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1.
Article in English | WPRIM | ID: wpr-922575

ABSTRACT

OBJECTIVE@#To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α).@*METHODS@#In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1β and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot.@*RESULTS@#In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1β, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05).@*CONCLUSION@#HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.


Subject(s)
Animals , Colitis, Ulcerative/drug therapy , Dextran Sulfate , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , NF-kappa B , Scutellaria baicalensis , Tumor Necrosis Factor-alpha
2.
Article in Chinese | WPRIM | ID: wpr-887962

ABSTRACT

The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.


Subject(s)
Animals , Colitis , Colitis, Ulcerative/drug therapy , Colon , Dextran Sulfate/toxicity , Disease Models, Animal , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Mice , Mice, Inbred C57BL , Sulfates
3.
Article in Chinese | WPRIM | ID: wpr-878931

ABSTRACT

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.


Subject(s)
Animals , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Colon , Dextran Sulfate/therapeutic use , Drugs, Chinese Herbal , Mice , Molecular Docking Simulation , Plasma
4.
Article in Chinese | WPRIM | ID: wpr-888117

ABSTRACT

This study explored the mechanism of Sanhuang Decoction(SHD) in treating dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice with Candida albicans(Ca) colonization via high-throughput transcriptome sequencing. Specifically, the animal model was established by oral administration of 3.0% DSS for 7 days followed by intragastrical administration of Ca suspension at 1.0 × 10~8 cells for 4 days and then the mice were treated with SHD enema for 7 days. Afterwards, the general signs were observed and the disease activity index(DAI) was recorded every day. After mice were sacrificed, colon length and colon mucosa damage index(CMDI) were determined and the histomorphology was observed with the HE staining method. The fungal loads of feces were detected with the plate method. Anti-saccharomyces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, and IL-6 in serum and colon were detected by ELISA. High-throughput RNA sequencing method was adopted to identify transcriptome of colon tissues from the control, model and SHD(15.0 g·kg~(-1)) groups. Differentially expressed genes(DEGs) among groups were screened and the GO and KEGG pathway enrichment analysis of the DEGs was performed. The expression levels of NLRP3, ASC, caspase-1, and IL-1β genes related to the NOD-like receptor signaling pathway which involved 9 DEGs, were examined by qRT-PCR and Western blot. The results demonstrated that SHD improved the general signs, decreased DAI and Ca loads of feaces, alleviated colon edema, erosion, and shortening, and lowered the content of β-1,3-glucan in serum and TNF-α, IL-1β, and IL-6 in serum and colon tissues of mice. Transcriptome sequencing revealed 383 DEGs between SHD and model groups, which were mainly involved in the biological processes of immune system, response to bacterium, and innate immune response. They were mainly enriched in the NOD-like signaling pathway, cytokine-cytokine interaction pathway, and retinol metabolism pathway. Moreover, SHD down-regulated the mRNA and protein levels of NLRP3, caspase-1, and IL-1β. In a word, SHD ameliorates DSS-induced UC in mice colonized with Ca, which probably relates to its regulation of NOD-like receptor signaling pathway.


Subject(s)
Animals , Candida albicans/genetics , Colitis, Ulcerative/genetics , Colon , Dextran Sulfate/toxicity , Disease Models, Animal , Drugs, Chinese Herbal , High-Throughput Nucleotide Sequencing , Mice , Transcriptome
5.
Article in Chinese | WPRIM | ID: wpr-888079

ABSTRACT

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.


Subject(s)
Animals , Colitis, Ulcerative/genetics , Dextran Sulfate , Heme Oxygenase-1/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Signal Transduction
6.
Article in English | WPRIM | ID: wpr-922773

ABSTRACT

Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4


Subject(s)
Animals , Azoxymethane/toxicity , CD8-Positive T-Lymphocytes , Colitis/genetics , Dextran Sulfate/toxicity , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Glycogen Synthase Kinase 3 beta , Mice , Mice, Inbred C57BL , RNA, Ribosomal, 16S , Wnt Signaling Pathway/drug effects
7.
Article in Chinese | WPRIM | ID: wpr-921798

ABSTRACT

Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1β and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.


Subject(s)
Animals , Colitis, Ulcerative/drug therapy , Dextran Sulfate , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Mice , Monoterpenes , Paeonia/chemistry , Plant Roots/chemistry
8.
Article in Chinese | WPRIM | ID: wpr-827996

ABSTRACT

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of β-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.


Subject(s)
Acrolein , Animals , Candida albicans , Colitis, Ulcerative , Colon , Dextran Sulfate , Disease Models, Animal , Lectins, C-Type , Mice , NF-kappa B , Signal Transduction
9.
Article in Chinese | WPRIM | ID: wpr-781245

ABSTRACT

OBJECTIVE@#To investigate whether kirenol, the major pharmacologically active compound of the Chinese medicinal herb , can protect mice from dextran sulfate sodium (DSS)-induced ulcerative colitis (UC).@*METHODS@#C57BL/6 mice with or without kirenol pretreatment were treated with DSS in drinking water for 7 days to induce UC. The symptoms of UC including weight loss, diarrhea and bloody stool were observed daily and graded using the disease activity index (DAI). Colon injury of the mice was assessed by measuring the length of the colon and HE staining of the colon tissue. The levels of inflammatory cytokines produced by the mesenteric lymph nodes (MLNs) lymphocytes were measured using enzyme-linked immunosorbent assay; the apoptosis of the lymphocytes and CD4 T cells was analyzed using flow cytometry.@*RESULTS@#The mice receiving pretreatment with kirenol showed obviously ameliorated symptoms of UC and milder pathological changes in the colon as compared with the control mice. Kirenol treatment significantly down-regulated the secretion of IFN-γ, IL-17A, IL-6 and TNF-α by the MLNs lymphocytes and increased the apoptosis of lymphocytes, especially CD4 T cells in the DSS-treated mice.@*CONCLUSIONS@#Kirenol can protect against T cell-mediated colon injury in DSS-treated mice possibly by suppressing the secretion of inflammatory mediators and inducing apoptosis of the inflammatory lymphocytes.


Subject(s)
Animals , Apoptosis , Colitis, Ulcerative , Cytokines , Dextran Sulfate , Diterpenes , Mice , Mice, Inbred C57BL , T-Lymphocytes
10.
Article in English | WPRIM | ID: wpr-764302

ABSTRACT

BACKGROUND: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized. METHODS: The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured. RESULTS: Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric. CONCLUSIONS: Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.


Subject(s)
Adenosine Triphosphate , Animals , Asian Continental Ancestry Group , Blotting, Western , Carcinogenesis , Colitis , Colon , Curcuma , Curcumin , Cyclin D1 , Cyclooxygenase 2 , Dextran Sulfate , Dextrans , DNA , Drinking Water , Herbal Medicine , Humans , Inflammatory Bowel Diseases , Mice , Nitric Oxide Synthase Type II , Phosphorylation , Phosphotransferases , Plants , Scutellaria baicalensis
11.
Article in Chinese | WPRIM | ID: wpr-774002

ABSTRACT

Objective To explore whether aging increases severity of colitis in mice and its mechanism.Methods Young (6-8 weeks)and aged (56 weeks) C57Bl/6 mice were divided into the control and experimental group (n=5,each). Dextran sodium sulfate(DSS) was used to induce acute colitis mouse model in the experimental group.The mRNA expressions of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in colon were measured by RT-PCR. Tight junctions (TJs) of intestinal epithelial cells was examined by transmission electron microscopy (TEM). Protein expressions of E-cadherin and occludin were detected by Western blotting and immunohistochemistry in colon.Results Compared with the young DSS-induced mice,the aged DSS-induced mice had more weight loss(t=3.679,P=0.006),higher disease indexes (t=2.496,P=0.037),higher histologic scores(U=0.000,P=0.008) and higher colonic IL-6 level (U=4.000,P=0.191). The TJs of intestinal epithelial cells were discontinuous in old healthy rats,and the TJs were destroyed significantly in both young and aged DSS-induced mice. Compared with the young DSS-induced mice,the aged DSS-induced mice had decreased protein expressions of E-cadherin (t=0.184,P=0.863)and occludin (t=0.399,P=0.710).Conclusions Aging leads to more severe disease following DSS challenge. Age-related deterioration in the functions of the gastrointestinal barrier and integrity may be one of the possible mechanisms.


Subject(s)
Animals , Colitis , Colon , Dextran Sulfate , Disease Models, Animal , Intestinal Mucosa , Mice , Mice, Inbred C57BL , Rats
12.
Article in Chinese | WPRIM | ID: wpr-773699

ABSTRACT

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.


Subject(s)
Animals , Anti-Inflammatory Agents , Pharmacology , Colitis, Ulcerative , Drug Therapy , Dextran Sulfate , Drugs, Chinese Herbal , Pharmacology , Glycyrrhiza , Chemistry , Mice , Plant Extracts , Pharmacology , Tripterygium , Chemistry
13.
Immune Network ; : e30-2018.
Article in English | WPRIM | ID: wpr-716247

ABSTRACT

Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.


Subject(s)
Animals , Colitis , Colitis, Ulcerative , Colon , Cytokines , Dextran Sulfate , Dextrans , Epithelial Cells , Homeostasis , Humans , Inflammation , Inflammatory Bowel Diseases , Interferons , Interleukin-10 , Interleukin-17 , Interleukin-6 , Lymph Nodes , Mice , Peroxidase , Spleen , STAT3 Transcription Factor , T-Lymphocytes
14.
Article in English | WPRIM | ID: wpr-740093

ABSTRACT

BACKGROUND: Curcumin, a yellow ingredient of turmeric (Curcuma longa Linn, Zingiberaceae), has long been used in traditional folk medicine in the management of inflammatory disorders. Although curcumin has been reported to inhibit experimentally-induced colitis and carcinogenesis, the underlying molecular mechanisms remain largely unresolved. METHODS: Murine colitis was induced by dextran sulfate sodium (DSS) which mimics inflammatory bowel disease. Curcumin or tetrahydrocurcumin was given orally (0.1 or 0.25 mmol/kg body weight daily) for 7 days before and together with DSS administration (3% in tap water). Collected colon tissue was used for histologic and biochemical analyses. RESULTS: Administration of curcumin significantly attenuated the severity of DSS-induced colitis and the activation of NF-κB and STAT3 as well as expression of COX-2 and inducible nitric oxide synthase. In contrast to curcumin, its non-electrophilic analogue, tetrahydrocurcumin has much weaker inhibitory effects. CONCLUSIONS: Intragastric administration of curcumin inhibited the experimentally induced murine colitis, which was associated with inhibition of pro-inflammatory signaling mediated by NF-κB and STAT3.


Subject(s)
Animals , Body Weight , Carcinogenesis , Colitis , Colon , Curcuma , Curcumin , Dextran Sulfate , Dextrans , Inflammatory Bowel Diseases , Medicine, Traditional , Mice , Nitric Oxide Synthase Type II
15.
Article in Chinese | WPRIM | ID: wpr-773813

ABSTRACT

OBJECTIVE@#To investigate the effects of deficiency of CHL1 in inflammatory bowel disease (IBD).@*METHODS@#Dextran Sulfate Sodium (DSS)-induced colitis model was used to study the effects of deficiency of CHL1 on the development of IBD. Ten CHL1(+/+) mice in C57/BL6 background were randomly divided into CHL1(+/+) group and DSS-induced CHL1(+/+) group. Ten CHL1(-/-) mice in C57/BL6 background were randomly divided into CHL1(-/-) group and DSS-induced CHL1(-/-) group. DSS-induced CHL1(+/+) group and DSS-induced CHL1(-/-)group were fed with 1.5% DSS for 7 days, and then drinking distilled water for 2 days. CHL1(+/+) group and CHL1(-/-) group as control group were fed with distilled water for 9 days. The changes of weight, survival, fecal blood and the change of colon length in this study were observed.@*RESULTS@#On the 7 day, the weight of DSS-induced CHL1(-/-) group were reduced significantly, and DSS-induced CHL1(-/-) group had extreme mortality on the 9th day. The fecal blood of DSS-induced CHL1(-/-) group also had higher score than that of DSS-induced CHL1(+/+) group. In the DSS-induced CHL1(-/-) group,the length of colon was shortened obviously.@*CONCLUSIONS@#The loss of CHL1 aggravates the development of IBD.


Subject(s)
Animals , Cell Adhesion Molecules , Genetics , Colitis , Genetics , Colon , Pathology , Dextran Sulfate , Disease Models, Animal , Mice , Mice, Inbred C57BL , Random Allocation
16.
Neuroscience Bulletin ; (6): 1058-1066, 2018.
Article in English | WPRIM | ID: wpr-775472

ABSTRACT

While inflammatory bowel disease (IBD) might be a risk factor in the development of brain dysfunctions, the underlying mechanisms are largely unknown. Here, mice were treated with 5% dextran sodium sulfate (DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-α levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSS-induced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis. These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here, we provide new information on the impact of colitis on the outcomes of cortical inflammation.


Subject(s)
Animals , Calcium-Binding Proteins , Metabolism , Caspase 3 , Metabolism , Cerebral Cortex , Pathology , Claudin-5 , Metabolism , Colitis , Pathology , Cytokines , Genetics , Metabolism , Dextran Sulfate , Toxicity , Disease Models, Animal , Encephalitis , Gene Expression Regulation , Mice , Microfilament Proteins , Metabolism , Occludin , Metabolism , Polysaccharides , Blood , Toxicity , Time Factors
17.
Article in Chinese | WPRIM | ID: wpr-775344

ABSTRACT

To observe the effect of total triterpenoids of Chaenomeles speciosa on PPARγ/SIRT1/NF-κBp65 signaling pathway and intestinal mucosal barrier of ulcerative colitis induced by dextran sulfate sodium (DSS) in mice, C57BL/6 mice were randomly divided into normal group, model group, total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) groups and sulfasalazine (250 mg·kg⁻¹) group. The ulcerative colitis (UC) model was induced by orally administering 2.5% DSS to the experimental mice, and the corresponding drugs were given to each group 3 days before the administration with 2.5% DSS. The normal group and the model group were given the equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage continuously for 10 days, q.d. The general conditions of the mice were observed on a daily basis, and the disease activity index (DAI) score was recorded. On the 10th day after the treatment, mice were put to death, the contents of TNF-α, IL-1β, IL-6, IFN-γ, IL-4 and IL-10 in the blood were detected, colon length was measured, colon mucosa damage index (CMDI) score was calculated, and MPO activity detection and histomorphology analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of E-cadherin, occluding,MUC2 and TFF3; the protein expressions of SIRT1, IKKβ, p-IKKβ, IκBα, p-IκBα and cytosol and nucleus PPARγ, NF-κBp65 in intestinal tissue were detected by western blot. The results indicated that total triterpenoids of C. speciosa (50, 100 mg·kg⁻¹) could significantly improve the general conditions of UC mice, reduce the DAI, CMDI and histopathological scores, increase the colon length, reduce the colonic mucosa ulcers, erosion and inflammatory infiltration, restore the normal intestinal mucosal barrier function, reduce the contents of TNF-α, IL-1β, IL-6, IFN-γ, increase the contents of IL-4 and IL-10 in the blood, inhibit MPO activity in colon tissue, up-regulate the mRNA expressions of E-cadherin, occludin, MUC2 and TFF3 in colon tissue, down-regulate the protein expressions of cytosol PPARγ, tissue p-IKKβ, p-IκBα and nucleus NF-κBp65 in the colon tissue, decrease the p-IKKβ/IKKβ and p-IκBα/IκBα ratios, up-regulate the protein expressions of nucleus PPARγ, tissue SIRT1 and cytosol NF-κBp65 (<0.05 or <0.01, respectively), with a dose-effect relationship between the total triterpenoids of C. speciosa treated groups. These findings suggested that total triterpenoids of C. speciosa had a significantly therapeutic effect on UC mice induced by DSS, its mechanism might be related to the regulation of PPARγ/SIRT1/NF-κBp65 signaling pathway, the inhibition of pro-inflammatory factor formation and the up-regulation of protein expression of protective factors.


Subject(s)
Animals , Colitis, Ulcerative , Drug Therapy , Colon , Dextran Sulfate , Disease Models, Animal , Intestinal Mucosa , Mice , Mice, Inbred C57BL , PPAR gamma , Metabolism , Random Allocation , Rosaceae , Chemistry , Signal Transduction , Sirtuin 1 , Metabolism , Transcription Factor RelA , Metabolism
18.
Article in English | WPRIM | ID: wpr-812124

ABSTRACT

Red ginseng is a well-known alternative medicine with anti-inflammatory activity. It exerts pharmacological effects through the transformation of saponin into metabolites by intestinal microbiota. Given that intestinal microflora vary among individuals, the pharmacological effects of red ginseng likely vary among individuals. In order to produce homogeneously effective red ginseng, we prepared probiotic-fermented red ginseng and evaluated its activity using a dextran sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of intestinal damage indicated that the administration of probiotic-fermented red ginseng significantly decreased the severity of colitis, compared with the control and the activity was higher than that induced by oral administration of ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL-6 and TNF-α, inflammatory biomarkers that are increased at the initiation stage of colitis, were significantly decreased in probiotic-fermented red ginseng-treated groups in comparison to the control group. The levels of inflammatory cytokines and mRNAs for inflammatory factors in colorectal tissues were also significantly decreased in probiotic-fermented red ginseng-treated groups. Collectively, oral administration of probiotic-fermented red ginseng reduced the severity of colitis in a mouse model, suggesting that it can be used as a uniformly effective red ginseng product.


Subject(s)
Administration, Oral , Animals , Colitis , Drug Therapy , Allergy and Immunology , Colon , Allergy and Immunology , Dextran Sulfate , Disease Models, Animal , Female , Fermentation , Humans , Interleukin-6 , Allergy and Immunology , Lactobacillus plantarum , Metabolism , Mice , Mice, Inbred BALB C , Panax , Chemistry , Metabolism , Microbiology , Plant Extracts , Chemistry , Metabolism , Powders , Metabolism , Probiotics , Metabolism , Tumor Necrosis Factor-alpha , Allergy and Immunology
19.
Gut and Liver ; : 655-666, 2017.
Article in English | WPRIM | ID: wpr-175164

ABSTRACT

BACKGROUND/AIMS: In inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration. METHODS: Murine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge. Acute colitis was induced with 7 days of dextran sulfate sodium (DSS) in male C57BL/6 mice, and extracts of AM and TH were administered for 2 weeks before DSS administration. RESULTS: In vitro studies demonstrated that AM or TH treatment reduced LPS-induced COX-2 and tumor necrosis factor-α mRNA levels but increased heme oxygenase-1 (HO-1). Oral preadministration of AM and TH rescued mice from DSS-induced colitis by inhibiting inflammatory mediators via inactivated extracellular signal regulated kinase and repressed nuclear factor κB and signal transducer and activator of transcription 3, but the effect was weaker for sulfasalazine than that for the extracts. Anti-inflammatory activities occurred via the inhibition of macrophage and T lymphocyte infiltrations. Unlike sulfasalazine, which did not induce HO-1, TH extracts afforded significant HO-1 induction. CONCLUSIONS: Because the AM or TH extracts were far superior in preventing DSS-induced colitis than sulfasalazine, AM or TH extracts can be considered natural agents that can prevent IBD relapse.


Subject(s)
Animals , Atractylodes , Colitis , Dextran Sulfate , Heme Oxygenase-1 , Heme , Humans , In Vitro Techniques , Inflammation , Inflammatory Bowel Diseases , Lymphocytes , Macrophages , Male , Mice , Necrosis , Phosphotransferases , Plant Extracts , Recurrence , Regeneration , RNA, Messenger , STAT3 Transcription Factor , Sulfasalazine , Taraxacum
20.
Article in English | WPRIM | ID: wpr-222889

ABSTRACT

Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases; however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid- and dextran sulfate sodium-induced inflammatory bowel disease and type II collagen-induced arthritis. Lenalidomide displayed a strong therapeutic effect in all these models of autoimmune/inflammatory diseases, while the effect of pomalidomide was less pronounced. In vitro experiments confirmed the immunosuppressive effect of both IMiDs on the proliferative response of stimulated human lymphocytes and on the balance of secreted cytokines toward an anti-inflammatory profile. We conclude that lenalidomide may offer a therapeutic opportunity against autoimmune/inflammatory diseases.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Cytokines , Dextran Sulfate , Humans , In Vitro Techniques , Inflammatory Bowel Diseases , Lymphocytes , Models, Theoretical , Thalidomide , Therapeutic Uses
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