scholarly journals The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Qing Zhou ◽  
Wei-xin Zhang ◽  
Zong-qi He ◽  
Ben-sheng Wu ◽  
Zhao-feng Shen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Activity Index ◽  
Disease Activity Index ◽  
Mucosal Barrier ◽  
Protective Mechanism ◽  
Inflammatory Signaling ◽  
Anti Inflammatory ◽  
Dehydrocostus Lactone ◽  
Inflammatory Effect

Background. Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. Methods. The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1β, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α-defensins) by ELISA or qRT-PCR. Results. DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1β, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), downregulated IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), repaired the key colorectal mucosal barrier protein-MUC2, and inhibited the downstream pathway (XBP1s and α-defensin). Conclusions. DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

scholarly journals Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 794
Author(s):  
Chenxi Luo ◽  
Chenglong Huang ◽  
Lijuan Zhu ◽  
Li Kong ◽  
Zhihang Yuan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Antioxidant Capacity ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Betulinic Acid ◽  
Molecular Mechanisms ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Trichothecene Mycotoxin ◽  
Anti Inflammatory

T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1β, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.

scholarly journals Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy

2018 ◽  
Vol 90 (2) ◽  
pp. 47-52 ◽  
Author(s):  
O V Knyazev ◽  
A V Kagramanova ◽  
N A Fadeeva ◽  
A A Lishchinskaya ◽  
O N Boldyreva ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Cytokines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Activity Index ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Crohn's disease (CD) is a chronic, recurring disease of the gastrointestinal tract of unclear etiology. One of the new approaches to CD therapy is the use of the possibilities of stem cells, in particular, mesenchymal stromal cells (MSCs). Currently, the use of MSC in clinical practice for the treatment of chronic inflammatory and autoimmune diseases is being studied in patients who receive concomitant therapy with other immunomodulatory medications. Aim. To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA). Materials and methods. The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received anti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1β, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1β (TGF-1β), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy. Results. The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of patients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro - and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1β - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pronounced anti-inflammatory effect. Conclusion. Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

scholarly journals Alleviative Effects of Exopolysaccharide Produced by Lactobacillus helveticus KLDS1.8701 on Dextran Sulfate Sodium-Induced Colitis in Mice

2021 ◽  
Vol 9 (10) ◽  
pp. 2086
Author(s):  
Yin Liu ◽  
Shujuan Zheng ◽  
Jiale Cui ◽  
Tingting Guo ◽  
Jingtao Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Lactobacillus Helveticus ◽  
Mucosal Barrier ◽  
Microbiota Composition ◽  
Mucosal Barrier Function ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

Ulcerative colitis (UC) is a non-specific chronic inflammatory disease with lesions located in the colon and rectum. The aim of this study was to evaluate the anti-inflammatory effects of exopolysaccharide-1 (EPS-1) isolated by L. helveticus KLDS1.8701 on UC. The anti-inflammatory effects of EPS-1 were studied using dextran sulphate sodium (DSS)-induced UC model. In vivo results showed that EPS-1 administration significantly ameliorated weight loss, colon shortening, disease activity index (DAI) score, myeloperoxidase (MPO) activity, and colon tissue damage. In addition, EPS-1 administration significantly decreased the levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. Meanwhile, EPS-1 administration significantly up-regulated the expression of tight junction proteins and mucin. Furthermore, EPS-1 administration modulated gut microbiota composition caused by DSS and increased the short-chain fatty acids (SCFAs) levels. Collectively, our study showed the alleviative effects of EPS- isolated by L. helveticus KLDS1.8701 on DSS-induced UC via alleviating intestinal inflammation, improving mucosal barrier function, and modulating gut microbiota composition.

scholarly journals Evaluation of Anti-Inflammatory Effect of Wedelolactone on Indomethacin Induced Colitis in Rats: Involvement of IL-6/STAT3 Pathway

2021 ◽  
Vol 12 (3) ◽  
pp. 2813-2825
Keyword(s):  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Group Iv ◽  
Rat Colon ◽  
Group Iii ◽  
Group I ◽  
Intestinal Immune System ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The present study was carried out to study coumestan derivative wedelolactone in Indomethacin-induced enterocolitis in rats. Wistar rats were randomly divided into three groups containing six animals per group. Group I served as normal control. Group II, Group III & Group IV receive 7.5 mg/kg, s.c, indomethacin on two consecutive days. Group III and Group IV have received a wedelolactone dose of 50 mg/kg, and 100 mg/kg per oral, respectively, for 14 days after the induction with indomethacin. The protective effect was measured based on intestinal parameters of the disease activity index, colitis score, myeloperoxidase (MPO) activity in the colon. The inflammation biomarkers were quantified by ELISA in the rat colon. Further, activity was ascertained by histopathology. Pro-inflammatory functions IL-1a, IL-1b, IL-2, TNF, INFγ, STAT3, and CCL-5 play an important role in the variation of the intestinal immune system. Wedelolactone showed significantly decreased Disease activity index, Colitis score, Myeoloperoxidase activity. Expression of pro-inflammatory was increased in indomethacin-induced groups and was significantly suppressed in animals administered with wedelolactone at 50 mg/kg & 100 mg/kg dose (p<0.01 & p<0.001). Histological reports also revealed that treated groups have comparatively less damage than that of the induced groups. We concluded that wedelolactone showed an anti-inflammatory effect by downregulation of the IL-6/STAT3 inflammatory signaling pathway and the equilibrium production of pro-inflammatory cytokines.

scholarly journals Salvia miltiorrhiza Ameliorates Disease Progression in Dextran-Sodium-Sulfate Induced Colitis in Mice

2021 ◽  
Author(s):  
Juan Chen ◽  
Danyu Chen ◽  
Lu Cheng ◽  
YongKang Yang ◽  
Weidong Gu ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Activity Index ◽  
Salvia Miltiorrhiza ◽  
Disease Activity Index ◽  
Cerebrovascular Diseases ◽  
Dextran Sodium Sulfate ◽  
Inflammatory Factors ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Salvia miltiorrhiza (SM, or Danshen) extract has been approved by China FDA for the treatment of cardiovascular and cerebrovascular diseases owing to its potent anti-inflammatory effects. Whether SM may be used to treat inflammatory bowel disease (IBD) remains elusive. In the current study, Dextran-Sodium-Sulfate (DSS) induced colitis in mice was used as a model of IBD, and SM was given orally for 7 days. SM administration has significantly reduced the disease activity index (DAI) score and weight lost and colon shortening in the DSS-induced colitis mice. The macrophage infiltration was significantly reduced in the SM treatment group. To explore the mechanisms, macrophage processor cell line Raw 264.7 was used to verify the anti-inflammatory effect of SM. SM treatment inhibited lipopolysaccharide (LPS)-induced macrophage activation in RAW264.7 cells and significantly reduced the production of pro-inflammatory factors. The current study provided evidence that oral administration of SM ameliorates pathological deterioration of IBD in mice, and warrants future clinical application of SM for the management of IBD.

scholarly journals Comparative Study of Anti-Inflammatory Effect on DSS-Induced Ulcerative Colitis Between Novel Glycyrrhiza Variety and Official Compendia

2021 ◽  
Vol 11 (4) ◽  
pp. 1545
Author(s):  
Sa-Haeng Kang ◽  
Young-Jae Song ◽  
Yong-Deok Jeon ◽  
Dong-Keun Kim ◽  
Jeong-Hyang Park ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Activity Index ◽  
Clinical Signs ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Fecal Microbiota ◽  
Specific Pattern ◽  
Plant Cultivation ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Glycyrrhizae radix (GR), a plant commonly referred to as licorice, is used as a medicine and food worldwide. However, the utilization of GR from wild areas has caused desertification and a depletion of natural resources. Environmental restrictions and low productivity have limited plant cultivation. For this reason, an improved Glycyrrhiza variety, Wongam (WG), in cultivation and quality has been developed by Korea Rural Development Administration. To evaluate the equivalence of efficacy, several comparative studies between already-registered species and new cultivars have been conducted. This study evaluated the anti-inflammatory effect of WG extracts in a dextran sulfate sodium (DSS)-induced colitis model, in comparison to that of GR extracts. WG extract significantly improved the clinical signs of DSS-induced ulcerative colitis, including disease activity index, body weight loss, and colon length shortening, which was equivalent to the effect of GR. Furthermore, the fecal microbiota was analyzed by terminal restriction fragment length polymorphism. The composition of the fecal microbiota did not show a specific pattern based on experimental groups; however, a tendency toward an increase in the proportion of Lactobacillales was observed. These findings showed an equivalence of efficacy and the possible utilization of WG as a medicinal resource with already-registered species.

scholarly journals The Anti-Inflammatory Effect of Guchangzhixie-Pill by Reducing Colonic EC Cell Hyperplasia and Serotonin Availability in an Ulcerative Colitis Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yong Yang ◽  
Xianwei Zhu ◽  
Yifei Qin ◽  
Guihai Chen ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Tryptophan Hydroxylase ◽  
Activity Index ◽  
Disease Activity Index ◽  
Trinitrobenzene Sulfonic Acid ◽  
Cell Hyperplasia ◽  
Bowel Diseases ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

Ulcerative colitis (UC) is one of the major types of inflammatory bowel diseases (IBD). Abnormal colonic enterochromaffin (EC) cell hyperplasia and serotonin availability have been described in UC. Guchangzhixie-pill (GCZX-pill), a Chinese herbal formula composed of six herbs, is modified based on a traditional formula (Jiechangyan-pill) for inflammatory and ulcerative gastrointestinal disorders. This study aims to investigate the anti-inflammatory effect and the underlying mechanisms of GCZX-pill on trinitrobenzene sulfonic acid- (TNBS-) induced UC in rats. After orally administrating a GCZX-pill to UC rats for 14 days, the results of the inflammation evaluation, such as disease activity index (DAI), macroscopic score (MS), myeloperoxidase (MPO) activity, and other methods, suggested that the GCZX-pill showed remarkable anti-inflammatory results in UC rats. In addition, the abnormal EC cell numbers, colonic tryptophan hydroxylase (TPH) expression, and serotonin (5-HT) contents in TNBS-induced UC rats were significantly reduced by the GCZX-pill. This data demonstrates that the GCZX-pill can attenuate the inflammation in UC rats and the anti-inflammatory effect of the GCZX-pill may be medicated by reducing colonic EC cell hyperplasia and 5-HT availability.

scholarly journals Impressic Acid Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Activating the AMPK/GSK3β/Nrf2 Axis in RAW264.7 Macrophages

2021 ◽  
Vol 22 (2) ◽  
pp. 762
Author(s):  
Gi Ho Lee ◽  
Ji Yeon Kim ◽  
Sun Woo Jin ◽  
Thi Hoa Pham ◽  
Jin Song Park ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.

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