Ibrutinib attenuated DSS-induced ulcerative colitis, oxidative stress, and inflammatory cascade by modulating PI3K/Akt and JNK/NFκB pathways

Hao, Liangliang; Alkry, Lina; Alattar, Abdullah; Faheem, Muhammad; Alshaman, Reem; Shah, Fawad Ali; Li, Shupeng

doi:10.5114/aoms/146792

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…28 Phagocytes such as neutrophils and hepatic macrophages release ROS physiologically, causing excessive oxidative stress in pathological states. 29 In our study, the expression of GSH-Px, SOD, and MDA was affected by DSS. Lipid peroxidation characterizes oxidative stress.…”

Section: Discussionsupporting

confidence: 46%

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Study on the Protective Effect and Mechanism of Umbilicaria esculenta Polysaccharide in DSS-Induced Mice Colitis and Secondary Liver Injury

Wang,

Liu,

Gao

et al. 2024

J. Agric. Food Chem.

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This study aimed to explore the ameliorative effects and potential mechanisms of Huangshan Umbilicaria esculenta polysaccharide (UEP) in dextran sulfate sodium-induced acute ulcerative colitis (UC) and UC secondary liver injury (SLI). Results showed that UEP could ameliorate both colon and liver pathologic injuries, upregulate mouse intestinal tight junction proteins (TJs) and MUC2 expression, and reduce LPS exposure, thereby attenuating the effects of the gut−liver axis. Importantly, UEP significantly downregulated the secretion levels of TNF-α, IL-1β, and IL-6 through inhibition of the NF-κB pathway and activated the Nrf2 signaling pathway to increase the expression levels of SOD and GSH-Px. In vitro, UEP inhibited the LPS-induced phosphorylation of NF-κB P65 and promoted nuclear translocation of Nrf2 in RAW264.7 cells. These results revealed that UEP ameliorated UC and SLI through NF-κB and Nrf2-mediated inflammation and oxidative stress. The study first investigated the anticolitis effect of UEP, suggesting its potential for the treatment of colitis and colitis-associated liver disease.

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Section: Discussionsupporting

confidence: 46%

“…It has been shown that crypt damage colitis similar to UC occurs in GSH-Px knockout mice at 11 weeks of age . Phagocytes such as neutrophils and hepatic macrophages release ROS physiologically, causing excessive oxidative stress in pathological states . In our study, the expression of GSH-Px, SOD, and MDA was affected by DSS.…”

Section: Discussionmentioning

confidence: 46%

Study on the Protective Effect and Mechanism of Umbilicaria esculenta Polysaccharide in DSS-Induced Mice Colitis and Secondary Liver Injury

Wang,

Liu,

Gao

et al. 2024

J. Agric. Food Chem.

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“…This is consistent with previous research results: Ying et al discovered that the AKT signal pathway is directly related to cell apoptosis [ 26 ]. Hao et al proposed that the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is implicated in multiple cellular processes, such as survival, proliferation, differentiation, and apoptosis, and the PI3K/Akt signaling pathway is linked to major degenerative diseases [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits lipopolysaccharide-induced proximal renal tubular epithelial cell death by regulating ADAMTS18 methylation and AKT/Notch pathways

Zhang

Lin

et al. 2023

Arch Med Sci

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IntroductionThis study aimed to explore the effect of curcumin on the activity of lipopolysaccharide (LPS)-induced proximal renal tubular epithelial cells (PRTECs) and to analyze the molecular mechanism by which curcumin regulates their occurrence.Material and methodsLPS-induced PRTECs were used to construct an inflammatory cell model. RT-qPCR and western blot (WB) were used to detect ADAMTS18 expression. Methylation-specific PCR was used to detect ADAMTS18 methylation levels. After curcumin treatment, MTT assay was used to analyze cell viability, flow cytometry was used to analyze apoptosis, and ADAMTS18 expression and methylation levels were detected again. After transfection with siADAMTS18, cell viability and apoptosis were analyzed again. The levels of inflammatory factors were measured by enzyme-linked immunosorbent assay, and the expression levels of AKT, Notch-1 and Notch-2 were analyzed by WB.ResultsCurcumin strongly inhibited LPS-induced PRTEC inflammatory lesions, restored normal cell proliferation, and reduced the apoptosis rate by downregulating ADAMTS18 methylation and restoring ADAMTS18 expression. After siADAMTS18, the ability of curcumin to improve cell viability was reduced, and the ability of curcumin to downregulate inflammatory factors was significantly reduced. Besides, curcumin could also inhibit the expressions of AKT, Notch-1 and Notch-2 simultaneously. siADAMTS18 attenuated the abovementioned effects of curcumin.ConclusionsCurcumin inhibits LPS-induced PRTECs death by regulating ADAMTS18 methylation and AKT/Notch pathways.

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“…Chronic inflammation, the increased turnover of epithelial cells, and ROS production are thought to contribute to the development of dysplastic lesions, which may then transform into CRC [ 55 ]. JUN is a proto-oncogene that can induce oncogenic transformation [ 56 ]. The mutation of the p53 gene is a critical genetic change, involved in the early stages of UC-associated carcinogenesis of the colorectum.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome

Zhai

Yang

et al. 2023

J. pharm. pharm. sci.

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Background: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) share various similarities in clinical symptoms, pathogenesis, and treatment. UC concurrent IBS tends toward more severe symptoms and worse prognosis, and promising feasible therapies for the overlapping symptoms remains a challenge. Rhubarb peony decoction (RPD) is a well-known traditional Chinese medicine that has been widely applied in treating UC. RPD may exert extensive therapeutic effects on both IBS and UC. However, the common mechanism of its treatment remains unclear. We aimed to assess the potential pharmacological mechanism of RPD in the treatment of overlapping IBS and UC.Methods: The active components and targets of RPD were retrieved from ETCM, TCMSP, BATMAN-TCM, and TCM databases. The disease targets were screened by searching the DrugBank, OMIM, TTD, and PharmGKB databases. PPI network analysis was performed and visualized via the STRING platform and Cytoscape software. GO and KEGG enrichment analyses of the hub genes of RPD were predicted to elucidate the potential molecular mechanism. Subsequently, molecular docking was carried out to verify the combination of active compounds with core targets.Results: By integrating all targets of RPD and disease, a total of 31 bioactive ingredients were identified including quercetin, kaempferol, aloe-emodin, beta-sitosterol, and (+)-catechin, etc. JUN, TP53, MAPK1, RELA, MYC, and ESR1 were explored as potential therapeutic targets among 126 common drug-disease-related targets. They were enriched in the AGE-RAGE signaling pathway in diabetic complications, as well as the NF-kappa B signaling pathway and MAPK signaling pathway. Additionally, some active ingredients were identified as candidates for binding to the hub targets via molecular docking, further suggesting their anti-inflammatory and antioxidative properties.Conclusion: RPD may exert the overall treatment effect for UC and IBS overlap syndrome via the biological mechanism of “multi-ingredients, multi-targets, and multi-pathways” on inflammation, oxidative stress, immune, oncogenicity, and gut microbiota dysbiosis.

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Ibrutinib attenuated DSS-induced ulcerative colitis, oxidative stress, and inflammatory cascade by modulating PI3K/Akt and JNK/NFκB pathways

Cited by 5 publications

References 36 publications

Study on the Protective Effect and Mechanism of Umbilicaria esculenta Polysaccharide in DSS-Induced Mice Colitis and Secondary Liver Injury

Study on the Protective Effect and Mechanism of Umbilicaria esculenta Polysaccharide in DSS-Induced Mice Colitis and Secondary Liver Injury

Curcumin inhibits lipopolysaccharide-induced proximal renal tubular epithelial cell death by regulating ADAMTS18 methylation and AKT/Notch pathways

Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome

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