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1.
The Effect of Transcription Factor MYB14 on Defense Mechanisms in Vitis quinquangularis-Pingyi.
Luo, Y, Wang, Q, Bai, R, Li, R, Chen, L, Xu, Y, Zhang, M, Duan, D
International journal of molecular sciences. 2020;(3)
Abstract
In the current study, we identified a transcription factor, MYB14, from Chinese wild grape, Vitis quinquangularis-Pingyi (V. quinquangularis-PY), which could enhance the main stilbene contents and expression of stilbene biosynthesis genes (StSy/RS) by overexpression of VqMYB14. The promoter of VqMYB14 (pVqMYB14) was shown to be induced as part of both basal immunity (also called pathogen-associated molecular pattern (PAMP)-triggered immunity, PTI) and effector-triggered immunity (ETI), triggered by the elicitors flg22 and harpin, respectively. This was demonstrated by expression of pVqMYB14 in Nicotiana benthamiana and Vitis. We identified sequence differences, notably an 11 bp segment in pVqMYB14 that is important for the PTI/ETI, and particularly for the harpin-induced ETI response. In addition, we showed that activation of the MYB14 promoter correlates with differences in the expression of MYB14 and stilbene pattern induced by flg22 and harpin. An experimental model of upstream signaling in V. quinquangularis-PY is presented, where early defense responses triggered by flg22 and harpin partially overlap, but where the timing and levels differ. This translates into a qualitative difference with respect to patterns of stilbene accumulation.
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2.
Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors.
Biswas, P, Dellanoce, C, Vezzoli, A, Mrakic-Sposta, S, Malnati, M, Beretta, A, Accinni, R
Nutrients. 2020;(11)
Abstract
The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.
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3.
Resveratrol and inflammatory bowel disease.
Shi, Y, Zhou, J, Jiang, B, Miao, M
Annals of the New York Academy of Sciences. 2017;(1):38-47
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn's disease (CD). Progression of IBD leads to long-term impairment of intestinal structure and function. The pathogenesis of IBD is complex, involving environmental, immunological, genetic, microbial, and psychological factors. The conventional therapies and many existing biopharmaceuticals for IBD have limited efficacy or adverse effects. As a promising safe and effective therapy for IBD, resveratrol has been studied widely, as it has shown anti-inflammatory and antioxidant activity. Resveratrol's mechanism of action involves multiple immune responses and signaling pathways; it is absorbed quickly and metabolized into various derivatives. However, the poor water solubility and low bioavailability of resveratrol limit its clinical applications. Further research should attempt to improve the stability and oral bioavailability of resveratrol by modification and various delivery systems.
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4.
Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.
Cremon, C, Stanghellini, V, Barbaro, MR, Cogliandro, RF, Bellacosa, L, Santos, J, Vicario, M, Pigrau, M, Alonso Cotoner, C, Lobo, B, et al
Alimentary pharmacology & therapeutics. 2017;(7):909-922
Abstract
BACKGROUND Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.
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5.
Seeking new anti-cancer agents from autophagy-regulating natural products.
Hua, F, Shang, S, Hu, ZW
Journal of Asian natural products research. 2017;(4):305-313
Abstract
Natural products are an important original source of many widely used drugs, including anti-cancer drugs. Early research efforts for seeking anti-cancer therapy from the natural products are mainly focused on the compounds with cytotoxicity capability. The good examples include vinblastine, vincristine, the camptothecin derivatives; topotecan, irinotecan, epipodophyllotoxin derivatives and paclitaxel. In a recent decade, the fundamental progression has been made in the understanding of molecular and cellular mechanisms regarding tumor initiation, metastasis, therapeutic resistance, immune escape, and relapse, which provide a great opportunity for the development of new mechanism-based anticancer drugs, especially drugs against new molecular and cellular targets. Autophagy, a critical cell homeostasis mechanism and promising drug target involved in a verity of human diseases including cancer, can be modulated by many compounds derived from natural products. In this review, we'll give a short introduction of autophagy and discuss the roles of autophagy in the tumorigenesis and progression. And then, we summarize the accumulated evidences to show the anti-tumor effects of several compounds derived from natural products through modulation of autophagy activity.
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6.
Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.
Toliopoulos, IK, Simos, YV, Oikonomidis, S, Karkabounas, SC
Indian journal of biochemistry & biophysics. 2013;(1):14-8
Abstract
Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 x 10(-3)M completely inhibited platelet aggregation (p < 0.05), decreased TXB2 levels (p < 0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p < 0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 +/- 34, 450 +/- 34 and 62 +/- 2.4% (p < 0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.
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7.
One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
Tomé-Carneiro, J, Larrosa, M, Yáñez-Gascón, MJ, Dávalos, A, Gil-Zamorano, J, Gonzálvez, M, García-Almagro, FJ, Ruiz Ros, JA, Tomás-Barberán, FA, Espín, JC, et al
Pharmacological research. 2013;:69-82
Abstract
Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8 mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.
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8.
Regulatory role of resveratrol on Th17 in autoimmune disease.
Petro, TM
International immunopharmacology. 2011;(3):310-8
Abstract
The immune system is balanced with cells that respond to microbes by developing into effector cells and cells that regulate the activity of effector cells. In many immune responses a subset of effector T cells termed Th17 are necessary for complete immunity because the cytokine IL-17 that they produce is critical to elimination of the pathogen. However, the activity of Th17 must be balance with development of regulatory T cells termed T(regs). Usually, when the activity of the effector cells is excessive and not balanced by regulatory cells of the immune system, there is the increased risk for development of autoimmune diseases. Therefore in many autoimmune diseases the activity of Th17 exceeds that of T(regs). Therapeutics for treatment of autoimmune diseases such as Multiple Sclerosis (MS) have focused upon immunosuppression, immunomodulation, or even immunoablation of effector cells such as Th17 followed by hematopoietic stem cell transplantation. Very few approaches have attempted to therapeutically increase immune regulatory cells such as T(regs) in the treatment of autoimmune disease. This review will focus upon the potential `or the use of resveratrol, a natural plant compound that has already been shown to be a potent anti-inflammatory compound, as a complementary therapeutic for MS that increases the activity of T(regs) even though it also increases development of Th17.
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9.
Effects of resveratrol on human immune cell function.
Falchetti, R, Fuggetta, MP, Lanzilli, G, Tricarico, M, Ravagnan, G
Life sciences. 2001;(1):81-96
Abstract
Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol found in grapes and grape products such as red wine, has been reported to exhibit a wide range of biological and pharmacological activities both in vitro and in vivo. Because many of the biological activities of resveratrol, like the inhibition of cyclooxygenase, induction of CD95 signaling-dependent apoptosis, effects on cell division cycle and modulation of NF-kB activation, suggest a possible effect on the immune system, we evaluated the in vitro effects of resveratrol in three immune response models: i) development of cytokine-producing CD4+ and CD8+ T cells induced by stimulation of peripheral blood mononuclear cells (PBMC) with anti-CD3/anti-CD28; ii) specific antigen-induced generation of cytotoxic T lymphocytes; iii) natural killer (NK) activity of PBMC. The results showed that in vitro exposure to resveratrol produces a biphasic effect on the anti-CD3/anti-CD28-induced development of both IFN-gamma- IL2- and IL4-producing CD8+ and CD4+ T cells, with stimulation at low resveratrol concentrations and suppression at high concentrations. Similarly, the compound was found to induce a significant enhancement at low concentrations and suppression at high concentrations of both CTL and NK cell cytotoxic activity. On the whole, the results of the study indicate that resveratrol modulates several human immune cell functions and suggest that this activity may be related to its effects on cytokine production by both CD4+ and CD8+ T cells.