. It was identified that Res decreased the mRNA levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88, TIR domain-containing adapter molecule 2, which suggested that Res may inhibit the activation of the TLR4 signaling pathway. It suppressed the expression levels of total and phosphorylated TLR4, NF-κB inhibitor, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and interferon (IFN) regulatory factor 3 (IRF3) proteins. Following treatment with Res or specific inhibitors, the production of pro-inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-6, IL-8 and IFN-β were decreased and the expression of anti-inflammatory mediator IL-10 was increased. These results suggested that Res may inhibit the signaling cascades of NF-κB, MAPKs and IRF3, which modulate pro-inflammatory cytokines. In conclusion, Res exhibited a therapeutic effect on LPS-induced inflammation through suppression of the TLR4-NF-κB/MAPKs/IRF3 signaling cascades. [ABSTRACT FROM AUTHOR]

Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute severe viral diarrhea in children (under 5 years old) and infant animals worldwide. Although vaccines are commonly used to prevent infection, episodes of diarrhea caused by RV frequently occur. Thus, this study was conducted to determine whether resveratrol had protective effects against RV infection in piglets. Following pretreatment with resveratrol dry suspension through adding into the basal diet for 3 weeks, the piglets were orally challenged with RV. We found that resveratrol could alleviate diarrhea induced by RV infection. Resveratrol-treatment inhibited the TNF-α production, indicating that the anti-RV activity of resveratrol may be achieved by reducing the inflammatory response. The IFN-γ level was elevated in 10mg/kg/d resveratrol-treated group and 30mg/kg/d resveratrol-treated group after RV infection. The ratios of CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected group, suggesting that resveratrol could maintain the immune function in RV-infected piglets. It was found that resveratrol could alleviate diarrhea induced by RV infection. These results revealed that resveratrol dry suspension could be a new control measure for RV infection. [ABSTRACT FROM AUTHOR]

Resveratrol, a polyphenolic plant antitoxin, has a wide range of pharmacological activities. In this study, we systematically evaluated the effects of resveratrol dry suspension (RDS) on immune function in piglets that were treated with different doses of RDS for 2 weeks. The results showed that the RDS has significant effects on the development, maturation, proliferation, and transformation of T lymphocytes. RDS could regulate humoral immune responses by upregulating the release of IFN-γ and downregulating the release of TNF-α. After piglets were vaccinated against classical swine fever virus and foot-and-mouth disease virus, the antibody titers were significantly increased. RDS treatment showed an excellent resistance to enhance T-SOD activity. Values of blood routine and blood biochemistry showed no toxicity. These results suggested that RDS could be considered as an adjuvant to enhance immune responses to vaccines, as well as dietary additives for animals to enhance humoral and cellular immunity. [ABSTRACT FROM AUTHOR]

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Background. Inflammation and pain are closely related to humans’ and animals’ health. Resveratrol (RSV) is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively. Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA. Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) infections in susceptible non-porcine species trigger uncontrolled inflammations and eventually fatal encephalitis. Resveratrol (Res) has broad pharmacological functions including anti-virus, anti-inflammation, and neuroprotective. We attempted to investigate the potential of Res in ameliorating PRV infection pathology in mice and decipher the mechanism of Res in treating PRV. The mice were infected by PRV to investigate the protective effect of Res. Blood-brain barrier (BBB) permeability, H&E/Nissl/TUNEL staining, Real-time PCR and ELISA analyses were performed. Primary microglia and neuron were isolated from mice and cultured. The co-culture model of microglia and neuron was established by transwell. Immunofluorescence assay and flow cytometry were used. In this study, we showed that Res ameliorated brain damage by reducing BBB permeability in PRV-infected mice, and diminished the expressions of MMP-2, MMP-9 and ZO-1 in the cortex. Pathological changes of neurons by H&E/Nissl/TUNEL staining suggested that Res could alleviate neuronal lesions. Moreover, Res inhibited the expressions of pro-inflammatory factors (IL-6, TNF-α) and chemokines (CCL3, CXCL10, MCP-1), but increased the expressions of anti-inflammatory factors (IL-4, IL-10) and neurotrophic factor (TGF-β, NGF and GDNF) in brain. In vitro cultured microglia cells, Res could suppress M1 microglia polarization and activate M2 microglia polarization. Co-culture of PRV-infected microglia with neuron cells by transwell system indicated that Res alleviated inflammatory response and neuronal apoptosis. This study provided evidence that Res could protect mice from PRV-induced encephalitis through regulation of microglia polarization and neuronal apoptosis suggesting the potential for treatment of viral encephalitis. [Display omitted] • Resveratrol ameliorated brain damage and inhibited inflammatory response following PRV infection. • Resveratrol regulates microglial M2 polarization and reduces neuronal apoptosis after PRV infection. • Promising potential of resveratrol in the therapeutic treatment of PRV infection. [ABSTRACT FROM AUTHOR]

[Display omitted] Co-localization of antigens and immunomodulators in the same antigen-presenting cells (APCs) can powerfully activate APCs and enhance immune responses. In this study, the immunomodulator resveratrol (Res) was encapsulated into quaternized chitosan (QCS) - coated liposomes for developing a new nanoparticle delivery system (QCS-Res-LP), and ovalbumin (OVA) was selected as a model antigen and adsorbed on the surface of QCS-Res-LP. The results showed that the particle size of QCS-Res-LP was 96.3 ± 3.52 nm; the PDI value was 0.280 ± 0.010; the Zeta potential was 9.59 ± 0.36 mV. QCS-Res-LP could encapsulate 76.22 ± 1.02 % resveratrol and adsorb 88.2 ± 16.3 % antigen. QCS-Res-LP effectively promoted the co-uptake of antigen and Res by dendritic cells (DCs) with 50-fold greater than resveratrol liposomes (Res-LP). QCS-Res-LP promoted expression levels of CD80, CD86, IL-2, and IL-12 in DCs. QCS-Res-LP did not cause hemolysis. The levels of ovalbumin-specific IgG antibodies and cytokines were significantly increased in mice vaccinated with ovalbumin-absorbed QCS-Res-LP, which induced a mixed Th1/Th2 immune response. In conclusion, these results demonstrated that QCS-coated liposomes enable the co-delivery of antigens and immunomodulators to induce strong and durable immune responses. [ABSTRACT FROM AUTHOR]

Duck enteritis virus (DEV) is a double-stranded DNA virus belonging to the alphaherpesvirinae subfamily of the herpesviridae . Although vaccines were wildly used in controlling this disease, some infection could still not be prevented and led to significant economic losses as a result of mortality and decreased egg production. However, there is no antiviral drug against DEV. Resveratrol was identified to exert its antiviral activity by inhibiting the DEV replication in preliminary investigations. In the present study, we confirmed that resveratrol significantly reduced the mortality of ducklings which infected with a virulent strain of DEV. With resveratrol treatment, the survival rate increased by almost 80% at 8 days post infection (dpi). Pathological symptoms of ducklings caused by DEV were also relieved by resveratrol. The virus load in blood and tissues were effectively depressed when compared with the untreated group. In the assay of immune cytokines, the resveratrol exerted a dual-regulation effect. These results suggest that resveratrol is expected to be a new alternative control measure for DEV infection. [ABSTRACT FROM AUTHOR]

Resveratrol, a kind of natural product found in over 70 plants, possesses both immunomodulatory and anticancer effects. Many reports have shown that resveratrol has the bidirectional regulation effects on antigen presenting and cellular immunity. However, few reports have evaluated the effects of resveratrol on reinforcing immunity recovery via activating nuclear factor -κappa B (NF-κB). In the present study, we investigated the effects of resveratrol on recovery and reconstruction of immune function by detecting nonspecific and specific immunity in immunosuppressive mice. We found that, compared to the immunosuppressive mice, the spleen index and spleen lymphocyte proliferation of resveratrol-treated mice (30 mg/kg body weight) were enhanced. After resveratrol-treatment (15 mg/kg body weight), the function of peritoneal macrophages was enhanced and the CD4 + cells were increased in peripheral blood. The expressions of serum cytokines related to immune function, including interleukin (IL)-1α/β, IL-2, tumor necrosis factor-α and NF-κB were up-regulated in a dose-dependent manner. The expression of the transcription factor NF-κB in spleen was enhanced after resveratrol-treatment. The immuno-enhancement effects of resveratrol were similar to that of levamisole (served as positive control). These results demonstrated that resveratrol had potent immune enhancement activity in immunosuppressive mice, and one possible mechanism of action was to activate the NF-κB. [ABSTRACT FROM AUTHOR]