Phytochemicals Targeting JAK–STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that consists of Crohn’s disease (CD) and ulcerative colitis (UC). Cytokines are thought to be key mediators of inflammation-mediated pathological processes of IBD. These cytokines play a crucial role through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways. Several small molecules inhibiting JAK have been used in clinical trials, and one of them has been approved for IBD treatment. Many anti-inflammatory phytochemicals have been shown to have potential as new drugs for IBD treatment. This review describes the significance of the JAK–STAT pathway as a current therapeutic target for IBD and discusses the recent findings that phytochemicals can ameliorate disease symptoms by affecting the JAK–STAT pathway in vivo in IBD disease models. Thus, we suggest that phytochemicals modulating JAK–STAT pathways are potential candidates for developing new therapeutic drugs, alternative medicines, and nutraceutical agents for the treatment of IBD.

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Comparison of Bacterial Composition, Concentration, and Metabolism of Short Chain Fatty Acid in Inflammatory Bowel Disease: A Systematic Review

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.01038 ◽

2021 ◽

pp. 5978-5984

Author(s):

David Nugraha ◽

Natasya Ariesta Selyardi Putri ◽

Visuddho Visuddho ◽

Citrawati Dyah Kencono Wungu

Keyword(s):

Systematic Review ◽

Inflammatory Bowel Disease ◽

Fatty Acid ◽

Bowel Disease ◽

Short Chain Fatty Acid ◽

Chain Fatty Acid ◽

Short Chain ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD), which consists of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the intestine. The etiology is heterogeneous and multifactorial, including genetic susceptibility, immune-mediated tissue damage, and changes of lumen microenvironment, especially short-chain fatty acid (SCFA) producing bacteria. Several studies reported a decrease in SCFA concentration in both CD and UC. In fact, SCFAs has important roles in accelerating disease remission. This systematic review aimed to evaluate the changes in SCFA concentration, the composition of SCFA-producing bacteria, and SCFA metabolism in IBD. A literature search was conducted via PubMed, Scopus, and CENTRAL by selecting studies according to inclusion and exclusion criteria. The quality and risk of bias assessment were performed using the Newcastle-Ottawa Scale (NOS). Overall, 160 UC and 127 CD patients from 5 studies were reviewed. The SCFA concentration was significantly reduced (p <0.05) in both PC and UC. Moreover, there was a decrease in major SCFA-producing bacteria. Clostridium coccoides were significantly decreased in the feces of active UC (p = 0.015) and CD (p = 0.04). Clostridium leptum was decreased on intestinal mucosal biopsy of active CD and UC (p <0.0001). Faecalibacterium prausnitzii were decreased in active CD faeces (p <0.0001) and UC (p = 0.0001). Butyrate oxidation rate was also reported to decrease in UC compared to control (p<0.0001). In conclusion, the ability of major SCFA-producing bacterial production in IBD was diminished, which implies a decreased protective and anti-inflammatory effect of SCFA that altered its metabolism.

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Renal involvement in paediatric inflammatory bowel disease

Pediatric Nephrology ◽

10.1007/s00467-019-04413-5 ◽

2019 ◽

Author(s):

Mohamed Mutalib

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Renal Involvement ◽

Host Immune System ◽

Inflammatory Disorder ◽

Extraintestinal Manifestation ◽

Metabolic Complications ◽

Chronic Inflammatory Disorder ◽

Renal Manifestation ◽

Inflammatory Bowel

AbstractInflammatory bowel disease (IBD), which includes Crohn’s disease, ulcerative colitis and inflammatory bowel disease unclassified, is a chronic inflammatory disorder that predominantly affects the gastrointestinal (GI) tract and has a rising incidence in both children and adults. Symptoms are caused by inappropriate inflammatory response triggered by interaction between the environment, gut microbiome and host immune system in a genetically susceptible individual. Extranintestinal manifestations of IBD are common and can affect any body system outside the gut; they can precede or run parallel to GI inflammation. Renal involvement in IBD is uncommon and can be part of extraintestinal manifestation or metabolic complications of IBD. Many medications used to treat IBD can cause renal damage. Renal manifestation in children with IBD can range from asymptomatic biochemical abnormalities to variable stages of renal impairment with significant morbidity and even mortality burden.

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Mediators of Inflammation in Children with Inflammatory Bowel Disease

European Journal of Inflammation ◽

10.1177/1721727x0300100203 ◽

2003 ◽

Vol 1 (2) ◽

pp. 65-71 ◽

Cited By ~ 1

Author(s):

M. Hatzistilianou-Sidiropoulou ◽

S. Nousia-Arvanitakis ◽

A. Galli-Tsinopoulou ◽

C. Agguridaki ◽

M. Xefteri ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cell Activation ◽

Inflammatory Mediators ◽

Bowel Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Parent Molecule ◽

Mediators Of Inflammation ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) in children remains a challenging problem. Crohn disease and ulcerative colitis are characterized by an activation of intestinal mononuclear cells and T-cells within the inflammed lesions. In the present study, we determined whether circulating inflammatory mediators, such as interleukins and adhesion molecules, may represent useful markers of immune activation in vivo. Serum concentrations of IL-2, IL-6, IL-8, IL-10, sIL-2R, sICAM-1 and sVCAM-1 were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) in 18 patients with IBD and 25 healthy subjects matched for age and sex (control group). According to our results, all the inflammatory mediators are significantly increased in patients with IBD as compared to the control group. Pro-inflammatory mediators (IL-6, IL-8, IL-10) are elevated in the serum of patients with active disease, suggesting that they act as naturally occuring initiators of the acute inflammatory process. Increased IL-2 and sIL-2R levels reflect T-cell activation. Increased circulating sICAM-1 and sVCAM-1 levels may reflect increased adhesiveness and signal transmission across cells, probably as a result of shedding of the parent molecule during local cellular immunoresponses in vivo. The measurement of inflammatory mediators may be a useful adjunct to the clinical assessment and to the routine laboratory testing of IBD pediatric patients.

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Role of epithelial ion transports in inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00369.2015 ◽

2016 ◽

Vol 310 (7) ◽

pp. G460-G476 ◽

Cited By ~ 8

Author(s):

Diogo Magalhães ◽

José Miguel Cabral ◽

Patrício Soares-da-Silva ◽

Fernando Magro

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Ionic Transport ◽

Current Evidence ◽

Sodium Absorption ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Potassium Secretion ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na+-K+-ATPase (NKA), Na+/H+ exchangers (NHEs), epithelial Na+ channels (ENaC), and K+ channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.

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Effect of Cynara cardunculus L. var. altilis (DC) in Inflammatory Bowel Disease

Applied Sciences ◽

10.3390/app11041629 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1629

Author(s):

Vanessa Mateus ◽

João Estarreja ◽

Inês Silva ◽

Paulo Barracosa ◽

Edite Teixeira-Lemos ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Animal Studies ◽

Inflammatory Disorder ◽

Cynara Cardunculus ◽

Trinitrobenzenesulfonic Acid ◽

Chronic Inflammatory Disorder ◽

Tnf Α ◽

Inflammatory Bowel ◽

Anti Inflammatory

Background: Cynara cardunculus L. var. altilis (DC) is a plant generally associated as an ingredient in the Mediterranean diet. The polyphenols present in this plant provide pharmacological and nutritional properties. C. cardunculus L. has been used throughout animal studies, which demonstrated an anti-inflammatory effect. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Since there is not a known cure, the research of new possible pharmacological approaches is essential. This study aims to evaluate the effect of an aqueous extract of C. cardunculus L. dry leaves in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model. Methods: CD-1 mice with TNBS-induced colitis received an intraperitoneal (IP) administration of C. cardunculus L. once per day for 4 days. Results: The C. cardunculus L. demonstrated a beneficial effect in this experimental model of IBD with anti-inflammatory action through the reduction of tumor necrosis factor (TNF)-α levels. It also demonstrated a beneficial influence on the extra-intestinal manifestations related to IBD, with the absence of significant side effects of its use. Conclusions: The extract of C. cardunculus L. dry leaves can become an interesting tool for new possible pharmacological approaches in the management of IBD.

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New biologics and small molecules in inflammatory bowel disease: an update

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819853208 ◽

2019 ◽

Vol 12 ◽

pp. 175628481985320 ◽

Cited By ~ 27

Author(s):

João Sabino ◽

Bram Verstockt ◽

Séverine Vermeire ◽

Marc Ferrante

Keyword(s):

Inflammatory Bowel Disease ◽

Small Molecules ◽

Bowel Disease ◽

Mucosal Healing ◽

Janus Kinase ◽

New Drugs ◽

Phase Iii ◽

Sustained Remission ◽

Inflammatory Disorders ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a spectrum of immune-mediated inflammatory disorders with a complex multifactorial pathogenesis, where different pathways may predominate in different individuals. This complexity will most likely require a panoply of drugs targeting different pathways if one wants to treat to steroid-free sustained remission and mucosal healing. Presently, the mainstay of medical management of IBD is based on 5-aminosalicylates, corticosteroids, thiopurines, methotrexate, antitumor necrosis factor, anti-alpha4 beta7 (α4β7) integrin and anti-interleukin (IL)-12/IL-23 therapies. The discovery of new pathways involved in the pathogenesis of IBD resulted in new drugs targeting Janus kinase/signal transducers and activators of transcription, IL-6, spingosine-1-phosphate, and phosphodiesterase 4, among others. These new therapies might result in more advantageous safety profiles. Several of these new drugs have already been successfully tested in other inflammatory disorders, such as psoriasis or rheumatoid arthritis. In this review, evidence from phase II and phase III randomized controlled clinical trials in patients with IBD involving new biologicals and small molecules are summarized.

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Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review

Mediators of Inflammation ◽

10.1155/2020/9706140 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Xueyan Ding ◽

Peng Bin ◽

Wenwen Wu ◽

Yajie Chang ◽

Guoqiang Zhu

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Regulatory T Cells ◽

Immune Cells ◽

Bowel Disease ◽

Kynurenine Pathway ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Inflammatory Bowel ◽

Treg Differentiation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from the homeostasis imbalance of intestinal microenvironment, immune dysfunction, environmental and genetic factors, and so on. This disease is associated with multiple immune cells including regulatory T cells (Tregs). Tregs are a subset of T cells regulating the function of various immune cells to induce immune tolerance and maintain intestinal immune homeostasis. Tregs are correlated with the initiation and progression of IBD; therefore, strategies that affect the differentiation and function of Tregs may be promising for the prevention of IBD-associated pathology. It is worth noting that tryptophan (Trp) metabolism is effective in inducing the differentiation of Tregs through microbiota-mediated degradation and kynurenine pathway (KP), which is important for maintaining the function of Tregs. Interestingly, patients with IBD show Trp metabolism disorder in the pathological process, including changes in the concentrations of Trp and its metabolites and alteration in the activities of related catalytic enzymes. Thus, manipulation of Treg differentiation through Trp metabolism may provide a potential target for prevention of IBD. The purpose of this review is to highlight the relationship between Trp metabolism and Treg differentiation and the role of this interaction in the pathogenesis of IBD.

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

Pharmaceutics ◽

10.3390/pharmaceutics13040484 ◽

2021 ◽

Vol 13 (4) ◽

pp. 484

Author(s):

Adhimoolam Karthikeyan ◽

Kim Na Young ◽

Mohammad Moniruzzaman ◽

Anteneh Marelign Beyene ◽

Kyoungtag Do ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Curcuma Longa ◽

In Vivo Studies ◽

Future Research ◽

Inflammatory Disorder ◽

Clinical Relapse ◽

Inflammatory Bowel

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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Paediatric Inflammatory Bowel Disease and its Relationship with the Microbiome

Microbial Ecology ◽

10.1007/s00248-021-01697-9 ◽

2021 ◽

Author(s):

Rachel S. Fitzgerald ◽

Ian R. Sanderson ◽

Marcus J. Claesson

Keyword(s):

Inflammatory Bowel Disease ◽

Digestive Tract ◽

Bowel Disease ◽

Inflammatory Disorder ◽

Healthy Children ◽

Chronic Inflammatory Disorder ◽

Disease States ◽

Paediatric Patients ◽

Potential Component ◽

Inflammatory Bowel

AbstractPaediatric inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract, comprising of Crohn’s disease (CD), ulcerative colitis (UC), and, where classification is undetermined, inflammatory bowel disease unclassified (IBDU). Paediatric IBD incidence is increasing globally, with prevalence highest in the developed world. Though no specific causative agent has been identified for paediatric IBD, it is believed that a number of factors may contribute to the development of the disease, including genetics and the environment. Another potential component in the development of IBD is the microbiota in the digestive tract, particularly the gut. While the exact role that the microbiome plays in IBD is unclear, many studies acknowledge the complex relationship between the gut bacteria and pathogenesis of IBD. In this review, we look at the increasing number of studies investigating the role the microbiome and other biomes play in paediatric patients with IBD, particularly changes associated with IBD, varying disease states, and therapeutics. The paediatric IBD microbiome is significantly different to that of healthy children, with decreased diversity and differences in bacterial composition (such as a decrease in Firmicutes). Changes in the microbiome relating to various treatments of IBD and disease severity have also been observed in multiple studies. Changes in diversity and composition may also extend to other biomes in paediatric IBD, such as the virome and the mycobiome. Research into biome differences in IBD paediatric patients may help progress our understanding of the aetiology of the disease.

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Artificial intelligence in inflammatory bowel disease endoscopy: current landscape and the road ahead

Therapeutic Advances in Gastrointestinal Endoscopy ◽

10.1177/26317745211017809 ◽

2021 ◽

Vol 14 ◽

pp. 263177452110178

Author(s):

Suneha Sundaram ◽

Tenzin Choden ◽

Mark C. Mattar ◽

Sanjal Desai ◽

Madhav Desai

Keyword(s):

Artificial Intelligence ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

The Road ◽

Severity Prediction ◽

Appropriate Therapy ◽

Inflammatory Bowel ◽

Individual Responsiveness

Inflammatory bowel disease is a complex chronic inflammatory disorder with challenges in diagnosis, choosing appropriate therapy, determining individual responsiveness, and prediction of future disease course to guide appropriate management. Artificial intelligence has been examined in the field of inflammatory bowel disease endoscopy with promising data in different domains of inflammatory bowel disease, including diagnosis, assessment of mucosal activity, and prediction of recurrence and complications. Artificial intelligence use during endoscopy could be a step toward precision medicine in inflammatory bowel disease care pathways. We reviewed available data on use of artificial intelligence for diagnosis of inflammatory bowel disease, grading of severity, prediction of recurrence, and dysplasia detection. We examined the potential role of artificial intelligence enhanced endoscopy in various aspects of inflammatory bowel disease care and future perspectives in this review.

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