<scp>CP</scp>‐25 exerts therapeutic effects in mice with dextran sodium sulfate‐induced colitis by inhibiting <scp>GRK2</scp> translocation to downregulate the <scp>TLR4‐NF‐κB‐NLRP3</scp> inflammasome signaling pathway in macrophages

Liu, Ying; Jiang, Meng-Ya; Chen, Jingyu; Xu, Zhouwei; Zhang, Jiawei; Li, Tao; Zhang, Lingling; Wei, Wei

doi:10.1002/iub.2564

Cited by 13 publications

(5 citation statements)

References 60 publications

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“…DSS is often used to induce a mouse model of UC [23]. A prior study has reported that the pathogenesis of DSS-induced UC may be related to the imbalance of macrophage polarization [24]. In this study, we investigated whether and how CJ affected macrophage polarization during the development of UC using a DSS-induced UC model.…”

Section: Discussionmentioning

confidence: 98%

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Sun

Zhao

Ding

et al. 2022

Mediators of Inflammation

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Background and Aims. Several components of Cayratia japonica (CJ) such as rutin and quercetin have shown anti-inflammatory effect, yet its function in ulcerative colitis (UC) remains to be clarified. This study focuses on the modulatory effect of CJ on UC as well as molecular mechanism by which CJ regulates macrophage polarization in UC. Methods. The targets related to CJ components and UC were, respectively, obtained through in silico analysis, and their intersection targets were selected for pathway enrichment analysis. RAW264.7 cells were stimulated with lipopolysaccharide (LPS) to induce M1 macrophages. Expression of the macrophage polarization M1 marker CD11b and M2 marker CD206 was measured to determine the phenotype of macrophages. The mouse model was treated with dextran sodium sulfate (DSS) to induce UC to observe the effects of CJ on UC in vivo. Results. The in silico analysis suggested the crucial significance of TLR4 and its downstream MAPK/NF-κB pathways in the modulatory effect of CJ on UC. Furthermore, experimental data revealed that CJ could promote M2 macrophage polarization but alleviate immune inflammation and reduce colon damage in DSS-evoked UC model. Additionally, CJ can inhibit the expression of TLR4/MAPK/NF-κB signaling pathway to enhance the M2-like polarization. Conclusion. Hence, CJ may exert anti-inflammatory effects and an inhibitory role in UC by inhibiting the TLR4/MAPK/NF-κB pathway and subsequent M1-like macrophage polarization.

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Section: Discussionmentioning

confidence: 98%

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Sun

Zhao

Ding

et al. 2022

Mediators of Inflammation

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“…Jiang et al [ 52 ] studied a DSS-induced mice model of colitis to evaluate the effectiveness of paeoniflorin-6′-O-benzene sulfonate, an active monomeric anti-inflammatory agent produced by chemical structural modifications of paeoniflorin, and showed decreased G-protein-coupled receptor kinase 2 (GRK2) translocation and TLR4-NF-kB-NLRP3 inflammasome signaling in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

et al. 2023

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Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn’s disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-κB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-KB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

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“…For instance, the introduction of IKK (IκB kinase) inhibitors weakened ENDRB-mediated contraction 35 . Also, GRK2 was involved in the regulation of NF-κB signaling pathway 36,37 . For instance, GRK2 inhibitor paroxetine markedly abated arginine vasopressin-evoked NF-κB activation in neonatal rat cardiac fibroblasts 37 .…”

Section: Discussionmentioning

confidence: 99%

Endothelin receptor B enhances liver injury and pro-inflammatory responses by increasing G-protein-coupled receptor kinase-2 expression in primary biliary cholangitis

Gong

et al. 2022

Sci Rep

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Severe diseases like cirrhosis and liver failure can be developed from primary biliary cholangitis (PBC). Endothelin-2 (EDN2) and endothelin receptor B (EDNRB) are related to the pathogenesis of PBC. However, the roles of EDN2 and EDNRB in PBC-related liver injury and inflammation along with molecular mechanisms are poorly defined. In this study, histopathologic alterations of liver tissues were assessed through hematoxylin–eosin staining. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), and γ-Glutamyltranspetidase (GGT) (4 liver function indexes) serum levels were detected with corresponding activity assay kits. Also, we determined the levels of M2 subtype anti-mitochondrial antibody (AMA-M2), interferon-gamma (IFN-γ), and tumor-necrosis factor alpha (TNFα) in serum with ELISA assay. Later, RT-qPCR assay was used to measure the expression of genes at mRNA levels, while western blotting and immunohistochemical techniques were used to detect protein levels of genes. Our results showed that the liver tissues of PBC patients and mice presented with severe hepatocyte injury and inflammatory cell infiltration as well as destruction of intrahepatic small bile ducts. ALP, AST, ALT, GGT, AMA-M2, IFN-γ, and TNF-α serum levels were higher in PBC patients and mice. Besides, EDN2 and EDNRB were highly expressed in serums and livers of PBC patients and mice. EDNRB potentiated PBC-related liver injury and pro-inflammatory responses, as evidenced by observation of serious liver pathologic injury and increased serum levels of ALP, AST, ALT, AMA-M2, IFN-γ, and TNF-α in PBC mice following EDNRB overexpression. EDNRB overexpression or activation via its agonist IRL-1620 TFA triggered liver injury and pro-inflammatory responses, increased GRK2 expression and induced NF-κB expression and activation in wild-type mice. EDNRB knockdown or inhibition by Bosentan alleviated liver damage and inflammation, reduced GRK2 expression, and inhibited NF-κB in PBC mice. These findings suggested EDNRB loss or inhibition weakened liver injury and pro-inflammatory responses by down-regulating GRK2 and inhibiting the NF-κB pathway in PBC mice.

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CP‐25 exerts therapeutic effects in mice with dextran sodium sulfate‐induced colitis by inhibiting GRK2 translocation to downregulate the TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway in macrophages

Cited by 13 publications

References 60 publications

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

Endothelin receptor B enhances liver injury and pro-inflammatory responses by increasing G-protein-coupled receptor kinase-2 expression in primary biliary cholangitis

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