The significant role of nutraceutical compounds in ulcerative colitis treatment

2021 ◽  
Vol 29 ◽  
Author(s):  
Azzurra Chiara De Maio ◽  
Giovanna Basile ◽  
Domenico Iacopetta ◽  
Alessia Catalano ◽  
Jessica Ceramella ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Intestinal Inflammation ◽  
Wide Spectrum ◽  
Antioxidant Defenses ◽  
Mucosal Inflammation ◽  
Aminosalicylic Acid ◽  
Positive Health ◽  
Biological Drugs ◽  
Nutraceutical Compounds

Abstract: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly affecting the colon and the rectum. Its main characters are represented by relapsing and remitting mucosal inflammation, starting in the rectum and typically extending continuously proximally through part or the entire colon. UC pathogenesis depends on multiple factors, such as genetic predisposition, defects in the epithelial barrier, dysregulated immune responses, and environmental causes. The most frequent symptoms are abdominal pain, weight loss, mucus discharge, bloody diarrhoea, incontinence, nocturnal defecations, fever, and anemia. Existing therapies for UC include 5-aminosalicylic acid (5-ASA) and its derivatives, steroids, immunosuppressants and biological drugs. However, limited efficacy and unwanted adverse effects hardly limit these strategies of treatment. In the last decades, research studies have been driven towards complementary and alternative medicines for the treatment of UC. Various nutraceuticals have exhibited promising results in modulating intestinal inflammation meanwhile improving symptoms. These compounds possess a wide spectrum of positive health effects evidenced by in vitro studies, characterized by their involvement in antioxidant defenses, cell proliferation, and gene expression. The present review analyzes the available data about the different types of nutraceuticals and their potential effectiveness as adjuvant therapy of IBD, with particular emphasis to UC.

Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Function Evaluation ◽  
Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

Retinoic Acid Is Elevated in the Mucosa of Patients With Active Ulcerative Colitis and Displays a Proinflammatory Role by Augmenting IL-17 and IFNγ Production

2020 ◽  
Vol 27 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Ritika Rampal ◽  
Nahidul Wari ◽  
Amit Kumar Singh ◽  
Ujjwalkumar Das ◽  
Sawan Bopanna ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Retinoic Acid ◽  
Crucial Role ◽  
Intestinal Inflammation ◽  
Γδ T Cells ◽  
Inflammatory Conditions ◽  
Invariant T Cells ◽  
Active Disease

Abstract Background All-trans retinoic acid (RA) plays a crucial role in promoting Foxp3+ Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN) γ and interleukin (IL)-17 differentiation in vitro. Methods In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFNγ, Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and γδ T cells) in patients with ulcerative colitis in remission or with active inflammation. Results This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFNγ in tissue CD4+, CD8+, mucosal associated invariant T+ cells, and γδ + T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL-17, IFNγ) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers.

Sulphasalazine and Derivatives, Natural Killer Activity and Ulcerative Colitis

1985 ◽  
Vol 69 (2) ◽  
pp. 177-184 ◽  
Author(s):  
P. R. Gibson ◽  
D. P. Jewell
Keyword(s):  
Ulcerative Colitis ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Activity ◽  
Aminosalicylic Acid ◽  
Lipoxygenase Inhibitor ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity

1. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), sulphapyridine and azodisalicylic acid (ADS) in vitro on the natural killer (NK) activity of peripheral blood mononuclear cells (MNC) have been examined and compared with those of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the cyclooxygenase inhibitor, indomethacin. 2. Sulphasalazine, sulphapyridine and ADS inhibited NK activity with 50% inhibitory concentrations (IC50) of 0.7, 2.5 and 4.0 mmol/l respectively. The effect was rapidly reversible. In contrast, 5-ASA minimally inhibited NK activity at 50 mmol/l only. 3. NDGA potently inhibited NK activity (IC50 27 μmol/l) but this was only partly reversible in short term incubations. Indomethacin had no effect at concentrations less than those inhibiting cyclo-oxygenase activity (1-10 μmol/l) but potently and reversibly inhibited NK activity at or above 25 μmol/l. 4. The inhibitory effects observed were unlikely to be due to direct toxicity of effector cells as 5-ASA, sulphapyridine and ADS had no effect on the viability of peripheral blood MNC, whereas NDGA and indomethacin lysed MNC only at maximal concentrations tested. Though sulphasalazine produced MNC lysis at and above 1 mmol/l, the rapid reversibility of the inhibition of NK activity at 1 mmol/l suggested that lysis of NK cells contributed little to the suppressive effect at this concentration. 5. The disparity of the therapeutic efficacy and effects on NK activity of sulphasalazine and its derivatives in vitro may suggest that NK activity is not a major pathogenic mechanism in ulcerative colitis. Any inhibitory effect on cellular immune function of indomethacin does not necessarily reflect an effect of cyclo-oxygenase inhibition.

scholarly journals The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection

2021 ◽  
Author(s):  
Ling Zhu ◽  
Audrey I.S. Andersen-Civil ◽  
Laura J. Myhill ◽  
Stig M. Thamsborg ◽  
Witold Kot ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Host Responses ◽  
Mucosal Inflammation ◽  
Enteric Infection ◽  
Intestinal Epithelial ◽  
Mesenteric Lymph Nodes

AbstractPhytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA significantly down-regulates transcriptional pathways connected to inflammation in the small intestine of mice. During infection with the enteric helminth Heligomosomoides polygyrus, CA-treated mice displayed higher growth rates and less worms, concomitant with altered T-cell populations in mesenteric lymph nodes. Furthermore, infection-induced changes in gene pathways connected to cell cycle and mitotic activity were counteracted by CA. Mechanically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Thus, CA down-regulates inflammatory pathways in the intestinal mucosa and regulates host responses to enteric infection. These properties appear to be largely independent of the gut microbiota and instead connected to CA’s ability to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.

scholarly journals The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Long He ◽  
Shuting Wen ◽  
Zhuotai Zhong ◽  
Senhui Weng ◽  
Qilong Jiang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Side Effects ◽  
Interaction Analysis ◽  
Synergistic Effects ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Aminosalicylic Acid

Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA.Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments.Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone.Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.

scholarly journals IMPORTANCE OF NANOCARRIERS AND PROBIOTICS IN THE TREATMENT OF ULCERATIVE COLITIS

2021 ◽  
pp. 77-85
Author(s):  
VANDANA THAKUR ◽  
BHUPENDRA SINGH ◽  
ANKITA SHARMA ◽  
NISHA KUMARI ◽  
INDER KUMAR ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Side Effects ◽  
Wide Spectrum ◽  
Gastrointestinal Diseases ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Bowel Distension ◽  
Inflammatory Reactions ◽  
Therapeutic Goals

Ulcerative colitis (UC) is an inflammatory chronic disease primarily affecting the colonic mucosa; the extent and severity of colon involvement are variable. Ulcerative colitis is identified by mucus diarrhea, tenesmus, bowel distension, and anemia. 5-aminosalicylic acid drugs, steroids, and immune suppressants are used for the therapy of ulcerative colitis. The mainchallenges in the management of thediseaseare drug-related side-effects and local targeting. To overcome these challengesprobiotics and micro and Nanoparticulate systemauspiciousapproaches to overcome drug-related adverse side effects and local targeting.Upon ingestion, the probiotics can result in beneficial health effects. Probiotics and micro and nanoparticulate approaches for suitable targeting and overcome the drug-associated side effect. Probiotics are mainly used as gut modulators but are also nowadays explored for their use in ulcerative colitis.The current therapeutic goals are to achieve clinical remission along with mucosal healing, avoidance of complications such as side effects of the drug and to improve the quality of life. The use of probiotics to increase the health of the intestine and used to block or manage intestinal disorders. They may prevent the induction of inflammatory reactions. Probiotics must be inspected for efficacy in the prevention and management of a wide spectrum of gastrointestinal diseases, like antibiotic-associated diarrhea.Micro and Nanoparticulate drug delivery system has been achieving huge importance for targeting of the drug to colon locally at a controlled and sustained rate.

scholarly journals Efficacy of quercetin derivatives in prevention of ulcerative colitis in rats

2013 ◽  
Vol 6 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Ruzena Sotnikova ◽  
Viera Nosalova ◽  
Jana Navarova
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Reductase Activity ◽  
Antioxidant Properties ◽  
Control Group ◽  
Wall Thickening ◽  
Quercetin Derivatives

Abstract Reactive oxygen species has been implicated to contribute significantly to tissue injury associated with ulcerative colitis. Thus compounds with antioxidant properties could be potential therapeutic agents in this disease. Flavonoid compounds are known to possess antioxidative and antiinflammatory properties. Two derivatives of the flavonoid quercetin (Q), chloronaphthoquinone quercetin (CNC) and monochloropivaloyl quercetin (MCP), showed improved antioxidant properties and moreover, they efficiently inhibited aldose reductase activity in vitro. The aim of the work was to test the potential efficacy of quercetin and these synthetic derivatives in vivo in prevention of intestinal inflammation during ulcerative colitis in rats. Colitis was induced by intracolonic administration of acetic acid (4% solution). The control group received the same volume of saline. The vehicle dimethyl sulfoxide (DMSO) and the drugs Q, CNC or MCP were administered orally two hours and then one hour before the acetic acid or saline instillation. After 48 hours, the animals were sacrificed and the colon was weighed, measured and scored for visible damage. Acetic acid triggered an intense inflammatory response of the colon, characterised by haemorrhage, ulceration and bowel wall thickening. From the drugs tested, only CNC (2 × 50 mg/kg) effectively depressed inflammatory damage of the colon. The mechanism of this beneficial effect remains to be elucidated.

scholarly journals The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Dorit Moradov ◽  
Helena Shifrin ◽  
Efrat Harel ◽  
Mirela Nadler-Milbauer ◽  
Marta Weinstock ◽  
...  
Keyword(s):  
Rat Model ◽  
Local Treatment ◽  
Experimental Colitis ◽  
Inflammatory Activity ◽  
Mucosal Inflammation ◽  
Activated Macrophages ◽  
Aminosalicylic Acid ◽  
Anti Inflammatory

A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and testedin vitro(LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity andin vivo(DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFαand IL-1β. It was found that P-5 decreased the levels of TNFαand the tested proinflammatory cytokines and chemokines in LPS-activated macrophages. In the colitis-induced rat model, P-5 was effective locally in reducing mucosal inflammation. This activity was equal to the activity of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be used for the local treatment of IBD (e.g., with the aid of colon-specific drug platforms). Its mode of action involves inhibition of the phosphorylation of MAPK ERK but not of p38 and had no effect on IκBα.

Sign in / Sign up

Export Citation Format

Share Document