Prevention Of Ulcerative Colitis Research Articles

Polyphenol Extracts from Ziziphus jujuba Mill. "Junzao" Attenuates Ulcerative Colitis by Inhibiting the NLRP3 and MAPKs Signaling Pathways and Regulating Gut Microbiota Homeostasis in Mice.

Polyphenols are the major active substances in red jujube fruit, and their anti-inflammatory and antioxidant activities suggest their potential utility in the prevention of ulcerative colitis (UC). In this study, the effect of polyphenol extracts from red jujube (Ziziphus jujuba Mill. "Junzao") (PERJ) on the dextron sulfate sodium (DSS)-induced UC mice is investigated. The result shows that PERJ effectively improves clinical symptoms, including food and water intake, the disease activity insex (DAI) and spleen index, and routine blood levels, and alleviates the shortening of the colon, in mice with DSS-induced UC. Meanwhile, PERJ remarkably decreases the expression of proinflammatory factors. Moreover, PERJ repairs intestinal barrier damage by increasing the expression level of mucin 2 and mucin 3, and the result is also confirmed in the histological assessment. Besides, the expression levels of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and mitogen-activated protein kinase cascade (MAPKs) signaling pathway-related proteins are inhibited by the PERJ administration. Finally, 16S rRNA sequencing analyses reveal that PERJ reverses intestinal microbiota dysbiosis by enhancing the abundance of Firmicutes and decreasing that of Proteobacteria and Bacteroidetes. PERJ probably inhibits the development of UC by suppressing the NLRP3 and MAPKs signaling pathways and regulating gut microbiota homeostasis, and can be considered as a potential resource for preventing UC.

Recent Updates on the Therapeutics Benefits, Clinical Trials, and Novel Delivery Systems of Chlorogenic Acid for the Management of Diseases with a Special Emphasis on Ulcerative Colitis.

Ulcerative colitis (UC) is a multifactorial disorder of the large intestine, especially the colon, and has become a challenge globally. Allopathic medicines are primarily available for the treatment and prevention of UC. However, their uses are limited due to several side effects. Hence, an alternative therapy is of utmost importance in this regard. Herbal medicines are considered safe and effective for managing human health problems. Chlorogenic acid (CGA), the herbal-derived bioactive, has been reported for pharmacological effects like antiinflammatory, immunomodulatory, antimicrobial, hepatoprotective, antioxidant, anticancer, etc. This review aims to understand the antiinflammatory and chemopreventive potential of CGA against UC. Apart from its excellent therapeutic potential, it has been associated with low absorption and poor oral bioavailability. In this context, colon-specific novel drug delivery systems (NDDS)are pioneering to overcome these problems. The pertinent literature was compiled from a thorough search on various databases such as ScienceDirect, PubMed, Google Scholar, etc., utilizing numerous keywords, including ulcerative colitis, herbal drugs, CGA, pharmacological activities, mechanism of actions, nanoformulations, clinical updates, and many others. Relevant publications accessed till now were chosen, whereas non-relevant papers, unpublished data, and non-original articles were excluded. The present review comprises recent studies on pharmacological activities and novel drug delivery systems of CGA for managing UC. In addition, the clinical trials of CGA against UC have been discussed.

Preventive Anti-inflammatory Effects of Apocynin on Acetic Acid-Induced Colitis in Rats.

Ulcerative colitis is an inflammatory bowel disease with a complex aetiology characterised by abnormal immune responses and oxidative stress-induced tissue injury. Inflammatory cells play an important role in the progression of this pathology through the overproduction of reactive oxygen species (ROS) from various sources including the NADPH oxidases (NOXs). The aim of this study was to investigate the preventive effect of apocynin, a natural antioxidant molecule and a selective inhibitor of NOXs, on acetic acid (AA)-induced ulcerative colitis in rats. Our results first confirmed that apocynin has a high free radical scavenging capacity as well as a potent iron chelating ability. Oral pretreatment of rats with apocynin (200mg/kg and 400mg/kg) for 7days prior to AA-induced colitis suppressed the increase in pro-oxidant markers in colonic homogenates and preserved colonic cytoarchitecture from acetic acid-induced damage. Oral administration of apocynin (200mg/kg and 400mg/kg) also reduced several systemic inflammatory markers such as alkaline phosphatase, iron, pro-inflammatory cytokines, C-reactive protein and myeloperoxidase. This study shows that apocynin protects rats from acetic acid-induced colonic inflammation and suggests that apocynin may have a promising beneficial effect in the prevention of ulcerative colitis.

The alleviating effect and mechanism of GLP-1 on ulcerative colitis.

Ulcerative Colitis (UC) is a major type of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. The incidence and prevalence of UC is increasing worldwide. The global burden of UC, which can substantially reduce quality of life, is clearly increasing. These data highlight the need for research into prevention of UC and innovations in health-care systems to manage this complex and costly disease. Glucagon-like peptide-1 (GLP-1), a new antidiabetic drug, is used to treat Type 2 Diabetes Mellitus (T2DM). Accumulating evidence suggests that GLP-1 has additional roles other than glucose-lowering effects. Despite the abundance of GLP-1 research, studies in UC have been less consistent, especially body weight; for example, body weight, colon length, colon injury score, intestinal microbiota, remain to be studied further. To date, the molecular mechanism of the protective effect of GLP-1 on UC remains obscure. The effect of GLP-1 was studied by using a dextran sulfate sodium (DSS)-induced colitic mice and lipopolysaccharide (LPS) treated RAW264.7 cells (macrophage cell line) under in vivo and in vitro conditions, respectively. Our results indicate that GLP-1 significantly relieves ulcerative colitis as it represses the production of proinflammatory mediators. In addition, GLP-1 blocks the activation of the protein kinase B (AKT)/nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC.

Panax quinquefolius polysaccharides ameliorate ulcerative colitis in mice induced by dextran sulfate sodium.

This study aimed to investigate the ameliorative effect of the polysaccharides of Panax quinquefolius (WQP) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice and to explore its mechanism. Male C57BL/6J mice were randomly divided into the control group (C), model group (DSS), positivecontrol mesalazine (100 mg/kg, Y) group, and low (50 mg/kg, L), medium (100 mg/kg, M) and high dose (200 mg/kg, H) of WQP groups. The UC model was induced by free drinking water with 2.5% DSS for 7 days. During the experiment, the general condition of the mice was observed, and the disease activity index (DAI) was scored. The conventional HE staining was used to observe pathological changes in mice's colon, and the ELISA method was used to detect the levels of interleukin-6 (IL-6), IL-4, IL-8, IL-10, IL-1β and tumor necrosis factor-α (TNF-α) in mice's colon. The changes in gut microbiota in mice were detected by high-throughput sequencing; the concentration of short-chain fatty acids (SCFAs) was determined by gas chromatography; the expression of related proteins was detected by Western blot. Compared with the DSS group, the WQP group showed a significantly lower DAI score of mice and an alleviated colon tissue injury. In the middle- and high-dose polysaccharides groups, the levels of pro-inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the colonic tissue were significantly decreased (P<0.05), while the levels of IL-4 and IL-10 were significantly increased (P<0.05). The 16S rRNA gene sequencing results showed that different doses of WQP could regulate the composition and diversity of gut microbiota and improve its structure. Specifically, at the phylum level, group H showed an increased relative abundance of Bacteroidetes and a decreased relative abundance of Firmicutes compared with the DSS group, which was closer to the case in group C. At the family level, the relative abundance of Rikenellaceae in L, M and H groups increased significantly, close to that in group C. At the genus level, the relative abundance of Bacteroides, Shigella and Oscillospira in the H group increased significantly, while that of Lactobacillus and Prevotella decreased significantly. The high-dose WQP group could significantly increase the contents of acetic acid, propionic acid, butyric acid, and total SCFAs. Different doses of WQP also increased the expression levels of tight junction proteins ZO-1, Occludin and Claudin-1. To sum up, WQP can regulate the gut microbiota structure of UC mice, accelerate the recovery of gut microbiota, and increase the content of Faecal SCFAs and the expression level of tight junction proteins in UC mice. This study can provide new ideas for the treatment and prevention of UC and theoretical references for the application of WQP.

Saccharina japonica Ethanol Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis via Reshaping Intestinal Microenvironment and Alleviating Inflammatory Response.

Saccharina japonica belongs to brown macro-alga with various potential health benefits; its antioxidant and anti-inflammatory activities indicate the potential to improve inflammatory bowel diseases. Here, the potential anti-colitis effect of Saccharina japonica extract (SJE) was evaluated on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57B/L6 mice. The mice were treated with mesalazine (MES) and various doses of SJE by gavage for 14 days. Results showed that both MES and SJE treatment decreased the disease activity index scores, relieving the short colon. SJE increased the occludin and zonula occludens-1 levels, and the beneficial effects were better than MES. MES and SJE exerted similar effects in decreasing inflammatory cytokines and oxidative stress. Moreover, SJE reshaped the intestinal microbiota by increasing α-diversity and reducing plenty of harmful bacteria. Dietary SJE was significant to relieving the reduction in short-chain fatty acids. The results revealed the protective effect of SJE on colitis and potential mechanisms, which is important for the rational use of SJE in UC prevention.

Therapeutic effects and the impact of statins in the prevention of ulcerative colitis in preclinical models: A systematic review.

Ulcerative Colitis (UC) is a chronic inflammatory condition of the large intestines. Although great advances have been made in the management of the disease with the introduction of immunomodulators and biological agents, the treatment of UC is still a challenge. So far, there are no definitive therapies for this condition. Statins are potent inhibitors of cholesterol biosynthesis, possess beneficial effects on primary and secondary prevention of coronary heart disease, and have high tolerability and safety. Furthermore, they may have potential roles in UC management due to their possible anti-inflammatory, immunomodulatory, and antioxidant activities. This systematic review aimed to gather information about the potential benefits of statins for managing UC, reducing inflammation and disease remission in animal models. A systematic search was performed in PubMed/MEDLINE, Scopus, Web of Science, and Virtual Health Library. The data were summarized in tables and critically analyzed. After the database search, 21 relevant studies were identified as eligible for this review. Preclinical studies using several colitis-induction protocols and various statins have shown numerous beneficial effects of these drugs on reducing disease activity, inflammatory profile, oxidative stress, and general clinical parameters of animals with UC. These studies revealed the potential of statins against the pathogenesis of UC. However, there are still important gaps regarding the molecular mechanisms of action of statins, leading to some contradictory results. Thus, more research on the molecular level to determine the roles of statins in colitis should be carried out to elucidate their mechanisms of action.

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis

To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1.

The improved effect and its mechanism of phytic acid on DSS-induced UC mice

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with an unknown etiology that is currently difficult to treat effectively. Phytic acid, a natural compound found in high-fiber foods, such as grains, has been shown to have many pharmacological functions, such as anti-inflammatory and blood-milk barrier maintenance. Our study investigated the effects of phytic acid on UC as well as the underlying mechanisms. We found that phytic acid ameliorated weight loss, shortened colon length, increased clinical scores, and decreased the release of pro-inflammatory factors (Il-1β, Il-6, and TNF-α) in mice with DSS-induced UC. Phytic acid was also found to protect intestinal barrier integrity in mice with UC by maintaining the expression of tight junction proteins (occludin, claudin-3 and ZO-1) and mucin-2. In LPS-stimulated Caco-2 cells, phytic acid significantly inhibited the upregulation of pro-inflammatory factors and the downregulation of tight junction proteins. Further experimental results confirmed that phytic acid inhibits the activation of the AKT/NF-κB signaling pathway in both mice with UC and Caco-2 cells. To sum up, this study proved that phytic acid has a beneficial ameliorative effect on mice with DSS-induced UC, suggesting that it may be used to develop functional foods for the treatment or prevention of UC.

Prevention of Ulcerative Colitis by Autologous Metabolite Transfer from Colitogenic Microbiota Treated with Lipid Nanoparticles Encapsulating an Anti-Inflammatory Drug Candidate.

Modulating the gut microbiota composition is a potent approach to treat various chronic diseases, including obesity, metabolic syndrome, and ulcerative colitis (UC). However, the current methods, such as fecal microbiota transplantation, carry a risk of serious infections due to the transmission of multi-drug-resistant organisms. Here, we developed an organism-free strategy in which the gut microbiota is modulated ex vivo and microbiota-secreted metabolites are transferred back to the host. Using feces collected from the interleukin-10 (IL-10) knockout mouse model of chronic UC, we found that a drug candidate (M13)-loaded natural-lipid nanoparticle (M13/nLNP) modified the composition of the ex vivo-cultured inflamed gut microbiota and its secreted metabolites. Principal coordinate analysis (PCoA) showed that M13/nLNP shifted the inflamed microbiota composition toward the non-inflamed direction. This compositional modification induced significant changes in the chemical profiles of secreted metabolites, which proved to be anti-inflammatory against in vitro-cultured NF-κβ reporter cells. Further, when these metabolites were orally administered to mice, they established strong protection against the formation of chronic inflammation. Our study demonstrates that ex vivo modulation of microbiota using M13/nLNP effectively reshaped the microbial secreted metabolites and that oral transfer of these metabolites might be an effective and safe therapeutic approach for preventing chronic UC.

Prevention of ulcerative colitis by Huangqin decoction: reducing the intestinal epithelial cell apoptosis rate through the IFN-γ/JAK/ETS signalling pathway

Context Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease that is closely related to inflammation and apoptosis. The traditional Chinese medicine compound preparation Huangqin decoction (HQD) has been widely used in the clinical treatment of UC, but the specific mechanism of its function is still inconclusive. Objective To explore the pathogenesis of UC based on the IFN-γ/JAK/ETS signalling pathway, and to clarify the biological mechanism of HQD. Materials and methods Forty 8-week-old male C57BL/6 mice were randomly divided into four groups: normal control, model, model + salazosulfapyridine group (500 mg/kg, p.o., pd) and model + HQD (9.1 g/kg, p.o., pd). Using Dextran sulphate sodium (DSS) salt (2.5%, p.o.)+high-fat diet + hot and humid environment to build a mouse model of UC. One month later, the changes of colon morphology, serum inflammatory factors, intestinal epithelial cell apoptosis and IFN-γ/JAK/ETS signalling pathway related protein changes in mice were observed. Results Compared with the model group, HQD significantly reduced the pathological score of the model mice’s colon (2.60 ± 0.25 vs. 4.80 ± 0.37), and reduced the serum IFN-γ (200.30 ± 8.45 vs. 413.80 ± 6.97) and other inflammatory factors, and reduced intestinal epithelial cell apoptosis (24.85 ± 4.87 vs. 214.90 ± 39.21). In terms of mechanism, HQD down-regulated IFN-γ/JAK/ETS signalling pathway related proteins in colon tissue of UC model mice. Conclusions These data indicate that HQD can improve UC by reducing intestinal inflammation and apoptosis, providing experimental evidence for the wide application of HQD in clinical practice of UC.

Prevention of Ulcerative Colitis in Mice by Sweet Tea (Lithocarpus litseifolius) via the Regulation of Gut Microbiota and Butyric-Acid-Mediated Anti-Inflammatory Signaling.

Sweet tea (Lithocarpus litseifolius [Hance] Chun) is a new resource for food raw materials, with plenty of health functions. This study aimed to investigate the preventive effect and potential mechanism of sweet tea extract (STE) against ulcerative colitis (UC). Briefly, BABL/c mice were treated with STE (100 and 400 mg/kg) for 2 weeks to prevent 3% dextran sulfate sodium (DSS)-induced UC. It was found that STE supplementation significantly prevented DSS-induced UC symptoms; suppressed the levels of pro-inflammatory mediators, such as myeloperoxidase and tumor necrosis factor-α; increased the levels of anti-inflammatory cytokines; and up-regulated the expression of tight junction proteins (Zonula occludens-1 and Occludin). STE also altered the gut microbiota profile of UC mice by increasing Bacteroidetes, Lactobacillus, Akkermansia, Lachnospiraceae_NK4A136_group, and Alistipes and inhibiting Firmicutes, Proteobacteria, and Helicobacter, accompanied by a significant increase in the content of butyric acid. Moreover, STE increased the expression of G-protein-coupled receptor (GPR) 43 and GPR109A and inhibited the expression of histone deacetylase 3 (HDAC3) and nuclear factor-κB p65 (NF-κB p65) in the colon. In conclusion, this study indicated that STE has a good preventive effect on UC by regulating gut microbiota to activate butyrate-GPR-mediated anti-inflammatory signaling and simultaneously inhibit HDAC3/NF-κB inflammatory signaling.

Nicotine Oral Administration Attenuates DSS-Induced Colitis Through Upregulation of Indole in the Distal Colon and Rectum in Mice.

Nicotine affects the gastrointestinal environment and modulates ulcerative colitis (UC). However, the associations among nicotine, gut metabolites, and UC are still largely unknown. We investigated whether orally administered nicotine affected gut metabolites and dextran sodium sulfate (DSS)-induced colitis. C57BL/6 male mice were orally administered nicotine solution in drinking water prior to inducing DSS-induced colitis. Short-chain fatty acids (SCFAs) and indole in gut contents and fecal samples were measured by GC-MS and hydroxylamine-based indole assays, respectively. Oral administration of nicotine increased indole concentration in feces, but, in contrast, SCFA values did not differ with nicotine administration. Indole levels were increased in the distal colon and rectum but not in the cecum and proximal colon. DSS-induced colitis was less severe clinically and histological changes were minimal in the rectum of orally nicotine-administered mice compared to mice drinking only water. 16S rRNA microbiome on the feces revealed an increasing in Clostridium and Porphyromonas in nicotine-administered mice. In conclusion, nicotine administration was associated with increased indole levels in the distal colon and rectum and attenuated DSS-induced colitis. Oral administration of nicotine may play a potential role in indole upregulation and prevention of UC.

Preventive and Prebiotic Effect of α-Galacto-Oligosaccharide against Dextran Sodium Sulfate-Induced Colitis and Gut Microbiota Dysbiosis in Mice.

β-Galacto-oligosaccharide (β-GOS) showed great potential in ulcerative colitis (UC) adjuvant therapy. Herein, the preventive and prebiotic effect of enzymatic-synthesized α-linked galacto-oligosaccharide (α-GOS) was investigated in dextran sodium sulfate-induced colitis and gut microbiota dysbiosis mice. Compared with β-GOS, the α-GOS supplement was more effective in improving preventive efficacy, promoting colonic epithelial barrier integrity, and alleviating inflammation cytokines. Moreover, the activation of the NOD-like receptor (NLR) family member NLRP3 inflammasome-mediated inflammation was significantly inhibited by both α-GOS and β-GOS. Gut microbiota analysis showed that α-GOS treatment reshaped the dysfunctional gut microbiota. The subsequent Spearman's correlation coefficient analysis indicated that these gut microbiota changes were significantly correlated with the inflammatory parameters. These results suggested that the enzymatic-synthesized α-GOS is a promising therapeutic agent in UC prevention and adjuvant treatment by maintaining intestinal homeostasis.

Design and formulation of Eudragit-coated zein/pectin nanoparticles for the colon delivery of resveratrol

Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin with beneficial effects on human health, including the treatment and prevention of ulcerative colitis and cancer. This work proposes the formulation and characterization of new nanoparticles (NPs) for the specific colon delivery of RSV. RSV was encapsulated in zein (Z) NPs, coated by a hydrophilic pectin (P) shell to significantly increase the dissolution rate of RSV in aqueous environments. Since the dissolved drug was strongly degraded in a simulated gastrointestinal tract, the ZP-NPs were coated with Eudragit S 100. The coated particles, even if aggregated, had a spherical morphology with diameters in the 100–200 nm range. Release studies of RSV from the ZP coated NPs evidenced their potential ability to induce a specific colon delivery of this drug so that this formulation can be proposed to enrich natural food products to enhance their preventive and therapeutic effects in the lower GI tract.

Galangin Protects against Symptoms of Dextran Sodium Sulfate-induced Acute Colitis by Activating Autophagy and Modulating the Gut Microbiota.

Galangin is a natural flavonoid that has been reported to provide substantial health benefits. Nevertheless, little is known about the potential effects of galangin against inflammatory bowel diseases. Here, an in vivo study was performed to investigate the preventive effects of galangin against dextran sulphate sodium (DSS)-induced acute murine colitis, which mimics the symptoms of human ulcerative colitis (UC). Pre-treatment with galangin (15 mg/kg, p.o.) resulted in a significant decreased in the macroscopic signs of DSS-induced colitic symptoms, including a decreased disease activity index, prevention of the colon length shortening, and alleviation of the pathological changes occurring in the colon. Colonic pro-inflammatory mediators, including tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6, as well as myeloperoxidase activities were decreased following galangin pre-treatment when compared with the DSS control group. Moreover, galangin pre-treatment significantly increased the expressions of autophagy-related proteins and promoted the formation of autophagosome in the colon. Galangin pre-treatment increased the diversity of the gut microbiota, and this was accompanied by increased levels of short-chain fatty acids. These observed changes could involve the modulating effects conferred by galangin in relation to some specific bacteria populations, including the recovery of Lactobacillus spp., and increased Butyricimonas spp. Overall, these results support the use of galangin in the prevention of UC.

Omega Fatty Acids and Inflammatory Bowel Diseases: An Overview

Inflammatory bowel diseases (IBD) are chronic, inflammatory processes that affect the gastrointestinal tract and are mainly represented by ulcerative colitis (UC) and Crohn’s disease (CD). Omega 3 (ω3) fatty acids (eicosapentanoic acid and docosahexaenoic acid) show an indispensable role in the inflammatory processes and, for these reasons, we aimed to review the effects of these acids on UC and CD. Databases such as PUMED and EMBASE were searched, and the final selection included fifteen studies that fulfilled the inclusion criteria. The results showed that ω3 fatty acids reduce intestinal inflammation, induce and maintain clinical remission in UC patients, and are related with the reduction of proinflammatory cytokines, decrease disease activity and increase the quality of life of CD patients. Furthermore, the consumption of these fatty acids may be related to a reduced risk of developing IBD. Many studies have shown the beneficial effects of ω3 as adjunctive in the treatment or prevention of UC or CD. Nevertheless, most were performed with a small number of patients and there are many variations in the mode of consumption, the type of food or the type of formulation used. All these factors substantially interfere with the results and do not allow reliable comparisons.

Schisandrin B prevents ulcerative colitis and colitis-associated-cancer by activating focal adhesion kinase and influence on gut microbiota in an in vivo and in vitro model

Colitis-associated cancer (CAC) has a close relationship with ulcerative colitis (UC). Therapeutic effect of Schisandrin B (SchB) on UC and CAC remains largely unknown. We investigated the preventative effect of SchB on the dextran sulphate sodium (DSS) model of UC and azoxymethane (AOM)/DSS model of CAC. Furthermore, focal adhesion kinase (FAK) activation and influence on commensal microbiota are important for UC treatment. Impact on FAK activation by SchB in UC development was evaluated in vivo and vitro. We also conducted 16S rRNA sequencing to detect regulation of gut microbiota by SchB. Enhanced protection of intestinal epithelial barrier by SchB through activating FAK contributed to protective effect on colon for the fact that protection of SchB can be reversed by inhibition of FAK phosphorylation. Furthermore, influence on gut microbiota by SchB also played a significant role in UC prevention. Our results revealed that SchB was potent to prevent UC by enhancing protection of intestinal epithelial barrier and influence on gut microbiota, which led to inhibition of CAC. SchB was potential to become a new treatment for UC and prevention of CAC.

Ameliorative effects of riboflavin on acetic acid-induced colonic injury in rats.

Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25mg/kg per day; p.o.) for 3days. The control and AA groups received saline (1mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100mg/kg per day; p.o.) for 3days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P<.05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-β1 in the AA group were elevated in all the treatment groups (P<.05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

Optimization of Aqueous Extraction and Biological Activity of Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model.

Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave-assisted aqueous Harpagophytum extract (1-1000μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis. In this context, we evaluated the effects on C2C12 and HCT116 viability, and on LPS-induced production of serotonin (5-HT), tumor necrosis factor (TNF)-α, prostaglandin (PG)E2 and 8-iso-prostaglandin (8-iso-PG)F2α . Harpagophytum extract was well tolerated by C2C12 cells, while reduced HCT116 colon cancer cell viability. On the other hand, Harpagophytum extract reduced H2 O2 -induced (1mM) reactive oxygen species (ROS) production, in both cell lines, and inhibited LPS-induced colon production of PGE2 , 8-iso-PGF2α , 5-HT and TNFα. Concluding, we demonstrated the efficacy of a microwave-assisted Harpagophytum aqueous extract in modulating the inflammatory, oxidative stress and immune response in an experimental model of inflammatory bowel diseases (IBD), thus suggesting a rational use of Harpagophytum in the management and prevention of ulcerative colitis in humans. Copyright © 2017 John Wiley & Sons, Ltd.