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

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.

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Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

10.21203/rs.3.rs-101537/v1 ◽

2020 ◽

Author(s):

Wenjun Shi ◽

Fei Yang ◽

Liting Wang ◽

Nankun Qin ◽

Chengxiang Wang ◽

...

Keyword(s):

Male Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

High Dose ◽

Intragastric Administration ◽

Group Model ◽

Model Group ◽

Tnf Α ◽

Plantaginis Semen ◽

Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

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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.

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Protective Effect of Spirulina platensis Extract against Dextran-Sulfate-Sodium-Induced Ulcerative Colitis in Rats

Nutrients ◽

10.3390/nu11102309 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2309 ◽

Cited By ~ 4

Author(s):

Mohamed A. Morsy ◽

Sumeet Gupta ◽

Anroop B. Nair ◽

Katharigatta N. Venugopala ◽

Khaled Greish ◽

...

Keyword(s):

Ulcerative Colitis ◽

Drinking Water ◽

Spirulina Platensis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Control Group ◽

Protective Effects ◽

Hydroalcoholic Extract ◽

Tnf Α

Inflammatory bowel disease is a multifactorial inflammatory condition. This study aimed to test the protective effects of Spirulina platensis against ulcerative colitis (UC). UC was induced in thirty-six male Wistar rats by adding dextran sulfate sodium (DSS) to their drinking water, while a control group received only drinking water. UC rats were equally-divided into six groups that received a single oral daily dose of vehicle (DSS), sulfasalazine (SSZ, 50 mg/kg/day), chloroform or the hydroalcoholic extracts of Spirulina platensis (100 or 200 mg/kg/day) for 15 days, and then blood and colon samples were harvested for determination of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), myeloperoxidase (MPO), and histopathology. At the end of the study, compared to time-matched controls, UC rats showed increased TNF-α (1.64-fold), IL-6 (5.73-fold), ESR (3.18-fold), and MPO (1.61-fold), along with loss of body weight (24.73%) and disease activity index (1.767 ± 0.216 vs. 0 ± 0), p < 0.001. These effects were prevented by SSZ treatment (p < 0.001 vs. DSS). The hydroalcoholic extract of Spirulina platensis dose-dependently modulated all DSS-induced inflammatory changes. However, the chloroform extract significantly lowered only IL-6 and ESR, but not TNF-α or MPO levels. The protective effects of the hydroalcoholic extract of Spirulina platensis against experimental UC involved mitigation of DSS-induced inflammation.

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Pharmacodynamic Study of QingFei Paidu Decoction in the Treatment of Acute Respiratory Distress Syndrome Caused by Coronavirus Disease-2019 (COVID-19)

10.21203/rs.3.rs-552799/v1 ◽

2021 ◽

Author(s):

Zhixian He ◽

Xinyv Wang ◽

Xing Wang ◽

Jinyue Wang

Keyword(s):

Male Rats ◽

Arterial Oxygen ◽

Good Effect ◽

Control Group ◽

Group Model ◽

Protective Effects ◽

Model Group ◽

Blank Control Group ◽

Expression Levels ◽

Tnf Α

Abstract Background: The outbreak of the Coronavirus Disease-2019 (COVID-19) has threatened the public health of the world, and may eventually lead to acute respiratory impoverishment syndrome (ARDS). ARDS is a clinical syndrome caused by intrapulmonary or extrapulmonary reasons, which has complex pathogenesis and high mortality rate, it’s also one of the important factors in death from the 2019 novel coronavirus (2019-nCoV) epidemic. It has been reported that traditional Chinese medicine (TCM) can exert a good effect in the process of treatment. The present study aimed to observe the protective effects of TCM formula Qingfei Paidu Decoction (QFPD) on ARDS rats and explore the pharmacodynamic mechanism of the compound. Methods: 24 male rats were randomly divided into 4 groups (n=6), blank control group, model group, QFPD group (18.6g·kg-1·d-1) and dexamethasone group (2mg·kg-1·d-1). Blank control group rats were given saline, whereas other groups were injected with oleic acid (OA) and lipopolysaccharide (LPS) successively to establish ARDS model, and observed the behavioral performance of rats after model building. The morphological changes of lung tissue under optical microscope were observed; rat lung index (LI) and lung permeability index (LPI) were measured; blood PH, partial arterial oxygen pressure (PaO2, mmHg), partial arterial carbon dioxide pressure (PaCO2, mmHg), arterial oxygen saturation (SaO2) were measured by blood gas analyzer; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-6, IL-8, IL-10), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), kerbs von lungren 6 antigen (KL-6), C-reactive protein (CRP), and the expression of superoxide dismutase (SOD) were measured via test kit.Results: Compared with the model group, the two treatment groups could improve the respiratory and lung injury in rats, and could restore the expression levels of thromboxane, various cytokines and protein to varying degrees.Conclusions: QFPD and dexamethasone have protective effects on ARDS rats induced by jointly injecting OA and LPS, and QFPD has the better effect in between. These may be related to reducing the expression levels of IL-1β, IL-6, IL-8, TNF-α, CRP, TXB2, KL-6, and increasing the contents of IL-10, 6Keto-PGF1a and SOD vitality in the body.

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Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

European Journal of Inflammation ◽

10.1177/20587392211000896 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110008

Author(s):

Meng Chen ◽

Xinyan Song ◽

Jifang Jiang ◽

Lei Xing ◽

Pengfei Wang

Keyword(s):

Carbon Tetrachloride ◽

Liver Toxicity ◽

Corn Oil ◽

Histopathological Examination ◽

Hepatoprotective Effect ◽

Control Group ◽

Group Model ◽

Protective Effects ◽

Model Group ◽

Expression Levels

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

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Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

The American Journal of Chinese Medicine ◽

10.1142/s0192415x12500929 ◽

2012 ◽

Vol 40 (06) ◽

pp. 1241-1255 ◽

Cited By ~ 9

Author(s):

Sae-Kang Ku ◽

Jae-Soo Kim ◽

Young-Bae Seo ◽

Yong-Ung Kim ◽

Seung-Lark Hwang ◽

...

Keyword(s):

Reflux Esophagitis ◽

Group Treatment ◽

Control Group ◽

Esophageal Mucosa ◽

Dependent Manner ◽

Protective Effects ◽

Model Group ◽

Curculigo Orchioides ◽

Intact Group ◽

Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

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Gardenia jasminoides Ellis Fruit Extracts Attenuated Colitis in 2,4,6-Trinitrobenzenesulfonic Acid-Induced Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9920379 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jing Liu ◽

Chao Yang ◽

Zhigui Wu ◽

Jianguo Pei ◽

Yao Chen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Chemical Components ◽

Protective Agent ◽

Protective Effects ◽

Trinitrobenzenesulfonic Acid ◽

Fruit Extracts ◽

Gardenia Jasminoides ◽

Tnf Α ◽

Ameliorative Effect ◽

Gardenia Jasminoides Ellis

Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Gardenia jasminoides Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction. Meanwhile, the chemical components of GFE were performed by UPLC-QTOF-MS/MS. GFE significantly decreased DAI scores and ameliorated macroscopic and histologic damage. It also reduced the levels of MPO, NO, MDA, IL-1β, TNF-α, and IL-6, while increasing the level of SOD. Moreover, 56 components were identified in GFE using a UPLC-QTOF-MS/MS method, which can be categorized into six structural groups. Our results indicated that GFE has an ameliorative effect on TNBS-induced colitis in rats, which may further verify its anti-inflammatory and antioxidative properties. Therefore, GFE can be a promising protective agent of colitis that deserves further investigation.

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Effects of Curcumin Chitosan Microspheres on the Expression of NF-κB, IL-1β, IL-4 and IL-6 in Rats with Ulcerative Colitis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2053 ◽

2019 ◽

Vol 9 (6) ◽

pp. 810-815

Author(s):

Shujiao Yu ◽

Yuanhua Huang ◽

Guodong Huang ◽

Jun Xiong ◽

Yan Wu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Colonic Mucosa ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

High Dose ◽

Trinitrobenzenesulfonic Acid ◽

Serum Samples ◽

Blank Control Group ◽

Chitosan Microspheres ◽

Model Control

The aim of this study was to observe the therapeutic effect of curcumin chitosan microspheres (CCM) on ulcerative colitis (UC) in rats. Rat UC model was prepared by 2,4,6-trinitrobenzenesulfonic acid (TNBS) method. All animals were divided into blank control group (BCG), model control group (MCG), mesalazine enteric-coated tablets group (MECT), curcumin chitosan microsphere low (CCML), medium (CCMM) and high dose groups (CCMH). Starting from the third day after model establishment, the rats were intra-gastrically administered for 10 days. On the 14th day of the experiment, the rats were sacrificed. The colon tissues and serum samples were collected and the expression of NF-κB P65 protein was detected by immune histochemical streptavidin-perosidase (SP) method. The levels of IL-1β, IL-4 and IL-6 in serum were determined by Enzyme Linked Immunosorbent Assay (ELISA). The colonic mucosal injury score of MCG was increased; The serum IL-1β and IL-6 levels were increased, while the IL-4 content was decreased; The expression of NF-κB in the colonic mucosa was reduced after TNBS challenge. The histological injury scores of colonic mucosa, the serum levels of IL-1β and IL-6 in CCM-treated rats were significantly decreased (P < 0.01) as compared with MECT group. While, the content of IL-4 was significantly higher than that of MCG and MECT groups (P < 0.01). Curcumin chitosan microspheres provide a potential therapeutic strategy for treating UC in clinic.

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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).

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Protective effects of emodin on lung injuries in rat models of liver fibrosis

Open Life Sciences ◽

10.1515/biol-2019-0069 ◽

2019 ◽

Vol 14 (1) ◽

pp. 611-618

Author(s):

Lili Zhang ◽

Huiying Zhang ◽

Limin Wang ◽

Yimin Fan ◽

Cuiying Zhang ◽

...

Keyword(s):

Liver Fibrosis ◽

Inflammatory Responses ◽

Control Group ◽

Protective Effects ◽

Model Group ◽

Lung Weight ◽

Rat Models ◽

Tnf Α ◽

Lung Injuries ◽

Weight Coefficients

AbstractObjectiveThe aim of this study is to investigate the protective effects of emodin (EMD) on the lung injuries in the rat models of liver fibrosis.MethodsLiver fibrosis was established in rats and the effect of intervention using EMD treatment was determined. Liver and lung weight coefficients were measured and lung content of TNF-α (tumor necrosis factor α), MDA (malondialdehyde), NO (nitric oxide), and ONOO- (peroxynitrite) were determined. Finally, histopathological changes were evaluated.ResultsCompared with the normal control group, the lung weight coefficient was significantly increased in the fibrosis model group. Moreover, pulmonary edema and inflammatory responses were observed. Levels of TNF-α, MDA, NO, and ONOO- in the lung homogenate were significantly increased in the fibrosis model group. After EMD treatment, the lung weight coefficients were significantly reduced. Moreover, pathological changes in the lung tissue were dramatically alleviated. Levels of TNF-α, MDA, NO, and ONOO- were significantly decreased.ConclusionEMD exhibits protective effects against lung injuries in a rat model of liver fibrosis.

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