Natural products targeting Nrf2/ARE signaling pathway in the treatment of inflammatory bowel disease

Li, Botong; Wang, Yixuan; Jiang, Xiaolin; Du, Hongwu; Shi, Yan; Xiu, Minghui; Liu, Yongqi; He, Jianzheng

doi:10.1016/j.biopha.2023.114950

Cited by 10 publications

(3 citation statements)

References 215 publications

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“…Nrf2 plays a pivotal role in mitigating oxidative stress, inflammatory reactions, and barrier impairment, making it a prime target for ROS inhibition. Targeting Nrf2 signaling presents an efficacious strategy for treating colitis and intestinal barrier damage [27]. In our current investigation, we have shown that MAs notably enhance the translocation of Nrf2 to the nucleus.…”

Section: Discussionmentioning

confidence: 58%

Microbe-Derived Antioxidants Protect IPEC-1 Cells from H2O2-Induced Oxidative Stress, Inflammation and Tight Junction Protein Disruption via Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway

Shen,

Luo,

et al. 2024

Antioxidants

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Oxidative stress can induce inflammation and tight junction disruption in enterocytes. The initiation of inflammation is thought to commence with the activation of the ROS/NLRP3/IL-1β signaling pathway, marking a crucial starting point in the process. In our previous studies, we found that microbe-derived antioxidants (MAs) showed significant potential in enhancing both antioxidant capabilities and anti-inflammatory effects. The main aim of this research was to investigate the ability of MAs to protect cells from oxidative stress caused by H2O2, to reduce inflammatory responses, and to maintain the integrity of tight junction proteins by modulating the ROS/NLRP3/IL-1β signaling pathway. IPEC-1 cells (1 × 104 cells/well) were initially exposed to 100 mg/L of MAs for 12 h, after which they were subjected to 1 mM H2O2 treatment for 1 h. We utilized small interfering RNA (siRNA) to inhibit the expression of NLRP3 and Nrf2. Inflammatory factors such as IL-1β and antioxidant enzyme activity levels were detected by ELISA. Oxidative stress marker ROS was examined by fluorescence analysis. The NLRP3/IL-1β signaling pathway, Nrf2/HO-1 signaling pathway and tight junction proteins (ZO-1 and Occludin) were detected by RT-qPCR or Western blotting. In our research, it was observed that MA treatment effectively suppressed the notable increase in H2O2-induced inflammatory markers (TNF-α, IL-1β, and IL-18), decreased ROS accumulation, mitigated the expression of NLRP3, ASC, and caspase-1, and promoted the expression of ZO-1 and Occludin. After silencing the NLRP3 gene with siRNA, the protective influence of MAs was observed to be linked with the NLRP3 inflammasome. Additional investigations demonstrated that the treatment with MAs triggered the activation of Nrf2, facilitating its translocation into the nucleus. This process resulted in a notable upregulation of Nrf2, NQO1, and HO-1 expression, along with the initiation of the Nrf2-HO-1 signaling pathway. Consequently, there was an enhancement in the activities of antioxidant enzymes like SOD, GSH-Px, and CAT, which effectively mitigated the accumulation of ROS, thereby ameliorating the oxidative stress state. The antioxidant effectiveness of MAs was additionally heightened in the presence of SFN, an activator of Nrf2. The antioxidant and anti-inflammatory functions of MAs and their role in regulating intestinal epithelial tight junction protein disruption were significantly affected after siRNA knockdown of the Nrf2 gene. These findings suggest that MAs have the potential to reduce H2O2-triggered oxidative stress, inflammation, and disruption of intestinal epithelial tight junction proteins in IPEC-1 cells. This reduction is achieved by blocking the ROS/NLRP3/IL-1β signaling pathway through the activation of the Nrf2 pathway.

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Section: Discussionmentioning

confidence: 58%

Microbe-Derived Antioxidants Protect IPEC-1 Cells from H2O2-Induced Oxidative Stress, Inflammation and Tight Junction Protein Disruption via Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway

Shen,

Luo,

et al. 2024

Antioxidants

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“…It is an important transcription factor regulating the cellular oxidative stress response as well as a central regulator of cellular redox homeostasis [96]. The imbalance between free radicals and antioxidants in the body may lead to excessive production of reactive oxygen species (ROS), which, in turn, aggravates cell damage and inflammation in patients with ischemia-reperfusion injury [97]. This pathway can regulate the expression of antioxidant proteins, reduce the damage of reactive oxygen species and electrophilic reagents to cells, and maintain the body's REDOX homeostasis, which is considered to be the most promising signaling pathway in the clinical improvement of ischemia-reperfusion injury [98].…”

Section: Nrf2 Signaling Pathwaymentioning

confidence: 99%

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Wang,

Xu,

Yan

et al. 2024

Biomedicines

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Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of the main causes of fatal diseases, which is an urgent clinical problem to be solved. Although great progress has been made in therapeutic methods, including surgical, drug, gene therapy, and transplant therapy for I/R injury, the development of effective methods to cure the injury remains a worldwide challenge. In recent years, exosomes have attracted much attention for their important roles in immune response, antigen presentation, cell migration, cell differentiation, and tumor invasion. Meanwhile, exosomes have been shown to have great potential in the treatment of I/R injury in organs. The study of the exosome-mediated signaling pathway can not only help to reveal the mechanism behind exosomes promoting reperfusion injury recovery, but also provide a theoretical basis for the clinical application of exosomes. Here, we review the research progress in utilizing various exosomes from different cell types to promote the healing of I/R injury, focusing on the classical signaling pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, and AMPK. The results suggest that exosomes regulate these signaling pathways to reduce oxidative stress, regulate immune responses, decrease the expression of inflammatory cytokines, and promote tissue repair, making exosomes a competitive emerging vector for treating I/R damage in organs.

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“…Nox4, miRNAs, the AGE/RAGE pathway, senescence pathway, and the Nrf2/ARE signaling pathway are also implicated in the mechanisms underlying fibrosis (Table 1 ). 25 , 26 , 30 , 31 , 32 , 33 , 34 , 35 …”

Section: Mechanismmentioning

confidence: 99%

Intestinal strictures in Crohn's disease: An update from 2023

Liu,

Huang,

Wang

et al. 2024

UEG Journal

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Crohn's disease (CD) is a chronic inflammatory disease that leads to intestinal stricture in nearly 35% of cases within 10 years of initial diagnosis. The unknown pathogenesis, lack of universally accepted criteria, and absence of an effective management approach remain unconquered challenges in structuring CD. The pathogenesis of stricturing CD involves intricate interactions between factors such as immune cell dysbiosis, fibroblast activation, and microecology imbalance. New techniques such as single‐cell sequencing provide a fresh perspective. Non‐invasive diagnostic tools such as serum biomarkers and novel cross‐sectional imaging techniques offer a precise understanding of intestinal fibrostenosis. Here, we provide a timely and comprehensive review of the worthy advancements in intestinal strictures in 2023, aiming to dispense cutting‐edge information regarding fibrosis and to build a cornerstone for researchers and clinicians to make greater progress in the field of intestinal strictures.

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Natural products targeting Nrf2/ARE signaling pathway in the treatment of inflammatory bowel disease

Cited by 10 publications

References 215 publications

Microbe-Derived Antioxidants Protect IPEC-1 Cells from H2O2-Induced Oxidative Stress, Inflammation and Tight Junction Protein Disruption via Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway

Microbe-Derived Antioxidants Protect IPEC-1 Cells from H2O2-Induced Oxidative Stress, Inflammation and Tight Junction Protein Disruption via Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Intestinal strictures in Crohn's disease: An update from 2023

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