curcumin and Inflammatory-Bowel-Diseases

Synthetic drugs and monoclonal antibodies are the typical treatments to combat inflammatory bowel disease (IBD). However, side effects are present when these treatments are used, and their continued application could be restricted by the high relapse rate of the disease. One potential alternative to these treatments is the use of plant-derived products. The use curcumin is one such treatment option that has seen an increase in usage in treating IBD. Curcumin is derived from a rhizome of turmeric (Curcuma longa), and the results of studies on the use of curcumin to treat IBD are promising. These studies suggest that curcumin interacts with cellular targets such as NF-κB, JAKs/STATs, MAPKs, TNF-α, IL-6, PPAR, and TRPV1 and may reduce the progression of IBD. Potentially, curcumin can be used as a therapeutic agent for patients with IBD when it reduces the incidence of clinical relapse. This review discusses the strategies utilized in designing and developing an oral colonic delivery dosage form of curcumin.

Topics: Colon; Curcuma; Curcumin; Drug Delivery Systems; Humans; Inflammatory Bowel Diseases; NF-kappa B

This systematic review was designed to determine the clinical efficacy and safety of curcumin supplementation for pediatric patients based on clinical trials in children. We systematically searched electronic databases including PubMed, EMBASE, Web of Science, and Scopus for all studies that investigated curcumin administration in the pediatric population without any time frame limitation. Finally, we identified 16 studies for this review. Clinical efficacy and safety of curcumin were assessed in children with inflammatory and immune disorders (including asthma, inflammatory bowel disease (IBD), and juvenile idiopathic arthritis (JIA)), metabolic disorders, autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot (TOF), and infectious diseases. Curcumin was administered in a wide range of doses (45 mg-4,000 mg daily) and durations (2-48 weeks). Overall, curcumin was well tolerated in all studies and improved the severity of inflammatory and immune disorders and metabolic diseases. However, more studies are needed to clarify the role of curcumin supplementation among children with ADPKD, CF, TOF, and infectious diseases. Because of substantial heterogeneity in methodological quality, design, outcomes, dose, duration of intake, formulations, and study populations across studies, no quantitative analysis was performed. Additional large-scale, randomized, placebo-controlled clinical trials are needed to confirm the results of the conducted studies.

Topics: Child; Curcumin; Dietary Supplements; Female; Humans; Inflammatory Bowel Diseases; Male; Polycystic Kidney, Autosomal Dominant; Treatment Outcome

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin antagonist, and salicylates are available but are associated with the various limitations and side-effects. None of the above treatments helps to achieve the ultimate goal of the therapy, i.e., maintenance of remission in the long-term. Natural remedies for the treatment of UC show comparatively less side effects as compared to conventional approaches, and affordable. The current review presents details on the role of herbal drugs in the treatment and cure of UC. Google, PubMed, Web of Science, and Scopus portals have been searched for potentially relevant literature to get the latest developments and updated information related to use of natural drugs in the treatment of UC. Natural products have been used over centuries to treat UC. Some of the essential herbal constituents exhibiting antiulcerogenic activity include gymnemic acid (Gymnema sylvestre), shagoal (Zingiber officinale), catechin (Camellia sinensis), curcumin (Curcuma longa), arctigenin (Arctium lappa), and boswellic acid (Boswellia serrata). Although many plant-derived products have been recommended for UC, further research to understand the exact molecular mechanism is still warranted to establish their usefulness clinically.

Topics: Colitis, Ulcerative; Curcumin; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Interleukins

Accumulating evidence has been reported regarding the effect of dietary antioxidants on clinical variables in IBD patients, however, findings are controversial. This systematic review and meta-analysis aimed to investigate effect of dietary antioxidants on clinical variables in patients with IBD or its subtypes.. We searched PubMed, Scopus, and ISI Web of Science from inception to January 2021 using relevant keywords. Data were pooled by using the random-effect model. All statistical analyses were done using STATA version 14.. Our meta-analysis was exclusively done on studies about the effect of curcumin on IBD patients, because limited studies were done on other antioxidants. Curcumin administration resulted in significant increment of clinical remission in patients with IBD (SMD: 0.86%, 95% CI: 0.16, 1.56, p = 0.016), significant remission in clinical symptoms (SMD: -0.96 score, 95% CI: -1.34, -0.57, p < 0.001), and significant increment in endoscopic remission in IBD patients (SMD: 0.51%, 95% CI: 0.16, 0.85, p = 0.004), comparing to control group. Curcumin supplementation also made better clinical response than control group (SMD: 0.74%, 95% CI: 0.22, 1.26, p = 0.005) and also resulted in significant improvement in quality of life of patients with IBD, as compared to control group (SMD: 1.23 score, 95% CI: 0.72, 1.74, p < 0.001).. Our meta-analysis showed that curcumin significantly improved clinical and endoscopic remissions in IBD patients. This supplementation also caused significant reduction in clinical symptoms of IBD patients along with better clinical response and the increased quality of life. Further researches with larger sample size and longer period of intervention are required to evaluate efficacy of dietary antioxidants on clinical variables in patients with IBD.

Topics: Antioxidants; Chronic Disease; Curcumin; Humans; Inflammatory Bowel Diseases; Quality of Life

Whether polyphenols could ameliorate inflammatory bowel disease (IBD) is still conflicting. To explore the efficacy of polyphenols as an adjuvant therapy for IBD, we conducted this systematic review and meta-analysis. Literature search was performed using PubMed, Web of Science, Scopus and Cochrane databases. Finally, 12 randomized controlled trials (RCTs) were included. In contrast to control group, curcumin treatment significantly improved clinical remission in intention-to-treat (ITT) (OR = 3.36, 95% CI: 1.09-10.37) and per-protocol (PP) analysis (OR = 5.13, 95% CI: 1.84-14.27). Meanwhile, curcumin could significantly ameliorate endoscopic remission (OR = 5.69, 95% CI: 1.28-25.27) and clinical response (OR = 4.69, 95% CI: 1.03-21.47) in PP analysis. Heterogeneity was present across the studies. In conclusions, polyphenols might be an effective adjuvant treatment for ameliorating IBD. Considering the relatively few studies included in our present study, further clinical trials are required to verify the effects of polyphenols on IBD.

Topics: Curcumin; Databases, Factual; Humans; Inflammatory Bowel Diseases; Polyphenols; Randomized Controlled Trials as Topic; Treatment Outcome

Inflammatory bowel disease (IBD) is an umbrella term used to describe chronic inflammatory disorders related to a substantial reduction in the quality of life of patients. Some patients with Crohn's disease (CD) and ulcerative colitis (UC) are refractory to conventional therapies, and

Topics: Colitis, Ulcerative; Crohn Disease; Curcumin; Humans; Inflammatory Bowel Diseases; Interleukin-12

Inflammatory bowel diseases (IBDs) may result from mutations in genes encoding for innate immunity, which can lead to exacerbated inflammatory response. Although some mono-targeted treatments have developed in recent years, IBDs are caused through several pathway perturbations. Therefore, targeting all these pathways is difficult to be achieved by a single agent. Moreover, those mono-targeted therapies are usually expensive and may cause side-effects. These limitations highlight the significance of an available, inexpensive and multi-targeted dietary agents or natural compounds for the treatment and prevention of IBDs. Curcumin is a multifunctional phenolic compound that is known for its anti-inflammatory and immunomodulatory properties. Over the past decades, mounting experimental investigations have revealed the therapeutic potential of curcumin against a broad spectrum of inflammatory diseases including IBDs. Furthermore, it has been reported that curcumin directly interacts with many signaling mediators implicated in the pathogenesis of IBDs. These preclinical findings have created a solid basis for the assessment of the efficacy of curcumin in clinical practice. In clinical trials, different dosages e.g., 550 mg /three times daily-1month, and 1 g /twice times daily-6month of curcumin were used for patients with IBDs. Taken together, these findings indicated that curcumin could be employed as a therapeutic candidate in the treatment of IBDs. Moreover, it seems that overcome to current limitations of curcumin i.e., poor oral bioavailability, and poor oral absorption with using nanotechnology and others, could improve the efficacy of curcumin both in pre-clinical and clinical studies.

Topics: Animals; Anti-Inflammatory Agents; Clinical Trials as Topic; Curcumin; Drug Evaluation, Preclinical; Humans; Inflammatory Bowel Diseases; Phytotherapy

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

The microbiome is an important contributor to a variety of fundamental aspects of human health, including host metabolism, infection, and the immune response. Gut dysbiosis has been identified as a contributor to the errant immune response in a variety of immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriatic disease (psoriasis and psoriatic arthritis). Given this, probiotics and prebiotics have been investigated as therapeutic options in these disease states. In our review, we highlight the current evidence on prebiotics and probiotics as well as other supplements (such as fish oils, vitamin D, and curcumin) as therapies for IBD. Recommendations, however, regarding the specific use of such supplements in IBD have been lacking, particularly from professional societies, often due to study limitations related to small sample sizes and design heterogeneity. Hence, we additionally examine the literature on the use of prebiotics, probiotics, and other supplements in related IMIDs, namely RA and psoriasis/psoriatic arthritis, as these diseases share many approved therapeutic options with IBD. Based on these combined findings, we offer additional evidence that may help guide clinicians in their treatment of patients with IBD (and other IMIDs) and provide recommendations on potential next steps in therapeutic research in this area.

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Curcumin; Dietary Supplements; Female; Fish Oils; Humans; Inflammatory Bowel Diseases; Male; Prebiotics; Probiotics; Psoriasis; Vitamin D

The objective of this study was to systematically review the literature to verify the efficacy and safety of curcumin as a complementary therapy for the maintenance or induction of remission in patients with inflammatory bowel disease (IBD). A comprehensive search was conducted by two independent authors in MEDLINE (PubMed), Scopus, Web of Science, the Cochrane Library, Lilacs, Food Science and Technology Abstracts, and ScienceDirect. The search terms "curcumin", "curcuma", "inflammatory bowel disease", "proctocolitis", "crohn disease", and "inflammation" were combined to create search protocols. This study considered randomized controlled trials (RCTs) published in any language before March 2020 that evaluated the effects of curcumin on inflammatory activity and the maintenance or remission of IBD patients. After duplicates were removed, 989 trials were identified, but only 11 met the eligibility criteria. Five of these were considered to be biased and were excluded. Therefore, six trials were considered in this review. All the studies included in the systematic review were placebo-controlled RCTs conducted on individuals with ulcerative colitis (UC). All the RCTs reported that curcumin was well tolerated and was not associated with any serious side effects. Studies show that curcumin may be a safe, effective therapy for maintaining remission in UC when administered with standard treatments. However, the same cannot be stated for Crohn's disease due to the lack of low bias risk studies. Further studies with larger sample sizes are needed before curcumin can be recommended as a complementary therapy for UC.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Complementary Therapies; Crohn Disease; Curcumin; Female; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Conventional medicine for the treatment of IBD is prevailingly composed of sulfadiazine, 5-aminosalicylic acid, glucocorticoid, and immunosuppressants, which have the merits of alleviating intestine inflammation, but long-term use of these drugs may cause toxic side effects; additionally, these drugs may be expensive. In the pursuit of novel and more economic therapies, patients may increasingly look at complementary and alternative medicine (CAM). Recently, CAM is increasingly favored by the general public on account of its safety, low toxicity, and effectiveness. As a branch of CAM, herbal plants and their extracts have a significant effect on the treatment of IBD. Treatment of IBD with herbaceous plants has been reported, but specific mechanisms and effects have not yet been elaborated.. English abstracts were identified in PubMed and Science Direct by multiple search terms, such as "herbal," "CAM," "IBD," "ulcerative colitis," "abdominal pain," and so on. Full-length articles were selected for review.. Herbaceous plants and their extracts have been shown to be effective against IBD in many studies, and herbaceous plants may be effective in treating symptoms such as abdominal pain, diarrhea, mucus, and bloody stools.. Herbal medications could be used as a complementary and alternative treatment for IBD, but they require more rigorous scientific testing.

Topics: Animals; Complementary Therapies; Curcumin; Disease Models, Animal; Herbal Medicine; Humans; Inflammatory Bowel Diseases; Plant Extracts; Randomized Controlled Trials as Topic

Topics: Animals; Autoimmune Diseases; Curcumin; Humans; Hypersensitivity; Inflammatory Bowel Diseases; Neoplasms; Organ Transplantation; Psoriasis; T-Lymphocytes, Helper-Inducer

Complementary therapies for inflammatory bowel disease (IBD) have earned growing interest from patients and investigators alike, with a dynamic landscape of research in this area. In this article, we review results of the most recent studies evaluating the role of cannabis and turmeric for the treatment of IBD and other intestinal illnesses.. Cannabinoids are well-established modulators of gut motility and visceral pain and have demonstrated anti-inflammatory properties. Clinical trials suggest that there may be a therapeutic role for cannabinoid therapy in the treatment of IBD, irritable bowel syndrome (IBS), nausea and vomiting, and GI motility disorders. Recent reports of serious adverse effects from synthetic cannabinoids highlight the need for additional investigation of cannabinoids to establish their efficacy and safety. Turmeric trials have demonstrated some promise as adjuvant treatment for IBD, though not in other GI disease processes. Evidence suggests that the use of cannabis and turmeric is potentially beneficial in IBD and IBS; however, neither has been compared to standard therapy in IBD, and thus should not be recommended as alternative treatment for IBD. For cannabis in particular, additional investigation regarding appropriate dosing and timing, given known adverse effects of its chronic use, and careful monitoring of potential bleeding complications with synthetic cannabinoids are imperative.

Topics: Complementary Therapies; Curcuma; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Medical Marijuana; Nausea; Plant Preparations; Vomiting

The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease and Ulcerative colitis that are characterized by chronic and relapsing inflammatory processes of the gastrointestinal system. Curcuma longa L. is a plant with several medicinal properties, including anti-inflammatory effects, and curcumin is the most important compound derived from its rhizomes. As curcumin has remarkable anti-inflammatory actions, the aim of this work is to review the potential use of this compound in IBD patients. We consulted MEDLINE (PubMed/PMC), and the literature search was performed with the following combinations of terms "Inflammatory Bowel Diseases" and "Curcumin," "Crohn's Disease" and "Curcumin," "Ulcerative colitis" and "Curcumin." The inclusion criteria were articles that showed original studies with human models and the exclusion criteria were not full-text articles, articles not in English, poster presentations, letters, editorials, and articles not available. Curcumin interacts with receptors, growth and transcription factors, cytokines, enzymes, and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis factor-α, interferon-γ, inducible nitric oxide synthase, transcriptional nuclear factor kappa B, and many other molecules associated with inflammatory processes. These molecules are critical factors in the positive regulation of inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be considered as a new therapeutic agent for patients with IBD. Curcumin is a natural anti-inflammatory agent that represents an attractive, safe and inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary to know the efficient and safe dose and consider its poor absorption.

Topics: Animals; Anti-Inflammatory Agents; Curcuma; Curcumin; Cytokines; Humans; Inflammatory Bowel Diseases; Plant Extracts

Nutrition and food items may improve or worsen symptoms in Crohn's disease and ulcerative colitis. Protein malnutrition and vitamin and mineral deficiencies are common, particularly deficiency of iron and vitamin D. Dietary fibres and omega-3 fatty acids are safe, but no evidence supports their use as treatment. The use of probiotics is not encouraged in patients with Crohn's disease, but it may maintain remission in ulcerative colitis. Curcumin, chamomile, and other herbal extracts are promising in the treatment of mild ulcerative colitis, but validation of products and monitoring of side effects are insufficient.

Topics: Celiac Disease; Chamomile; Curcuma; Diet; Dietary Fiber; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Inflammatory Bowel Diseases; Lactose Intolerance; Micronutrients; Nutritional Status; Vitamin D

Inflammatory bowel diseases (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic ailments of the gastrointestinal tract, characterized by recurrent inflammation. Current therapeutic strategies are based on the mitigation of symptoms, including inflammatory remission and healing of mucosal manifestations. Extensive studies have suggested that continuous oxidative damage can lead to the inflammatory signaling cascade in IBD. Curcumin, a potent modulator of cell signaling, is popular for its antioxidant and anti-inflammatory activities, and has already been shown remarkable therapeutic results in IBD. Here, we review and discuss the effects of curcumin as a therapeutic agent in the chemoprevention of IBD.

Topics: Anti-Inflammatory Agents; Antioxidants; Chemoprevention; Curcumin; Humans; Inflammatory Bowel Diseases

Inflammatory bowel disease is a complex, chronic, multifactorial inflammatory disorder of the digestive tract. Standard therapies include immunosuppressive and biological treatments, but there is increasing interest in the potential benefit of complementary and alternative medicine for the treatment of inflammatory bowel disease. Given the high prevalence of use of complementary and alternative medicine among inflammatory bowel disease patients, gastroenterologists must remain knowledgeable regarding the risks and benefits of these treatment options. This article reviews the updated scientific data on the use of biologically based complementary and alternative therapies for the treatment of inflammatory bowel disease.

Topics: Aloe; Andrographis; Animals; Cannabis; Complementary Therapies; Curcumin; Fatty Acids, Omega-3; Fecal Microbiota Transplantation; Humans; Inflammatory Bowel Diseases; Phytotherapy; Plant Extracts; Plants, Medicinal; Trichuris; Triticum

Inflammatory bowel diseases (IBDs) often take a chronic debilitating course. Given the chronicity of IBD, the limitations of the available medications, their potential side effects, and the impact of the disease on patients' quality of life, it is not surprising IBD patients are ranked among the highest users of complementary and alternative medicine (CAM). Since CAM has become very popular in real-life practice of Western Communities, caregivers must gain more knowledge about these therapies, their mechanism of action, benefits, and risks. This article reviews and discusses up-to-date scientific and clinical data regarding the most prevalent herbal CAM therapies.

Topics: Animals; Complementary Therapies; Curcumin; Disease Models, Animal; Humans; Inflammatory Bowel Diseases; Medical Marijuana; Phytotherapy

Inflammatory bowel diseases (IBD) are chronic immune disorders of unclear aetiology. Dietary deficiencies may be a potential pathogenic factor in their development. Patients often take food supplements without knowledge of any evidence base. We have therefore assessed the evidence for food supplementation in the management of IBD. A PubMed search was performed for the terms Inflammatory bowel disease; nutritional deficiencies; dietary supplements; curcumin; green tea; vitamin D/other vitamins; folic acid; iron; zinc; probiotics; andrographis paniculata; and boswellia serrate. PubMed was used to search for all relevant articles published between January 1975 and September 2015. Curcumin supplementation has been reported to be effective in reducing the symptoms and the inflammatory indices in IBD patients. Similar results have been observed for green tea; however, pertinent studies are limited. Vitamin D supplementation may help to increase bone mineral density in IBD patients and to reduce disease activity. IBD patients with ileal resections higher than 20 cm may develop vitamin B12 deficiency that requires parenteral supplementation. There is no current evidence to support fat-soluble vitamin supplementation in IBD patients. Zinc and iron should be supplemented in selected cases. Probiotics (VSL#3) may reduce disease activity in IBD patients with pouchitis. Complementary and alternative medicines are used by IBD patients and some studies have shown promising results. In summary, attention to dietary factors such as curcumin, green tea and vitamins, including vitamins D and B12, appears to be beneficial and, if necessary, supplementation may be appropriate.

Topics: Andrographis; Boswellia; Curcumin; Dietary Supplements; Digestive System Surgical Procedures; Folic Acid; Humans; Ileum; Inflammatory Bowel Diseases; Iron; Malnutrition; Plant Preparations; Probiotics; Tea; Trace Elements; Vitamin B 12 Deficiency; Vitamin B Complex; Vitamin D; Vitamin D Deficiency; Vitamins; Zinc

For many years, there has been confusion about the role that nutrition plays in inflammatory bowel diseases (IBD). It is apparent that good dietary advice for one individual may prove inappropriate for another. As with many diseases, genome-wide association studies across large collaborative groups have been important in revealing the role of genetics in IBD, with more than 200 genes associated with susceptibility to the disease. These associations provide clues to explain the differences in nutrient requirements among individuals. In addition to genes directly involved in the control of inflammation, a number of the associated genes play roles in modulating the gut microbiota. Cell line models enable the generation of hypotheses as to how various bioactive dietary components might be especially beneficial for certain genetic groups. Animal models are necessary to mimic aspects of the complex aetiology of IBD, and provide an important link between tissue culture studies and human trials. Once we are sufficiently confident of our hypotheses, we can then take modified diets to an IBD population that is stratified according to genotype. Studies in IBD patients fed a Mediterranean-style diet have been important in validating our hypotheses and as a proof-of-principle for the application of these sensitive omics technologies to aiding in the control of IBD symptoms.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Gastrointestinal Microbiome; Gene Expression Profiling; Humans; Inflammatory Bowel Diseases; Metabolomics; Nutritional Status; Proteomics

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

Topics: Anti-Inflammatory Agents; Boswellia; Curcumin; Dietary Supplements; Fish Oils; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Phytotherapy; Plant Preparations; Prebiotics; Probiotics; Synbiotics; Vitamin D

Crohn's disease and ulcerative colitis are the two most common categories of inflammatory bowel disease (IBD), which are characterized by chronic inflammation of the intestine that comprises the patients' life quality and requires sustained pharmacological and surgical treatments. Since their aetiology is not completely understood, nonfully efficient drugs have been developed and those that show effectiveness are not devoid of quite important adverse effects that impair their long-term use. Therefore, many patients try with some botanical drugs, which are safe and efficient after many years of use. However, it is necessary to properly evaluate these therapies to consider a new strategy for human IBD. In this report we have reviewed the main botanical drugs that have been assessed in clinical trials in human IBD and the mechanisms and the active compounds proposed for their beneficial effects.

Topics: Aloe; Andrographis; Artemisia absinthium; Boswellia; Cannabis; Curcuma; Humans; Inflammatory Bowel Diseases; Phytotherapy; Plant Extracts

The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.

Topics: Boswellia; Complementary Therapies; Curcumin; Herbal Medicine; Humans; Inflammatory Bowel Diseases; Lythraceae; Treatment Outcome

Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn's disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Clinical Trials as Topic; Curcumin; Humans; Inflammatory Bowel Diseases; Molecular Targeted Therapy; Nanotechnology; Treatment Outcome

Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

Topics: Arthritis; Clinical Trials as Topic; Curcumin; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Neoplasms; Peptic Ulcer; Vitiligo

Increased recognition of the limits of conventional medicine has helped drive the growing interest in complementary and alternative medicine which is now being commonly used in patients with chronic diseases, including individuals with Crohn's disease and ulcerative colitis. Recently, scientific interest has unraveled the beneficial pharmacological effects of curcumin. We present an updated concise review of currently available in vitro, animal and clinical studies demonstrating the therapeutic effect of herbal medication in inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Humans; Inflammatory Bowel Diseases; Mice; Phytotherapy; Plant Preparations; Rats

To evaluate the use of curcumin in inflammatory bowel disease.. ALTMEDEX, Comprehensive Database of Natural Medicines, MEDLINE/PubMed were searched from January 1980 through May 2009 using the terms curcumin, turmeric, ulcerative colitis, Crohn's disease, Curcuma longa, Curcuma domestica, Indian saffron, inflammatory bowel disease. Data was limited to human trials. References of identified articles were reviewed.. Data evaluating the use of curcumin in inflammatory bowel disease (including ulcerative colitis and Crohn's disease) is limited to two studies comprising data for only 99 patients. Curcumin in conjunction with mainstream therapy, consisting of sulfasalazine (SZ) or mesalamine (5-aminosalicylic acid [5-ASA] derivatives) or corticosteroids was shown to improve patient symptoms and allow for a decrease in the dosage of corticosteroids or 5-ASA derivatives. In one small study of 10 patients, some patients even stopped taking corticosteroids or 5-ASA.. Although two small studies have shown promising results, all authors conclude that larger-scale, double-blind trials need to be conducted to establish a role for curcumin in the treatment of ulcerative colitis. In addition to improving results when used in conjunction with conventional medications for UC, curcumin may pose a less-expensive alternative.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis; Curcumin; Dose-Response Relationship, Drug; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Patient Satisfaction; Randomized Controlled Trials as Topic

Curcumin is the active ingredient of turmeric. It is widely used as a kitchen spice and food colorant throughout India, Asia and the Western world. Curcumin is a major constituent of curry powder, to which it imparts its characteristic yellow colour. For over 4000 years, curcumin has been used in traditional Asian and African medicine to treat a wide variety of ailments. There is a strong current public interest in naturally occurring plant-based remedies and dietary factors related to health and disease. Curcumin is non-toxic to human subjects at high doses. It is a complex molecule with multiple biological targets and different cellular effects. Recently, its molecular mechanisms of action have been extensively investigated. It has anti-inflammatory, antioxidant and anti-cancer properties. Under some circumstances its effects can be contradictory, with uncertain implications for human treatment. While more studies are warranted to further understand these contradictions, curcumin holds promise as a disease-modifying and chemopreventive agent. We review the evidence for the therapeutic potential of curcumin from in vitro studies, animal models and human clinical trials.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antineoplastic Agents; Antioxidants; Cell Line; Cell Line, Tumor; Clinical Trials as Topic; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Inflammatory Bowel Diseases; Neoplasms; Randomized Controlled Trials as Topic; Transcription Factors

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting condition that afflicts millions of people throughout the world and impairs their daily functions and quality of life. While the aetiology of IBD is not understood well, it appears to be driven by inflammatory cytokines such as tumor necrosis factor (TNF)-alpha. Hence, there is a strong interest in agents that can block the generation or actions of inflammatory cytokines. Curcumin is a bioactive substance present in the rhizomes of the herb "Curcuma longa" which has been used for centuries in Asia, both in traditional medicine and in cooking as turmeric which gives food an exotic natural yellow color. Further, in recent years, a large number of research papers have reported intriguing pharmacologic effects associated with curcumin. These include inhibitory effects on cyclooxygenases 1, 2 (COX-1, COX-2), lipoxygenase (LOX), TNF-alpha, interferon gamma (IFN-gamma), inducible nitric oxide synthase (iNOS), and the transcriptional nuclear factor kappa B (NF-kappaB), in addition to a strong anti-oxidant effect. NF-kappaB is a key factor in the upregulation of inflammatory cytokines that have a high profile in inflammatory diseases, suggesting that curcumin could be a novel therapeutic agent for patients with IBD. Therefore, in recent years, the efficacy of curcumin has been investigated in several experimental models of IBD. The results indicate striking suppression of induced IBD colitis and changes in cytokine profiles, from the pro-inflammatory Th1 to the anti-inflammatory Th2 type. In human IBD, up to now, only one open study has achieved encouraging results. In this study, patients were given curcumin (360 mg/dose) 3 or 4 times/day for three months. Further, curcumin significantly reduced clinical relapse in patients with quiescent IBD. The inhibitory effects of curcumin on major inflammatory mechanisms like COX-2, LOX, TNF-alpha, IFN-gamma, NF-kappaB and its unrivalled safety profile suggest that it has bright prospects in the treatment of IBD. However, randomized controlled clinical investigations in large cohorts of patients are needed to fully evaluate the clinical potential of curcumin.

Topics: Animals; Clinical Trials as Topic; Colitis, Ulcerative; Curcumin; Cytokines; Disease Models, Animal; Humans; Inflammatory Bowel Diseases; Treatment Outcome

Crohn's disease and ulcerative colitis are chronic inflammatory disease of the intestine,which frequently require surgery for complications or failure of medical therapy.. We seek evidence and provide direction for clinicians about the optimal use of biologic therapy in order to enable steroid free remission in inflammatory bowel disease.. Scientific literature was reviewed using MEDLINE with a specific focus on biologic medical therapies for inducing and maintaining remission of Crohn disease and ulcerative colitis.. Several therapies have demonstrated efficacy for the treatment of active, moderate-to-severe Crohn disease and ulcerative colitis. These include agents which induce remission [infliximab, certolizumaband adalimumab (CD only)] or maintain remission and spare corticosteroids [infliximab,certolizumab and adalimumab (CD only)]. In the patient with UC there is evidence about the efficacy of Infliximab for induce remission in moderate to-severe cases. We present additional information about new drugs in development for the treatment of both diseases.. There are evidence about the efficacy and safety of biologic therapies that maximize remission and minimize corticosteroid dependence in patients with moderate-to-severe CD and UC.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Biological Therapy; Cell Adhesion Molecules; Colitis, Ulcerative; Crohn Disease; Curcumin; Humans; Immunity, Innate; Inflammatory Bowel Diseases; Interferons; Steroids

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non-systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

Topics: Aminosalicylic Acids; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Blood Component Removal; Clinical Trials as Topic; Curcumin; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Intercellular Signaling Peptides and Proteins; Nicotine; Nicotinic Agonists; Probiotics; Remission Induction; Steroids; Trichuris

Curcumin has long been expected to be a therapeutic or preventive agent for several major human diseases because of its antioxidative, anti-inflammatory, and anticancerous effects. In phase I clinical studies, curcumin with doses up to 3600-8000 mg daily for 4 months did not result in discernible toxicities except mild nausea and diarrhea. The pharmacokinetic studies of curcumin indicated in general a low bioavailability of curcumin following oral application. Nevertheless, the pharmacologically active concentration of curcumin could be achieved in colorectal tissue in patients taking curcumin orally and might also be achievable in tissues such as skin and oral mucosa, which are directly exposed to the drugs applied locally or topically. The effect of curcumin was studied in patients with rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers. Although the preliminary results did support the efficacy of curcumin in these diseases, the data to date are all preliminary and not conclusive. It is imperative that well-designed clinical trials, supported by better formulations of curcumin or novel routes of administration, be conducted in the near future.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Biological Availability; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Curcumin; Dose-Response Relationship, Drug; Drug Administration Schedule; Forecasting; Humans; Inflammatory Bowel Diseases; Neoplasm Metastasis; Precancerous Conditions; Psoriasis; Tissue Distribution

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in the absence of a recognized etiology. The primary therapies are medications that possess anti-inflammatory or immunosuppressive effects. Given the high use of complementary alternative medicines in pediatric IBD, a prospective tolerability study of curcumin, an herbal therapy with known anti-inflammatory effects, was conducted to assess possible dosage in children with IBD.. Prospectively, patients with Crohn disease or ulcerative colitis in remission or with mild disease (Pediatric Crohn's Disease Activity Index [PCDAI] <30 or Pediatric Ulcerative Colitis Activity Index [PUCAI] score <34) were enrolled in a tolerability study. All patients received curcumin in addition to their standard therapy. Patients initially received 500 mg twice per day for 3 weeks. Using the forced-dose titration design, doses were increased up to 1 g twice per day at week 3 for a total of 3 weeks and then titrated again to 2 g twice per day at week 6 for 3 weeks. Validated measures of disease activity, using the PUCAI and PCDAI, and the Monitoring of Side Effect System score were obtained at weeks 3, 6, and 9.. All patients tolerated curcumin well, with the only symptom that was consistently reported during all 3 visits being an increase in gassiness, which occurred in only 2 patients. Three patients saw improvement in PUCAI/PCDAI score.. This pilot study suggests that curcumin may be used as an adjunctive therapy for individuals seeking a combination of conventional medicine and alternative medicine.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Colitis, Ulcerative; Combined Modality Therapy; Crohn Disease; Curcumin; Dietary Supplements; Female; Flatulence; Humans; Inflammatory Bowel Diseases; Male; Medicine, Ayurvedic; Mesalamine; Pilot Projects; Remission Induction; Severity of Illness Index; Tumor Necrosis Factor-alpha

Curcumin may have promising application in the prevention and amelioration of inflammatory bowel disease (IBD). However, the underlying mechanisms underpinning the ability of curcumin to interact with the gut and liver in IBD remains to be defined, which is the exploration aim of this study.. Curcumin supplementation not only prevented further loss of body weight and colon length in IBD mice but also improved diseases activity index (DAI), colonic mucosal injury, and inflammatory infiltration. Meanwhile, curcumin restored the composition of the gut microbiota, significantly increased Akkermansia, Muribaculaceae_unclassified, and Muribaculum, and significantly elevated the concentration of propionate, butyrate, glycine, tryptophan, and betaine in the intestine. For hepatic metabolic disturbances, curcumin intervention altered 14 metabolites, including anthranilic acid and 8-amino-7-oxononanoate while enriching pathways related to the metabolism of bile acids, glucagon, amino acids, biotin, and butanoate. Furthermore, SCC analysis revealed a potential correlation between the upregulation of intestinal probiotics and alterations in liver metabolites.. The therapeutic mechanism of curcumin against IBD mice occurs by improving intestinal dysbiosis and liver metabolism disorders, thus contributing to the stabilization of the gut-liver axis.

Topics: Animals; Chromatography, Liquid; Colitis; Colon; Curcumin; Dextran Sulfate; Disease Models, Animal; Dysbiosis; Inflammatory Bowel Diseases; Liver Diseases; Mice; Mice, Inbred C57BL; Tandem Mass Spectrometry

Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon.. In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment.. It's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.

Topics: Alginates; Anti-Inflammatory Agents; Curcumin; Emodin; Humans; Hydrogels; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa

Co-delivery of anti-inflammatory drugs and reactive oxygen species (ROS) scavengers by stimuli-responsive oral nanoparticles is deemed to be a favorable strategy for inflammatory bowel disease (IBD) therapy. In this study, using micelles formed by CUR conjugated hydroxyethyl starch (HES) as vehicles, dexamethasone (DEX)-loaded HES-CUR nanoparticles (DHC NPs) with desirable size, negative surface charge, good stability in the harsh gastric environment, and excellent ROS scavenging activity are developed as a colon-targeted oral formulation for treating IBD. Due to the degradation of HES in response to α-amylase overexpressed in the inflamed colon, the DHC NPs release drugs in an α-amylase-responsive manner. Meanwhile, the DHC NPs can be effectively internalized by macrophages and show excellent cytocompatibility with macrophages since they are composed of food-derived compounds. Importantly, in vivo studies reveal that the DHC NPs are capable of targeting the inflamed colon induced by dextran sulfate sodium (DSS), and the targeted and combination therapy enhances the efficacy of free DEX and significantly relieves the impairment caused by DSS-induced ulcerative colitis. Incorporating the merits of targeted drug delivery and combined therapy with an anti-inflammatory drug and ROS scavenger, the DHC NPs are promising for developing novel oral formulations for IBD therapy.

Topics: alpha-Amylases; Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Curcumin; Humans; Inflammatory Bowel Diseases; Nanoparticles; Reactive Oxygen Species; Starch

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract with unclear etiology and insufficient therapeutic efficacy. The development of specific, effective and safe IBD treatment drugs is of great clinical significance. Curcumin (Cur) is a good candidate to prevent and manage inflammatory diseases (such as IBD) due to its antioxidant and anti-inflammatory effects with safety profile. However, its poor aqueous solubility and instability under physiological conditions greatly limit its therapeutic efficacy. Herein, we exploited a Cur precursor Cur-FFEYp to locally deliver and slowly release Cur at inflamed regions for treatment of IBD by a sequential self-assembly and disassembly strategy. The much higher catalytic efficiency of alkaline phosphatase (ALP) than esterase towards Cur-FFEYp validated the sequential ALP-induced self-assembly with the formation of Cur hydrogel and esterase-guided disassembly with the slow release of Cur. In cell and animal experiments, Cur-FFEYp can effectively enhance the anti-inflammatory effect of Cur on inflammatory macrophages and significantly alleviate two types of IBD. We envision that by using other biomarkers to conduct the sequential self-assembly and disassembly processes and replacing other drugs, our smart strategy could be easily adjusted for the treatment of more diseases or cancers.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Esterases; Hydrogels; Inflammatory Bowel Diseases

Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD.. To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling.. Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1β, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins.. After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1β, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19. Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Topics: Animals; Colitis; Curcumin; Cytokines; Dextran Sulfate; Disease Models, Animal; Inflammatory Bowel Diseases; Interleukin-10; Interleukin-6; Memory B Cells; Mice; Mice, Inbred C57BL; Signal Transduction; Tumor Necrosis Factor-alpha

Inflammatory bowel diseases are a group of inflammatory disorders of the gastrointestinal tract. Their prevalence is still low in Brazil, but the incidence is increasing annually. A variety of compounds present in Curcuma longa L., particularly curcumin, have been shown to reduce oxidative stress and aid in the prevention of associated diseases. This study aimed to assess the effect of curcumin transdermal gel on oxidative stress and intestinal inflammation in IL-10 knockout mice. Female mice were divided into four groups: a control group (C0) treated with vehicle and three experimental groups treated with transdermal gel containing 50 (C50), 75 (C75), and 100 (C100) mg curcumin kg-1 body weight. Colon malondialdehyde concentrations were lower in C50 and C75 groups. C100 treatment led to reduced catalase activity in the small intestine, whereas C50, C75, and C100 treatments resulted in decreased catalase activity in the colon. In contrast, superoxide dismutase activity increased in the small intestine of C50 and C75 mice and decreased in the colon of C50, C75, and C100 mice. Glutathione S-transferase activity increased in the small intestine and decreased in the colon of C75 animals. These findings suggest that curcumin transdermal gel exerts a protective effect against oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Female; Inflammatory Bowel Diseases; Interleukin-10; Mice; Mice, Knockout

A major drawback of oral treatment of inflammatory bowel disease (IBD) is the non-specific distribution of drugs during long-term treatment. Despite its effectiveness as an anti-inflammatory drug, curcumin (CUR) is limited by its low bioavailability in IBD treatment. Herein, a pH-sensitive composite hyaluronic acid/gelatin (HA/GE) hydrogel drug delivery system containing carboxymethyl chitosan (CC) microspheres loaded with CUR was fabricated for IBD treatment. The composition and structure of the composite system were optimized and the physicochemical properties were characterized using infrared spectroscopy, X-ray diffraction, swelling, and release behavior studies. In vitro, the formulation exhibited good sustained release property and the drug release rate was 65% for 50 h. In vivo pharmacokinetic experiments indicated that high level of CUR was maintained in the colon tissue for more than 24 h; it also played an anti-inflammatory role by evaluating the histopathological changes through hematoxylin and eosin (H&E), myeloperoxidase (MPO), and immunofluorescent staining. Additionally, the formulation substantially inhibited the level of the main pro-inflammatory cytokines of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secreted by macrophages, compared to the control group. The pharmacodynamic experiment showed that the formulation group of CUR@gels had the best therapeutic effect on colitis in mice. The composite gel delivery system has potential for the effective delivery of CUR in the treatment of colitis. This study also provides a reference for the design and preparation of a new oral drug delivery system with controlled release behavior.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Chitosan; Colitis; Colon; Curcumin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Gelatin; Hyaluronic Acid; Hydrogels; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Interleukin-6; Macrophages; Mice; Microscopy, Electron, Scanning; Microspheres; Rheology; Spectroscopy, Fourier Transform Infrared; Tumor Necrosis Factor-alpha; X-Ray Diffraction

The role of mitochondrial dysfunction in the pathogenesis of inflammatory bowel diseases (IBD) is still being investigated. This study evaluated the therapeutic effect of curcumin (Cur), a polyphenolic electrophile in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis and mitochondrial dysfunction, in mice.. Colitis was induced by rectal instillation to mice of 30 mg kg. In vitro, a short-term Cur treatment controlled the dose and time dependent mitochondrial toxicity induced by TNBS, by collapsing the generation of superoxide anion and hydroperoxy lipids, rebalancing nitric oxide synthase and aconitase activities, and recoupling mitochondria. In vivo, a daily low-dose Cur abolished mice mortality which reached 27% in model group. Cur improved in a time dependent manner mucosal redox homeostasis, cell apoptosis, mucin depleted crypts and crypt abscesses by controlling prooxidant activity of myeloperoxidase and NO synthase associated to phagocytes influx, quenching hydroperoxy lipids, and reboosting GSH levels.. Cur, by quenching intra and extra mitochondrial ROS generation, rebalancing aconitase/fumarase and MDA/GSH ratios, and recoupling mitochondria, may support mithormesis priming and remitting in IBD.

Topics: Aconitate Hydratase; Animals; Apoptosis; Colitis; Colon; Curcumin; Inflammatory Bowel Diseases; Intestinal Mucosa; Lipid Peroxides; Male; Mice; Mitochondria; Mucins; Nitric Oxide Synthase; Oxidation-Reduction; Peroxidase; Reactive Oxygen Species; Superoxides; Trinitrobenzenesulfonic Acid

The objective of the present work was to develop and optimize multiparticulate pH-dependent bioadhesive pellets of curcumin and cyclosporine for the management of intestinal bowel disease (IBD). The bioadhesive sustained release pellets were intended for targeting the affected site for an improved therapeutic effect. Bioadhesive pellet cores of curcumin and cyclosporine were formulated using Carbopol 940 (CP940) and hydroxypropyl cellulose (HPC-H) by the extrusion/spheronization method, and drug delivery to the colon was controlled by the pH-sensitive polymer Eudragit® S100. Microcrystalline cellulose (Avicel PH101) was found to be the best forming agent for pellet core. The ratio of CP940 to HPC-H was kept at 1:1 to achieve 100% bioadhesion. The in vitro dissolution profiles of coated pellets depicted that 12.327 ± 0.342% of curcumin and 14.751 ± 0.112% of cyclosporine were released at the end of 6 h (at pH 6.8), whereas 71.278 ± 0.100% of curcumin and 76.76 ± 0.195% of cyclosporine were released at the end of 24 h (at pH 7.4). The drug release profile was found to follow zero-order kinetics for both drugs. The selected formulation was evaluated on an acetic acid-induced ulcerative colitis in the rat model to evaluate the efficiency of drug-loaded pellets coated with Eudragit®S100. The pharmacodynamic study revealed the therapeutic efficacy of Eudragit®S100-coated pellets of curcumin and cyclosporine in alleviating the conditions of the acetic acid-induced colitis model as reflected by weight gain as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis, as compared with free curcumin and cyclosporine. The combination of curcumin and cyclosporine has been proven to have a synergistic effect for the successful management of IBD when used in a low dose as compared with individual drugs with high doses. Hence, curcumin- and cyclosporine-loaded bioadhesive pellets may act as a promising targeted drug delivery system in the management of IBD. Graphical abstract.

Topics: Animals; Colitis; Colon; Curcumin; Cyclosporine; Drug Delivery Systems; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Rats; Solubility

Current efforts on inflammatory bowel diseases (IBD) treatment are focused on strategies for localised drug delivery at the intestinal mucosa. Despite the potential of curcumin (CC) for IBD treatment, its low solubility and stability limit its application. Thus, the design of nanocarriers that focus CC delivery at the intestinal epithelium is an area of interest. This work proposes α-tocopherol nanoemulsions (NE) stabilised by ascorbyl-2,6-dipalmitate (ADP) as intestinal CC-carriers. The antioxidant capacity of α-tocopherol and ADP could have a synergistic effect on IBD-affected tissues, characterised by an oxidative environment. We obtained nanoemulsions (NE-ADP) with size below 200 nm, negative surface charge, stable in gastrointestinal media and no toxic in the Caco-2 cell model. Intracellular retention of NE-ADP in Caco-2 cells was observed by confocal microscopy. The extremely low P

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Biological Transport; Caco-2 Cells; Curcumin; Drug Carriers; Drug Delivery Systems; Emulsions; Humans; Inflammatory Bowel Diseases; Lecithins; Nanoparticles; Palmitates; Particle Size; Reactive Oxygen Species; Solubility

Inflammatory bowel diseases (IBD), which include Crohn disease and ulcerative colitis, affect several million individuals worldwide. Curcumin as a complementary therapy has been used to cure the IBD, yet the efficacy and safety of curcumin remains to be assessed. In this study, we aim to draw up a protocol for systematic review to evaluate the efficacy and safety of curcumin for IBD.. We will search the following electronic databases from inception to September 31, 2020: PubMed, Cochrane Library, EMBASE, Web of Science, Medline, the China National Knowledge Infrastructure Database, Wan Fang Database, the Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. Clinical trial registrations, potential gray literatures, relevant conference abstracts and reference list of identified studies will also be searched. Relevant randomized controlled clinical trials were enrolled and analyzed. The literature selection, data extraction, and quality assessment will be completed by 2 independent authors. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. Clinical remission will be evaluated as the primary outcome. Clinical response, endoscopic remission, inflammatory markers and adverse events will be assessed as the secondary outcomes. The RevManV.5.3.5 will be used for Meta-analysis. Subgroup analyses of doses, delivery way, frequency of treatment and the degree of IBD severity or different forms of IBD were also conducted.. This study will provide a synthesis of current evidence of curcumin for IBD from several aspects, such as clinical remission, clinical response, endoscopic remission, inflammatory markers, and adverse events.. The conclusion of our study will provide updated evidence to judge whether curcumin is an effective solution to IBD patients.. INPLASY202090065.

Topics: China; Colitis, Ulcerative; Coloring Agents; Complementary Therapies; Crohn Disease; Curcumin; Data Management; Female; Humans; Inflammatory Bowel Diseases; Male; Meta-Analysis as Topic; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Safety; Systematic Review as Topic; Treatment Outcome

This study was focussed on development of curcumin loaded solid binary lipid nanoparticles (C-SBLNs) to ameliorate stability, uptake and therapeutic potential of curcumin during inflammatory bowel disease (IBD). C-SBLNs with nano-size range (210.56 ± 41.22 nm) and high entrapment efficiency (83.12 ± 6.57%) were prepared by solvent emulsification evaporation method using binary lipids i.e. stearic acid and tristearin after optimizing various formulation and process variables. Physicochemical characterization of C-SBLNs by ATR-FTIR confirmed drug entrapment whereas thermal and pXRD study corroborated loss of crystallinity of drug into C-SBLNs. Lyophilized C-SBLNs were found to be spherical shaped with good gastrointestinal stability and prolonged drug release up to 24 h. Optimized C-SBLNs formulation displayed significantly enhanced cellular uptake and localization in inflamed tissues during IBD. Oral administration of C-SBLNs in DSS induced colitis model revealed significant reduction in leucocyte infiltration, oxidative stress, pro-inflammatory cytokine (TNF-α) secretion and maintenance of colonic structure similar to healthy animal group compared to curcumin. Thus, in vitro and preclinical findings of study clearly confirmed that C-SBLNs could be a stable and efficacious alternative platform for curcumin delivery with strong competence in IBD chemotherapy.

Topics: Administration, Oral; Animals; Biological Transport; Body Fluids; Curcumin; Drug Carriers; Drug Compounding; Drug Design; Drug Liberation; Guinea Pigs; Inflammatory Bowel Diseases; Lipids; Nanoparticles; Particle Size

The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 μM or 1.6 μM half maximal effective concentration (EC

Topics: Animals; Anti-Inflammatory Agents; Colitis; Curcumin; Humans; Inflammatory Bowel Diseases; Interleukin-4; Interleukin-6; Leukocytes, Mononuclear; Male; NF-kappa B; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The most common question asked by patients with inflammatory bowel disease (IBD) is, "Doctor, what should I eat?" Findings from epidemiology studies have indicated that diets high in animal fat and low in fruits and vegetables are the most common pattern associated with an increased risk of IBD. Low levels of vitamin D also appear to be a risk factor for IBD. In murine models, diets high in fat, especially saturated animal fats, also increase inflammation, whereas supplementation with omega 3 long-chain fatty acids protect against intestinal inflammation. Unfortunately, omega 3 supplements have not been shown to decrease the risk of relapse in patients with Crohn's disease. Dietary intervention studies have shown that enteral therapy, with defined formula diets, helps children with Crohn's disease and reduces inflammation and dysbiosis. Although fiber supplements have not been shown definitively to benefit patients with IBD, soluble fiber is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects. Addition of vitamin D and curcumin has been shown to increase the efficacy of IBD therapy. There is compelling evidence from animal models that emulsifiers in processed foods increase risk for IBD. We discuss current knowledge about popular diets, including the specific carbohydrate diet and diet low in fermentable oligo-, di-, and monosaccharides and polyols. We present findings from clinical and basic science studies to help gastroenterologists navigate diet as it relates to the management of IBD.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Crohn Disease; Curcumin; Diet; Diet Therapy; Dietary Fats; Dietary Fiber; Dietary Supplements; Dysbiosis; Emulsifying Agents; Fatty Acids, Omega-6; Fatty Acids, Volatile; Fermentation; Fruit; Gastrointestinal Microbiome; Humans; Inflammation; Inflammatory Bowel Diseases; Risk Factors; Vegetables; Vitamin D Deficiency

Inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Herein, an amphiphilic curcumin polymer (PCur) composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic curcumin (Cur) linked by disulfide bond was synthesized and characterized. The sufficient solubility, nano-scaled size and close to the neutral surface potential of PCur lead to preferential accumulation of the active drug in the inflamed regions of the gut. Moreover, PCur showed limited drug release and enhanced robustness under the physiological pH of the gastrointestinal tract (GIT), and a significantly elevated release was observed when responding to a bacterial reduction in the colon. Furthermore, cellular studies confirmed PCur had low cytotoxicity and increased transmembrane permeability, resulting in improved oral bioavailability evidenced by in vivo pharmacokinetics of rats. Finally, with DSS-induced murine model of IBD, we demonstrated that orally administered PCur ameliorated the inflammatory progression in the colon and could protect mice from IBD. In conclusion, it is illustrated that the developed PCur conjugate could potentially be employed as a colon-specific candidate for IBD treatment.

Topics: Administration, Oral; Animals; Bacteria; Caco-2 Cells; Cell Line, Tumor; Colon; Curcumin; Drug Carriers; Drug Delivery Systems; Female; Humans; Hydrophobic and Hydrophilic Interactions; Inflammation; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL; Particle Size; Permeability; Polyethylene Glycols; Polymers; Rats; Rats, Sprague-Dawley

This investigation deals with the development and evaluation (in vitro and in vivo) of pH triggered Eudragit-coated chitosan microspheres of curcumin (CUR) for treating ulcerative colitis.. CUR-loaded chitosan microspheres were initially prepared by emulsion cross linking method followed by coating with Eudragit S-100. The pharmacodynamics of the developed formulation was analyzed in mice by acetic acid induced colitis model.. The developed microspheres were of uniform spherical shape with high entrapment efficiency. CUR-chitosan microspheres showed less intense peaks compared to free CUR confirming inclusion of drug within microspheres as revealed by X-ray diffractogram. Uncoated CUR-chitosan microspheres exhibited burst release within initial 4 h while microspheres coated with Eudragit S-100 prevented premature release of CUR and showed controlled release up to 12 h following Higuchi model. In vivo organ biodistribution study showed negligible amount of CUR in stomach and small intestine confirming integrity of microsphere in upper gastrointestinal tract (GIT). In vivo study revealed significant reduction in severity and extent of colonic damage with CUR-loaded microspheres as compared to pure CUR which was further confirmed by histopathological study.. In vitro and in vivo studies proved the developed formulations as a promising system for pH-dependent delivery of drug to colon in ulcerative colitis.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Chitosan; Cross-Linking Reagents; Curcumin; Drug Delivery Systems; Excipients; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Mice; Microspheres; Polymethacrylic Acids; Tissue Distribution

The aim of this study was to provide insight into how curcumin reduces colon inflammation in the Mdr1a(-/-) mouse model of human inflammatory bowel disease using a combined transcriptomics and proteomics approach. Mdr1a(-/-) and FVB control mice were randomly assigned to an AIN-76A (control) diet or AIN-76A+0.2% curcumin. At 21 or 24weeks of age, colonic histological injury score (HIS) was determined, colon mRNA transcript levels were assessed using microarrays and colon protein expression was measured using 2D gel electrophoresis and LCMS protein identification. Colonic HIS of Mdr1a(-/-) mice fed the AIN-76A diet was higher (P<.001) than FVB mice fed the same diet; the curcumin-supplemented diet reduced colonic HIS (P<.05) in Mdr1a(-/-) mice. Microarray and proteomics analyses combined with new data analysis tools, such as the Ingenuity Pathways Analysis regulator effects analysis, showed that curcumin's antiinflammatory activity in Mdr1a(-/-) mouse colon may be mediated by activation of α-catenin, which has not previously been reported. We also show evidence to support curcumin's action via multiple molecular pathways including reduced immune response, increased xenobiotic metabolism, resolution of inflammation through decreased neutrophil migration and increased barrier remodeling. Key transcription factors and other regulatory molecules (ERK, FN1, TNFSF12 and PI3K complex) activated in inflammation were down-regulated by dietary intervention with curcumin.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Colitis; Curcumin; Diet; Disease Models, Animal; Inflammatory Bowel Diseases; Mice; Models, Molecular

Selective drug delivery to inflamed tissues is of widespread interest for the treatment of inflammatory bowel disease (IBD). Because a lack of physiological lipids has been described in patients suffering IBD, and some lipids present immunomodulatory properties, we hypothesize that the combination of lipids and anti-inflammatory drugs together within a nanocarrier may be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the in vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced colitis model. These nanocarriers included self-nanoemulsifying drug delivery systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell protamine nanocapsules (NC). In vitro, a 30-fold higher CC permeability across Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC>SNEDDS>NLC and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, only CC NLC were able to significantly decrease neutrophil infiltration and TNF-α secretion and, thus, colonic inflammation. Our results show that a higher CC permeability does not correlate with a higher efficacy in IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC retention at the intestinal site, rather than increased CC permeability are efficient treatments of IBD.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Caco-2 Cells; Cell Line; Cell Survival; Colitis; Curcumin; Dextran Sulfate; Drug Carriers; Drug Delivery Systems; Female; Humans; Inflammatory Bowel Diseases; Lipids; Macrophages; Mice, Inbred C57BL; Microscopy, Confocal; Nanoparticles; Tumor Necrosis Factor-alpha

In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease.

Topics: Animals; Chitosan; Colitis; Colon; Curcumin; Drug Carriers; Inflammatory Bowel Diseases; Mesalamine; Polymethacrylic Acids; Rats

This study investigates the protective effects of turmeric (Curcuma longa, CL) on acetic acid-induced colitis in rats.. Inflammatory bowel disease (IBD) was induced in male Wistar rats by intra-rectal administration of 1 ml of 4% acetic acid at 8 cm proximal to the anus for 30 s. Curcuma longa (CL) powder, (1, 10, or 100 mg/kg/day) was administered for either 3 days before or after IBD for 7 days. The body weight, macroscopic and microscopic analysis of the colon of CL-treated IBD rats and that of control rats (no IBD, no CL) were performed on 0 day, 2, 4 and 7th day. Myeloperoxidase (MPO), IL-23 and glutathione levels in control, untreated and treated rats were measured by ELISA.. CL significantly (P < 0.05) improved IBD-induced reduction in mean body weight and mean macroscopic ulcer score. Administration of CL also significantly (P < 0.01) reduced the mean microscopic ulcer score when compared to untreated IBD control. Intake of CL by rats resulted in a significant (P < 0.05) increase in the mean serum glutathione level compared to untreated control. CL reduced both MPO and IL-23 levels in the colonic mucosa of the rat.. CL improved body weight gain, mean macroscopic and microscopic ulcer scores in the colon of rats suffering from acetic acid-induced IBD. CL reduced both MPO and IL-23 in the mucosa of the colon. The increase in the mean serum glutathione level may help in the reduction of oxidative stress associated with IBD.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Body Weight; Colitis, Ulcerative; Colon; Curcuma; Glutathione; Inflammatory Bowel Diseases; Interleukin-23; Intestinal Mucosa; Male; Oxidative Stress; Peroxidase; Phytotherapy; Plant Extracts; Rats, Wistar; Ulcer

Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study is to evaluate the effect of flunixin and curcumin in experimentally induced ulcerative colitis in rats. Animals were randomly divided into four groups, each consisting of 12 animals: normal control group, acetic acid group, curcumin-treated group, and flunixin-treated group. Induction of colitis by intracolonic administration of 4% acetic acid produced severe macroscopic inflammation in the colon, 14 days after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, edema, and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), colonic alkaline phosphatase (ALP), and myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxide formation and depleted reduced glutathione concentrations in colonic tissues. After induction of colitis, treatment with curcumin (50 mg/kg daily, p.o.) and flunixin (2.5 mg/kg daily, s.c.) decreased serum LDH, ALP, interleukin (IL)-1β, and tumor necrosis factor-α levels, as well as colonic MPO and lipid peroxide levels, whereas increased colonic prostaglandin E2 and IL-10 concentrations were observed. Moreover, effective doses of curcumin and flunixin were effective in restoring the histopathological changes induced by acetic acid administration. The findings of the present study provide evidence that flunixin may be beneficial in patients with inflammatory bowel disease.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Clonixin; Colon; Curcumin; Cytokines; Disease Models, Animal; Inflammation Mediators; Inflammatory Bowel Diseases; Lipid Peroxidation; Male; Organ Size; Rats, Wistar

Nano-scaled particles have been found to preferentially accumulate in inflamed regions. Local delivery of anti-inflammatory drugs loaded in nanoparticles to the inflamed colonic site is of great interest for inflammatory bowel disease (IBD) treatment. Curcumin (CC) is an anti-inflammatory local agent, which presents poor ADME properties. Hence, we evaluated, both in vitro and in vivo, the local delivery of CC using pH-sensitive polymeric nanoparticles (NPs) combining both poly(lactide-co-glycolide) acid (PLGA) and a polymethacrylate polymer (Eudragit(®) S100). CC-NPs significantly enhanced CC permeation across Caco-2 cell monolayers when compared to CC in suspension. CC-NPs significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, CC-NPs significantly decreased neutrophil infiltration and TNF-α secretion while maintaining the colonic structure similar to the control group in a murine DSS-induced colitis model. Our results support the use of nanoparticles made of PLGA and Eudragit(®) S100 combination for CC delivery in IBD treatment.

Topics: Animals; Anti-Inflammatory Agents; Caco-2 Cells; Cell Line; Colitis; Colon; Curcumin; Dextran Sulfate; Disease Models, Animal; Drug Carriers; Female; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Lactic Acid; Macrophages; Mice, Inbred C57BL; Nanoparticles; Neutrophils; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymethacrylic Acids; Tumor Necrosis Factor-alpha

The present study was aimed to develop and optimize the microsponges of curcumin for colon specific drug delivery in a view to bypass the upper gastrointestinal tract (GIT) for enhanced therapeutic effect. Microsponges were developed by quasi emulsion solvent diffusion method using 3(2) full factorial design. Prepared microsponges were optimized in order to analyze the effects of independent variables (volume of ethanol and Eudragit L100) on the encapsulation efficiency, particle size, and drug release. The optimized formulation was subjected to in vivo study using acetic acid induced colitis model in rats. The F7 was selected as optimized formulation based on particle size of 41.63 μm, % entrapment efficiency of 78.13%, and % cumulative drug release of 84.12%, and desirability factor of 0.83. Release studies revealed that microsponges prevented the premature release of curcumin in upper GIT and specifically released the drug at colonic pH. The drug release profile of F7 formulation was subjected to different kinetic models and based upon the best correlation coefficient (r(2) = 0.9927) the release was found to follow Higuchi model, which suggested diffusion as the main mechanism of drug release. Pharmacodynamic study showed that curcumin loaded microsponges causes a significant decrease in edema, necrosis, and hemorrhage of colon as compared to free curcumin. This study proves that curcumin loaded microsponges may act as a promising drug delivery system for treatment of ulcerative colitis.

Topics: Animals; Colon; Curcumin; Drug Administration Routes; Drug Delivery Systems; Edema; Hemorrhage; Humans; Inflammatory Bowel Diseases; Male; Necrosis; Rats

Inflammatory bowel disease (IBD) is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual's capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae) has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F) and increasing anti-inflammatory cytokine gene promoter activity (IL-10, -1082A). The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions.

Topics: Curcuma; Curcumin; Epithelial Cells; HEK293 Cells; Humans; In Vitro Techniques; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Organic Cation Transport Proteins; Plant Extracts; Symporters

Treatment of inflammatory bowel disease (IBD) by synthetic active ingredients leads to many side effects. The objective of this study was to manage IBD using natural products as curcumin and Ginkgo biloba. Rats were divided into four groups (control, IBD, curcumin treated, and ginkgo treated). Inflammation was assessed by determination of myeloperoxidase, matrix metalloproteinases, metalloproteinase-1 inhibitor, nitric oxide, hydroxyproline, tumor necrosis factor-alpha, ceruloplasmin, and histopathological scoring. IBD induction significantly increased all measured parameters. Treated groups had significantly lower levels when compared with the IBD group. In conclusion, curcumin and ginkgo were effective in prevention and treatment of IBD.

Topics: Animals; Biomarkers; Ceruloplasmin; Colon; Curcumin; Drugs, Chinese Herbal; Gene Expression; Ginkgo biloba; Hydroxyproline; Inflammatory Bowel Diseases; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Nitric Oxide; Peroxidase; Rats; Rats, Wistar; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha

Inflammatory bowel disease (IBD) is a major source of morbidity in children and adults. Its incidence is rising, particularly in young people. IBD carries a lifelong risk of cancer, which is proportional to disease duration. Drug and surgical treatments rarely offer cure and often carry a high side effect burden. Dietary therapy is highly effective in Crohn's disease. For these reasons, there is much interest in developing novel dietary treatments in IBD. Curcumin, a component of the spice turmeric, and an anti-inflammatory and anti-cancer agent, shows preclinical and clinical potential in IBD. Its mechanisms of action are unknown. Our aim was to assess the effect of curcumin on key disease mediators p38 mitogen-activated protein kinase (MAPK), IL-1beta, IL-10 and matrix metalloproteinase-3 (MMP-3) in the gut of children and adults with IBD. Colonic mucosal biopsies and colonic myofibroblasts (CMF) from children and adults with active IBD were cultured ex vivo with curcumin. p38 MAPK, NF-kappaB and MMP-3 were measured by immunoblotting. IL-1beta and IL-10 were measured by ELISA. We show reduced p38 MAPK activation in curcumin-treated mucosal biopsies, enhanced IL-10 and reduced IL-1beta. We demonstrate dose-dependent suppression of MMP-3 in CMF with curcumin. We conclude that curcumin, a naturally occurring food substance with no known human toxicity, holds promise as a novel therapy in IBD.

Topics: Acetylation; Adolescent; Biopsy; Child; Colon; Curcumin; Enzyme Activation; Fibroblasts; Humans; Inflammatory Bowel Diseases; Interleukin-10; Interleukin-1beta; Intestinal Mucosa; Matrix Metalloproteinase 3; p38 Mitogen-Activated Protein Kinases; Phosphorylation

Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Multidrug resistance gene-deficient (mdr1a-/- ) mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. The present study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets (control (AIN-76A), control +0.2% curcumin or control +0.1% rutin) and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways, probably mediated by pregnane X receptor (Pxr) and peroxisome proliferator-activated receptor alpha (Ppara) activation of retinoid X receptor (Rxr). These results indicate the potential of global gene expression and pathway analyses to study and better understand the effect of foods in modulating colonic inflammation.

Topics: Animals; Anti-Inflammatory Agents; ATP Binding Cassette Transporter, Subfamily B; Base Sequence; Colitis; Colon; Curcumin; Dietary Supplements; Fibrosis; Gene Expression; Gene Expression Regulation; Genome-Wide Association Study; Inflammatory Bowel Diseases; Liver; Mice; Mice, Knockout; Models, Animal; Molecular Sequence Data; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Rutin; Staining and Labeling

Seven N-unsubstituted curcuminoid pyrazoles have been synthesized from the corresponding beta-diketones (including curcumin). We evaluated the possibility of curcuminoid pyrazoles regulating the activity of matrix metalloproteinases (MMPs) by human intestinal epithelial cells in vitro. Zymographic analysis revealed that three compounds significantly down-regulated MMP-9 activity on inflammation-induced intestinal epithelial cells, making them original candidates for the treatment of inflammatory bowel disease (IBD).

Topics: Caco-2 Cells; Curcumin; Gelatinases; Humans; Inflammatory Bowel Diseases; Interleukin-1beta; Matrix Metalloproteinase Inhibitors; Pyrazoles; Tumor Necrosis Factor-alpha

Topics: Animals; Curcumin; Cytokines; Humans; Inflammatory Bowel Diseases; Interleukin-6; Intestinal Mucosa; Intestines; Leukapheresis; Macrophage Migration-Inhibitory Factors

Curcumin (diferulolylmethane) has been shown to have a protective role in mouse models of inflammatory bowel diseases (IBD) and to reduce the relapse rate in human ulcerative colitis (UC), thus making it a potentially viable supportive treatment option. Trinitrobenzene sulfonic acid (TNBS) colitis in NKT-deficient SJL/J mice has been described as Th1-mediated inflammation, whereas BALB/c mice are believed to exhibit a mixed Th1/Th2 response.. We therefore investigated the effect of dietary curcumin in colitis induced in these 2 strains.. In the BALB/c mice, curcumin significantly increased survival, prevented weight loss, and normalized disease activity. In the SJL/J mice, curcumin demonstrated no protective effects. Genomewide microarray analysis of colonic gene expression was employed to define the differential effect of curcumin in these 2 strains. This analysis not only confirmed the disparate responses of the 2 strains to curcumin but also indicated different responses to TNBS. Curcumin inhibited proliferation of splenocytes from naive BALB/c mice but not SJL/J mice when nonspecifically stimulated in vitro with concanavalin A (ConA). Proliferation of CD4(+) splenocytes was inhibited in both strains, albeit with about a 2-fold higher IC(50) in SJL/J mice. Secretion of IL-4 and IL-5 by CD4(+) lymphocytes of BALB/c mice but not SJL/J mice was significantly augmented by ConA and reduced to control levels by curcumin.. The efficacy of dietary curcumin in TNBS colitis varies in BALB/c and SJL/J mouse strains. Although the exact mechanism underlying these differences is unclear, the results suggest that the therapeutic value of dietary curcumin may differ depending on the nature of immune dysregulation in IBD.

Topics: Animals; Colitis; Concanavalin A; Curcumin; Diet; Disease Models, Animal; Inflammatory Bowel Diseases; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Microarray Analysis; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Trinitrobenzenesulfonic Acid

To explore the mechanism of modulation of intestinal mucosal inflammatory factors by curcumin, the inhibitor of the transcriptional factor nuclear factor -kappaB (NF-kappaB), in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis, and screen for a targeted therapeutic agent for treatment of inflammatory bowel disease (IBD).. Rats with TNBS-induced colitis were fed with diet containing 2.0% curcumin (treatment group), 0.5% sulfasalazine (SASP, positive control group), and normal diet (model group and negative control group). Changes in colonic mucosal histological scores were evaluated and the cytokine mRNA expressions in the colonic tissue assessed by semiquantitative reverse transcriptional PCR (RT-PCR).. Treatment with curcumin ameliorated the histopathologic signs in rats with TNBS-induced intestinal inflammation. Curcumin and sulfasalazine obviously suppressed the high expression of proinflammatory cytokine interleukin (IL)-1beta mRNA and increased the low expression of IL-10 mRNA in the colonic mucosa. Expression of the anti-inflammatory cytokine IL-4 mRNA was detected in none of the groups.. Curcumin could modulate the expressions of IL-1beta and IL-10 mRNA in murine model of IBD, which suggests the potential of curcumin as a targeted therapeutic agent for IBD.

Topics: Animals; Curcumin; Inflammatory Bowel Diseases; Interleukin-1; Interleukin-10; Interleukin-4; Intestinal Mucosa; Male; NF-kappa B; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Trinitrobenzenesulfonic Acid