The pathogenic mechanism and effective treatment of inflammatory bowel disease (IBD) are still unknown. In the present study, we examined the protective effect of hawthorn fruit (Crataegi fructus) on two murine colitis models: dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding and weight loss within 10 days. However, hawthorn fruit (2 g/kg body weight) restored the body weight and colon length and increased hemoglobin count in these animals. Hawthorn fruit not only decreased signs of inflammation such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions, but also showed improvement of leukotriene B4 (LTB4), a biochemical parameter of inflammation mass. TNBS colitis mice had significantly lower rates of survival than normal control animals; however, treatment with hawthorn fruit significantly improved survival in TNBS colitis mice. The results suggest that hawthorn fruit and the Kampo formula that contains this ingredient may have potential therapeutic utility in patients with IBD.
Inflammatory bowel disease (IBD) affects the mucosal lining of the gastrointestinal tract; the etiology is unknown and treatment is directed at systemic immunosuppression. Natural products, including medicinal herbs, have provided approximately half of the drugs developed for clinical use over the past 20 years. The purpose of our current study was to determine the effects of a novel combination of herbal extracts on intestinal inflammation using a murine model of IBD. Female Swiss-Webster mice were randomized to receive normal water or 5% dextran sulfate sodium (DSS) drinking water to induce colitis. Mice were treated with either a novel combination of herbal aqueous extracts or vehicle control per os (po) or per rectum (pr) every 24 hours for 7–8 days. Disease activity index score (DAI) was determined daily; mice were sacrificed and colons were analyzed by H & E staining, MPO assay, and cytokine (TNF-α, IL-6) ELISAs. Mice treated with the combination of herbal extracts, either po or pr, had significantly less rectal bleeding and lower DAI scores compared to the vehicle-treated group. Moreover, colonic ulceration, leukocytic infiltration, and cytokine levels (TNF-α and IL-6) were also decreased in the colons of herbal-treated mice, reflected by H & E staining, MPO assay, and cytokine ELISA. Treatment with the combination of medicinal herbs decreases leukocyte infiltration and mucosal ulceration, ameliorating the course of acute colonic inflammation. This herbal remedy may prove to be a novel and safe therapeutic alternative in the treatment of IBD.
Inflammatory bowel disease (IBD) is a group of autoimmune diseases, including ulcerative colitis and Crohn’s disease, characterized by nonspecific inflammation in the gut. Total glycoside of peony (TGP) has been widely used for treatment of autoimmune diseases because of its pharmacological effects. However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD. Hence, the aim of this study was to investigate the effects of TGP on experimental colitis mice and the related mechanisms. In the present study, we demonstrated that administration of TGP effectively attenuates colonic inflammation of TNBS-induced colitis mice, mainly reflected in significantly improved clinical parameters, reduced inflammatory response and myeloperoxidase (MPO) activity, even stronger systemic immune ability and effective improvement of Th17/Treg immune disorders. In addition, there was a stronger immunosuppressive ability in a positive cluster of differentiation 4 (CD4+) T-lymphocytes from the TGP treated mouse colon, characterized by the inhibition of high levels of inflammatory factors and increased regulatory T cells. Importantly, high-dose TGP has similar therapeutic effects as salicylazosulfapyridine (SASP) on IBD treatment. The potential mechanisms might be, at least in part, related to the adjustment of imbalance of Th17/Treg cells and the inhibition of IL-23/IL17 inflammatory signal axis.
Viscum coloratum has been used as a component for traditional medicine for therapy of inflammatory diseases. Nonetheless, effect of Viscum coloratum on inflammatory bowel disease is unknown. Therefore, we investigated whether the ethanol extract of Viscum coloratum (VCE) could suppress inflammatory responses in dextran sodium sulfate (DSS)-treated mice and mast cell-derived inflammatory mediator (MDIM)-activated Caco-2 cells. VCE significantly attenuated body weight loss, shortened colon length, enteric epithelium disruption, enterorrhagia and colonic edema in DSS-treated mice. Additionally, VCE decreased the levels of immunoglobulin E, interleukin-6 and tumor necrosis factor-α in serum and the activity of myeloperoxidase in colonic tissue. Moreover, VCE inhibited the infiltration of immune cells as well as the activity and expression of both matrix metalloprotease-2 and matrix metalloprotease-9. Furthermore, VCE restored zonula occludens-1 expression. Consistent with in vivo studies, VCE suppressed the activity and expression of matrix metalloprotease-2 and matrix metalloprotease-9 in MDIM-activated Caco-2 cells. In addition, VCE reinstated the expression of zonula occludens-1 through inhibiting activation of janus kinase 2/signal transducer and activator of transcription 3 in the cells. In conclusion, VCE exerts anticolitic action through inhibiting the activation of mast cells. Therefore, VCE may be useful as a phytomedicine or functional food for inflammatory bowel disease.
The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).
Panax notoginseng saponins (PNS) are the main active ingredients of Panax notoginseng (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed in vitro and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-α, IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β), IκBα and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.
Artemisia gmelinii Web. ex Stechm. (AG), a popular medicinal herb in Asia, has been used as a common food ingredient in Korea and is traditionally known for its anti-inflammatory properties. Therefore, in this study, we aimed to investigate whether AG relieves IBD, a classic chronic inflammatory disease of the gastrointestinal tract. We identified 35 chemical compounds in AG ethanol extract using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. In mice with DSS-induced IBD, AG administration attenuated the disease activity index and the serum and colonic levels of inflammatory cytokines and chemokines. AG treatment decreased nuclear factor-κB (NF-κB) signaling, a key mediator of inflammation, in the mouse colons. Additionally, AG extract enhanced immune responses in lymphoid tissues such as spleen and Peyer’s patches. Thus, AG consumption potently ameliorated IBD symptoms and improved immune signaling in lymphoid tissues.
This study aimed to verify the efficacy of a combined treatment of Jakyakgamcho-tang (JGT) and acupuncture (CV12, ST25, CV4) on colitis induced by dextrane sulfate sodium (DSS). Changes in immuno-mediated factors and metabolites were investigated. Colitis symptoms such as body weight loss and elevated disease activity index were alleviated by the combined treatment. Moreover, treatment with JGT and acupuncture restored the disturbed architecture of colon by suppressing inflammatory cytokine levels of IFN-γ (P < 0.05), IL-5 (P < 0.05), and IL-13 (P < 0.0001) compared with the DSS group. Analysis of metabolic profiles of serum revealed that treatment groups were clearly separated from the DSS group, suggesting that JGT and acupuncture treatment altered serum metabolites. Furthermore, treatments caused opposite metabolite patterns for dimethylbenzimidazole, 1,5-anhydro-D-glucitol, proline, phosphate, glycolic acid, aspartic acid, tryptophan, phthalic acid, ornithine, and glutamic acid compared with the DSS group. The combined treatment group induced more effective metabolite patterns than the JGT group, implying that acupuncture treatment can restore metabolic changes caused by DSS induction. These results indicate that the simultaneous treatment of JGT administration and acupuncture procedure provides better management of the immune function and inflammatory expression of colitis than a single treatment. It is assumed that intestinal microbial control can be achieved by acupuncture stimulation as well as by taking herbal medicine.
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Today, IBD has no successful treatment. As a result, it is of paramount importance to develop novel therapeutic agents for IBD prevention and treatment. Astragalus membranaceus (AMS) is a traditional Chinese medicine found in the AMS root. Modern pharmacological studies indicate that AMS and its constituents exhibit multiple bioactivities, such as anti-inflammatory, anti-oxidant, immune regulatory, anticancer, hypolipidemic, hypoglycemic, hepatoprotective, expectorant, and diuretic effects. AMS and its active constituents, which have been reported to be effective in IBD treatment, are believed to be viable candidate drugs for IBD treatment. These underlying mechanisms are associated with anti-inflammation, anti-oxidation, immunomodulation, intestinal epithelial repair, gut microbiota homeostasis, and improved energy metabolism. In this review, we summarize the efficacy and underlying mechanisms involved in IBD treatment with AMS and its active constituents in preclinical studies.
Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10−∕−). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF-α levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10−∕− mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae, Sutterellaceae, Erysipelotrichaceae, Burkholderiaceae, Desulfovibrionaceae, and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.
Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.
Acupuncture and moxibustion are widely acknowledged as effective complementary therapies for managing inflammatory bowel disease (IBD) in traditional Chinese medicine. However, the regulatory mechanisms by which these two therapies exert their therapeutic effects in IBD are yet to be fully elucidated. The objective of this study was to investigate the mechanisms of action underlying acupuncture and moxibustion and the regulative differences between them as therapeutic interventions for IBD. Using a dextran sodium sulfate-induced IBD mice model, the effects of the two treatments were evaluated by examination of body weight, stool samples, colon morphology, inflammatory factors, gut microbiota, and metabolites. The results indicated that both acupuncture and moxibustion mitigated body weight reduction; improved the structural characteristics of intestinal tissues; increased levels of anti-inflammatory cytokines including interleukin (IL)-10; and decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), IL-6, IL-1β, and IL-17. Acupuncture and moxibustion had distinct effects on the regulation of the intestinal microbiota and metabolic pathways in IBD mice. Moxibustion regulated a greater number of metabolic pathways than acupuncture, the majority of which were associated with amino acid metabolism, brain signal transmission, energy metabolism, and anti-inflammatory pathways. These findings provide a scientific basis for the differential applications of acupuncture and moxibustion in clinical practice.
Rheumatic manifestations are the most common extraintestinal features in the inflammatory bowel disease. The aim of this study was to determine the effectiveness of 99mtechnetium-labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy, to detect peripheral joint inflammation in patients with enteropathic arthropathy. Nineteen patients (Crohn disease: 4, colitis ulcerosa: 15) with either pain and/or swelling of peripheral joints, underwent 99mTc-IgG scintigraphy. The results were correlated with clinical, and laboratory activity parameters, as well as with radiological findings. The mean duration of bowel disease was 7.55 ± 6.11 years. In 19 patients 17 peripheral joints were swollen and 58 were tender. Taking tenderness as a potential indicator of joint involvement; 31 (53%) of the joints revealed abnormality on 99mTc-IgG scintigraphy. The most frequently affected sites were the knees, ankles and tarsals. The total scintigraphic scores were significantly correlated with tenderness and swelling scores. No correlation was observed between the scores of 99mTc-IgG scintigraphy and radiological findings. In conclusion 99mTc-IgG scintigraphy can be appropriate for detecting inflammation of peripheral joints and can be used to establish the extent of arthritis in patients with inflammatory bowel disease.
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For the month of January 2021, APBN features a cover story on innovations in home-based faecal calprotectin test for self-management of inflammatory bowel disease. Also, in the Features section, we bring you highlights of the new technologies and trends in cell-line research and development Taking a dive into healthcare technology, the Spotlights section covers interviews from two different experts on data analytics in healthcare as well as mitigating cybersecurity threats in healthcare systems. Keeping to this same umbrella of health technology, the Columns section the articles cover on the use of artificial intelligence in healthcare.
Inflammatory bowel disease (IBD) is a chronic disease whose incidence and prevalence increase every year; however, the pathogenesis of IBD is still unclear. Thus, identifying IBD-related proteins is important for understanding its complex disease mechanism. Here, we propose a new and simple network-based approach using a reverse k-nearest neighbor (RkNN) search to identify novel IBD-related proteins. Protein–protein interactions (PPI) and Genome-Wide Association Studies (GWAS) were used in this study. After constructing the PPI network, the RkNN search was applied to all of the proteins to identify sets of influenced proteins among their k-nearest neighbors (RkNNs). An observed protein whose influenced proteins were mostly known IBD-related proteins was statistically identified as a novel IBD-related protein. Our method outperformed a random aspect, kNN search, and centrality measures based on the network topology. A total of 39 proteins were identified as IBD-related proteins. Of these proteins, 71% were reported at least once in the literature as related to IBD. Additionally, these proteins were found over-represented in the IBD pathway and enriched in importantly functional pathways in IBD. In conclusion, the RkNN search with the statistical enrichment test is a great tool to identify IBD-related proteins to better understand its complex disease mechanism.
We report a 49-year-old lady with ulcerative colitis (UC) who subsequently developed systemic lupus erythematosus (SLE) ten years later. By reviewing the drug history and serum autoimmune panel, we hypothesize that systemic lupus erythematosus may occur in a patient with a history of inflammatory bowel disease as a coexisting disease, or triggered by drugs used in inflammatory bowel disease, such as disease-modifying anti-rheumatic drugs (DMARDs). This case raises the discussion that patients with Inflammatory bowel disease (IBD) may have a genetic predisposition for developing other autoimmune diseases, and explores the possibility of drugs used in the treatment of IBD as a trigger for SLE development. Being able to differentiate the two has important implications in management and prognosis.
Colon cancer is one of the most common spread cancers in the world, which leads to total death of 10%. Prediction of onset of cancer, and the cause of its development in these patients can be of an enormous help and relief to those affected, as they can get back their “normal” life. Data mining and machine learning are important intelligent tools for classification, prediction and hidden relation extraction between patient information. We collected data from Shahid Faghihi Hospital in Shiraz. Features collected are as follows: Gender, age, duration of cancer before surgery, number of times the patients used bathroom, taking anti-inflammatory drug prednisolone, duration of drug use and dosage, kind of surgery and number of times consulted and retreatment of surgery, incontinence, etc. After pre-processing and data cleaning stages, effective features were extracted, and also occurrence of cancer predicts by using different classification algorithms. Then association rule mining algorithms like Apriori were used for obtaining any internal hidden relation between entries. Approaching them with different algorithms and assessing them with support vector machine was with highest prediction accuracy (84%). Due to unbalanced dataset, we chose cost sensitive support vector machine. In another aspect, after applying Apriori algorithm, the conditions of non-inflammation were extracted based on dataset features. Some significant outcomes are in what follows. If surgery treatment or diagnosed was less than 5 years, the possibility of developing colon cancer is lower. Also, as the duration of disease increases, the possibility of reoperation increases, as confirmed by the interiors. Since this issue with these features was raised for the first time in this paper at the suggestion of internists, early detection of cancer and also the extraction of effective laws can be of help to the medical community. In future, to get higher accuracy, the improvement of the dataset in terms of number of samples and colonoscopy image features is considered.
Chronic diseases like rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are debilitating life-long morbid conditions caused by a dysregulated immune profile in the affected individuals. These conditions afflict millions of individuals throughout the world with symptoms that impair performance and quality of life. Considering IBD per se, the chronic nature of the immune disorders means that patients may require life-long medications often at high doses, but the currently available pharmacological preparations are aimed at reducing the symptoms or suppressing exacerbations, without a lasting effect on the underlying cause. Further, long-term drug therapy often leads to drug dependency and loss of response together with adverse side effects. Indeed, drug side effects become an additional morbidity factor in many patients on long-term medications…
Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), has a significant genetic component and is increasingly prevalent due to environmental factors. Current polygenic risk scores (PRS) have limited predictive power and cannot inform time of symptom onset. Circulating proteomics profiling offers a novel, non-invasive approach for understanding the inflammatory state of complex diseases, enabling the creation of proteomic risk scores (ProRS). This study utilizes data from 51,772 individuals in the UK Biobank to evaluate the unique and combined contributions of PRS and ProRS to IBD risk prediction. We developed ProRS models for CD and UC, assessed their predictive performance over time, and examined the benefits of integrating PRS and ProRS for enhanced risk stratification. Our findings are the first to demonstrate that combining genetic and proteomic data improves IBD incidence prediction, with ProRS providing time-sensitive predictions and PRS offering additional long-term predictive value. We also show that the ProRS achieves better predictive performance among individuals with high PRS. This integrated approach highlights the potential for multi-omic data in precision medicine for IBD.
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