Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disorder of the small intestine and colon. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), and it is a major factor for the development of colon cancer, referred to as colitis-associated cancer (CAC). The current treatment of IBD mainly includes the use of synthetic drugs and monoclonal antibodies. However, these drugs have side effects over long-term use, and the high relapse rate restricts their application. In the recent past, many studies had witnessed a surge in applying plant-derived products to manage various diseases, including IBD. Curcumin is a bioactive component derived from a rhizome of turmeric (Curcuma longa). Numerous in vitro and in vivo studies show that curcumin may interact with many cellular targets (NF-κB, JAKs/STATs, MAPKs, TNF-γ, IL-6, PPARγ, and TRPV1) and effectively reduce the progression of IBD with promising results. Thus, curcumin is a potential therapeutic agent for patients with IBD once it significantly decreases clinical relapse in patients with quiescent IBD. This review aims to summarize recent advances and provide a comprehensive picture of curcumin’s effectiveness in IBD and offer our view on future research on curcumin in IBD treatment.

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Supplementation of Bovine Colostrum in Inflammatory Bowel Disease: Benefits and Contraindications

Advances in Nutrition ◽

10.1093/advances/nmaa120 ◽

2020 ◽

Author(s):

Michał Sienkiewicz ◽

Patrycja Szymańska ◽

Jakub Fichna

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Immunosuppressive Agents ◽

Bovine Colostrum ◽

In Vivo Studies ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

ABSTRACT Inflammatory bowel disease (IBD) is a group of chronic relapsing disorders whose etiology has not been fully explained. Therefore, available therapeutic approaches for IBD patients are still insufficient. Current treatment strategies are targeted to immune system dysfunctions, often associated with alternations in the microbiota, which contribute to the development of chronic intestinal inflammation. Therapeutics include anti-inflammatory drugs such as aminosalicylates and corticosteroids, immunosuppressive agents, antibiotics, and biological agents such as infliximab and vedolizumab. Auxiliary therapies involve a balanced and personalized diet, healthy lifestyle, avoiding stress, as well as dietary supplements. In this review, we discuss the use of bovine colostrum (BC) as a therapeutic agent, including its advantages and contraindications. We summarize our knowledge on well-researched BC constituents and their effects on the gastrointestinal tract as evidenced in in vitro and in vivo studies.

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Development of melatonin loaded pectin nanoparticles for the treatment of inflammatory bowel disease: In vitro and in vivo studies

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102861 ◽

2021 ◽

pp. 102861

Author(s):

Serkan Yener ◽

Kazime Gonca Akbulut ◽

Resul Karakuş ◽

Deniz Erdoğan ◽

Füsun Acartürk

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

In Vivo Studies ◽

Inflammatory Bowel

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Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.010143 ◽

2020 ◽

Vol 295 (13) ◽

pp. 4237-4251 ◽

Cited By ~ 1

Author(s):

Jie Zhang ◽

Min Xu ◽

Weihua Zhou ◽

Dejian Li ◽

Hong Zhang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Epithelial Cell ◽

Bowel Disease ◽

Intestinal Epithelial Cell ◽

Intestinal Inflammation ◽

Intestinal Epithelial ◽

P53 Expression ◽

Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

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P.1.218: INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS ON ANTI TNF-ALPHA TREATMENT: RESPONSE TO THE INFLUENZA A/H1N1 VACCINE IN VIVO AND IN VITRO

Digestive and Liver Disease ◽

10.1016/s1590-8658(11)60446-5 ◽

2011 ◽

Vol 43 ◽

pp. S220

Author(s):

G. Andrisani ◽

D. Frasca ◽

A. Armuzzi ◽

A. Papa ◽

M. Marzo ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Treatment Response ◽

Bowel Disease ◽

Influenza A ◽

Tnf Alpha ◽

H1n1 Vaccine ◽

Influenza A H1n1 ◽

Inflammatory Bowel

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Inflammatory Bowel Disease–associated GP2 Autoantibodies Inhibit Mucosal Immune Response to Adherent-invasive Bacteria

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa069 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1856-1868

Author(s):

Stefanie Derer ◽

Ann-Kathrin Brethack ◽

Carlotta Pietsch ◽

Sebastian T Jendrek ◽

Thomas Nitzsche ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Ex Vivo ◽

Expression Patterns ◽

Mucosal Immune Response ◽

Disease Manifestation ◽

Inflammatory Bowel

Abstract Adherent-invasive Escherichia coli have been suggested to play a pivotal role within the pathophysiology of inflammatory bowel disease (IBD). Autoantibodies against distinct splicing variants of glycoprotein 2 (GP2), an intestinal receptor of the bacterial adhesin FimH, frequently occur in IBD patients. Hence, we aimed to functionally characterize GP2-directed autoantibodies as a putative part of IBD’s pathophysiology. Ex vivo, GP2-splicing variant 4 (GP2#4) but not variant 2 was expressed on intestinal M or L cells with elevated expression patterns in IBD patients. The GP2#4 expression was induced in vitro by tumor necrosis factor (TNF)-α. The IBD-associated GP2 autoantibodies inhibited FimH binding to GP2#4 and were decreased in anti-TNFα-treated Crohn’s disease patients with ileocolonic disease manifestation. In vivo, mice immunized against GP2 before infection with adherent-invasive bacteria displayed exacerbated intestinal inflammation. In summary, autoimmunity against intestinal expressed GP2#4 results in enhanced attachment of flagellated bacteria to the intestinal epithelium and thereby may drive IBD’s pathophysiology.

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In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2016.08.075 ◽

2016 ◽

Vol 26 (19) ◽

pp. 4587-4591 ◽

Cited By ~ 9

Author(s):

Suhrid Banskota ◽

Han-eol Kang ◽

Dong-Guk Kim ◽

Sang Won Park ◽

Hyeonjin Jang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Inhibitory Activity ◽

Inflammatory Bowel

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Protective Mechanisms of Butyrate on Inflammatory Bowel Disease

Current Pharmaceutical Design ◽

10.2174/1381612824666181001153605 ◽

2019 ◽

Vol 24 (35) ◽

pp. 4154-4166 ◽

Cited By ~ 23

Author(s):

João P.B. Silva ◽

Kely C. Navegantes-Lima ◽

Ana L.B. Oliveira ◽

Dávila V.S. Rodrigues ◽

Sílvia L.F. Gaspar ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Current Knowledge ◽

In Vivo Studies ◽

Whole Body ◽

Protective Mechanisms ◽

Mucus Production ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a multifactorial chronic disease, commonly associated with alteration in the composition and function of gut microbiota. This process can lead to a decreased production of short chain fatty acids (SCFAs) by the gut microbiota, mainly butyrate, which is an important immunomodulatory molecule in the intestine. Butyrogenic bacteria normally produces butyrate through carbohydrate fermentation or amino acids degradation pathways. This molecule plays an important protective role in intestinal homeostasis acting in both adaptive immunity and innate immunity. This review summarizes the current knowledge about the role of butyrate on the development of IBD and the protective mechanisms of this metabolite on the intestinal mucosa and the whole body, as reported by in vitro and in vivo studies. Thus, butyrate can regulate the activation of regulatory T cells, increasing the acetylation of histones and decreasing the activation of NF-κB. In addition, it can also stimulate the mucus production from epithelial cells and the rearrangement of tight junction proteins.

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Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease: effects of anti-TNF-α treatment

Thrombosis and Haemostasis ◽

10.1160/th16-02-0167 ◽

2016 ◽

Vol 116 (09) ◽

pp. 486-495 ◽

Cited By ~ 7

Author(s):

Marco Guerci ◽

Paola Simeone ◽

Sandro Ardizzone ◽

Alessandro Massari ◽

Paolo Giuffrida ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Platelet Activation ◽

Bowel Disease ◽

Infliximab Treatment ◽

Soluble Cd40 Ligand ◽

Tnf Α ◽

Inflammatory Bowel ◽

Vitro Effect

SummaryPatients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here measured the urinary F2-isoprostane 8-iso-prostaglandin (PG)2α (8-iso-PGF2α), urinary 11–dehydro–thromboxane (TX) B2 (11-dehydro–TXB2) and plasma CD40L in IBD patients, and explored the in vitro action of anti-tumour necrosis factor (TNF)–α antibody infliximab on IBD differentiating megakaryocytes. Urinary and blood samples were collected from 124 IBD patients and 37 healthy subjects. Thirteen IBD patients were also evaluated before and after 6–week infliximab treatment. The in vitro effect of infliximab on patient-derived megakaryocytes was evaluated by immunoflorescence microscopy and by flow cytometry. IBD patients had significantly (p<0.0001) higher urinary 8–iso–PGF2α and 11–dehydro–TXB2 as well as plasma CD40L levels than controls, with active IBD patients displaying higher urinary and plasma values when compared to inactive patients in remission. A 6-week treatment with infliximab was associated with a significant reduction of the urinary excretion of 8–iso–PGF2α and 11–dehydro–TXB2 (p=0.008) and plasma CD40L (p=0.001). Infliximab induced significantly rescued pro-platelet formation by megakaryocytes derived from IBD patients but not from healthy controls. Our findings provide evidence for enhanced in vivo TX–dependent platelet activation and lipid peroxidation in IBD patients. Anti-TNF–α therapy with infliximab down-regulates in vivo isoprostane generation and TX biosynthesis in responder IBD patients. Further studies are needed to clarify the implication of infliximab induced-proplatelet formation from IBD megakaryocytes.Supplementary Material to this article is available online at www.thrombosis-online.com.

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