stilbenes and Inflammatory-Bowel-Diseases

Topics: Animals; Benzoquinones; Biological Products; Biomimetics; Caffeic Acids; Curcumin; Cytokines; Exosomes; Humans; Inflammation; Inflammatory Bowel Diseases; Insecta; Macromolecular Substances; Nanomedicine; Oxidative Stress; Phenylethyl Alcohol; Phytochemicals; Plant Extracts; Polysaccharides; Quercetin; Resveratrol; Stilbenes; Transcription Factors; Translational Research, Biomedical; Vasoactive Intestinal Peptide; Zingiber officinale

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.

Topics: Anti-Inflammatory Agents; Antioxidants; Humans; Inflammatory Bowel Diseases; Resveratrol; Stilbenes; Treatment Outcome

Inflammatory bowel disease (IBD) is an idiopathic chronic, relapsing inflammation of the bowel which is caused by dysregulation of the mucosal immune system. Polyphenols as the secondary plant metabolites universally present in vegetables and fruits and are the most abundant antioxidants in the human diet. There is evidence demonstrating the beneficial health effects of dietary polyphenols. This review criticizes the potential of commonly used polyphenols including apple polyphenol, bilberry anthocyanin, curcumin, epigallocatechin-3-gallate (EGCG) and green tea polyphenols, naringenin, olive oil polyphenols, pomegranate polyphenols and ellagic acid, quercetin, as well as resveratrol specifically in IBD with an emphasis on cellular mechanisms and pharmaceutical aspects. Scientific research confirmed that dietary polyphenols possess both protective and therapeutic effects in the management of IBD mediated via down-regulation of inflammatory cytokines and enzymes, enhancing antioxidant defense, and suppressing inflammatory pathways and their cellular signaling mechanisms. Further preclinical and clinical studies are needed in order to understand safety, bioavailability and bioefficacy of dietary polyphenols in IBD patients.

Topics: Animals; Curcumin; Disease Management; Fruit; Humans; Inflammatory Bowel Diseases; Oxidative Stress; Plant Extracts; Polyphenols; Resveratrol; Stilbenes; Tea

Crohn's disease and ulcerative colitis presently have no cure and are treated with anti-inflammatory drugs or monoclonal antibodies targeting pro-inflammatory cytokines. A variety of rodent models have been used to model chronic and acute colitis. Dietary polyphenols in foods and botanicals are of considerable interest for prevention and treatment of colitis. Many dietary polyphenols have been utilized for prevention of colitis in rodent models. Berries, green tea polyphenols, curcumin, and stilbenes have been the most extensively tested polyphenols in rodent models of colitis. The majority of polyphenols tested have inhibited colitis in rodents, but increasing doses of EGCG and green tea, isoflavones, flaxseed, and α-mangostin have exacerbated colitis. Few studies have examined combination of polyphenols or other bioactives for inhibition of colitis. Translating polyphenol doses used in rodent models of colitis to human equivalent doses reveals that supplemental doses are most likely required to inhibit colitis from a single polyphenol treatment. The ability to translate polyphenol treatments in rodent models is likely to be limited by species differences in xenobiotic metabolism and microbiota. Given these limitations, data from polyphenols in rodent models suggests merit for pursuing additional clinical studies for prevention of colitis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Coumaric Acids; Dietary Supplements; Disease Models, Animal; Flavonoids; Functional Food; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Phenols; Plant Extracts; Polyphenols; Stilbenes; Xanthones

Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Benzopyrans; Carbazoles; Carvedilol; Diabetes Mellitus; Disease Models, Animal; Ethanolamines; Humans; Hydrogen Peroxide; Inflammatory Bowel Diseases; Nebivolol; Neoplasms; Neurodegenerative Diseases; Osteoporosis; Oxidative Stress; Propanolamines; Reactive Oxygen Species; Resveratrol; Stilbenes; Vascular Diseases

Inflammatory bowel disease (IBD) can be divided into two major categories, ulcerative colitis (UC) and Crohn disease (CD). While the main cause(s) of IBD remain unknown, a number of interventional and preventive strategies have been proposed for use against CD and UC. Many reports have focused on the use of alternative natural medicines as potential therapeutic interventions in IBD patients with minimal side effects. While the use of alternative medicines may be effective in IBD patients that are refractory to corticosteroids or thiopurins, alternative treatment strategies are limited and require extensive clinical testing before being optimized for use in patients.

Topics: Adrenal Cortex Hormones; Animals; Clinical Trials as Topic; Complementary Therapies; Humans; Inflammatory Bowel Diseases; Phytotherapy; Plants; Resveratrol; Rutin; Stilbenes

Inflammatory bowel disease (IBD) comprises a group of idiopathic chronic intestinal inflammation syndromes that are very common in developed countries. It is characterized by intermittent episodes of clinical remission and relapse, with recurrent inflammatory injury that can lead to structural damage of the intestine. The uncontrolled intestinal immune response to bacterial antigens leads to the production of abundant cytokines and chemokines, by activated leukocytes and epithelial cells, which trigger inflammatory and oxidative reactions. The current treatment of IBD consists in long-term anti-inflammatory therapy that, however, does not exclude relapses and side effects, frequently resulting in surgical intervention. Polyphenols have been acknowledged to be anti-oxidant and anti-inflammatory and therefore, have been proposed as an alternative natural approach to prevent or treat chronic inflammatory diseases. Most studies have been in animal models of colitis, using chemical inducers or mice defective in anti-inflammatory mediators and in intestinal cell lines treated with pro-inflammatory cytokines or lipid oxidation products. These studies provide evidence that polyphenols can effectively modulate intestinal inflammation. They exert their effects by modulating cell signaling pathways, mainly activated in response to oxidative and inflammatory stimuli, and NF-kB is the principal downstream effector. Polyphenols may thus be considered able to prevent or delay the progression of IBD, especially because they reach higher concentrations in the gut than in other tissues. However, knowledge of the use of polyphenols in managing human IBD is still scanty, and further clinical studies should afford more solid evidence of their beneficial effects.

Topics: Anti-Inflammatory Agents; Antioxidants; Complementary Therapies; Cytokines; Dietary Supplements; Flavonoids; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Lignans; NF-kappa B; Polyphenols; Stilbenes

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

Topics: Animals; Cell Differentiation; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Glucosides; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL; STAT3 Transcription Factor; Stilbenes; T-Lymphocytes, Regulatory; Th17 Cells; Trinitrobenzenesulfonic Acid

Inflammatory bowel disease (IBD) has emerged a global disease and the ascending incidence and prevalence is accompanied by elevated morbidity, mortality, and substantial healthcare system costs. However, the current typical one-size-fits-all therapeutic approach is suboptimal for a substantial proportion of patients due to the variability in the course of IBD and a considerable number of patients do not have positive response to the clinically approved drugs, so there is still a great, unmet demand for novel alternative therapeutic approaches. Spleen tyrosine kinase (Syk), a cytoplasmic nonreceptor protein tyrosine kinase, plays crucial roles in signal transduction and there are emerging data implicating that Syk participates in pathogenesis of several gut disorders, such as IBD. In this study, we observed the Syk expression in IBD patients and explored the effects of therapeutic Syk inhibition using small-molecule Syk inhibitor piceatannol in bone marrow-derived macrophages (BMDMs). In addition, due to the poor bioavailability and pharmacokinetics of small-molecule tyrosine kinase inhibitors and superiority of targeting nanoparticles-based drug delivery system, we herein prepared piceatannol-encapsulated poly(lactic-co-glycolic acid) nanoparticles that conjugated with chemokine C-C motif ligand 4 (P-NPs-C) and studied its therapeutic effects in vitro in BMDMs and in vivo in experimental colitis model. Our results indicated that in addition to alleviating colitis, oral administration of P-NPs-C promoted the restoration of intestinal barrier function and improved intestinal microflora dysbiosis, which represents a promising treatment for IBD.

Topics: Animals; Caco-2 Cells; Chemokine CCL4; Disease Models, Animal; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Ligands; Male; Mice; Mice, Inbred C57BL; Nanoparticle Drug Delivery System; Stilbenes; Syk Kinase; THP-1 Cells

The DNAX adaptor protein 12 (DAP12) is a transmembrane adaptor molecule that signals through the activation of Syk (Spleen Tyrosine Kinase) in myeloid cells. The purpose of this study is to investigate the role of DAP12 and Syk pathways in inflammatory bowel diseases (IBDs).. DAP12 deficient and DAP12 transgenic, overexpressing an increased amount of DAP12, mice and Syk deficient mice in the C57/BL6 background were used for these studies. Colitis was induced by administering mice with dextran sulfate sodium (DSS), in drinking water, or 2,4,6-trinitrobenzene sulfonic acid (TNBS), by intrarectal enema.. Abundant expression of DAP12 and Syk was detected in colon samples obtained from Crohn's disease patients with expression restricted to immune cells infiltrating the colonic wall. In rodents development of DSS colitis as measured by assessing severity of wasting diseases, global colitis score,and macroscopic and histology scores was robustly attenuated in DAP12-/- and Syk-/- mice. In contrast, DAP12 overexpression resulted in a striking exacerbation of colon damage caused by DSS. Induction of colon expression of proinflammatory cytokines and chemokines in response to DSS administration was attenuated in DAP12-/- and Syk-/- mice, whereas opposite results were observed in DAP12 transgenic mice. Treating wild-type mice with a DAP-12 inhibitor or a Syk inhibitor caused a robust attenuation of colitis induced by DSS and TNBS.. DAP12 and Syk are essential mediators in inflammation-driven immune dysfunction in murine colitides. Because DAP12 and Syk expression is upregulated in patients with active disease, present findings suggest a beneficial role for DAP12 and Syk inhibitors in IBD.

Topics: Adaptor Proteins, Signal Transducing; Adult; Animals; Antipruritics; Colitis; Cytokines; Disease Models, Animal; Female; Humans; Inflammation; Inflammatory Bowel Diseases; Intestinal Diseases; Ketotifen; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Stilbenes; Syk Kinase

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease in humans constituting a major health concern today whose prevalence has been increasing over the world. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in IBD subjects have been reported. Antioxidants may play a significant role in IBD treatment. This study aimed at evaluating ameliorative effects of intraperitoneal resveratrol pretreatment on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Thirty five Wistar-Albino female rats were divided equally into five groups. Inflammation was induced by the intrarectal administration of TNBS under anesthesia. Intraperitoneal administration of resveratrol (RSV) at a concentration of 10mg/kg/day for 5 days before the induction of colitis significantly reduced microscopy score and malondialdehyde (MDA) levels and increased glutathione peroxidase (GSH Px) activity compared to TNBS and vehicle groups. Also an insignificant increase in catalase (CAT) activity was observed in the RSV treated group compared to TNBS and vehicle groups. In this paper, the most recent patent on the identification and treatment of IBD was indicated. In conclusion, antioxidant RSV proved to have a beneficial effect on TNBS colitis in rats. In light of these advantageous results, the RSV can be considered as adjuvant agent in IBD treatments.

Topics: Animals; Antioxidants; Colitis; Female; Inflammatory Bowel Diseases; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Resveratrol; Stilbenes; Superoxide Dismutase; Trinitrobenzenesulfonic Acid

We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis.. Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically.. The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone.. Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Cell Line; Colon; Cytokines; Delayed-Action Preparations; Disease Models, Animal; Inflammatory Bowel Diseases; Nanoparticles; Particle Size; Rats; Resveratrol; Silk; Stilbenes

Resveratrol, a polyphenol abundantly found in grapes and red wine, exhibits beneficial health effects due to its anti-inflammatory properties. In the present study, we evaluated the effect of resveratrol on inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 and SW480 cell lines. In the LPS-treated intestinal cells, resveratrol dose-dependently inhibited the expression of inducible NO synthase (iNOS) mRNA as well as protein expression, resulting in a decreased production of NO. In addition, Toll-like receptor-4 expression was significantly diminished in LPS-stimulated cells after resveratrol pre-treatment. To investigate the mechanisms by which resveratrol reduces NO production and iNOS expression, we examined the activation of inhibitor of κB (IκB) in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the phosphorylation, as well as the degradation, of the IκB complex. Overall, these results show that resveratrol is able to reduce LPS-induced inflammatory responses by intestinal cells, interfering with the activation of NF-κB-dependent molecular mechanisms.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Caco-2 Cells; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Dietary Supplements; Down-Regulation; Enterocytes; Humans; I-kappa B Proteins; Inflammatory Bowel Diseases; Lipopolysaccharides; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Protein Processing, Post-Translational; Proteolysis; Resveratrol; RNA, Messenger; Stilbenes; Toll-Like Receptor 4

Inflammatory tissue injury has been implicated in tumor promotion and progression. 3,5,4'-trihydroxy-trans-stilbene (resveratrol) and 3,4,3', 5'-tetrahydroxy-trans-stilbene (piceatannol), 2 structurally related plant polyphenols, have been reported to possess antioxidant, anti-inflammatory, and chemopreventive properties. This study was aimed at investigating the possible protective effects of resveratrol and piceatannol against dextran sulfate sodium (DSS)-induced inflammation in mouse colonic mucosa. Administration of DSS (2.5%) in drinking water for 7 days to male ICR mice resulted in colitis and elevated expression of inducible nitric oxide synthase (iNOS) and activation of nuclear factor-kappa B (NF-kappaB), a major transcription factor known to upregulate proinflammatory gene expression. Phosphorylation of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription-3 (STAT3) was also enhanced after DSS treatment. Oral administration of resveratrol or piceatannol (10 mg/kg body weight each) for 7 constitutive days attenuated the DSS-induced inflammatory injury, upregulation of iNOS expression, and activation of NF-kappaB, STAT3, and ERK.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis; Colonic Neoplasms; Dextran Sulfate; DNA-Binding Proteins; Down-Regulation; Drug Therapy, Combination; Extracellular Signal-Regulated MAP Kinases; I-kappa B Kinase; Inflammatory Bowel Diseases; Male; Mice; Mice, Inbred ICR; NF-kappa B; Nitric Oxide Synthase Type II; Phosphorylation; Resveratrol; STAT3 Transcription Factor; Stilbenes; Time Factors