Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation

ABSTRACT The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), andH. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-α) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-α secretion may serve to protect H. pylori-induced gastric mucosal damage.

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Anticolitic Effect of Berberine in Rat Experimental Model: Impact of PGE2/p38 MAPK Pathways

Mediators of Inflammation ◽

10.1155/2020/9419085 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Li Jia ◽

Kuijin Xue ◽

Junheng Liu ◽

Ola A. Habotta ◽

Lianhai Hu ◽

...

Keyword(s):

Mrna Expression ◽

P38 Mapk ◽

Experimental Colitis ◽

Mucosal Damage ◽

Isoquinoline Alkaloid ◽

Protective Mechanism ◽

Colon Mucosa ◽

Tnf Α ◽

Anti Inflammatory ◽

High Doses

Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.

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Η μελέτη της αντιοξειδωτικής και αντιφλεγμονώδους δράσης μορίων (U-74389G και σιλδεναφίλης) σε πειραματικό πρότυπο χημικής αιμορραγικής κολίτιδας σε επίμυες

10.12681/eadd/42136 ◽

2014 ◽

Author(s):

Γεώργιος-Αντώνιος Μαργώνης

Keyword(s):

Body Weight ◽

Combined Treatment ◽

Damage Index ◽

Mucosal Damage ◽

Group 4 ◽

Tnf Α ◽

Male Wistar Rats ◽

Experimental Rat Model ◽

Anti Inflammatory ◽

Group 5

BACKGROUND: Crohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidativeeffects are tested in various preclinical models of the disease. Our aim was to investigate theeffects of sildenafil and lazaroid U-74389G in an experimental rat model oftrinitrobenzenesulfonic acid-induced colitis.MATERIALS AND METHODS:Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for therats belonging to the first group. For 6 days, the animals in group 3 were administered dailysildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and therats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. Therats in groups 1 and 2 were not administered any treatment. During the study, the weightswere recorded as a marker of clinical condition. The colon damage was evaluated usingmacroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), andbiochemical methods (tissue tumor necrosis factor [TNF]-αΝandΝmalondialdehydeΝ[εϊχ]ΨέRESULTS:Sildenafil reduced TNF-αΝtissueΝlevelsΝandΝincreasedΝbodyΝweightέΝU-74389G reduced TNF-α,Νthe macroscopic index of mucosal damage score (CMDI) and increased body weight. Thecombined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-αΝandΝMDA, lowered CMDI and microscopic Geboes score, and increased body weight. CONCLUSIONS:U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reducecolonic TNF-α,ΝωεϊIΝscore, and improve weight change. We confirmed that sildenafil hasanti-inflammatory capacity by reducing colonic TNF-αΝandΝbyΝimprovingΝbodyΝweightέΝόinally,Νthe combined treatment showed superior effects by reducing colonic TNF-α,ΝcolonicΝεϊχ,ΝCMDI score, Geboes score, and by improving weight.

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New Therapy for Orolaryngeal Manifestations of Crohn's Disease

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940311200108 ◽

2003 ◽

Vol 112 (1) ◽

pp. 37-39 ◽

Cited By ~ 17

Author(s):

Francesco Ottaviani ◽

Antonio Schindler ◽

Mara Petrone ◽

Pasquale Capaccio ◽

Gabriele Bianchi Porro

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Mucosal Damage ◽

Chimeric Antibody ◽

Cell Mediated Immunity ◽

Tissue Destruction ◽

Relative Safety ◽

Tnf Α ◽

Necrosis Factor ◽

Entire Gastrointestinal Tract

Crohn's disease is a chronic inflammation that may involve the entire gastrointestinal tract, from the mouth to the anus. The most widely accepted etiologic theory involves an immunologic aberration leading to local tissue destruction. Cell-mediated immunity with increased tumor necrosis factor (TNF) production may play a role in mucosal damage. Oral and laryngeal involvement are rare manifestations of Crohn's disease that are usually treated successfully by steroids. We here report a rare case of extra-intestinal Crohn's disease resistant to steroid therapy, which was successfully treated with infliximab, a chimeric antibody directed against TNF-α that is the only registered agent for the treatment of Crohn's disease. The relative safety, efficacy, and efficiency of infliximab make it an alternative treatment of which otolaryngologists should be aware.

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Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats

Human & Experimental Toxicology ◽

10.1177/0960327114537095 ◽

2014 ◽

Vol 34 (3) ◽

pp. 227-239 ◽

Cited By ~ 15

Author(s):

I-C Lee ◽

H-S Baek ◽

S-H Kim ◽

C Moon ◽

S-H Park ◽

...

Keyword(s):

Gastric Ulcer ◽

Antioxidant Enzyme ◽

Enzyme Activities ◽

Organosulfur Compound ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Antioxidant Enzyme Activities ◽

Diallyl Disulfide ◽

Protective Effects ◽

Tnf Α

This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic ( Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities.

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Oral administration of Bifidobacterium longum CECT 7347 ameliorates gliadin-induced alterations in liver iron mobilisation

British Journal Of Nutrition ◽

10.1017/s0007114513001098 ◽

2013 ◽

Vol 110 (10) ◽

pp. 1828-1836 ◽

Cited By ~ 10

Author(s):

José Moisés Laparra ◽

Marta Olivares ◽

Yolanda Sanz

Keyword(s):

Oral Administration ◽

Intestinal Inflammation ◽

Bifidobacterium Longum ◽

Autoimmune Disorder ◽

Mucosal Damage ◽

Liver Iron ◽

Expression Levels ◽

Tnf Α ◽

Ifn Γ ◽

Hb Concentration

Coeliac disease is an autoimmune disorder triggered by gluten intake, causing intestinal inflammation and mucosal damage commonly associated with the malabsorption of nutrients and ferropenic anaemia. The present study evaluates the effects of the oral administration of Bifidobacterium longum CECT 7347 on gliadin-mediated alterations in hepatic Fe deposition and Hb concentration, liver transferrin receptor (TfR)-2, IL-6, TNF-α and hepcidin (Hamp) expression (mRNA), and active hepcidin peptide production by liquid chromatography–MS/MS. Weanling rats, sensitised or not with interferon (IFN)-γ, were fed with gliadins and/or the bifidobacterial strain. Gliadin feeding increased hepatic Fe deposition; however, only gliadin-fed sensitised animals showed lower Hb concentrations than the controls. TfR2 expression decreased after gliadins were fed to both sensitised and non-sensitised animals, and restored by the administration of B. longum. These observations were accompanied by increases in IL-6 expression levels in all the treatment groups; however, TNF-α expression only increased significantly in animals fed gliadins alone or together with B. longum if they had previously been sensitised with IFN-γ. Liver expression levels of Hamp diminished in all cases to the lowest values in animals sensitised with IFN-γ after being fed with gliadins and/or bifidobacteria. In these animals, plasma Hamp active peptide concentrations significantly increased when compared with the controls. Significant correlations were calculated between Hamp expression and liver Fe contents (liver Fe = 1/0·0032+0·032 × Hampexp), and Hb concentrations (Hb = 11·49+10·13 × (Hampexp)1/2). These data indicate that oral administration of B. longum ameliorates gliadin-mediated perturbations in liver Fe deposition and mobilisation.

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The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00103.2012 ◽

2013 ◽

Vol 304 (2) ◽

pp. G193-G202 ◽

Cited By ~ 9

Author(s):

Jung Mogg Kim ◽

Su Hyun Kim ◽

Su Hyuk Ko ◽

Jireh Jung ◽

Jaeyoung Chun ◽

...

Keyword(s):

Epithelial Cells ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Mucosal Inflammation ◽

Histological Evaluation ◽

Dependent Manner ◽

Gastric Epithelial Cells ◽

Gastric Mucosal Lesions ◽

Tnf Α ◽

Mucosal Lesions

Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.

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Inflammation and matrix remodeling during repair of ventilator-induced lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00010.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. L500-L509 ◽

Cited By ~ 41

Author(s):

Adrián González-López ◽

Aurora Astudillo ◽

Emilio García-Prieto ◽

María Soledad Fernández-García ◽

Antonio López-Vázquez ◽

...

Keyword(s):

High Pressure ◽

Acute Respiratory Distress Syndrome ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Distress Syndrome ◽

Matrix Remodeling ◽

Epithelial Repair ◽

Ventilator Induced Lung Injury ◽

Tnf Α ◽

Repair Phase

High-pressure ventilation triggers different inflammatory and matrix remodeling responses within the lung. Although some of them may cause injury, the involvement of these mediators in repair is largely unknown. To identify mechanisms of repair after ventilator-induced lung injury (VILI), mice were randomly assigned to baseline conditions (no ventilation), injury [90 min of high-pressure ventilation without positive end-expiratory pressure (PEEP)], repair (injury followed by 4 h of low-pressure ventilation with PEEP), and ventilated controls (low-pressure ventilation with PEEP for 90 and 330 min). Histological injury and lung permeability increased during injury, but were partially reverted in the repair group. This was accompanied by a proinflammatory response, together with increases in TNF-α and IFN-γ, which returned to baseline during repair, and a decrease in IL-10. However, macrophage inflammatory protein-2 (MIP-2) and matrix metalloproteinases (MMP)-2 and -9 increased after injury and persisted in being elevated during repair. Mortality in the repair phase was 50%. Survivors showed increased cell proliferation, lower levels of collagen, and higher levels of MIP-2 and MMP-2. Pan-MMP or specific MMP-2 inhibition (but not MIP-2, TNF-α, or IL-4 inhibition) delayed epithelial repair in an in vitro wound model using murine or human alveolar cells cultured in the presence of bronchoalveolar lavage fluid from mice during the repair phase or from patients with acute respiratory distress syndrome, respectively. Similarly, MMP inhibition with doxycycline impaired lung repair after VILI in vivo. In conclusion, VILI can be reverted by normalizing ventilation pressures. An adequate inflammatory response and extracellular matrix remodeling are essential for recovery. MMP-2 could play a key role in epithelial repair after VILI and acute respiratory distress syndrome.

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E.coli JM83 Damages Mucosal Barrier Inducing Hirschsprung-Associated Enterocolitis via Activated TLR4 / NF-κB / P-p38 Signaling

10.21203/rs.3.rs-1047222/v1 ◽

2021 ◽

Author(s):

Zebing Zheng ◽

Mingjuan Gao ◽

Chengyan Tang ◽

Lu Huang ◽

Yuan Gong ◽

...

Keyword(s):

Mucosal Damage ◽

Mucosal Barrier ◽

Endothelin Receptor ◽

Oral Gavage ◽

E Coli ◽

Treatment And Prevention ◽

Tnf Α ◽

Study Results ◽

Actin Protein

Abstract Purpose Hirschsprung-associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and unbalance of intestinal microbiota. Recent studies have shown that the TLR4/NF-κB/p-p38 signaling in the intestine is of great importance to intestinal mucosal integrity. This study aimed to investigate the role of TLR4/NF-κB/p-p38 signaling in the pathogenesis of HAEC in Escherichia coli (E. coli) JM83 infected Endothelin receptor B (Ednrb)−/− mice. Methods Ednrb −/− mice were administered with E. coli JM83 by oral gavage to establish the HAEC model, mice were randomly divided into WT group, Ednrb−/− group and Ednrb−/−+ E. coli JM83 group. The role of TLR4/NF-κB/p-p38 signaling was evaluated by vivo study. Results The activation of the TLR4/NF-κB/p-p38 signaling induced by E. coli JM83 caused HAEC in Ednrb−/− mice, which was evidenced by a significantly increased expression of TNF-α, TGF-β and IL-10, decreased density of F-actin protein. While TLR4 knockdown improved the degree of enterocolitis and attenuated the expression of IL-10, TNF-α, TGF-β and increased the density of F-actin protein in Ednrb−/− mice after E. coli infection. Conclusions These results indicate that E. coli JM83 activates TLR4/NF-κB/p-p38 signaling to promote the development of HAEC. However, inhibition of this signaling may be benefit to the treatment and prevention of HAEC.

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Electroacupuncture Inhibits Inflammatory Response in Rats With Interstitial Cystitis

Acupuncture & Electro-Therapeutics Research ◽

10.3727/036012921x16258618048412 ◽

2021 ◽

Author(s):

Ji-wei Feng ◽

Wen Li ◽

Jian-dang Liu ◽

Jun-wei Hu ◽

Zhi-hao Li ◽

...

Keyword(s):

Mast Cell ◽

Inflammatory Response ◽

Interstitial Cystitis ◽

Continuous Wave ◽

Bladder Capacity ◽

Mucosal Damage ◽

Mast Cell Tryptase ◽

Bladder Tissue ◽

Tnf Α ◽

Mechanism Research

OBJECTIVE: Electroacupuncture (EA) has been clinically utilized to manage interstitial cystitis (IC), but its related mechanism research is remained to be researched. This study aimed to explore the role of EA in inhibiting the inflammatory response of IC rats, and research the possible mechanism based on the changes of urodynamics, mast cell tryptase expression and the content of inflammatory substances. METHODS: EA (continuous wave, 30 Hz, 1 mA) was applied to stimulate the Ciliao point (BL32) and the Huiyang point (BL35) of rats. Changes of urodynamics, mast cell tryptase expression and the content of IL-6 and TNF-α were detected after 24 hours of the treatment. RESULTS: The results showed that after EA treatment, compared with the model group, the initial urination time of the rats was prolonged (3.23 ± 0.60 to 5.27 ± 0.27 min), the bladder capacity was increased (0.80 ± 0.15 to 1.31 ± 0.07 ml), and the degree of bladder mucosal damage was restored. The expression of mast cell tryptase, and the content of IL-6 and TNF-α in its bladder tissue and urine were reduced. CONCLUSION: These findings suggested that EA could suppress bladder overactivity and inhibit inflammatory response of IC rats, and its mechanism was proved to be related to the inhibition of mast cell degranulation and the down-regulation of inflammatory substances IL-6 and TNF-α in bladder tissue.

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