Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation

Elshawi, Omama E.; Nabeel, A.I.

doi:10.1016/j.jphotobiol.2019.01.006

Cited by 18 publications

(8 citation statements)

References 34 publications

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“…Studies have shown that IL‐1β and TNF‐α stimulate cells to increase the level of iNOS as well as upregulate the expression of COX‐2 (Au et al, 2007). COX‐2 and iNOS regulate inflammation and immune function (Fukunaga et al, 2005; Tiwari et al, 2019), and are overexpressed in inflammatory lesions (Elshawi & Nabeel, 2019). The overexpression of iNOS and COX‐2 results in NO and PGE2 accumulation.…”

Section: Discussionmentioning

confidence: 99%

Schisandrin improves lipopolysaccharide‐induced acute lung injury by inhibiting the inflammatory response in vivo and in vitro

Liu

Huang

et al. 2022

Journal of Food Biochemistry

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Acute lung injury (ALI) is characterized by an excessive inflammatory response, closely related to sepsis occurrence and development. It has been reported that Schisandrin (Sch) exhibits anti-inflammatory activity. However, whether the beneficial effects of Sch exists during ALI remains to be studied. In this study, the impact of Sch was evaluated by studying lung tissue damage, measuring the concentrations of pro-inflammatory factors, and the expression of apoptotic proteins in the LPS-induced ALI mice model. Protein expression of inflammation-related signaling pathway within the lung tissue and A549 cells were also measured. In addition, the effect of Sch on A549 cell apoptosis and inflammatory markers was also detected. Animal experiments demonstrated that pre-feeding Sch alleviated the production of inflammation mediators, abnormal pathological injuries, and blocked the progression of apoptotic events in the lung tissue. The in vitro experiments showed that Sch pretreatment reduced LPS upregulated interleukin-1β (IL-1β), IL-18, and IL-6 levels, and improved LPS-induced abnormal apoptosis. Sch and the pathway inhibitor AG490 also inhibited the expression levels of p-JAK2 and p-STAT3 in A549 cells. Moreover, pretreatment with Sch significantly inhibited the activation of NLRP3 inflammasomes, reduced inducible nitric oxide synthase, and cyclooxygenase 2 proteins expression during ALI in vitro and in vivo. Overall, Sch effectively alleviated ALI and provided a new mechanism to support the protective effect of Sch for sepsis-induced ALI. Practical implicationsALI is characterized by inflammatory injury of the lungs, which is an important cause of high morbidity and mortality in severe patients. Sch is considered as a botanical active ingredient with various pharmacological activities, such as neuroprotective and vascular protective effects. However, the effect of Sch on ALI and its mechanism remains largely unknown. Research data indicate that Sch exerts an anti-inflammatory effect by reducing the production of inflammatory factors and abnormal apoptosis of cells, further alleviating lung damage. The protective effect of Sch was associated with inhibition of the activation of NLRP3 and the JAK2/STAT3 inflammatory pathways. The study, therefore, confirmed that Sch has a potential as an effective drug to prevent ALI diseases.

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Section: Discussionmentioning

confidence: 99%

Schisandrin improves lipopolysaccharide‐induced acute lung injury by inhibiting the inflammatory response in vivo and in vitro

Liu

Huang

et al. 2022

Journal of Food Biochemistry

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“…A history of acute diarrheal illness preceding the onset of irritable bowel symptoms in some patients has suggested that the development of IBS occurs following infectious enteritis. The increased risk of post-infectious IBS is associated with bacterial, protozoan, helminth, and viral infections [41,42,43,44,45] . Some meta-analyses have shown an increased risk of IBS in patients who had experienced an episode of acute gastroenteritis [46,47] .…”

Section: Discussionmentioning

confidence: 99%

“…contributed to the development of chronic in ammatory diseases [42,43] . PGE2 plays an important role in the initiation of in ammation and pain.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Effects of Changping Decoction on Irritable Bowel Syndrome by Pathway and Pharmacology Network Bioinformatics Analysis

Ding

et al. 2020

Preprint

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Background An increasing body of research has confirmed the effectiveness of Traditional Chinese Medicine (TCM) for the treatment of irritable bowel syndrome (IBS).Methods We explored the potential mechanism of Changping decoction (CPD) in the treatment of IBS through pathway analysis based on a network pharmacology approach. Public databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Gene Expression Omnibus, and STRING, were used to screen the active ingredients and targets of CPD. Enrichment analysis was performed using the R-3.6.0 software to expound the biological functions and related pathways of CPD targets. The Cytoscape software was used to construct a “disease-CPD-target” network and identify hub genes of CPD relevant for the treatment of IBS. Employing rat models, pathological observation and abdominal withdrawal reflex tests were used to verify the effectiveness of CPD in the treatment of IBS. Immunohistochemistry was used to confirm the relationship between the CPD treatment and hub genes.Results Network pharmacological analysis of CPD for the treatment of IBS identified 159 active ingredients. A total of 118 key targets were identified, including MAPK8, VEGFA, PTGS2, and others. A series of signaling pathways, such as MAPK, Kaposi sarcoma-associated herpesvirus infection, and IL-17 signaling pathway were found to play an important role in the therapeutic mechanism of CPD in the treatment of IBS. Pathological observation and abdominal withdrawal reflex tests confirmed that the symptoms of IBS in rats were relieved by CPD. Moreover, immunohistochemistry confirmed that CPD could inhibit the expression of inflammation-associated factors, such as VEGFA, MAPK8, and PTGS2.Conclusions Based on network pharmacology analysis, the present study provides insights into the potential mechanism of CPD in the treatment of IBS after successfully screening for associated key target genes and signaling pathways. These findings establish a theoretical basis for the development of CPD-derived therapeutics.

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“…demonstrated in mice that COX2 inhibition with a benzopyran compound mitigated radiation-induced NF-κB and COX2 activity. The treatment also ameliorated other radiotherapy-induced effects such as the increase of cytokines and decrease of liver enzymes ( 400 ). Celecoxib, another COX2 inhibitor, reduces radiation-induced skin toxicity in mice ( 401 ), which has been confirmed by other studies, reporting that celecoxib treatment enhances radiosensitization and reduces tumor growth ( 399 , 402 , 403 ).…”

Section: Protecting Normal Tissue During Radiotherapymentioning

confidence: 99%

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

2021

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To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatment. These strategies, capable of either sensitizing or protecting tissues, target either tumor or normal tissue and are often focused on modulating of tissue oxygenation, hypoxia-inducible factor (HIF) stabilization, glucose metabolism, mitochondrial function and the redox balance. Several compounds or therapies are still in under (pre-)clinical development, while others are already used in clinical practice. Here, we describe different strategies from bench to bedside to optimize the therapeutic ratio through modulation of the cellular metabolism. This review gives an overview of the current state on development and the mechanism of action of modulators affecting cellular metabolism with the aim to improve the radiotherapy response on tumors or to protect the normal tissue and therefore contribute to an improved therapeutic ratio.

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Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation

Cited by 18 publications

References 34 publications

Schisandrin improves lipopolysaccharide‐induced acute lung injury by inhibiting the inflammatory response in vivo and in vitro

Schisandrin improves lipopolysaccharide‐induced acute lung injury by inhibiting the inflammatory response in vivo and in vitro

Exploring the Effects of Changping Decoction on Irritable Bowel Syndrome by Pathway and Pharmacology Network Bioinformatics Analysis

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

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