Influence of Rosiglitazone on the Expression of PPARγ, NF-κB, and TNF-αin Rat Model of Ulcerative Colitis

Aim. To observe the disease activity index (DAI) and the colonic mucosa damage index (CMDI), detect the colonic mucosal expression of PPARγ, NF-κB, and TNF-αin rats with ulcerative colitis (UC), and to investigate the protective role of rosiglitazone in UC.Methods. Sprague-Dawley (SD) rats were divided into three groups: a control group, a rosiglitazone treatment group, and a UC model group. Rats were sacrificed on days 7, 14, 21, or 35 following administration of treatment after enema and DAI, CMDI and colonic expression of PPARγ, NF-κB, and TNF-αwere assessed.Results. In the UC model group, DAI, CDMI and the colonic expression of NF-κB and TNF-αincreased significantly compared to the control group at all timepoints, but PPARγdecreased significantly. Furthermore, in the rosiglitazone treatment group, DAI and CMDI decreased significantly on the 14-day, 21-day, and 35-day timepoints compared to the UC model group; the colonic expression of NF-κB and TNF-αdecreased compared to UC model group at all timepoints, but the PPARγexpression increased significantly.Conclusions. Rosiglitazone can alleviate colonic mucosal inflammation and have the protective role on UC by upregulating PPARγexpression and downregulating NF-κB and TNF-αexpression.

Download Full-text

Dynamic Changes in MMP1 and TIMP1 in the Antifibrotic Process of Dahuang Zhechong Pill in Rats with Liver Fibrosis

Open Chemistry ◽

10.1515/chem-2019-0041 ◽

2019 ◽

Vol 17 (1) ◽

pp. 346-356

Author(s):

Jiayu Lin ◽

Chaowen Deng ◽

Yanzhong Peng ◽

Jie Zheng ◽

Liya Wei ◽

...

Keyword(s):

Treatment Group ◽

Liver Fibrosis ◽

Differentially Expressed ◽

Tissue Inhibitor Of Metalloproteinase ◽

Control Group ◽

Model Group ◽

Sprague Dawley ◽

Dynamic Changes ◽

Matrix Metalloproteinase 1 ◽

Liver Tissues

AbstractOn the basis of carbon tetrachloride (CCl4)induced liver fibrosis in rats, this study aims to investigate the dynamic changes in matrix metalloproteinase 1 (MMP1) and the tissue inhibitor of metalloproteinase 1 (TIMP1) in the antifibrotic process of Dahuang Zhechong Pill (DHZCP). A total of 50 male Sprague Dawley rats, aged 8 weeks, were randomly divided into 3 groups: the control group, the model group (the group treated with CCl4), and the treatment group (the group treated with CCl4 and DHZCP). Rats were sacrificed at Weeks 4 and 8. Liver tissues were separated for RNA sequencing and bioinformatics analysis. Real-time PCR, Western blot analysis, and histological staining were conducted to confirm the gene expression and pathological change in liver tissues. Compared with control group, rats in model group showed poor mental state and slow weight gain. The liver tissues of the rats in the model group exhibited a damaged hepatic lobule structure, fibrous connective tissue hyperplasia, and inflammatory cell infiltration among the hyperplastic tissues. DHZCP could significantly improve the appearance of rats and alleviate CCl4-induced fibrosis. Compared to model group, 798 differentially expressed mRNAs were found in the treatment group, of which 120 were up-regulated and 678 were down-regulated. Differentially expressed mRNAs between the CCl4-induced group and the DHZCP-treated group were mainly focused on the following KEGG pathways: focal adhesion, phagosome, tight junction, and ECM–receptor interactions. Relative to those in the control group, MMP1 was downregulated, whereas, TIMP1 and Col1A1 were upregulated in the CCl4-induced group at Weeks 4 and 8. DHZCP could reverse MMP1, TIMP1, and Col1A1 expression.DHZCP protects against liver injury and exerts an antifibrotic effect on liver fibrosis induced by CCl4 in rats. Its mechanism may be related to the upregulation of MMP1, downregulation of TIMP1, and promotion of collagen degradation.

Download Full-text

Maggot protein ameliorates dextran sulphate sodium-induced ulcerative colitis in mice

Bioscience Reports ◽

10.1042/bsr20181799 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 4

Author(s):

Rong Wang ◽

Lei Wang ◽

Yongzheng Luo ◽

Daojuan Wang ◽

Ronghui Du ◽

...

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Water Model ◽

Inflammatory Factors ◽

Control Group ◽

Sterile Water ◽

Dextran Sulphate ◽

Model Group ◽

Dextran Sulphate Sodium ◽

Body Weights

Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Maggots are known as a traditional Chinese medicine named as ‘wu gu chong’. The aim of the present study was to investigate the therapeutic effect of the maggot protein on dextran sulphate sodium (DSS)-induced colitis in C57BL/6 mice. In the present study, female C57BL/6 mice were given sterile water containing 3% DSS to establish the model of UC. Mice were randomly divided into five groups: control group (sterile water), model group (DSS), treatment group (DSS + maggot protein), mesalazine group (DSS + mesalazine), and maggot protein group (sterile water + maggot protein). The mental state, defecate traits, and changes in body weights were recorded daily. The disease activity index (DAI) as a disease severity criterion was calculated based on body weights and stool consistency and bleeding. All the mice were killed on the 12th day. Colon length, colon histological changes, and other inflammatory factors were analyzed and evaluated. The results showed that colitis models of mice were established successfully. Administration of maggot protein markedly suppressed the severity of UC compared with the DSS model group. Furthermore, maggot protein potently ameliorated DSS-induced weight loss, colon shortening, and colon histological injury. Moreover, the maggot protein exerted anti-inflammatory effects via inhibition of the activation of the nuclear factor κB (NFκB) signaling pathway. In summary, treatment by maggot protein was able to improve not only the symptoms of colitis, but also the microscopic inflammation in mice with DSS-induced colitis. The present study may have implications for developing an effective therapeutic strategy for inflammatory bowel diseases (IBDs).

Download Full-text

Protective effects of pterostilbene on ulcerative colitis in rats via suppressing NF-κB pathway and activating PPAR-γ

European Journal of Inflammation ◽

10.1177/2058739219840152 ◽

2019 ◽

Vol 17 ◽

pp. 205873921984015

Author(s):

Liu Shi ◽

Qing Liu ◽

Jian-hua Tang ◽

Jian-jun Wen ◽

Chen Li

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Group Model ◽

Protective Effects ◽

Model Group ◽

Trinitrobenzenesulfonic Acid ◽

Ppar Γ ◽

Tnf Α

Our study aimed to investigate the protective effects and potential mechanisms of pterostilbene on rats with ulcerative colitis (UC). We established 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis rat model. Rats were randomly divided into three groups, including control group, model group, and pterostilbene group (30 mg/kg). Disease activity index (DAI) including body weight, stool consistency, and gross bleeding was measured. The concentration of superoxide dismutases (SODs), glutathione superoxide (GSH-px), malondialdehyde (MDA), and methylpropanediol (MPO) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The levels of interleukin-1 beta (IL-1β), IL-17, IL-6, and tumor necrosis factor–alpha (TNF-α) in serum were also analyzed by ELISA kits. Histological evaluations of colons were conducted. The levels of peroxisome-proliferator-activated receptor–γ (PPAR-γ), nuclear factor-κB (NF-κB), ZO-1, and Occludin were analyzed by immunohistochemistry. Compared with model group, pterostilbene notably suppressed the production of TNF-α, IL-17, IL-1β, IL-6, MDA and MPO in serum, and markedly increased the SOD and GSH-Px activity in serum. Pterostilbene significantly attenuated macroscopic damage and histological injury, when compared with model rats. Furthermore, pterostilbene also markedly activated the expression of PPAR-γ, ZO-1, and Occludin, and suppressed the expression of NF-κB. The protective effects of pterostilbene might be associated with suppression of NF-κB and activation of PPAR-γ. Pterostilbene might be a promising therapeutic agent for colitis treatment.

Download Full-text

Improvement of Oxazolone-Induced Ulcerative Colitis in Rats Using Andrographolide

Molecules ◽

10.3390/molecules25010076 ◽

2019 ◽

Vol 25 (1) ◽

pp. 76 ◽

Cited By ~ 3

Author(s):

Liuhong Zhang ◽

Ning Cao ◽

Yuwen Wang ◽

Youxu Wang ◽

Chao Wu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Specific Binding ◽

Disease Activity Index ◽

Interleukin 4 ◽

Control Group ◽

Colonic Disease ◽

Bloody Stool ◽

Sprague Dawley ◽

Main Compound

Ulcerative colitis (UC) is usually accompanied with symptoms of abdominal pain, diarrhea, and bloody stool, which impair the quality of life of patients. Previous studies have shown that Andrographis paniculata extracts, which have andrographolide (AND) as their main compound, can relieve UC symptoms in patients. The aim of the study was to investigate the alleviating effect of AND on UC using the oxazolone (OXZ)-induced UC rat model. A total of 66 healthy male Sprague Dawley rats were used to evaluate the efficacy and mechanism of AND on UC (n = 11 per group) and grouped into control, model, SASP (sulfasalazine, positive control group, 500 mg/kg), AND-L (40 mg/kg), AND-M (80 mg/kg), and AND-H (120 mg/kg). The colonic disease activity index (DAI), colon length, spleen coefficient, pathological damage, and inflammation-related cytokine and protein expression levels were used as indices for evaluation. Results showed that the AND groups had reduced DAI and mortality, and significantly improved colon length and spleen coefficient compared with the model group. Furthermore, OXZ-induced histological injury was relieved significantly after AND treatment due to an improved crypt structure and reduced infiltration of inflammatory cells. Moreover, AND inhibited myeloperoxidase (MPO) activity and the secretion of interleukin-4 (IL-4), IL-13, and tumor necrosis factor α (TNF-α). The results of the anti-inflammatory mechanism revealed that AND blocked the signal transduction by reducing IL-4/IL-13 specific binding to IL-4 receptor (IL-4R) and inhibiting the phosphorylation of the signal transducer and activator of transcription 6 (p-STAT6). In conclusion, aside from natural plants, AND may be a candidate ingredient for UC therapy.

Download Full-text

Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan

Military Medical Research ◽

10.1186/s40779-021-00324-5 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Li-Yao Duan ◽

Yan Liang ◽

Wen-Ping Gong ◽

Yong Xue ◽

Jie Mi ◽

...

Keyword(s):

Gene Expression ◽

Chinese Medicine ◽

Treatment Group ◽

Mechanism Of Action ◽

Cell Damage ◽

Control Group ◽

Therapeutic Effects ◽

Model Group ◽

Lung Histopathology ◽

Th17 Cytokines

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

Download Full-text

Fasudil ameliorated liposaccharide-induced acute kidney injury in mice by inhibiting NLRP3

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i10.7 ◽

2021 ◽

Vol 20 (10) ◽

pp. 2055-2062

Author(s):

Xueqian Li ◽

Chengzhi Zhao

Keyword(s):

Acute Kidney Injury ◽

Treatment Group ◽

Cell Growth ◽

Mesangial Cells ◽

Kidney Injury ◽

Inflammatory Factors ◽

Control Group ◽

Model Group ◽

Blank Control Group ◽

Tissue Homogenates

Purpose: To determine the influence of fasudil on LPS-mediated acute kidney injury (AKI) in mice.Methods: Healthy C57 mice (n = 140) of largely similar weight were used in this study. They were assigned to a treatment group (n = 40), a model group (n = 50), and a blank control group (n = 50). Mice in treatment and model groups were injected with lipopolysaccharide (LPS). In the treatment group, each mouse was injected intravenously with fasudil daily before the establishment of the mouse model of AKI. All mice were sacrificed 6 h after establishing the AKI model. Portions of the kidney from mice were used for preparation of tissue homogenates, while the remaining portions were subjected to primary culture. Transformed C3H Mouse Kidney-1 (TCMK1) and mesangial cells from mouse glomeruli (SV40-MES-13) cells were used for assays of cell growth and apoptosis. Blood samples were alsocollected from the mice. Thereafter, the levels of blood urea nitrogen (BUN) and creatinine (Cr) in kidney homogenates of the three groups were determined. Moreover, levels of NLRP3, nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in the homogenates and blood were assayed. Cell growth and apoptosis were also measured.Results: The treatment group and model group showed higher levels of BUN and Cr than the control group, with a higher level observed in model mice than in the treatment mice. There were significantly higher relative levels of NF-κB, NLRP3 and TLR4 in treatment and model groups than in controls, with a higher level observed in model mice than in treatment mice. There were significantly higher concentrations of inflammatory factors in treatment and model mice groups than in control mice, with higher levels observed in model mice than in treatment mice. The TCMK1 and SV40-MES-13 cells in the two groups showed slower cell growth and stronger apoptosis than those in control group (p < 0.05).Conclusion: Fasudil relieved LPS-mediated AKI in mice by suppressing TLR4/NF-κB signal pathway and lowering NLRP3. Thus, fasudil has potential as a new adjunctive agent for the treatment of AKI.

Download Full-text

P187 The significance of netrin-1 level in the clinical activity of ulcerative colitis, its association between TNF-α and IL-6

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.316 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S232-S232

Author(s):

H Korkmaz ◽

K Fidan

Keyword(s):

Ulcerative Colitis ◽

Proinflammatory Cytokines ◽

Activity Index ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Clinical Activity ◽

Tnf Α ◽

Significant Difference ◽

And Control ◽

Control Study

Abstract Background In this study, we investigated the importance of netrin-1 levels in ulcerative colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-α. Methods This study is a type of case–control study. Sixty-seven patients with UC (36 of them activation, 31 of remission) and 50 healthy controls were included in the study. UC patients; ‘Truelove Witts clinical activity index by remission (n = 31), mild activation (n = 21), moderate activation (n = 6) and severe activation (n = 9) were divided into groups. Netrin, IL-6 and TNF-α measurements in plasma samples were performed using enzyme-linked immunosorbent assay kit. Results Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-α, neutrophil, platelet (p < 0.05 for all). The plasma netrin-1 mean of UC with severe activation group (139.21 ± 48.09 pg/ml) was statistically significantly higher than that of the mild activation (p = 0,037), remission group (p = 0,001) and control group(p = 0,011). The plasma netrin-1 mean of UC with moderate activation group was statistically significantly higher than that of the mild activation(p = 0,045) and remission group(p = 0,004). Conclusion Our results reveal that plasma netrin-1 levels have been shown to be associated with UC activation, similar to proinflammatory cytokines such as TNF-α and IL-6, in UC.

Download Full-text

POSITIVE CORRELATION BETWEEN DISEASE ACTIVITY INDEX AND MATRIX METALLOPROTEINASES ACTIVITY IN A RAT MODEL OF COLITIS

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032014000200007 ◽

2014 ◽

Vol 51 (2) ◽

pp. 107-112 ◽

Cited By ~ 8

Author(s):

Luiz Gustavo de OLIVEIRA ◽

André Luiz da CUNHA ◽

Amaury Caiafa DUARTE ◽

Maria Christina Marques Nogueira CASTAÑON ◽

Júlio Maria Fonseca CHEBLI ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Dextran Sulfate ◽

Tissue Injury ◽

Activity Index ◽

Disease Activity Index ◽

Blue Staining ◽

Control Group ◽

Alcian Blue Staining ◽

Increased Activity

ContextInflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases.ObjectivesEvaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium.MethodsColitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined.ResultsDextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group.ConclusionsIn this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.

Download Full-text

BuPiHeWei Decoction Ameliorates 5-Fu-Induced Intestinal Mucosal Injury in the Rats by Regulating the TLR-4/NF-κB Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5673272 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Zhi-gao Sun ◽

Ya-zhuo Hu ◽

Yu-guo Wang ◽

Jian Feng ◽

Yong-qi Dou

Keyword(s):

Body Weight ◽

Signaling Pathway ◽

Bacillus Licheniformis ◽

Mucosal Injury ◽

Protective Role ◽

Inflammatory Factors ◽

Control Group ◽

Sprague Dawley ◽

Intestinal Mucosal Injury ◽

Group 5

BuPiHeWei (BPHW) decoction, a classic Traditional Chinese Medicinal (TCM) prescription, has been widely used in clinical practice to relieve digestive symptoms caused by chemotherapy, such as diarrhea and vomiting. The present study aimed to investigate whether BPHW decoction exerted a protective role in the 5-Fu-induced intestinal mucosal injury in the rats by regulating the mechanisms of TLR-4/NF-κB signaling pathway. There were 35 Sprague Dawley rats randomly divided into four groups: normal control group, 5-Fu group, 5-Fu + BPHW decoction group (10.5 g/kg, for five continuous days), and 5-Fu + Bacillus licheniformis capsule group (0.2 g/kg, for five continuous days). Animal models were established by intraperitoneal injection of 5-Fu (30 mg/Kg, for five consecutive days). At the end of the treatment period, body weight, diarrhea score, and histological examination were examined. Furthermore, the expression of TLR-4/NF-κB pathway was detected to reveal its mechanism. The results showed that BPHW decoction effectively reduced diarrhea score and increased body weight and height of villi after 5-Fu chemotherapy. In addition, BPHW decoction could significantly inhibit the expression of TLR-4, NF-κB, and inflammatory factors (including TNF-α, IL-1β, and IL-6) in the intestine, and the efficacy was significantly higher than that of Bacillus licheniformis capsule. In summary, BPHW decoction might be considered an effective drug to alleviate intestinal mucosal injury in the rats induced by 5-Fu.

Download Full-text

Effect of Qingxin Kaiqiao Fang on Hippocampus mRNA Expression of the Inflammation-Related Genes IL-1β, GFAP, and Aβin an Alzheimer’s Disease Rat Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9267653 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Dan-Dan Mao ◽

Wen-Yu Yang ◽

Yan Li ◽

Jian-Wei Lin ◽

Shi-Yu Gao ◽

...

Keyword(s):

Rat Model ◽

Particle Deposition ◽

Therapeutic Potential ◽

Interleukin 1 ◽

Control Group ◽

Model Group ◽

Sprague Dawley ◽

Amyloid A ◽

Sprague Dawley Rats ◽

High Doses

Objective. To investigate the effects of QKF on expression of amyloid-beta (Aβ), interleukin-1 beta (IL-1β), and glial fibrillary acidic protein (GFAP) using a rat model of AD.Materials and Methods. Fifty-six male Sprague-Dawley rats were randomly divided into seven groups (eight rats each): control group, sham-operated group, AD model group, groups of AD rats administered with low, medium, and high doses of QKF, and the donepezil group. AD was established by bilateral injection ofβ-amyloid (Aβ) 1–40 into the hippocampus. Two days after AD was established, drugs were administered by gavage. After 14 days of treatment, we used RT-PCR, Western blotting, and immunohistochemistry to measure the transcript expression and protein abundance of Aβ, IL-1β, and GFAP, and methenamine silver staining was used to detect amyloid protein particle deposition.Results. Compared to the control group, the rats from the AD model group showed significantly greater expression levels of Aβ, IL-1β, and GFAP. However, these differences in expression were abolished by treatment with QKF or donepezil.Conclusion. QKF possesses therapeutic potential against AD because it downregulated Aβ, IL-1β, and GFAP in the hippocampus of AD rats. Future studies should further examine the mechanisms through which QKF produces its effects and the consequences of long-term QKF administration.

Download Full-text