curcumin and Colitis--Ulcerative

Curcumin, an active polyphenol extracted from Traditional Chinese medicine Curcuma longa (turmeric), has shown many health-related benefits and pharmacological effects. Adjuvant curcumin therapy for ulcerative colitis has become increasingly popular, but its efficacy and safety of which is still controversial. The purpose of this study is to evaluate the efficacy and safety of adjuvant curcumin therapy in ulcerative colitis.. The Medline, EMBASE, the Cochrane Library, CNKI, VIP, WanFang, and SinoMed databases were searched from inception to June 2021, to identify all randomized controlled clinical trials with adjuvant curcumin therapy in ulcerative colitis. The primary outcomes were clinical and endoscopic remission, and subgroup analyses were also performed.. Six randomized trials with a total of 385 participants were included in this study. Qualified trials recommended that adjuvant curcumin therapy for ulcerative colitis was effective in inducing clinical remission (RR = 2.10, 95% CI 1.13 to 3.89), but not in clinical improvement (RR = 1.62, 95% CI 1.00 to 2.61), endoscopic remission (RR = 4.17, 95% CI 0.63 to 27.71) or endoscopic improvement (RR = 4.13, 95% CI 0.20 to 87.07). Included studies showed that appropriate dosage, formation, longer duration, and topical medication may have a greater potential advantage. No severe adverse effects had been reported.. Available evidence suggested that adjuvant curcumin therapy may be effective for clinical remission in ulcerative colitis patients without causing severe adverse effects. The appropriate methods of administration can achieve better curative effect, which requires further study to verify.

Topics: Colitis, Ulcerative; Curcuma; Curcumin; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Medicine, Chinese Traditional; Randomized Controlled Trials as Topic; Remission Induction

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

To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases.. Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software.. A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet 's disease (BD) involves one RCT, Crohn 's disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ' s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs.. Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.

Topics: Arteritis; Arthritis, Rheumatoid; Colitis, Ulcerative; Crohn Disease; Curcuma; Curcumin; Humans; Lichen Planus, Oral; Lupus Erythematosus, Systemic; Plant Extracts; Psoriasis; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease with multiple genetic and a variety of environmental risk factors. Although current drugs significantly aid in controlling the disease, many people have led to the application of complementary therapies due to the common belief that they are natural and safe, as well as due to the consideration of the side effect of current drugs. Curcumin, cannabinoids, wheatgrass, Boswellia, wormwood and Aloe vera are among the most commonly used complementary medicines in UC. However, these treatments may have adverse and toxic effects due to unintended interactions with drugs or drug-metabolizing enzymes such as cytochrome P450s; thus, being ignorant of these interactions might cause deleterious effects with severe consequences. In addition, the lack of complete and controlled long-term studies with the use of these complementary medicines regarding drug metabolism pose additional risk and unsafety. Thus, this review aims to give an overview of the potential interactions of drug-metabolizing enzymes with the complementary botanical medicines used in UC, drawing attention to possible adverse effects.

Topics: Colitis, Ulcerative; Complementary Therapies; Curcumin; Cytochrome P-450 Enzyme System; Drug-Related Side Effects and Adverse Reactions; Humans

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum, characterized by unpredictable exacerbation and remission phases. Conventional treatment options for UC include mesalamine, glucocorticoids, immunosuppressants, and biologics. The management of UC is challenging, and other therapeutic options are constantly being sought. In recent years more attention is being paid to curcumin, a main active polyphenol found in the turmeric root, which has numerous beneficial effects in the human body, including anti-inflammatory, anticarcinogenic, and antioxidative properties targeting several cellular pathways and making an impact on intestinal microbiota. This review will summarize the current knowledge on the role of curcumin in the UC therapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Humans; Inflammation; Mesalamine

Although previous studies have examined the impact of curcumin supplementation on cytokine levels in patients with autoimmune disorders, we were unable to find a systematic review of the effect of curcumin supplementation on inflammatory biomarkers such as CRP and ESR in patients with rheumatoid arthritis or ulcerative colitis; therefore we conducted this systematic review and meta-analysis.. Relevant studies published from inception to December 2020 were systematically searched through the PubMed, SCOPUS, and google scholar databases. We conducted our systematic review and meta-analysis according to the 2020 PRISMA guidelines. The quality of the papers were assessed by using the Cochrane Collaboration's risk of bias tool. Included studies were randomized clinical trials on the effects of supplementation with curcumin or its derivative on inflammatory factors in patients with rheumatoid arthritis and ulcerative colitis. Pooled effect sizes were calculated using a random-effects model and reported as the weighted mean difference (WMD) and 95 % CI.. In all, six studies met the inclusion criteria for this study. Curcumin supplementation in doses of 250-1500 mg/day over 8-12 weeks was observed to be associated with decreases in CRP and ESR in adult patients with rheumatoid arthritis and ulcerative colitis in comparison with the control group (WMD: -0.42; 95 % CI: -0.59, -0.26, I. Curcumin supplementation was associated with significant reductions in levels of CRP and ESR in patients with rheumatoid arthritis and ulcerative colitis. Earlier studies reported curcumin as a safe complementary therapy for several diseases. However, a handful of studies were found on the effect of curcumin on autoimmune diseases despite our comprehensive search. Further studies are therefore warranted in this area.

Topics: Adult; Arthritis, Rheumatoid; Biomarkers; Colitis, Ulcerative; Curcumin; Dietary Supplements; Humans; Randomized Controlled Trials as Topic

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

Gastrointestinal (GI) diseases are highly prevalent worldwide, with considerable morbidity and mortality. Curcumin has been used for many years as a plant-derived product for the management of various conditions such as abdominal pain and poor digestion. This systematic review was undertaken with the aim of investigating the effect of curcumin or turmeric supplementation on GI diseases. A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science and Google Scholar up to March 2020 to identify clinical trials assessing the effect of curcumin/turmeric alone or in combination with other herbs or nutrients on GI diseases. Twenty-one studies comprising 1478 GI patients were included in the study. Four out of seven studies showed a beneficial effect of curcumin/turmeric supplementation on irritable bowel syndrome (IBS) and six out of seven showed positive effects of these herbs on ulcerative colitis. Two out of four studies highlighted the potential role of curcumin/turmeric in eradication of H. pylori infection. Both studies conducted on peptic ulcer disease and two out of four studies performed on Crohn's disease demonstrated positive effects of curcumin/turmeric supplementation. One study showed curcumin supplementation had no effect on familial adenomatous polyposis. However, in another study, curcumin had favorable effects on proctosigmoiditis. Nine studies reported some minor adverse effects. The results of this systematic review suggest a beneficial effect of curcumin/turmeric supplementation on the management of GI diseases. More randomized clinical controlled trials are needed to confirm these results.

Topics: Colitis, Ulcerative; Crohn Disease; Curcuma; Curcumin; Humans

Aminosalicylic acids are recognized to be the first-line treatment options for ulcerative colitis. Currently, the effectiveness of curcumin as an adjuvant treatment in ulcerative colitis has been investigated, which was still controversial. This study aimed to systematically review and meta-analyze the efficacy and safety of curcumin as an adjuvant treatment in ulcerative colitis.. The PubMed, EMBASE, and Cochrane Library databases were searched from original to July 2019, and relevant randomized controlled clinical trials were enrolled and analyzed. The primary outcomes were clinical and endoscopic remission; meanwhile, the secondary outcomes were clinical and endoscopic improvement. Subgroup analyses of doses, delivery way, form, and intervention time of curcumin were also conducted.. Six randomized controlled clinical trials with a total of 349 patients were included. Eligible trials suggested that adjuvant curcumin treatment in ulcerative colitis was effective in inducing clinical remission (odds ratio [OR] = 5.18, 95% confidence interval [CI]: 1.84-14.56, P = 0.002), endoscopic remission (OR = 5.69, 95% CI: 1.28-25.27, P = 0.02), and endoscopic improvement (OR = 17.05, 95% CI: 1.30-233.00, P = 0.03), but not in clinical improvement (OR = 4.79, 95% CI: 1.02-22.43, P = 0.05). We can see the potential advantages in large dosage, topical enema, special drug form, and longer duration from the enrolled studies. There were no severe side effects reported.. Curcumin, as an adjuvant treatment of mesalamine, was proved to be effective and safe in ulcerative colitis. Better efficacy can be achieved with suitable dose, delivery way, formation, and intervention time, which needs further study to verify.

Topics: Chemotherapy, Adjuvant; Colitis, Ulcerative; Curcumin; Dosage Forms; Phytotherapy; Randomized Controlled Trials as Topic; Treatment Outcome

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

Despite significant advances in the study of Ulcerative colitis (UC) management, up to a third of patients may be refractory to conventional therapy, and specialists have considered natural compounds such as curcumin.. The meta-analyzes found in the literature compare the effects of curcumin used in different administration routes or compare patients in remission with patients with active disease. Due to the biases in these studies, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) that investigated the efficacy of orally administrated curcumin in mild-to-moderate active UC.. Curcumin produces relevant anti-inflammatory and antioxidant effects that are crucial in inducing remission in UC patients. Unfortunately, in the treatment of UC, we have not observed studies with standardization of dose and routes of administration. Existing meta-analyses are biased because they compare studies using different administration routes and patients in different stages of the disease. Our meta-analysis is the only one that tried to make a comparison with a few of biases as possible and show that curcumin can help in the induction of remission in UC subjects.

Topics: Anti-Inflammatory Agents; Antioxidants; Colitis, Ulcerative; Curcumin; Humans; Randomized Controlled Trials as Topic; Remission Induction

Crohn's Disease (CD) and Ulcerative Colitis (UC) result from an overreaction of the bowel to multifactorial stimuli leading to discomfort, pain, and it is associated with high morbidity and lethality. The medications commonly used are expensive and associated with multiple side effects. Curcuma longa exerts anti-inflammatory and antioxidant actions and has shown positive effects on CD and UC treatment, possibly due to the presence of curcuminoids. The objective of this review was to evaluate the role of curcuminoids in the treatment of IBD. A search for articles associating curcuminoids and CD and UC was performed using MEDLINE-PubMed. It has been found that curcumin can reduce oxidative stress and inhibit the migration of neutrophils and inducible nitric oxide synthase in the intestine. It may also improve micro and macroscopic lesions, prevent apoptosis of intestinal cells and also induce the restoration of the mitogen-activated protein kinase immune reaction. As the incidence of CD and UC is growing in many populations, there is an urgency to find an appropriate and accessible therapeutic approach to improve quality of life of patients. The use of curcumin is cheap, efficient and associated with no side effects, and may become an alternative to the IBD treatment.

Topics: Adjuvants, Immunologic; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cell Movement; Colitis, Ulcerative; Crohn Disease; Curcuma; Curcumin; Databases, Factual; Diarylheptanoids; Humans; Neutrophils; Nitric Oxide Synthase Type II; Oxidative Stress; Plant Extracts; Quality of Life

Intestinal inflammatory diseases, such as Crohn's disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.

Topics: Biological Products; Colitis, Ulcerative; Crohn Disease; Curcumin; Gastrointestinal Microbiome; Humans; Inflammation; Intestinal Mucosa; Intestines

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Autoimmune Diseases; Colitis, Ulcerative; Curcumin; Diabetes Mellitus, Type 2; Humans; Lupus Nephritis; Multiple Sclerosis; Osteoarthritis; Randomized Controlled Trials as Topic; Rheumatic Diseases; Treatment Outcome

Nutritional strategies have been explored as primary or adjunct therapies for inflammatory bowel disease (IBD). Exclusive enteral nutrition is effective for the induction of remission in Crohn disease and is recommended as a first-line therapy for children. Dietary strategies focus on adjusting the ratio of consumed nutrients that are proinflammatory or antiinflammatory. Treatments with dietary supplements focus on the antiinflammatory effects of the individual supplements (eg, curcumin, omega-3 fatty acids, vitamin D) or their positive effects on the intestinal microbiome (eg, prebiotics, probiotics). This article discusses the role of diets and dietary supplements in the treatment of IBD.

Topics: Colitis, Ulcerative; Crohn Disease; Curcumin; Diet; Diet, Gluten-Free; Dietary Fiber; Dietary Sugars; Dietary Supplements; Enteral Nutrition; Fatty Acids, Omega-3; Glutamine; Humans; Immunoglobulin G; Parenteral Nutrition; Prebiotics; Probiotics; Vitamin D

Ulcerative colitis (UC) is a chronic, relapsing, remitting, and inflammatory disorder that afflicts millions of people around the world. It carries a substantial economic burden, reducing the quality of life, ability to work, and increasing disability. Conventional medical treatment of UC includes the use of aminosalicylates, corticosteroids, and immunosuppressive drugs. However, these medicines are not always effective due to some serious side effects. Nuclear factor-kappa B (NF-κB) is a key factor in the inflammatory setting and strongly affects the course of mucosal inflammation in UC. This review aims to describe the complex role of NF-κB in UC and discuss existing pharmacological attempts by curcumin for blocking NF-κB activation to develop new therapeutic strategies in UC. Several studies have shown intriguing pharmacologic effects associated with curcumin, which inhibits NF-κB expression by regulating NF-κB/IkB pathway and down-regulation expression of pro-inflammatory cytokines, such as Interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The efficacy of curcumin has been confirmed in several experimental models of UC. Furthermore, curcumin significantly induced clinical remission in active mild-to-moderate UC patients and reduced clinical relapse in quiescent UC patients. The inhibitory effects of curcumin on NF-κB and its unrivaled safety profile indicate that it remains effective for the treatment of UC. In addition, curcumin is a nontoxic, inexpensive, and easily available natural polyphenol. In conclusion, curcumin can be used as a potential and safe drug in the management of patients with remission and mild-to-moderate UC.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Colitis, Ulcerative; Curcumin; Down-Regulation; Humans; Interleukins; NF-kappa B; Signal Transduction; Treatment Outcome; Tumor Necrosis Factor-alpha

Ulcerative Colitis (UC) is characterized by chronic inflammation of the mucosal layers of the colon. Treatment of refractory UC is challenging and has a huge healthcare burden. Although there have been advancements in immunomodulatory therapies, these require a step-up financially, and these medications are also associated with significant adverse events. Curcumin, an active ingredient of turmeric, has been studied in the past and found to be useful in the treatment of UC when used as an adjuvant along with mesalamine. We did a systematic review and meta-analysis to explore the role curcumin plays in clinical and endoscopic remission in patients with UC.. A comprehensive literature review was conducted by first searching the MEDLINE, Pubmed, and Embase databases through December 2017 to identify all studies that compared the use of curcumin when used along with mesalamine with placebo for clinical and endoscopic improvement and remission.. Three randomized controlled trials including 142 patients were included in the study. Use of curcumin along with mesalamine was associated with increased odds of clinical remission (pooled odds ratio of 6.78, 95% CI: 2.39-19.23, P = 0.042). Clinical improvement, endoscopic remission and improvement rate also trended higher in the curcumin group compared to placebo.. This study demonstrates higher clinical remission rates when curcumin was used in combination with mesalamine to achieve remission in patients with UC. Curcumin, due to its cost effectiveness and safer side effect profile, can decrease the healthcare burden and morbidity associated with this relapsing and remitting disease.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Endoscopy; Humans; Mesalamine; Remission Induction

Curcumin has demonstrated anti-inflammatory properties and has been investigated as an adjuvant therapy of ulcerative colitis (UC). The scope of this study was to systematically review and meta-analyze the efficacy of oral curcumin administration as an adjuvant therapy of UC. MEDLINE, Cochrane/CENTRAL, ClinicalTrials.gov, WHO-ICT Registry, EMBASE and grey literature were searched for relevant randomized controlled trials (RCTs). The primary outcome was clinical remission (attainment) and the secondary outcome was clinical response (maintenance/failure). Risk of bias was assessed with the Cochrane tool. Odds ratios (OR) were calculated with a Mantel-Haenszel (M-H) random effects model and with a beta-binomial (B-B) random effects model when zero events/cells occurred. Four RCTs met the criteria, but one was removed from the analyses due to inconsistency in protocol details. With the M-H method, treatment with curcumin was significantly superior to placebo in attaining remission in the per-protocol (PP) analysis (OR = 5.83, 95%CI = 1.24⁻27.43), but not in the intention-to-treat (ITT) analysis (OR = 4.33, 95%CI = 0.78⁻24.00). However, with the more accurate B-B method, both analyses were insignificant (for PP OR = 4.26, 95%CI = 0.59⁻31.00, for ITT OR = 3.80, 95%CI = 0.55⁻26.28). Based on the current available evidence, oral curcumin administration does not seem superior to placebo in attaining remission in patients with UC. Future RCTs should be planned more cautiously with sufficient size and adhere to the ITT analysis in all outcomes.

Topics: Administration, Oral; Anti-Inflammatory Agents; Colitis, Ulcerative; Curcumin; Female; Humans; Male; Treatment Outcome

treatment guidelines for ulcerative colitis (UC) not yet established. Currently, mesalazine, corticosteroids, and immunomodulators are treatment options for UC. However, they are known to have unpleaseant side effects such as nausea, vomiting, headaches, hepatitis, and male infertility. Curcumin is found in Turmeric plants (Curcuma longa L.), which possesses both anti-inflammatory and antioxidant properties. This study aimed to determine whether curcumin as adjuvant therapy can induce or maintain remission in UC patients.. structured search in three database (Cochrane, PubMed, Proquest) using "Curcumin", "remission" and "Ulcerative Colitis" as keywords. Inclusion criteria is randomized controlled trials (RCTs), meta-analysis, or systematic review using curcumin as adjuvant therapy in adult UC patients.. we found 49 articles. After exclusion, three RCTs were reviewed; two examined curcumin efficacy to induce remission and one for remision maintenance in UC. Curcumin was significantly more effective than placebo in all RCTs. The efficacy of curcumin could be explained by its anti-inflammatory properties, which inhibit NF-kB pathway. Regulation of oxidant/anti-oxidant balance can modify the release of cytokines. However, methods varied between RCTs. Therefore, they cannot be compared objectively. Futhermore, the sample size were small (n= 50, 45, 89) therefore the statistical power was not enough to generate representative results in all UC patients.. Available evidence showed that curcumin has the potential to induce and maintain remission in UC patients with no serious side effects. However, further studies with larger sample size are needed to recommend it as adjuvant therapy of ulcerative colitis.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Chemotherapy, Adjuvant; Colitis, Ulcerative; Curcumin; Humans; Randomized Controlled Trials as Topic; Remission Induction

Accurate. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.. Results showed that the EEG responses at lower levels of the independent variables were significantly high than at higher levels; except for oxygen content, the EEG responses at lower levels were considerably lower than at a higher level. It also showed that an upsurge in the physical demand increased lifting frequency and replication and caused decreasing in alpha power, theta/beta, alpha/beta, (theta + alpha)/beta, (theta + alpha)/(alpha + beta) and increasing in the theta power and the gamma power. Furthermore, several interactions among independent variables had significant effects on the EEG responses.. The EEG implementation for the investigation of neural responses to physical demands allows for the possibility of newer nontraditional and faster methods of human performance monitoring. These methods provide effective and reliable results as compared to other traditional methods. This study will safeguard the physical capabilities and possible health risks of industrial workers. And the applications of these tasks can occur in almost all working environments (factories, warehouses, airports, building sites, farms, hospitals, offices, etc.) that are at high altitudes. It can include lifting boxes at a packaging line, handling construction materials, handling patients in hospitals, and cleaning.

Topics: Action Potentials; Adolescent; Adult; Aged; Alanine Transaminase; Analgesics; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Arrhythmias, Cardiac; Atrial Fibrillation; Biological Transport; Biomarkers; Blood Gas Analysis; Blood-Brain Barrier; Blotting, Western; Bone and Bones; Bone Marrow; Bone Neoplasms; Brain; Breast Neoplasms; Calcium; Carbon Tetrachloride; Cartilage, Articular; Case-Control Studies; CD59 Antigens; CDC2 Protein Kinase; Celastrus; Cell Cycle; Cell Division; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemical Fractionation; Colitis, Ulcerative; Colon; Computer Simulation; Curcumin; Cyclin B1; Cymenes; Cytokines; Dextran Sulfate; Dipeptidyl Peptidase 4; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Ectodysplasins; Electroencephalography; Endothelial Cells; Epithelial Cells; Epithelial-Mesenchymal Transition; Exosomes; Female; Flavonoids; G2 Phase; Gene Expression Regulation; Glial Cell Line-Derived Neurotrophic Factor; Heart Atria; Heart Conduction System; Heart Ventricles; HeLa Cells; Hemodynamics; Humans; Image Interpretation, Computer-Assisted; Indoles; Inflammation; Interleukin-1beta; Interleukin-6; Iridoid Glycosides; Ki-1 Antigen; Lens, Crystalline; Lifting; Liver; Liver Cirrhosis; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Microelectrodes; Middle Aged; Models, Cardiovascular; Multiparametric Magnetic Resonance Imaging; Myeloid Differentiation Factor 88; NADPH Oxidase 1; Neoplasm Grading; NF-kappa B; Osteoarthritis; Osteoblasts; Osteoclasts; Oxidative Stress; Oxygen; Patch-Clamp Techniques; PC-3 Cells; Permeability; Peroxidase; Plant Extracts; Plant Leaves; Prostate; Prostatic Neoplasms; Protective Agents; Proto-Oncogene Proteins c-akt; Psychophysics; Purpura, Thrombocytopenic, Idiopathic; Rabbits; Rats; Rats, Sprague-Dawley; Recovery of Function; Retrospective Studies; RNA, Long Noncoding; ROC Curve; Safety; Shoes; Signal Transduction; Sodium; Sonication; Spinal Cord; Spinal Cord Injuries; Syringa; Tight Junctions; Tissue Inhibitor of Metalloproteinase-1; Toll-Like Receptor 2; Transforming Growth Factor beta2; Transient Receptor Potential Channels; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Umbilical Cord; Up-Regulation; Ventricular Function; Young Adult

Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.

Topics: Animals; Antioxidants; Colitis, Ulcerative; Curcuma; Curcumin; Cyclooxygenase Inhibitors; Cytokines; Free Radical Scavengers; Humans; India; Medicine, Traditional; NF-kappa B; Nitric Oxide Synthase Type II; Peroxidase; Protein Kinases; Signal Transduction

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon characterized by episodes of disease activity and symptom-free remission.There is paucity of evidence regarding the efficacy and safety of complementary or alternative medicines for the management of UC. Curcumin, an anti-inflammatory agent, has been used in many chronic inflammatory conditions such as rheumatoid arthritis, esophagitis and post-surgical inflammation. The efficacy of this agent for maintenance of remission in patients with UC has not been systematically evaluated.. The primary objective was to systematically review the efficacy and safety of curcumin for maintenance of remission in UC.. A computer-assisted literature search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed on July 11, 2012 to identify relevant publications. Proceedings from major gastroenterology meetings and references from published articles were also searched to identify additional studies.. Randomized placebo-controlled trials (RCT) of curcumin for maintenance of remission in UC were included. Studies included patients (of any age) who were in remission at the time of recruitment. Co-interventions were allowed.. Two authors independently extracted data and assessed the methodological quality of the included studies using the Cochrane risk of bias tool. Data were analyzed using Review Manager (RevMan 5.1). We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each dichotomous outcome. For continuous outcomes we calculated the mean difference (MD) and 95% CI.. Only one trial (89 patients) fulfilled the inclusion criteria. This trial randomized 45 patients to curcumin and 44 patients to placebo. All patients received treatment with sulfasalazine or mesalamine. The study was rated as low risk of bias. Curcumin was administered orally in a dose of 2 g/day for six months. Fewer patients relapsed in the curcumin group than the placebo group at six months. Four per cent of patients in the curcumin group relapsed at six months compared to 18% of patients in the placebo group (RR 0.24, 95% CI 0.05 to 1.09; P = 0.06). There was no statistically significant difference in relapse rates at 12 months. Twenty-two per cent of curcumin patients relapsed at 12 months compared to 32% of placebo patients (RR 0.70, 95% CI 0.35 to 1.40; P = 0.31). A total of nine adverse events were reported in seven patients. These adverse events included sensation of abdominal bulging, nausea, transient hypertension, and transient increase in the number of stools. The authors did not report which treatment group the patients who experienced adverse events belonged to. The clinical activity index (CAI) at six months was significantly lower in the curcumin group compared to the placebo group (1.0 + 2.0 versus 2.2 + 2.3; MD -1.20, 95% CI -2.14 to -0.26). The endoscopic index (EI) at six months was significantly lower in the curcumin group than in the placebo group (0.8 + 0.6 versus 1.6 + 1.6; MD -0.80, 95% CI -1.33 to -0.27).. Curcumin may be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine. However, further research in the form of a large scale methodologically rigorous randomized controlled trial is needed to confirm any possible benefit of curcumin in quiescent UC.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Drug Therapy, Combination; Humans; Maintenance Chemotherapy; Mesalamine; Randomized Controlled Trials as Topic; Recurrence; Sulfasalazine

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

The aim of this study was to assess the efficacy and safety of a novel, hydrophilic, bioenhanced curcumin (BEC) as add-on therapy in inducing clinical and endoscopic remission in mild to moderately active ulcerative colitis (UC).. Mild to moderately active UC patients (partial Mayo score 2 to 6 with endoscopic Mayo score >1) on standard dose of mesalamine were randomized to either 50 mg twice daily BEC or an identical placebo. Clinical response (≥2 reduction of partial Mayo score), clinical remission (partial Mayo score ≤1), and endoscopic remission (endoscopic Mayo score of ≤1) were evaluated at 6 weeks and 3 months. Responders were followed-up at 6 and 12 months for assessing maintenance of remission.. Sixty-nine patients were randomly assigned to BEC (n=34) and placebo (n=35). At 6 weeks, clinical and endoscopic remission occurred in 44.1% (15/34) and 35.3% (14/34) patients, respectively, compared with none in the placebo group (P<0.01). Clinical response was also significantly higher in the BEC group (18/34, 52.9%) compared with placebo (5/35, 14.3%) (P=0.001). The clinical remission, clinical response, and endoscopic remission rates at 3 months were 55.9% (19/34), 58.8% (20/34), 44% (16/34) and 5.7% (2/35), 28.6% (10/35), 5.7% (2/35) in BEC and placebo groups, respectively. At 6 and 12 months, 95% (18/19) and 84% (16/19) of the responders to BEC maintained clinical remission. None of the responders to placebo maintained clinical remission at 6 months. BEC appeared safe with no significant side effects.. A low-dose BEC as add-on therapy was superior to placebo in inducing sustained clinical and endoscopic remission in patients with mild-to-moderately active UC on maximal dose of mesalamine (ClinicalTrials.gov: NCT02683733).

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Double-Blind Method; Humans; Mesalamine; Pilot Projects; Remission Induction; Treatment Outcome

Curcumin has anti-inflammatory properties. The aim of this study was to evaluate the effect of curcumin on improvement of the disease activity in ulcerative colitis (UC).. In this randomized double-blind clinical trial, 70 patients with mild-to-moderate UC were randomly assigned to curcumin (1,500 mg/day) or placebo intake for 8 weeks. Disease clinical activity, quality of life, serum levels of tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) values, and complete blood count were measured.. Changes in Simple Clinical Colitis Activity Index score were significantly higher in the curcumin than the placebo group (-5.9 ± 2.08 vs. -2.1 ± 2.6; p = .001). The scores of Inflammatory Bowel Disease Questionnaire-9 and quality of life were significantly higher in the intervention group compared to the control group (p = .006). Furthermore, the curcumin supplementation reduced the serum hs-CRP concentration (-6.3 ± 13.6 vs. 3.7 ± 11.6 μg/ml; p = .01) and ESR levels significantly (-1.6 ± 2.7 vs. -0.09 ± 2.4 mm/hr; p = .02) in comparison with the control group. No significant changes were observed in the TNF-α levels of both groups.. Consumption of the curcumin supplement, along with drug therapy, is associated with significant improvement of the clinical outcomes, quality of life, hs-CRP, and ESR in patients with mild-to-moderate UC.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Double-Blind Method; Female; Humans; Male; Middle Aged; Quality of Life; Young Adult

Curcuminoids are polyphenols with documented anti-inflammatory activity and has been shown to improve the symptoms of several inflammatory diseases. We aimed to evaluate the effectiveness of a nanoformulation of curcuminoids in the treatment of ulcerative colitis.. This randomized double-blinded controlled trial was conducted on 56 patients aged 18 years or older with the final diagnosis of mild to moderate ulcerative colitis according to the Simple Clinical Colitis Activity Index (SCCAI). The patients were randomly assigned (using a computerized random sampling table) to receive curcuminoids nanomicelles (80 mg, three times daily, orally) plus mesalamine (3 g/24 hours, orally) as the treatment group and placebo plus mesalamine (3 g/24 hours, orally) as the control group for a period of four weeks. The severity of disease was assessed at baseline and at the end of the second and fourth weeks of the treatment according to the SCCAI.. The score for urgency of defecation reduced significantly more in case group as compared with control group at four weeks after beginning the treatment. The patients in case group experienced better general condition than the control ones after 4 weeks of treatment. Overall, the mean SCCAI score was significantly lower in the patients received curcuminoids nanomicelles plus mesalamine as compared with the group received placebo plus mesalamine at fourth week after the treatment (1.71 ± 1.84 vs 2.68 ± 2.09, p = 0.050).. Adding curcuminoids nanomicelles to routine treatment of patients with ulcerative colitis is associated with a significant improvement of symptoms, including reduced frequency of urgent defecation, improved patients' self-reported well-being and reduced clinical activity of ulcerative colitis. ClinicalTrials. "IRCT2017052634142N1".

Topics: Adult; Colitis, Ulcerative; Curcumin; Double-Blind Method; Female; Humans; Male; Mesalamine; Micelles; Middle Aged; Self Report; Treatment Outcome; Young Adult

The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC.. We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded.. In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups.. Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Double-Blind Method; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Mesalamine; Middle Aged; Placebos; Treatment Outcome; Young Adult

Curcumin, an active ingredient of turmeric with anti-inflammatory properties, has been demonstrated to be useful in experimental models of ulcerative colitis (UC). It's efficacy in humans needs to be investigated.. A randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (<25 cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Primary end point was disease response, defined as reduction in Ulcerative Colitis Diseases Activity Index by 3 points at 8 weeks, and secondary end points were improvement in endoscopic activity and disease remission at 8 weeks.. Response to treatment was observed in 56.5% in NCB-02 group compared to 36.4% (p=0.175) in placebo group. At week 8, clinical remission was observed in 43.4% of patients in NCB-02 group compared to 22.7% in placebo group (p=0.14) and improvement on endoscopy in 52.2% of patients in NCB-02 group compared to 36.4% of patients in placebo group (p=0.29). Per protocol analysis revealed significantly better outcomes in NCB-02 group, in terms of clinical response (92.9% vs. 50%, p=0.01), clinical remission (71.4% vs. 31.3%, p=0.03), and improvement on endoscopy (85.7% vs. 50%, p=0.04).. In this pilot study we found some evidence that use of NCB-02 enema may tend to result in greater improvements in disease activity compared to placebo in patients with mild-to-moderate distal UC. The role of NCB-02 as a novel therapy for UC should be investigated further.

Topics: Administration, Rectal; Adult; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Enema; Female; Humans; Male; Mesalamine; Middle Aged; Pilot Projects; Remission Induction; Severity of Illness Index; Young Adult

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 is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC).. Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up.. Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed.. Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colonoscopy; Curcumin; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Mesalamine; Middle Aged; Retrospective Studies; Sulfasalazine; Treatment Outcome

Topics: Animals; B-Lymphocytes, Regulatory; Colitis; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Disease Models, Animal; Interleukin-1 Receptor-Associated Kinases; Mice; Myeloid Differentiation Factor 88; NF-kappa B; Signal Transduction

Our study aimed to elucidate the correlation of macrophage (mø) with the inflammatory reaction in ulcerative colitis (UC) and the influence of curcumin (Cur) on mø chemotaxis in mice with UC.. A total of 49 patients with UC (research group; RG) admitted between June 2020 and October 2021 and 56 healthy individuals (control group; CG) who visited concurrently were selected as the study participants. The peripheral blood mononuclear cells (PBMCs) were analyzed, and M1-type/M2-type mø and inflammatory factors (IFs) interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) were detected. In addition, 15 BALB/c mice were purchased and divided into the normal group fed normally, the UC model group established with sodium dextran sulfate (DSS) and the Cur group induced by DSS + Cur feeding. Colon tissue mø was collected from mice to measure mø activity via CCK-8 and to quantify levels of IFs and chemokine CCL2 by polymer chain reaction (PCR)c and Western blotting.. The RG had a higher percentage of peripheral blood M1-type mø and a lower percentage of M2-type mø and M1/M2 mø ratio than the CG (P < .05). In the RG, IL-1, IL-6 and TNF-α all increased and were inversely correlated with the ratio of M1/M2 mø, while IL-10 and TGF-β decreased, with a positive connection with the M1/M2 mø ratio. In the UC model mice, mø activity increased, but the apoptosis rate decreased. mø activity was lower in the Cur group than in the model and normal groups; mø apoptosis in the Cur group was higher than in the model group but lower than in the normal group. In addition, proIFs increased and anti-IFs decreased in the model group, and Cur also ameliorated this process. Finally, CCL2 and MCP-1 levels in the model group were also increased, while those in the Cur group were lower compared with the model group.. In UC, the M1/M2 mø ratio is severely misadjusted, activation of M1-type mø is enhanced and pro-IFs are released in large quantities. Cur can ameliorate the abnormal activation of mø in mice with UC, inhibit mø chemotaxis and alleviate the inflammatory reaction, which may make it a new option for UC treatment in the future.

Topics: Animals; Chemotaxis; Colitis, Ulcerative; Curcumin; Disease Models, Animal; Inflammation; Interleukin-10; Interleukin-6; Leukocytes, Mononuclear; Macrophages; Mice; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through β-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment.

Topics: Colitis, Ulcerative; Curcumin; Drug Carriers; Drug Delivery Systems; Folic Acid; Humans; Lactoferrin; Nanoparticles

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1β, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis; Colitis, Ulcerative; Colon; Curcumin; Inflammation; Interleukin-6; Occludin; Quality of Life; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vitamin D

Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC).. To evaluate the real-world experience with the Curcumin-QingDai (CurQD) herbal combination to induce remission in active UC.. A retrospec-tive multicentre adult cohort study from five tertiary academic centres (2018-2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8-12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid-free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 μg/g for patients with FC ≥300 μg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment.. Eighty-eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5-9) to 2 (IQR:1-3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid-free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 μg/g (IQR:392-2772) at baseline to 75 μg/g (IQR:12-136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged.. In this real-world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.

Topics: Adult; Biological Products; Biomarkers; Cohort Studies; Colitis, Ulcerative; Curcumin; Humans; Leukocyte L1 Antigen Complex; Remission Induction

We prepared one type of bilayer microgels for oral administration with three effects: pH responsiveness, time lag, and colon enzyme degradation. Combined with the dual biological effects of curcumin (Cur) for reducing inflammation and promoting repair of colonic mucosal injury, targeted colonic localization and release of Cur according to the colonic microenvironment were enhanced. The inner core, derived from guar gum and low-methoxyl pectin, afforded colonic adhesion and degradation behavior; the outer layer, modified by alginate and chitosan via polyelectrolyte interaction, achieved colonic localization. The porous starch (PS)-mediated strong adsorption allowed Cur loading in inner core to achieve a multifunctional delivery system. In vitro, the formulations exhibited good bioresponses at different pH conditions, potentially delaying Cur release in the upper gastrointestinal tract. In vivo, dextran sulfate sodium-induced ulcerative colitis (UC) symptoms were significantly alleviated after oral administration, accompanied by reduced levels of inflammatory factors. The formulations facilitated colonic delivery, allowing Cur accumulation in colonic tissue. Moreover, the formulations could alter gut microbiota composition in mice. During Cur delivery, each formulation increased species richness, decreased pathogenic bacterial content, and afforded synergistic effects against UC. These PS-loaded bilayer microgels, exhibiting excellent biocompatibility, multi-bioresponsiveness, and colon targeting, could be beneficial in UC therapy, allowing development into a novel oral formulation.

Topics: Administration, Oral; Animals; Colitis, Ulcerative; Colon; Curcumin; Drug Delivery Systems; Mice; Microgels; Porosity; Starch

Overexpression of classically activated macrophages (M1) subtypes and assessed reactive oxygen species (ROS) levels are often observed in patients with ulcerative colitis. At present, the treatment system of these two problems has yet to be established. Here, the chemotherapy drug curcumin (CCM) is decorated with Prussian blue analogs in a straightforward and cost-saving manner. Modified CCM can be released in inflammatory tissue (acidic environment), eventually causing M1 macrophages to transform into M2 macrophages and inhibiting pro-inflammatory factors. Co(III) and Fe(II) have abundant valence variations, and the lower REDOX potential in CCM-CoFe PBA enables ROS clearance through multi-nanomase activity. In addition, CCM-CoFe PBA effectively alleviated the symptoms of UC mice induced by DSS and inhibited the progression of the disease. Therefore, the present material may be used as a new therapeutic agent for UC.

Topics: Animals; Colitis, Ulcerative; Curcumin; Macrophages; Mice; Phenotype; Polymers; Reactive Oxygen Species

Topics: Colitis, Ulcerative; Curcumin; Drugs, Chinese Herbal; Humans

Topics: Colitis, Ulcerative; Curcumin; Drugs, Chinese Herbal; Humans

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on β-cyclodextrin (β-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC.

Topics: Animals; Colitis, Ulcerative; Curcumin; Disease Models, Animal; Inflammation; Mice; Reactive Oxygen Species; Saccharomyces cerevisiae

The oral delivery of anti-inflammatory drugs has been a promising strategy for enhancing the clinical efficacy of ulcerative colitis (UC) treatment strategies. However, achieving site specific drug delivery to colon tissues and target cells is a challenging task for formulation scientists. In this study, macrophages-targeted liposome-loaded pectin-chitosan hydrogels were developed for UC treatment via oral administration. Folate-functionalized cholesterol was synthesized as lipid membrane materials for the liposomes containing curcumin (CUR). The incorporation of the liposomal CUR within pectin-chitosan hydrogels resulted in a matrix that exhibited considerable sensitivity to colonic enzymes during in vitro release. The targeted delivery of hybrids was able to effectively reach macrophages. They also showed enhanced capability to downregulate TNF-α, IL-6, and IL-1β in the lipopolysaccharide-induced Raw 264.7 cells model. DSS-induced mice modelshowed improved anti-UC effects, including accelerated mucosal repair and decreased inflammation and modulate the immune balance in the intestinal tissue of mice with colitis, which may be attributable to increased drug accumulation in the colonic lumen and improved internalization to target cells. Therefore, the incorporation of folate-modified liposomes containing CUR and pectin-chitosan physical hydrogels could potentially serve as a favorable approach for treating UC through an oral colon-targeted drug delivery system.

Topics: Animals; Chitosan; Colitis, Ulcerative; Colon; Curcumin; Cyclooxygenase Inhibitors; Folic Acid; Hydrogels; Liposomes; Macrophages; Mice; Nanoparticles; Pectins

Restoration of immune homeostasis by targeting the balance between memory T helper (mTh) cells and memory follicular T helper (mTfh) cells is a potential therapeutic strategy against ulcerative colitis (UC). Because of its anti-inflammatory and immunomodulatory properties, curcumin (Cur) is a promising drug for UC treatment. However, fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis.. To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium (DSS) in mice by regulating the mTh and mTfh immune homeostasis.. Cur effectively mitigates DSS-induced colitis, facilitates the restoration of mouse weight and colonic length, and diminishes the colonic weight and colonic weight index. Simultaneously, it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane. While the percentage of Th1, mTh1, Th7, mTh7, Th17, mTh17, Tfh1, mTfh1, Tfh7, mTfh7, Tfh17, and mTfh17 cells decreased after Cur treatment of the mice for 7 d, and the frequency of mTh10, Th10, mTfh10, and Tfh10 cells in the mouse spleen increased. Further studies revealed that Cur administration prominently decreased the SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in the colon tissue.. Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage, potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Disease Models, Animal; Mice; Mice, Inbred C57BL; NF-kappa B

Solid evidence has emerged supporting the role of nonextractable polyphenols (NEPs) and dietary fibers (DFs) as gut microbiota modulators. This study aims to elucidate gut microbiota-dependent release of turmeric NEPs and examine the possible anti-inflammatory mechanism in the dextran sulfate sodium-induced ulcerative colitis (UC) model. 1.5% DSS drinking water-induced C57BL/6J mice were fed a standard rodent chow supplemented with or without 8% extractable polyphenols (EPs), NEPs, or DFs for 37 days. The bound curcumin, demethoxycurcumin, and bisdemethoxycurcumin in NEPs were released up to 181.5 ± 10.6, 65.2 ± 6.0, and 69.5 ± 7.6 μg/mL by in vitro gut microbiota-simulated fermentation and released into the colon of NEP-supplemented mice by 5.7-, 11.0-, and 7.8-fold higher than pseudo germ-free mice, respectively (

Topics: Animals; Coleoptera; Colitis; Colitis, Ulcerative; Colon; Curcuma; Dextran Sulfate; Dietary Fiber; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Mice; Mice, Inbred C57BL; Polyphenols

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.

Topics: Animals; Chondroitin Sulfates; Colitis, Ulcerative; Curcumin; Drug Carriers; Drug Delivery Systems; Esters; Hydrogen-Ion Concentration; Macrophages; Mice; Nanoparticles; Particle Size; Reactive Oxygen Species

Diabetes mellitus (DM) is one of the most common complications in patients with ulcerative colitis (UC). Curcumin has a wide range of bioactive and pharmacological properties and is commonly used as an adjunct to the treatment of UC and DM. However, the role of curcumin in UC complicated by DM has not been elucidated. Therefore, this study was conducted to construct a model of UC complicating diabetes by inducing UC in DB mice (spontaneously diabetic) with dextran sodium sulfate. In this study, curcumin (100 mg/kg/day) significantly improved the symptoms of diabetes complicated by UC, with a lower insulin level, heavier weight, longer and lighter colons, fewer mucosal ulcers and less inflammatory cell infiltration. Moreover, compared to untreated DB mice with colitis, curcumin-treated mice showed weaker Th17 responses and stronger Treg responses. In addition, curcumin regulated the diversity and relative abundance of intestinal microbiota in mice with UC complicated by DM at the phylum, class, order, family and genus levels. Collectively, curcumin effectively alleviated colitis in mice with type 2 diabetes mellitus by restoring the homeostasis of Th17/Treg and improving the composition of the intestinal microbiota.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Gastrointestinal Microbiome; Homeostasis; Humans; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory

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

The pathogenesis of ulcerative colitis (UC) remains unclear, and it is believed that an imbalance of regulatory T (Treg) cells and T helper 17 (Th17) cells is related to the occurrence of UC. Curcumin has been confirmed to exert anti-inflammatory effects in bronchial asthma and osteoarthritis by regulating the balance of Treg/Th17 cells. This study aimed to explore the therapeutic potential of curcumin in dextran sulfate sodium (DSS)-induced UC rats by regulating the balance of Treg/Th17 cells. Disease activity index (DAI) scores were calculated. Changes in colon inflammation were observed using hematoxylin and eosin staining. Treg and Th17 cells in the spleen were detected by flow cytometry, and the levels of interleukin (IL)-10 and IL-17A were determined using enzyme-linked immunosorbent assay. In DSS-induced colitis, curcumin significantly ameliorated colitis symptoms by reducing the DAI and increasing colon length. Additionally, curcumin significantly increased the expression of Treg cells and decreased the expression of Th17 cells and the extent of histopathological damage. Furthermore, curcumin increased the expression of IL-10 and decreased the expression of IL-17A. Curcumin attenuates DSS-induced UC injury by regulating Treg/Th17 balance and related cytokine secretion. Thus, curcumin may be a promising therapeutic drug for treating UC.

Topics: Animals; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Disease Models, Animal; Interleukin-17; Rats; T-Lymphocytes, Regulatory; Th17 Cells

To examine the effects of a negatively charged nanostructured curcumin microemulsion in experimental ulcerative colitis (UC) in rats.. Four percent acetic acid was used to induce UC. The animals were treated for seven days and randomly assigned to four groups: normal control (NC), colitis/normal saline (COL/NS), colitis/curcumin (COL/CUR), and colitis/mesalazine (COL/MES). The nanostructured curcumin was formulated with a negative zeta potential (-16.70 ± 1.66 mV). Dosage of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin 6 (IL-6), and antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), macro and microscopic evaluation of the colon tissue were analyzed.. The COL/CUR group had a higher level of antioxidant enzymes compared to the COL/MESgroup. The levels of TNF-α, IL-1β and IL-6 were significantly lower in the colonic tissue of the COL/CUR group rats, when compared to the COL/NS and COL/MES groups (p < 0.001). The presence of ulcers in the colonic mucosa in rats of the COL/NSgroup was significantly higher than in the COL/MES group (p < 0.001). In the NC and COL/CUR groups, there were no ulcers in the colonic mucosa.. The nanostructured microemulsion of curcumin, used orally, positively influenced the results of the treatment of UC in rats. The data also suggests that nanostructured curcumin with negative zeta potential is a promising phytopharmaceutical oral delivery system for UC therapy. Further research needs to be done to better understand the mechanisms of the negatively charged nanostructured curcumin microemulsion in UC therapy.

Topics: Animals; Antioxidants; Colitis; Colitis, Ulcerative; Colon; Curcumin; Interleukin-6; Rats; Tumor Necrosis Factor-alpha

Curcumin's role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples' collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.

Topics: Acetic Acid; Animals; Antioxidants; Colitis, Ulcerative; Colon; Curcumin; Male; Microspheres; Oxidative Stress; Rats; Rats, Wistar

Anti-inflammatory drugs for ulcerative colitis (UC) treatment should specifically penetrate and accumulate in the colon tissue. Herein, a multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded heterogeneous double-membrane microgels (CUR@microgels) for oral administration was fabricated in this study, in which the inner core was derived from polyvinyl alcohol (PVA) and guar gum (GG) and the outer gel was decoration with alginate and chitosan by polyelectrolyte interactions. The structure and morphology of microgels were characterized. In vitro, the formulation exhibited good bio-responses at different pH conditions and sustained-release properties in simulated colon fluid with a drug-release rate of 84.6 % over 34 h. With the assistance of the outlayer gels, the microgels effectively delayed the premature drug release of CUR in the upper gastrointestinal tract. In vivo studies revealed that CUR@microgels specifically accumulated in the colon tissue for 24 h, which suggest that the interlayer gels were apt to reach colon lesion. As expected, the oral administration of microgels remarkably alleviated the symptoms of UC and protected the colon tissue in DSS-induced UC mice. The above results indicated that these facilely fabricated microgels which exhibited excellent biocompatibility and multi-bioresponsive drug release, had an apparent effect on the treatment of UC, which represents a promising drug delivery strategy for CUR in a clinical application.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Gels; Mice; Microgels; Polyvinyl Alcohol

A series of β-ionone-curcumin hybrid derivatives were designed and chosen to merge the biological characteristics of two parent molecules and to obtain a leading compound with higher biological activity. Through the initial screening, the structure activity relationship of their hybrid derivatives as inhibitors of nitric oxide (NO) production showed that meta-substituted derivatives exhibited the best inhibitory activity, among which 1h was the best one. In lipopolysaccharide-induced Raw264.7 macrophage cells, 1h showed anti-inflammatory activity by inhibiting the productions of NO and reactive oxygen species, the expressions of Interleukin-1β and tumor necrosis factor-α, and the translocation of nuclear factor (NF)-κB from the cytosol to the nucleus. Furthermore, molecular docking simulation displayed that 1h could interact with cluster of differentiation 14 to inhibit the toll-like receptor 4/NF-κB signaling. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) of mice, 100 mg/kg of 1h could significantly reduce the colon length shortening and protect against colon injury, liver injury and oxidative stress in DSS-induced UC of mice. Besides, 1h was safety in vivo. In conclusion, 1h was the potential anti-inflammatory agent, and further investigations were underway in our laboratory.

Topics: Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Disease Models, Animal; Interleukin-1beta; Lipopolysaccharides; Mice; Molecular Docking Simulation; NF-kappa B; Nitric Oxide; Norisoprenoids; Reactive Oxygen Species; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed.. For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (- 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis.. Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis; Colitis, Ulcerative; Curcuma; Disease Models, Animal; Exosomes; Inflammation; Mice; Mice, Transgenic; NF-kappa B

Inflammatory bowel disease is characterized by a radical imbalance of inflammatory signaling pathways in the gastrointestinal tract, and it is categorized into two diseases, such as Crohn's disease and ulcerative colitis. In this study, we investigated anti-inflammatory activities using fermented Curcuma that contains butyrate (FB). Nitric oxide production in RAW 264.7 cells and the expression of inducible nitric oxide synthase in the intestinal mucosa appears to be enhanced in active ulcerative colitis. Here, the cytotoxicity, physiological activity, and anti-inflammatory efficacy of FB in colitis animals were investigated. To verify the anti-inflammatory effect, this study was conducted using the dextran sulfate sodium (DSS)-induced colitis mice model. As a result, non-toxicity was confirmed, and anti-inflammatory effects were revealed by inducing a reduction of LPS-induced NO production. In the DSS-induced colitis, reduced weight was recovered and a decrease in inflammatory factors Ig-E and TNF-α in the mesenteric lymph node (MLN) and spleen was induced, and it was confirmed to help with the morphological remodeling of the intestine. In conclusion, this paper suggests that FB can help to alleviate intestinal inflammation and to improve the intestinal environment, with the help of morphological remodeling.

Topics: Animals; Anti-Inflammatory Agents; Butyrates; Colitis; Colitis, Ulcerative; Colon; Curcuma; Cytokines; Dextran Sulfate; Disease Models, Animal; Mice; Mice, Inbred C57BL

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Colon; Curcuma; Cytokines; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Mice; Mice, Inbred C57BL; Nanoparticle Drug Delivery System

Curcumin has a therapeutic effect on ulcerative colitis, but the underlying mechanism has yet to be elucidated. The aim of the present study was to clarify the possible mechanisms. Dextran sulfate sodium‑induced colitis mice were treated with curcumin via gavage for 7 days. The effects of curcumin on disease activity index (DAI) and pathological changes of colonic tissue in mice were determined. Interleukin (IL)‑6, IL‑10, IL‑17 and IL‑23 expression levels were measured by ELISA. Flow cytometry was used to detect the ratio of mouse spleen regulatory T cells (Treg)/Th17 cells, and western blotting was used to measure the nuclear protein hypoxia inducible factor (HIF)‑1α level. The results demonstrated that curcumin can significantly reduce DAI and spleen index scores and improve mucosal inflammation. Curcumin could also regulate the re‑equilibration of Treg/Th17. IL‑10 level in the colon was significantly increased, while inflammatory cytokines IL‑6, IL‑17 and IL‑23 were significantly reduced following curcumin treatment. No significant difference in HIF‑1α was observed between the colitis and the curcumin group. It was concluded that oral administration of curcumin can effectively treat experimental colitis by regulating the re‑equilibration of Treg/Th17 and that the regulatory mechanism may be closely related to the IL‑23/Th17 pathway. The results of the present study provided molecular insight into the mechanism by which curcumin treats ulcerative colitis.

Topics: Administration, Oral; Animals; Colitis, Ulcerative; Curcumin; Cytokines; Dextran Sulfate; Disease Models, Animal; Gene Expression Regulation; Male; Mice; Mice, Inbred BALB C; Signal Transduction; T-Lymphocytes, Regulatory; Th17 Cells; Treatment Outcome

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Drug Liberation; Male; Mice; Mice, Inbred Strains; Nanoparticles; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; RAW 264.7 Cells; Reactive Oxygen Species; Surface Properties

Curcumin liposomes (CUR-LPs) was identified by evaluating morphology, appearance, zeta potential, particle diameter, and drug encapsulation efficiency. The results indicated that particle diameter, surface charge and polydispersity index (PDI) of curcumin (CUR)-loaded anionic liposomes were 167 nm, -34 mV and 0.09, respectively. CUR-LPs is high stable pseudo-pH-sensitive nanoparticles system which has a favorable stability in simulated gastric fluid and slower degradation rate allowing CUR sustained release for prolonged times in simulated intestinal fluid. Within 1 h, the CUR consumption was 21.82% in simulated gastric fluid (SGF) and 27.32% in simulated intestinal fluid (SIF), respectively. CUR-LPs could attenuate clinical symptoms including weight loss, diarrhea and fecal bleeding. Especially, it could also prevent dextran sulfate sodium salt (DSS)-inducedcolon tissue damage and colon shortening, and reduce the production of malondialdehyde (MDA), colonic myeloperoxidase (MPO), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in animal model. Our study illustrated that liposomes (LPs) was a potential carrier to develop the colon-specific drug delivery system incorporating CUR for treating ulcerative colitis.

Topics: Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Colon; Curcumin; Drug Delivery Systems; Interleukin-6; Liposomes; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Models, Animal; Peroxidase; Tumor Necrosis Factor-alpha

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by dysregulation of colon immune response. Curcumin (Cur) has strong anti-inflammatory activities, but the application is severely hindered by the extremely hydrophobicity and pitiful bioavailability. Alginate (Alg), a natural polysaccharide with ideal solubility and biosafety, was introduced to prepare the esterified alginate-curcumin conjugate (Alg-Cur) and constructed stable Alg-Cur micelle in physiological solutions. Compared with crystalline Cur, the target anti-inflammatory activities of Alg-Cur were systematically investigated. The results showed that Alg-Cur exerted effective anti-inflammatory effects in Raw 264.7 cells. After oral administration, 92.32 % of Alg-Cur reached colon, and the ester bonds were quickly sheared by abundant esterase produced by commensal anaerobic flora. The released Cur was quickly absorbed in-situ in monomolecular state, and effectively ameliorated the colonic inflammation and tissue damage by inhibiting the TLR4 expression in colonic epithelial cell, reducing the transcription and expression of the pro-inflammation cytokines downstream, as well as the infiltration of lymphocytes, macrophages and neutrophils. The Alg-Cur micelle effectively enhanced the hydrophilicity and bioavailability of Cur, and the commensal flora triggered Cur release showed great potential for UC treatment.

Topics: Alginates; Anti-Inflammatory Agents; Colitis, Ulcerative; Curcumin; Humans; Micelles

Telocytes (TCs) are a distinct type of interstitial cells that play a vital role in the pathogenesis of ulcerative colitis and colonic tissue hemostasis. The aim of this study was to examine the effect of nanocurcumin (NC) on the morphometric and immunohistochemical characterization of TCs in the ulcerative colitis (UC) rat model.. Forty rats were randomly divided into control, NC, UC, and UC+NC groups. At the end of the experiment, the colon was dissected and prepared for histopathological and immunohistochemical assessment. Tissue homogenates were prepared for real-time PCR assessment of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-. NC successfully targeted the colonic tissue, improved the mucosal lesion, preserve TCs distribution, and count through its anti-inflammatory and fibrinolytic properties.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Curcumin; Disease Models, Animal; Fibrinolysis; Gene Expression Regulation; Immunohistochemistry; Inflammation; Interleukin-6; Intestinal Mucosa; Male; Nanoparticles; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Telocytes; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Vimentin

Gut barrier dysfunction is triggered by gut microbiota dysbiosis that is closely associated with ulcerative colitis. Recently, more attention has been devoted to the ability of the non-digestively colon-targeted plant polysaccharides to regulate the function and composition of the intestinal microbiota. Here, we first studied the prophylactic capacity of turmeric polysaccharides (TPS) to ameliorate dextran sulfate sodium (DSS)-induced gut microbiota imbalance. The results revealed that TPS administration could greatly improve the pathological phenotype, gut barrier disruption and colon inflammation in colitis mice. Besides, targeted metabolomics or 16S rRNA-based microbiota analysis demonstrated that TPS alleviated gut microbiota dysbiosis caused by DSS, especially increasing the abundance of probiotics associated with tryptophan metabolism, such as

Topics: Animals; Colitis, Ulcerative; Curcuma; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Polysaccharides; Protective Agents; Tryptophan

Mucus is a viscoelastic biological hydrogel that protects the epithelial surface from penetration by most nanoparticles, which limits the efficiency of oral drug delivery. Pursuing highly efficient, biocompatible, and biodegradable oral drug vehicles is of central importance to the development of promising nanomedicine. Here, we prepared five peptosomes (PSs) with various sizes, shapes, and rigidities based on self-assembly of amphiphilic α-lactalbumin (α-lac) peptides from partial enzymolysis and cross-linking. The mucus permeation of α-lac PSs and release of curcumin (Cur) encapsulated in these PSs were evaluated. Compared with a long nanotube, big nanosphere, small nanosphere, and cross-linked short nanotube, we demonstrated that a short nanotube (SNT) exhibits excellent permeability in mucus, which enables it to arrive at epithelial cells quickly. Besides, SNT exhibits the highest cellular uptake and transmembrane permeability on Caco-2/HT29-MTX (E12) 3D coculture model. In vivo pharmacokinetic evaluation revealed that SNT formulation shows the highest curcumin bioavailability, which is 6.85-folds higher than free Cur. Most importantly, Cur loaded in SNT exhibits the optimum therapeutic efficacy for in vivo treatment of dextran sulfate sodium (DSS)-induced ulcerative colitis. In the end, the mechanism of the high permeability of SNTs through mucus was explained by coarse-grained molecular dynamics simulations, which indicated that short time scale jiggling and flying across pores of mucus network played key roles. These findings revealed the tubular α-lac PSs could be a promising oral drug delivery system targeted to mucosal for improving absorption and bioavailability of hydrophobic bioactive ingredients.

Topics: Animals; Biological Availability; Caco-2 Cells; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Drug Carriers; Humans; Intestines; Lactalbumin; Mice; Mucus; Nanoparticles; Nanospheres; Nanotubes; Permeability

To elucidate the impacts of particle size on the cell internalization and anti-inflammatory activity of oral nanotherapeutics, curcumin (CUR)-loaded polymeric nanoparticles (NPs) with different particle sizes were fabricated. The obtained NPs with particle sizes (185-884 nm) and negative zeta potentials (approximately -25 mV) had desirable CUR loading amounts (5.1-6.1 %) and high CUR encapsulation efficiency (73.2-89.6 %). In vitro cellular uptake assays revealed that the cell internalization efficiencies of NPs were increased with the increase of their particle sizes, and NPs (900) showed the highest phagocytosis efficiency in macrophages among all the tested NPs. Importantly, NPs (900) exhibited significantly stronger capability to downregulate the production of the main pro-inflammatory cytokines from macrophages when they were compared with NPs (200) and NPs (500). Further animal studies suggested that oral administration of hydrogel (chitosan and alginate)-embedding NPs (900) could efficiently accumulate in colitis tissue in a manner that was comparable to that of NPs (200) and NPs (500) and could achieve the best treatment efficacy against ulcerative colitis (UC). Collectively, these findings can serve as a guideline for the rational design of nanotherapeutics with desirable accumulation profiles in colitis tissue, maximized cellular uptake efficiency in macrophages, and good therapeutic outcomes against UC.

Topics: Administration, Oral; Alginates; Animals; Anti-Inflammatory Agents; Chitosan; Colitis, Ulcerative; Curcumin; Drug Carriers; Drug Liberation; Hydrogels; Interleukin-6; Macrophages; Mice; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Phagocytosis; Polylactic Acid-Polyglycolic Acid Copolymer; RAW 264.7 Cells; Tumor Necrosis Factor-alpha; X-Ray Diffraction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.

Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Colitis, Ulcerative; Curcumin; Drug Combinations; Galactose; Inflammation; Intestinal Mucosa; Male; Mannosides; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Trigonella

Curcumin (CUR) is a promising edible phytochemical compound with ideal ulcerative colitis (UC) treatment activity; however, it is characteristically instable in the digestive tract and has a short retention time in colon. Therefore, we designed and fabricated an oral food-grade nanocarrier composed of tannic acid (TA)-coated, Genipin (Gnp)-crosslinked human serum albumin (HSA) to encapsulate CUR (TA/CUR-NPs). The resulting CUR nanoparticles (NPs) were about 220 nm and -28.8 mV. With the assistance of TA layer and Gnp-crosslinking, the entire nano-scaled system effectively delayed CUR release in simulated gastric fluid, prolonged its colon adhesion and increased its uptake in Caco-2 cells. As expected, TA/CUR-NPs oral administration significantly alleviated colitis symptoms in DSS-treated mice when compared with controls by inhibiting the TLR4-linked NF-κB signaling pathway. Collectively, this study indicates that we have developed a convenient, eco-friendly, nano-scaled vehicle for oral delivery of CUR with anti-UC benefit.

Topics: Administration, Oral; Animals; Caco-2 Cells; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Humans; Iridoids; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Serum Albumin, Human; Tannins

In this study, we developed oral core-shell nanoparticles composed of curcumin nanocrystals in the core and chitosan/alginate multilayers in the shell for inflammation-targeted alleviation of ulcerative colitis (UC). The release rate of curcumin from the core-shell nanoparticles was low at a pH mimicking the stomach and small intestine, whereas it was higher at a pH mimicking the colon. Further, biodistribution studies in the gastrointestinal tract of mice showed that distribution of nanoparticles was significantly higher in the colon than that in the stomach and small intestine. Quantitative analysis of drugs in colonic tissues and confocal imaging of colons revealed preferential accumulation of nanoparticles in inflamed tissues than that in healthy tissues.

Topics: Animals; Colitis, Ulcerative; Curcumin; Drug Carriers; Drug Delivery Systems; Hydrogen-Ion Concentration; Inflammation; Mice; Nanoparticles; Polyelectrolytes; Tissue Distribution

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

Orally targeted delivery of anti-inflammatory drugs to macrophages has attracted great attention for minimizing the symptoms of ulcerative colitis (UC). In this investigation, we encapsulated curcumin (CUR) into polymeric nanoparticles (NPs), and conjugated chondroitin sulfate (CS) to their surfaces. The resulting CS-NPs had an average diameter of 281 nm, monodisperse size distribution and negatively charged surface. Cell experiments indicated that these NPs showed excellent biocompatibility, and yielded significantly higher cell internalization efficiency in Raw 264.7 macrophages than their counterparts (carboxymethyl cellulose-functionalized CUR-encapsulated NPs, CUL-NPs). Moreover, CS-NPs exhibited a dramatically stronger capacity to inhibit the secretion of the major pro-inflammatory cytokines from lipopolysaccharide-stimulated macrophages compared with CUL-NPs. In vivo experiments revealed that oral administration of chitosan/alginate hydrogel embedding CS-NPs achieved better therapeutic outcomes against UC comparied with CUL-NPs. Collectively, our results demonstrated that CS-NP-embedded hydrogel held a great promise to be developed as a macrophage-targeted drug delivery system for UC treatment.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Colitis, Ulcerative; Colon; Curcumin; Cytokines; Drug Delivery Systems; Lipopolysaccharides; Macrophages; Mice; Nanoparticles; Particle Size; RAW 264.7 Cells; Surface Properties

Oral administrations of microparticles (MPs) and nanoparticles (NPs) have been widely employed as therapeutic approaches for the treatment of ulcerative colitis (UC). However, no previous study has comparatively investigated the therapeutic efficacies of MPs and NPs.. In this study, curcumin (CUR)-loaded MPs (CUR-MPs) and CUR-loaded NPs (CUR-NPs) were prepared using a single water-in-oil emulsion solvent evaporation technique. Their therapeutic outcomes against UC were further comparatively studied.. The resultant spherical MPs and NPs exhibited slightly negative zeta-potential with average particle diameters of approximately 1.7 µm and 270 nm, respectively. It was found that NPs exhibited a much higher CUR release rate than MPs within the same period of investigation. In vivo experiments demonstrated that oral administration of CUR-MPs and CUR-NPs reduced the symptoms of inflammation in a UC mouse model induced by dextran sulfate sodium. Importantly, CUR-NPs showed much better therapeutic outcomes in alleviating UC compared with CUR-MPs.. NPs can improve the anti-inflammatory activity of CUR by enhancing the drug release and cellular uptake efficiency, in comparison with MPs. Thus, they could be exploited as a promising oral drug delivery system for effective UC treatment.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell-Derived Microparticles; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Drug Carriers; Drug Delivery Systems; Female; Humans; Inflammation; Macrophages; Mice; Nanoparticles

To improve the penetration and accumulation of anti-inflammatory drugs in colitis tissue, we functionalized the surface of porous poly(lactic-co-glycolic acid) nanoparticles (NPs) using pluronic F127 (PF127) and loaded curcumin (CUR) into the resulting NPs to obtain porous PF127-functionalized CUR-loaded NPs (porous PF127-NPs). These NPs had an average hydrodynamic diameter of about 270 nm with a highly monodisperse size distribution, slightly negative surface charge and controllable CUR release profile. It was found that they had good biocompatibility and yielded a much higher cellular uptake rate of CUR than porous CUR-loaded NPs without PF127 modification (porous NPs). In addition, porous PF127-NPs showed a greater capacity to inhibit the major pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) secreted from lipopolysaccharide-activated macrophages than porous NPs and non-porous PF127-NPs. In vivo experiments suggested that porous PF127-NPs achieved the best therapeutic outcomes against ulcerative colitis (UC) in mice compared with porous NPs and non-porous PF127-NPs. Our results clearly demonstrate that these fabricated porous PF127-NPs show a great promise as an efficient CUR nanocarrier for UC therapy.

Topics: Administration, Oral; Animals; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Drug Carriers; Female; Lipopolysaccharides; Mice; Nanoparticles; Poloxamer; Polyglycolic Acid; RAW 264.7 Cells

Porous microparticles (MPs) have been regarded as a promising vehicle for drug delivery. Herein, porous MPs and their counterparts (nonporous MPs) were produced by a conventional emulsion-solvent evaporation method in the presence and absence of ammonium bicarbonate, and curcumin was encapsulated into these MPs during the preparation process. The obtained MPs possessed desirable diameters of around 1.2 μm and negative zeta potentials of approximately -28 mV. It was found that the release rate of curcumin was remarkably increased with the introduction of pores in MPs. Furthermore, orally administered porous MPs achieved statistically significantly better therapeutic outcomes against ulcerative colitis mouse model induced by dextran sulfate sodium, in comparison to nonporous MPs. These findings confirmed that porous MPs could be served as a promising platform for the treatment of ulcerative colitis via oral route.

Topics: Administration, Oral; Animals; Bicarbonates; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Drug Carriers; Drug Delivery Systems; Female; Mice; Nanoparticles; Particle Size; Polymers; Porosity

The requirement for the favorable therapeutics against ulcerative colitis (UC) is that anti-inflammatory drugs can be specifically internalized by macrophages and subsequently be on-demand released to suppress inflammation. Herein, we developed a type of multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded nanoparticles (NPs) that were derived from natural silk fibroin and followed by surface functionalization with chondroitin sulfate (CS). The generated CS-CUR-NPs had a desired average particle size (175.4 nm), a uniform size distribution and negative surface charge (-35.5 mV). Strikingly, these NPs exhibited excellent bioresponsibility when triggered with the intrinsic stimuli (acidity, glutathione and reactive oxygen species) within activated macrophages, indicating that they could conceivably confer the on-demand intracellular drug release. Furthermore, we found that CS functionalization yielded notably targeted drug delivery to macrophages, and thereby enhanced the anti-inflammatory activities of NPs. Most importantly, animal experiments revealed that these nanotherapeutics could remarkably alleviate the symptoms of UC, maintain the homeostasis of intestinal microbiota and improve the survival rate of mice with UC through the route of oral administration or intravenous injection. Our results suggest that these facilely fabricated CS-CUR-NPs, which exhibit excellent biocompatibility, multi-bioresponsive drug release and macrophage-targeted capacity, could be exploited as a promising therapeutic platform for clinical UC treatment.

Topics: Animals; Anti-Inflammatory Agents; Biocompatible Materials; Chondroitin Sulfates; Colitis, Ulcerative; Curcumin; Cytoplasm; Drug Liberation; Endocytosis; Fibroins; Gastrointestinal Microbiome; Hyaluronan Receptors; Mice; Nanoparticles; RAW 264.7 Cells; Tissue Distribution

Oral microparticles (MPs) have been considered as promising drug carriers in the treatment of ulcerative colitis (UC). Here, a facile strategy based on a conventional emulsion-solvent evaporation technique was used to fabricate bowl-shaped MPs (BMPs), and these MPs loaded with anti-inflammatory drug (curcumin, CUR) during the fabrication process. The physicochemical properties of the resultant BMPs were characterized by dynamic light scattering, scanning electron microscope, confocal laser scanning microscope and X-ray diffraction as well as contact angle goniometer. Results indicated that BMPs had a desirable hydrodynamic diameter (1.84 ± 0.20 μm), a negative zeta potential (-26.5 ± 1.13 mV), smooth surface morphology, high CUR encapsulation efficiency and controlled drug release profile. It was found that CUR molecules were dispersed in an amorphous state within the polymeric matrixes. In addition, BMPs showed excellent hydrophilicity due to the presence of Pluronic F127 and poly(vinyl alcohol) on their surface. More importantly, orally administered BMPs could efficiently alleviate UC based on a dextran sulfate sodium-induced mouse model. These results collectively suggest that BMP can be exploited as a readily scalable oral drug delivery system for UC therapy.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Female; Hydrodynamics; Mice; Mice, Inbred Strains; Particle Size; Surface Properties; Wettability

Inflammatory bowel disease (IBD) is a known medical burden in most developed countries and a significant cause of morbidity. The IBD label includes Crohn's disease (CD) and ulcerative colitis (UC). Pharmacological and surgical intervention are the two main management approaches for IBD. Some drugs have been developed for IBD therapy, but accessibility is limited due to high costs. Furthermore, these agents have demonstrated inactivity over long-term treatment courses. Therefore, an urgent need is present for new treatment options that are safe, able to sustain clinical remission, and improve mucosal gut healing. Seaweed has received much attention in the pharmacological field owing to its various biomedical properties, including the prolongation of blood clotting time, as well as antitumor, anti-inflammation, and antioxidant effects. This study therefore aimed to examine the effects of a dietary polysaccharide-rich extract obtained from Eucheuma cottonii (EC) on a model of colitis. Colitis was induced in male BALB/c mice by the administration of 2.5% (w/v) dextran sulfate sodium (DSS) for 7 days. DSS-induced mice were treated with either one of three different doses of EC extracts (0.35, 0.70, and 1.75 g/kg body weight) or curcumin as a positive control (0.10 g/kg). Mice were sacrificed post-treatment and blood samples were collected. The disease activity index (DAI) and inflammatory cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10) were measured. After treatment for 7 days, EC extract administration protected against weight loss and decreased the colon weight per length ratio. EC extract administration also decreased pro-inflammatory cytokine expression, increased IL-10 levels, and reduced colonic damage. Therefore, a dietary polysaccharide-rich extract from E. cottonii reduced DSS-induced bowel inflammation, thereby becoming a promising candidate for the treatment of colitis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Curcumin; Cytokines; Dextran Sulfate; Disease Models, Animal; Humans; Intestinal Mucosa; Male; Mice; Mice, Inbred BALB C; Plant Extracts; Polysaccharides; RAW 264.7 Cells; Rhodophyta; Seaweed; Signal Transduction; Treatment Outcome

Turmeric has been used as a medicinal herb for thousands of years for treatment of various disorders. Although curcumin is the most studied active constituents of turmeric, accumulating evidence suggests that other components of turmeric have additional anti-inflammatory and anti-tumorigenic properties. Herein, we investigated anti-inflammatory efficacy and associated gene expression alterations of a specific, curcumin preparation containing essential turmeric oils (ETO-curcumin) in comparison to standard curcumin at three specific doses (0, 5, 25 or 50 mg/kg), in an animal model of dextran sodium sulfate (DSS)-induced colitis. The present study showed that both ETO and standard curcumin treatments provided protection against DSS-induced inflammation. However, ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-inflammatory efficacy of standard curcumin remained constant, suggesting that ETO-curcumin may provide superior anti-inflammatory efficacy compared to standard curcumin. Gene expression analysis revealed that anti-inflammatory cytokines including IL-10 and IL-11 as well as FOXP3 were upregulated in the colon by ETO-curcumin. Collectively, these findings suggest that the combined treatment of curcumin and essential turmeric oils provides superior protection from DSS-induced colitis than curcumin alone, highlighting the anti-inflammatory potential of turmeric.

Topics: Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Colon; Curcuma; Curcumin; Cytokines; Dextran Sulfate; Forkhead Transcription Factors; Male; Mice; Mice, Inbred C57BL; Oils, Volatile

To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay). Colonic tissues with the most obvious lesions were obtained using a surgical scissor. A routine hematoxylin-eosin (HE) staining method was used to stain pathological specimens and images of staining results were obtained. Histological injury scores of colonic mucosa were calculated. Ulcerative colitis model rats had the highest macroscopic damage scores and histological injury scores of colonic mucosa. After treatment the contents of TNF-α and IL-8 decreased significantly in the group of curcumin plus soy oligosaccharide compared with the model group with statistical significance (P <0.01) while the contents were close to those in the SASP group. There was no statistical significance (P> 0.05). The treatment could decrease TNF-α and IL- 8 expression and reduce colonic mucosa inflammation and tissue damage.

Topics: Animals; Colitis, Ulcerative; Curcumin; Cytokines; Escherichia coli; Feces; Gastrointestinal Microbiome; Glycine max; Intestinal Mucosa; Intestines; Male; NF-kappa B; Oligosaccharides; Rats, Sprague-Dawley; Reference Standards

The aim of present investigation was to prepare Curcumin-Zn(II) complex in a view to enhance solubility, stability and pharmacodynamic effect in experimentally induced ulcerative colitis.. Curcumin-Zn(II) complex was prepared by stirring curcumin with anhydrous zinc chloride at a molar ratio of 1:1. The prepared curcumin metallocomplex was characterized by TLC, FTIR, UV spectroscopy and (1)H NMR. In vitro kinetic degradation and solubility of Curcumin and Curcumin-Zn(II) complex was analyzed spectrophotometrically. Pharmacodynamic evaluation of curcumin and its metal complex was assessed in ulcerative colitis in mice.. Curcumin showed chelation with zinc ion as confirmed by the TLC, FTIR, UV spectroscopy and (1)H NMR. The results of TLC [Rf value], IR Spectroscopy [shifting of stretching vibrations of υ(C=C) and υ(C=O)], UV spectra [deconvoluted with absorption band at 432-466.4 nm] of Curcumin-Zn(II) complex compared to curcumin confirmed the formation of metallocomplex. (1)HNMR spectra of Curcumin-Zn(II) showed the upfield shift of Ha and Hb. Kinetic stability studies showed metallocomplex with zinc exhibited good stability. In vivo study revealed significant reduction in severity and extent of colonic damage with Curcumin-Zn(II) which were further confirmed by histopathological study.. This study recognizes higher solubility and stability of Curcumin-Zn(II) complex and suggested better pharmacodynamic effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Drug Stability; Mice; Solubility; Zinc

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Female; Humans; Male; Mesalamine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Humans; Immunologic Factors; Mesalamine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Female; Humans; Male; Mesalamine

Increases in the risk of infections and malignancy due to immune suppressive therapies of inflammatory bowel diseases (IBDs) have led the researchers to focus on more nontoxic and acceptable natural products like curcumin. Here we investigate whether prophylactic and therapeutic application of the curcumin alters the enzyme activities of paraoxonase (PON), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and cytosolic β-glucosidase in dextran sulphate sodium (DSS)-induced ulcerative colitis mice. Prophylactic application of curcumin resulted in higher MPO activity, less body weight loss and longer colon lengths compared to therapeutic group indicating preventive role of curcumin in IBDs. DSS-induced decrease in liver and serum PON activities were completely recovered by prophylactic administration of curcumin. DSS-induced reduction in liver cytosolic β-glucosidase activity was not affected by curcumin neither in the prophylactic group nor in the therapeutic group. Erythrocyte CA activity was significantly increased in curcumin groups, however no remarkable change in G6PD activity was observed.

Topics: Animals; Aryldialkylphosphatase; beta-Glucosidase; Colitis, Ulcerative; Curcumin; Dextran Sulfate; Female; Glucosephosphate Dehydrogenase; Mice; Mice, Inbred BALB C

To explore the probable pathway by which curcumin (Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells (DCs).. Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine (Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4(+)CD25+Foxp3(+) T cells (Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay.. Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules (CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur.. Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Curcumin; Cytokines; Dendritic Cells; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Ethanol; Humans; Intestinal Mucosa; Lymphoid Tissue; Male; Mesalamine; Mice; Mice, Inbred C57BL; Random Allocation; Signal Transduction; T-Lymphocytes, Regulatory; Trinitrobenzenesulfonic Acid

Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Biological Products; Cell Line; Colitis, Ulcerative; Colon; Curcumin; Drug Carriers; Drug Therapy, Combination; Epithelial Cells; Fusion Regulatory Protein-1; Hyaluronic Acid; Inflammation; Intestinal Mucosa; Lactic Acid; Macrophages; Male; Mice; Molecular Targeted Therapy; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; RNA, Small Interfering; Treatment Outcome

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

Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated that the synthetic method using tertiary (±)-8-acylmethyldihydroberberine-type alkaloids as key intermediates is superior to that of using tertiary dihydroberberine-type alkaloids as intermediates. Ten target compounds were synthesized using quaternary berberine chloride and quaternary coptisine chloride as starting materials, respectively, and the anti-UC activity of some target compounds was evaluated in an in vitro x-box-binding protein 1 (XBP1) transcriptional activity assay using dual luciferase reporter detection. At 10 μM, the tested compounds were found to activate the transcription of XBP1 target at almost the same level as that of quaternary coptisine chloride. The synthesized target compounds were also found to share higher liposolubility than the inorganic acid salts of quaternary berberine-type alkaloid.

Topics: Berberine; Colitis, Ulcerative; Hydrastis; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Regulatory Factor X Transcription Factors; Salts

Ulcerative Colitis (UC) is a chronic inflammatory disease of colon mucosa, which results from inappropriate inflammatory response. Pharmacological treatments that are used to manage UC are usually targeted to moderate the inflammatory response, however, they are associated with significant adverse effects, which call for finding additional treatment options. Curcumin is a polyphenol that is extracted from turmeric (Curcuma longa). This medicinal plant has been traditionally used in India and in China since ancient times. Recently curcumin has been demonstrated to possess anti-inflammatory, anti-proliferative and antibacterial properties. Based on these reports, our article describes a case report of a patient treated with curcumin in addition to 5-Aminosalicylic acid (5ASA) and presents an integrative approach for the treatment of ulcerative colitis.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Drug Therapy, Combination; Female; Humans; Mesalamine; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Female; Humans; Male; Mesalamine

Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system (SMEDDS) to improve the stability and water-solubility of CUR and enhance its anti-colitis activity. The formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic components CUR and PIP, and then was characterized by assessing appearance, morphology, particle size, zeta potential and drug encapsulation efficiency. The appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation. The mean size of microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 ± 0.76 nm, and the drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 ± 2.18)% and (90.78 ± 2.56)%, respectively. The vitro stability investigation of CUR-PIP-SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co-encapsulated with PIP, CUR was more stable than drug solution in colons site. Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS-induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue through retention enema administration. Our study illustrated that the developed CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific drug delivery system of CUR for ulcerative colitis treatment.

Topics: Alkaloids; Animals; Benzodioxoles; Chemistry, Pharmaceutical; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Drug Stability; Emulsions; Male; Mice; Mice, Inbred BALB C; Particle Size; Piperidines; Polyunsaturated Alkamides; Solubility

The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Drug Evaluation, Preclinical; Female; Gene Expression; Granulocyte Colony-Stimulating Factor; Interleukin-3; Intestinal Mucosa; MAP Kinase Signaling System; Mice, Inbred BALB C; p38 Mitogen-Activated Protein Kinases; Recombinant Fusion Proteins; Tumor Necrosis Factor-alpha

Oral colon-specific drug delivery is of great interest for ulcerative colitis (UC) therapy. Here, an emulsion-solvent evaporation method was used to fabricate microparticles (MPs) with pH-sensitive Eudragit S100 (ERS100) and poly(lactide-co-glycolide) (PLGA), and the MPs were loaded with curcumin (an efficient anti-inflammatory agent). The resultant spherical MPs had a desirable particle size ranging from 1.52 to 1.91 μm. Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA, with some MPs exhibiting loading efficiencies over 80%. It was observed that the fast release of curcumin from MPs in buffers (pH 1.2 and 6.8) could be significantly decreased by increasing the PLGA content. ERS100/PLGA MPs with a weight ratio of 1:2 (MPs-4) were able to maintain sustained release of curcumin, releasing ∼ 48% of the initial drug load at pH 7.2-7.4 during a 20 h-incubation. Most importantly, in vivo experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model, compared to curcumin. Collectively, our one-step-fabricated curcumin-loaded MPs have the properties of pH-sensitivity, controlled drug release and colon targeting, and thus, may hold promise as a readily scalable drug carrier for the efficient clinical treatment of UC.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Delayed-Action Preparations; Dextran Sulfate; Drug Carriers; Drug Delivery Systems; Female; Hydrogen-Ion Concentration; Lactic Acid; Mice; Nanoparticles; Organ Size; Particle Size; Peroxidase; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymethacrylic Acids

Inflammatory bowel diseases, which largely comprise ulcerative colitis (UC) and Crohn's disease, are increasingly posing as a global threat because of the incompetence of the current therapy in the entire patient population. This necessitates the identification of alternative therapeutic molecules or their combinations, which may serve as effective first-line or maintenance therapeutics. In this quest, celecoxib, a selective cyclooxygenase-2 inhibiting nonsteroidal anti-inflammatory agent and curcumin, a natural antioxidant and anti-inflammatory agent, have both been found to be useful in alleviating UC. Furthermore, studies involving their combination have proved synergistic action of these two agents. In the current investigation, we have formulated pH-sensitive nanoparticles of curcumin-celecoxib combination as a potential therapy for UC. Synergistic action of the drug combination, delivery advantages of nanosized carriers, and pH-sensitive nature of the polymer were collectively hypothesized to reduce the overall toxicity and total dose of celecoxib and provide enhanced efficacy for mitigating UC. The hypothesis was confirmed in a UC model in rats, where pH-sensitive nanoparticles of the drug combination were found to be more efficacious than nanoparticles of either drugs or drug/s suspension. Further, the blank nanoparticles did not exhibit any therapeutic effect, thereby confirming efficacy of the drug combination for treating UC.

Topics: Algorithms; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Celecoxib; Colitis, Ulcerative; Colon; Curcumin; Cyclooxygenase 2 Inhibitors; Drug Combinations; Drug Compounding; Drug Synergism; Electrochemistry; Excipients; Freeze Drying; Hydrogen-Ion Concentration; Lipid Peroxidation; Male; Nanoparticles; Particle Size; Peroxidase; Pyrazoles; Rats; Rats, Sprague-Dawley; Sulfonamides; Superoxide Dismutase

The present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid. Rats were randomly divided into three groups: control, acetic acid, and acetic acid+curcumin. Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days. Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls. In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis. Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis. Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats. The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38- and JNK-MAPK pathways.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Colitis, Ulcerative; Colon; Curcuma; Curcumin; Dietary Supplements; Disease Models, Animal; Inflammation; Intestinal Mucosa; JNK Mitogen-Activated Protein Kinases; Male; Malondialdehyde; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Peroxidase; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Signal Transduction

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Curcumin; Female; Humans; Middle Aged; Remission Induction; Salvage Therapy; Treatment Outcome

We have addressed in this study the possible protective role of the main principle of turmeric pigment; curcumin on a murine model of ulcerative colitis (UC). Colitis was induced by administration of dextran sulfate sodium (DSS) (3% W/V) in drinking water to male Swiss albino rats for 5 consecutive days. DSS challenge induced UC model that was well characterized morphologically and biochemically. DSS produced shrinkage of colon length and increased the relative colon weight/length ratio accompanied by mucosal edema and bloody stool. Histologically, DSS produced submucosal erosions, ulceration, inflammatory cell infiltration and crypt abscess as well as epithelioglandular hyperplasia. The model was confirmed biochemically, and the test battery entailed elevated serum tumor necrosis factor (TNF-alpha) and colonic activity of myleoperoxidase (MPO). Colonic glutathione-S-transferase (GST) activity and its substrate concentration; GSH, were notably reduced, while lipid peroxidation, expressed as malondialdehyde (MDA) level, and total nitric oxide (NO) were significantly increased. Prior administration of curcumin (100mg/kg, IP) for 7 consecutive days ahead of DSS challenge mitigated the injurious effects of DSS and ameliorated all the altered biochemical parameters. These results suggest that curcumin could possibly have a protective role in ulcerative colitis probably via regulation of oxidant/anti-oxidant balance and modulation of the release of some inflammatory endocoids, namely TNF-alpha and NO.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Curcumin; Dextran Sulfate; Glutathione; Glutathione Transferase; Intestinal Mucosa; Lipid Peroxidation; Male; Malondialdehyde; Mice; Nitric Oxide; Peroxidase; Rats; Tumor Necrosis Factor-alpha

To evaluate the efficacy and mechanism of action of NCB 02, a standardized Curcumin preparation, against 2, 4 dinitrochlorobenzene (DNCB) induced ulcerative colitis in rats.. Ulcerative colitis was induced in male rats by sensitizing with topical application of DNCB in acetone for 14 d and intra-colonol challenge with DNCB on day 15. A separate group of animals with vehicle treatment in similar fashion served as control group. Colitis rats were divided into different groups and treated with NCB-02 at doses of 25, 50 and 100 mg/kg b.wt p.o. for 10 d. Sulfasalazine at a dose of 100 mg/kg b.wt for 10 d served as a reference group. On day 10 after respective assigned treatment, all the animals were euthanized and the length of the colon, weight of entire colon and distal 8 cm of the colon were recorded. The distal part of the colon was immediately observed under a stereomicroscope and the degree of damage was scored. Further distal 8 cm of the colon was subject to the determination of colonic myeloperoxidase (MPO), lipid peroxidation (LPO) and alkaline phosphatase (ALP) activities. A small piece of the sample from distal colon of each animal was fixed in 10% neutral buffered formalin and embedded in paraffin wax and sectioned for immunohistochemical examination of NFkappa-B and iNOS expression.. NCB-02 showed a dose dependent protection against DNCB-induced alteration in colon length and weight. NCB-02 treatment also showed a dose dependent protection against the elevated levels of MPO, LPO and ALP, induced by DNCB. NCB-02 demonstrated a significant effect at a dose of 100 mg/kg b.wt., which was almost equipotent to 100 mg/kg b.wt. of sulfasalazine. Treatment with sulfasalazine and curcumin at a dose of 100 mg/kg b.wt. inhibited the DNCB-induced overexpression of NFkappa-B and iNOS in the colon.. Curcumin treatment ameliorates colonic damage in DNCB induced colitic rats, an effect associated with an improvement in intestinal oxidative stress and downregulation of colonic NFkappa-B and iNOS expression.

Topics: Alkaline Phosphatase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Curcumin; Dinitrochlorobenzene; Dose-Response Relationship, Drug; Down-Regulation; Gene Expression Regulation; Irritants; Lipid Peroxidation; Male; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Peroxidase; Rats; Rats, Wistar

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bias; Colitis, Ulcerative; Curcumin; Humans; Mesalamine; Treatment Outcome