scholarly journals Pingkui Enema Alleviates TNBS-Induced Ulcerative Colitis by Regulation of Inflammatory Factors, Gut Bifidobacterium, and Intestinal Mucosal Barrier in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hai-Feng Yun ◽  
Rui Liu ◽  
Dan Han ◽  
Xin Zhao ◽  
Jin-Wei Guo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Survival Rate ◽  
Serum Concentration ◽  
Mucosal Barrier ◽  
Inflammatory Factors ◽  
High Dose ◽  
Trinitrobenzene Sulfonic Acid ◽  
Sprague Dawley ◽  
Intestinal Mucosal Barrier ◽  
Intestinal Mucus

Background. Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon, and clinical outcome of UC is still unsatisfied. Pingkui enema, a traditional Chinese medicine prescription, has been safely applied for the treatment of diarrhea and dysentery in clinic for many years. However, its mechanism is still elusive. The present study is designed to investigate the effect of Pingkui enema on trinitrobenzene sulfonic acid- (TNBS-) induced ulcerative colitis (UC) and possible mechanism in rats. Methods. UC was induced by intracolonic instillation of TNBS in male Sprague-Dawley rats, which were treated with different dosages of Pingkui enema (low, medium, and high) or sulfasalazine for ten days. Survival rate was calculated. A clinical disease activity score was evaluated. Histological colitis severity was analyzed by hematoxylin-eosin (HE) staining. Content of Bifidobacterium in intestinal tissue was analyzed by RT-PCR. Concentration of IL-8, IL-13, TNF-α, D-lactic acid (D-LA), and diamine oxidase (DAO) in serum and contents of adhesin and receptor of Bifidobacterium adhesion in rat intestinal mucus were measured by ELISA. Results. The results showed that Pingkui enema treatment with high dosage markedly improved the survival rate compared with untreated and sulfasalazine treated groups. All dosages of Pingkui enema reduced pathological score. High dosage of Pingkui enema and sulfasalazine treatments significantly reduced the serum concentration of IL-8, TNF-α, D-LA, and DAO and markedly increased the serum concentration of IL-13. In addition, high-dose Pingkui enema and sulfasalazine treatments increased gut content of Bifidobacterium, gut mucus expressions of adhesin, and adhesin receptor of Bifidobacterium. Conclusions. Pingkui enema has therapeutic effect on TNBS-induced UC, and possible mechanism may be via regulation of gut probiotics (Bifidobacterium) and inflammatory factors and protection of intestinal mucosal barrier.

scholarly journals Sishen Pill Maintained Colonic Mucosal Barrier Integrity to Treat Ulcerative Colitis via Rho/ROCK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiao-Yun Zhang ◽  
Hai-Mei Zhao ◽  
Yi Liu ◽  
Xiu-Yun Lu ◽  
Yan-Zhen Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Connexin 43 ◽  
Clinical Symptoms ◽  
Rho Kinase ◽  
Gastrointestinal Diseases ◽  
Mucosal Barrier ◽  
Trinitrobenzene Sulfonic Acid ◽  
Injury Score ◽  
Intestinal Mucosal Barrier

Sishen Pill (SSP) is a classical prescription of traditional Chinese medicine and often used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, its mechanism is still unclear. We aimed to determine the mechanism of SSP in the treatment of UC by investigating if it maintains the integrity of the intestinal mucosal barrier via the Rho A/Rho kinase (ROCK) signaling pathway. Administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) successfully induced chronic UC in rats, while the treatment effect of SSP was evaluated by body weight change, colonic length, colonic weight, colonic weight index, histological injury score, and pathological injury score after colitis rats were treated for 7 days. TNF-α and IL-1β levels were analyzed by ELISA, and the proteins of PI3K/Akt and RhoA/ROCK signaling pathway and junction proteins expression were measured by western blotting assay, and the distribution of Claudin 5 was shown by immunofluorescence. SSP significantly improved the clinical symptoms of colitis in rats and reduced the expression of p-RhoA, ROCK1, PI3K, and Akt in the colon mucosa, while it increased the expression of p-Rac and related proteins (Claudin-5, JAM1, VE-cadherin, and Connexin 43). In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier.

Lactobacillus acidophilus and Clostridium butyricum ameliorate colitis in murine by strengthening the gut barrier function and decreasing inflammatory factors

2018 ◽  
Vol 9 (5) ◽  
pp. 775-787 ◽  
Author(s):  
Y. Wang ◽  
Y. Gu ◽  
K. Fang ◽  
K. Mao ◽  
J. Dou ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Lactobacillus Acidophilus ◽  
Barrier Function ◽  
Clostridium Butyricum ◽  
In Vivo Studies ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Barrier Function ◽  
Anti Inflammatory

Ulcerative colitis is a type of chronic inflammation present in the intestines for which the aetiology is not yet clear. The current therapies for ulcerative colitis cannot be considered to be long-term management strategies due to their significant side effects. Therefore, it is essential to identify an alternative therapeutic strategy for ulcerative colitis. The present study focused on the evaluation of the anti-inflammatory activities of Lactobacillus acidophilus CGMCC 7282 and Clostridium butyricum CGMCC 7281. The roles of both single and combination of L. acidophilus CGMCC 7282 and C. butyricum CGMCC 7281 in ulcerative colitis were investigated in 2,4,6-trinitrobenzenesulfonic acid-induced acute colitis (Th1-type colitis) in Sprague-Dawley rats and oxazolone-induced chronic colitis (Th2-type colitis) in BALB/c mice. The in vivo studies showed that the administration of L. acidophilus CGMCC 7282, C. butyricum CGMCC 7281 and L. acidophilus CGMCC 7282 plus C. butyricum CGMCC 7281 could reduce the Th1-type colitis as well as the Th2-type colitis, and the combination of the two strains exhibited the most notable effects, as indicated by the reduced mortality rates, the suppressed disease activity indices, the improved body weights, the reduced colon weight/colon length and colon weight/body weight ratios, and the improved gross anatomic characteristics and histological features (ameliorations of neutrophil infiltration and ulceration in the colon). It was found that the alterations of the gut microbiome, the barrier function changing and the selected inflammation-related cytokines are observed in the ulcerative colitis rats/mice treated with L. acidophilus CGMCC 7282 and C. butyricum CGMCC 7281. The combination of L. acidophilus CGMCC 7282 plus C. butyricum CGMCC 7281 also exerted a stronger anti-inflammatory effect than either of the single strains alone in vitro. These findings provide evidence that the administration of L. acidophilus CGMCC 7282 plus C. butyricum CGMCC 7281 may be a promising therapy for ulcerative colitis.

scholarly journals INT-777 Improves Cognitive Impairment after Sepsis by Attenuating Neuroinflammation Through the TGR5/cAMP/PKA/CREB Signaling Axis in Rats

2020 ◽  
Author(s):  
Peng Jin ◽  
Shuixiang Deng ◽  
Mi Tian ◽  
Pengju Wei ◽  
Yao Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Survival Rate ◽  
Cell Activation ◽  
Cecal Ligation ◽  
Clinical Score ◽  
Inflammatory Factors ◽  
Experimental Sepsis ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Sepsis Survivors

Abstract Background: Sepsis survivors are left with significant cognitive and behavioral impairments after discharge, but research on the relevant mechanisms and interventions remains lacking. TGR5 plays a neuroprotective role in many neurologic disease models through different mechanisms. To date, no studies have assessed the effects of TGR5 on neuroinflammation or cognitive or behavioral changes in sepsis models.Methods: A total of 267 eight-week-old male Sprague-Dawley rats were used in this study. Sepsis was induced by cecal ligation and puncture (CLP). All animals received volume resuscitation. The rats were given TGR5 CRISPR oligonucleotide intracerebroventricularly 48 hours before CLP surgery. INT-777 was administered intranasally 1 hour after CLP, and the cAMP inhibitor SQ22536 was administered intracerebroventricularly 1 hour after CLP. Survival rate, bodyweight change, clinical score, neurobehavioral tests, western blot, and immunofluorescence staining were performed. The cognitive function of rats was measured by Morris water maze during 15-20 days after CLP.Results: The expression of TGR5 in the rat hippocampus was upregulated and peaked at 3 days after CLP. The survival rate of rats after CLP was less than 50%, and the growth rate in terms of weight was significantly decreased, while these changes were not improved by INT-777 treatment. However, INT-777 treatment reduced the clinical scores of rats at 24 hours after CLP. On day 15 and later, the surviving mice completed a series of behavioral tests. CLP rats showed spatial and memory deficits and anxiety-like behaviors, and INT-777 treatment significantly improved these effects. Mechanistically, immunofluorescence analysis showed that INT-777 treatment reduced the number of microglia in the hippocampus, neutrophil infiltration and the expression of inflammatory factors after CLP in rats. Moreover, INT-777 treatment significantly increased the expression of TGR5, cAMP, p-PKA, and p-CREB and downregulated the expression of IL-1β, IL-6 and TNF-α. CRISPR-mediated TGR5 knockdown and SQ22536 treatment abolished the neuroprotective effects of TGR5 activation after CLP.Conclusion: This study demonstrates that INT-777 treatment reduced neuroinflammation and microglial cell activation, and then improved cognitive impairment in the experimental sepsis rats. TGR5 has translational potential as a therapeutic target to improve neurological outcomes in sepsis survivors.

scholarly journals The Protective Effects of a Combination of an Arginine Silicate Complex and Magnesium Biotinate Against UV-Induced Skin Damage in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Demet Cicek ◽  
Betul Demir ◽  
Cemal Orhan ◽  
Mehmet Tuzcu ◽  
Ibrahim Hanifi Ozercan ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Inflammatory Factors ◽  
High Dose ◽  
Activator Protein 1 ◽  
Protective Effects ◽  
Uvb Radiation ◽  
Skin Damage ◽  
Sprague Dawley ◽  
Uvb Exposure ◽  
Silicate Complex

The purpose of this study was to observe the effects of a novel combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on the prevention of skin damage after UVB exposure in rats. Forty-nine Sprague-Dawley rats were randomized into one of the following groups (Farage et al., 2008): NC, normal control (Gragnani et al., 2014), SC, shaved control (Pandel et al., 2013), UVB (exposed to UVB radiation) (Binic et al., 2013), ASI + MgB-L (Low Dose) (Dunaway et al., 2018), ASI + MgB-H (High Dose) (Dorner et al., 2009), ASI + MgB-L + MgB cream (Durmus et al., 2017), ASI + MgB-H + MgB cream. The results showed that ASI + MgB treatment alleviated the macroscopic and histopathological damages in the skin of rats caused by UVB exposure. Skin elasticity evaluation showed a similar trend. ASI + MgB increased serum Mg, Fe, Zn, Cu, Si, biotin, and arginine concentrations and skin hydroxyproline and biotinidase levels while decreasing skin elastase activity (p < 0.05) and malondialdehyde (MDA) concentration (p < 0.001). Moreover, ASI + MgB treatment increased skin levels of biotin-dependent carboxylases (ACC1, ACC2, PC, PCC, MCC) and decreased mammalian target of rapamycin (mTOR) pathways and matrix metalloproteinase protein levels by the regulation of the activator protein 1 (AP-1), and mitogen activated protein kinases (MAPKs) signaling pathways. In addition, ASI + MgB caused lower levels of inflammatory factors, including TNF-α, NFκB, IL-6, IL-8, and COX-2 in the skin samples (p < 0.05). The levels of Bax and caspase-3 were increased, while anti-apoptotic protein Bcl-2 was decreased by UVB exposure, which was reversed by ASI + MgB treatment. These results show that treatment with ASI and MgB protects against skin damage by improving skin appearance, elasticity, inflammation, apoptosis, and overall health.

scholarly journals The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Boxun Zhang ◽  
Rensong Yue ◽  
Yuan Chen ◽  
Xiaoying Huang ◽  
Maoyi Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Diabetic Rats ◽  
Mucosal Barrier ◽  
Inflammatory Factors ◽  
Pathological State ◽  
Intestinal Mucosal Barrier ◽  
Metabolic Inflammation ◽  
Anti Inflammatory

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

The Combined Effect of Vitamin C and Vitamin D3 on the Intestinal Epithelial Barrier by Regulating Notch Signaling Pathway

2019 ◽  
Author(s):  
Fubin Qiu ◽  
Zehui Zhang ◽  
Ying Ma ◽  
Linxue Yang ◽  
Rui Li
Keyword(s):  
Vitamin D ◽  
Vitamin C ◽  
Tight Junction ◽  
Mucosal Barrier ◽  
Control Group ◽  
High Dose ◽  
Tight Junction Proteins ◽  
Intestinal Mucosal Barrier ◽  
Notch Signal ◽  
Junction Proteins

Abstract Background: Tight junction proteins play crucial role in maintaining the intestinal mucosal barrier. Although previous studies had shown that the Notch signal is closely related to tight junction proteins, the mechanism by which it does so remains unknown. The goal of the present study was to investigate whether vitamin C combined with vitamin D3 affects intestinal mucosal barrier stability through Notch signal pathway.Results: To assess the effect of vitamin C combined with vitamin D3 on the intestinal mucosal barrier, electron microscopic observation of ultrastructure of tight junctions was done. And tight junction proteins gene and Notch signal gene expression were analyzed by quantitative reverse-transcription polymerase chain reaction, expression of tight junction protein in SW480 cells interfered with by LPS were examined by western blot. We found that vitamin C combined with vitamin D3 had protective effect on DSS-induced ulcerative colitis in guinea pig intestinal mucosa. Electron microscopy results showed that both low dose and high dose of vitamin C combined with vitamin D3 could maintain DSS-induced ulcerative colitis in guinea pig intestinal epithelium tight junction, however, the combination of medium dose vitamin C and vitamin D3 did not have this effect; Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, the cell migration and repair ability of different concentrations of vitamin C combined with vitamin D3 group were significantly improved, the protein expression of Notch-1 was increased, but the protein expression of claudin-2 was significantly decreased. Conclusions: our results of this experiment showed that the appropriate amount of vitamin C combined with vitamin D3 might regulate the expression of claudin-2 by regulating Notch-1, slow the intestinal mucosal barrier destruction, and promote the damage repair of cell mucosal barrier.

scholarly journals Simvastatin Ameliorates PAK4 Inhibitor-Induced Gut and Lung Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Shuming Pan ◽  
Zengbin Wu ◽  
Xuan Liu ◽  
Jiameng Chen ◽  
Huiqi Wang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Mitogen Activated Protein Kinase ◽  
Mucosal Barrier ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Intestinal Mucosal Barrier ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
P21 Activated Kinase ◽  
D Values

P21 activated kinase 4 (PAK4), a key regulator of cytoskeletal rearrangement and endothelial microparticles (EMPs), is released after lipopolysaccharide (LPS) stimulation. In addition, it participates in LPS-induced lung injury. In this study, forty-eight Sprague Dawley (SD) rats were divided into two groups, including PAK4 inhibitor (P) and PAK4 inhibitor + simvastatin (P + S) treatment groups. All rats were given PAK4 inhibitor (15 mg/kg/d) orally. Immediately after PAK4 inhibitor administration, simvastatin was injected intraperitoneally to P + S group animals at 20 mg/kg/day. Then, treatment effects on the intestinal mucosal barrier and lung injury caused by PAK4 inhibitor and simvastatin were assessed. The results showed that gut Zonula Occludens- (ZO-) 1, PAK4, mitogen-activated protein kinase 4 (MPAK4), and CD11c protein levels were reduced, while plasma endotoxin levels were increased after administration of PAK4 inhibitor. Furthermore, compared with normal rats, wet-to-dry (W/D) values of lung tissues and circulating EMP levels were increased in the treatment group, while PAK4 and CD11c protein amounts were reduced. Therefore, in this lung injury process induced by PAK4 inhibitor, the protective effects of simvastatin were reflected by intestinal mucosal barrier protection, inflammatory response regulation via CD11c+ cells, and cytoskeleton stabilization. In summary, PAK4 is a key regulator in the pathophysiological process of acute lung injury (ALI) and can be a useful target for ALI treatment.

scholarly journals Mechanism underlying effect of Sijunzi decoction on intestinal mucosal barrier of mice with ulcerative colitis

2015 ◽  
Vol 23 (27) ◽  
pp. 4326
Author(s):  
Jing-Yu Huang ◽  
Hui Nong ◽  
Xian Pei ◽  
Xue Huang ◽  
Zhi-Rou Tan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mucosal Barrier ◽  
Intestinal Mucosal Barrier
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