scholarly journals Cinacalcet Targets the Neurokinin-1 Receptor and Inhibits PKCδ/ERK/P65 Signaling to Alleviate Dextran Sulfate Sodium-Induced Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuehong Chen ◽  
Huan Liu ◽  
Qiuping Zhang ◽  
Yubin Luo ◽  
Liang Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Structural Integrity ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Therapeutic Effects ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Objective: Inflammatory bowel disease is an immune-mediated chronic inflammatory disease of the gastrointestinal tract for which curative drugs are currently not available. This study was performed to assess the therapeutic effects of cinacalcet on dextran sulfate sodium (DSS)-induced colitis.Methods: Primary macrophages obtained from bone marrow and the macrophage cell line RAW264.7 were used to examine the inhibitory effect of cinacalcet on cytokine production, the PKCδ/ERK/P65 signaling pathway, and NF-κB P65 translocation. Colitis was induced using DSS to assess the treatment effect of cinacalcet. Bioinformatics approaches were adopted to predict potential targets of cinacalcet, and a drug affinity responsive target stability (DARTs) assay was performed to confirm binding between cinacalcet and potential target.Results:In vivo analysis showed that cinacalcet reduced the disease activity score, prevented shortening of the colon, diminished inflammatory cell infiltration, and protected the structural integrity of the intestinal wall. Cinacalcet also reduced production of the inflammatory cytokines TNFα, IL-1β, and IL-6 in the colon and sera of mice with DSS-induced colitis. In vitro studies revealed that cinacalcet suppressed the translocation of P65 and inhibited production of the inflammatory cytokines IL-1β and IL-6. Mechanistic studies revealed that the target of cinacalcet was neurokinin-1 receptor (NK1R) and their binding was confirmed by a DARTs assay. Furthermore, the inhibition of NK-κB P65 activation was found to occur via the suppression of PKCδ/ERK/P65 signaling mediated by cinacalcet.Conclusion: Cinacalcet inhibits the activation of NF-κB and reduces the production of inflammatory cytokines by suppressing the PKCδ/ERK/P65 signaling pathway via targeting NK1R, suggesting that it can be used to treat inflammatory diseases, particularly colitis.

scholarly journals Protective Effects of L-Theanine on IPEC-J2 Cells Growth Inhibition Induced by Dextran Sulfate Sodium Via p53 Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7002
Author(s):  
Longlin Zhang ◽  
Mengmeng Ma ◽  
Zhengyi Li ◽  
Haihan Zhang ◽  
Xi He ◽  
...  
Keyword(s):  
Amino Acid ◽  
Signaling Pathway ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Nucleotide Metabolism ◽  
Normal Operation ◽  
Protective Effects ◽  
P53 Signaling ◽  
P53 Signaling Pathway

L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

scholarly journals Lactobacillus reuteri Ameliorates Intestinal Inflammation and Modulates Gut Microbiota and Metabolic Disorders in Dextran Sulfate Sodium-Induced Colitis in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2298
Author(s):  
Gang Wang ◽  
Shuo Huang ◽  
Shuang Cai ◽  
Haitao Yu ◽  
Yuming Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Intestinal Bacteria ◽  
Ht 29

Lactobacillus reuteri, a commensal intestinal bacteria, has various health benefits including the regulation of immunity and intestinal microbiota. We examined whether L. reuteri I5007 could protect mice against colitis in ameliorating inflammation, modulating microbiota, and metabolic composition. In vitro, HT-29 cells were cultured with L. reuteri I5007 or lipopolysaccharide treatment under three different conditions, i.e., pre-, co- (simultaneous), and posttreatment. Pretreatment with L. reuteri I5007 effectively relieves inflammation in HT-29 cells challenged with lipopolysaccharide. In vivo, mice were given L. reuteri I5007 by gavage throughout the study, starting one week prior to dextran sulfate sodium (DSS) treatment for one week followed by two days without DSS. L. reuteri I5007 improved DSS-induced colitis, which was confirmed by reduced weight loss, colon length shortening, and histopathological damage, restored the mucus layer, as well as reduced pro-inflammatory cytokines levels. Analysis of 16S rDNA sequences and metabolome demonstrates that L. reuteri I5007 significantly alters colonic microbiota and metabolic structural and functional composition. Overall, the results demonstrate that L. reuteri I5007 pretreatment could effectively alleviate intestinal inflammation by regulating immune responses and altering the composition of gut microbiota structure and function, as well as improving metabolic disorders in mice with colitis.

Hepatoblastoma cells express truncated neurokinin-1 receptor and can be growth inhibited by aprepitant in vitro and in vivo

2014 ◽  
Vol 60 (5) ◽  
pp. 985-994 ◽  
Author(s):  
Michael Berger ◽  
Olaf Neth ◽  
Matthias Ilmer ◽  
Agnès Garnier ◽  
Manuel Vicente Salinas-Martín ◽  
...  
Keyword(s):  
Neurokinin 1 Receptor ◽  
Neurokinin 1

scholarly journals Alleviation Effects of Bifidobacterium animalis subsp. lactis XLTG11 on Dextran Sulfate Sodium-Induced Colitis in Mice

2021 ◽  
Vol 9 (10) ◽  
pp. 2093
Author(s):  
Nana Wang ◽  
Song Wang ◽  
Baofeng Xu ◽  
Fei Liu ◽  
Guicheng Huo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Intestinal Barrier Function ◽  
Spleen Weight ◽  
Colon Tissue ◽  
Bifidobacterium Animalis

Inflammatory bowel disease (IBD) is a chronic immune-related disease, which can occur through the dysfunction of the immune system caused by the imbalance of gut microbiota. Previous studies have reported the beneficial effects of Bifidobacterium on colitis, while the related mechanisms behind these effects have not been fully elucidated. The aim of our study is to investigate the alleviation effect of Bifidobacterium animalis subsp. lactis XLTG11 (B. lactis) on dextran sulfate sodium (DSS)-induced colitis and its potential mechanism. The results showed that B. lactis XLTG11 significantly decreased weight loss, disease activity index score, colon shortening, myeloperoxide activity, spleen weight, and colon tissue damage. Additionally, B. lactis XLTG11 significantly decreased the levels of pro-inflammatory cytokines and increased the level of anti-inflammatory cytokine. Meanwhile, high doses of B. lactis XLTG11 significantly up-regulated the expression of tight junction proteins and inhibited activation of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MYD88)/nuclear factor-κB (NF-κB) signaling pathway. Furthermore, B. lactis XLTG11 increased the gut microbiota diversity and modulated gut microbiota composition caused by DSS. Moreover, Spearman’s correlation analysis also found that several specific gut microbiota were significantly correlated with colitis-related indicators. These results demonstrated that B. lactis XLTG11 can alleviate DSS-induced colitis by inhibiting the activation of the TLR4/MYD88/NF-κB signaling pathway, regulating inflammatory cytokines, improving intestinal barrier function, and modulating the gut microbiota.

scholarly journals Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis

2021 ◽  
Author(s):  
Hogjuan Ning ◽  
Haixu Chen ◽  
Jingyu Deng ◽  
Chun Xiao ◽  
Lina Shan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathway ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
Cell Based Therapy ◽  
Anti Inflammation

Abstract Background Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secreted more exosomes, but little was known on MI repair. Methods Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis, and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Results Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs–Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF-κB signaling pathway and upregulated Nrf2/HO-1 Axis. Conclusions FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.

scholarly journals Schisantherin A Inhibits Pulmonary Fibrosis via Regulating ERK Signaling Pathway

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094835
Author(s):  
Wenyue Zhuang ◽  
Na Zhao ◽  
Di Li ◽  
Xiaoming Su ◽  
Yueyang Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Erk Signaling ◽  
Mesenchymal Transition ◽  
Tgf Β1 ◽  
Schisantherin A

There is no effective method for treating pulmonary fibrosis (PF) until now. This study investigated the anti-fibrotic effect of schisantherin A (SCA) extracted from Schisandra chinensis and its potential molecular mechanism in PF. A bleomycin-induced PF mouse model in vivo and transforming growth factor (TGF)-β1-induced A549 epithelial-mesenchymal transition (EMT) cell model in vitro were used for assessing the anti-fibrotic effect of SCA. Histopathological examination was conducted after hematoxylin and eosin and Masson staining. The level of TGF-β1 was tested by ELISA. The expression levels of α-smooth muscle actin, E-cadherin, and inflammatory cytokines (COX2, IL-1β, IL-6, and TNF-α) were determined by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of extracellular signal-regulated kinase (ERK) was tested in lung tissues and cells by Western blot. The in vivo experiments revealed that SCA treatment markedly improved body weight and pulmonary index and reformed the destruction of the lung tissue structure. We observed that SCA inhibited the process of TGF-β1-induced EMT in the in vitro experiments. Inflammatory cytokines were reduced greatly in lung tissues and cells by SCA. Our study also indicated that SCA decreased phosphorylated ERK. It was concluded that SCA can attenuate PF by regulating the ERK signaling pathway, which suggests that SCA may be used as a potential therapeutic drug for PF.

In vitro and in vivo pharmacological characterization of Pronetupitant, a prodrug of the neurokinin 1 receptor antagonist Netupitant

Peptides ◽  
2015 ◽  
Vol 69 ◽  
pp. 26-32 ◽  
Author(s):  
Chiara Ruzza ◽  
Anna Rizzi ◽  
Davide Malfacini ◽  
Stefano Molinari ◽  
Claudio Giuliano ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Pharmacological Characterization ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

scholarly journals Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongjuan Ning ◽  
Haixu Chen ◽  
Jingyu Deng ◽  
Chun Xiao ◽  
Moyan Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathway ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
Cell Based Therapy ◽  
Anti Inflammation

Abstract Background Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair. Methods Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Results Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF‐κB signaling pathway and upregulated Nrf2/HO-1 Axis. Conclusions FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.

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