Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signaling

Fan, Hui‐Ning; Chen, Wei; Zhu, Jingde; Zhang, Jing; Peng, Siyun

doi:10.1016/j.intimp.2019.105909

Cited by 54 publications

(35 citation statements)

References 37 publications

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“…In the case of colitis, one study [46] demonstrated that inflammasome activation could be inhibited via activation of Nrf2 and its downstream response protein heme oxygenase-1 (HO-1), responsible for intracellular antioxidant defenses (Figure 1). Consistent with this, treatment of macrophages with the tripeptide toosendanin increased Nrf2 signaling, which attenuated NLRP3 inflammasome activation, decreasing the polarization of macrophages towards the pro-inflammatory (M1) phenotype, thus ameliorating the pathological damages of colitis [46]. Another cellular redox system known to regulate the activation of the NLRP3 inflammasome is the thioredoxin-interacting protein (TXNIP) [47].…”

Section: Cell Stress and Redox Regulationmentioning

confidence: 99%

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

Meyers

Zhu

2020

Cells

132

100

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In response to inflammatory stimuli, immune cells reconfigure their metabolism and bioenergetics to generate energy and substrates for cell survival and to launch immune effector functions. As a critical component of the innate immune system, the nucleotide-binding and oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome can be activated by various endogenous and exogenous danger signals. Activation of this cytosolic multiprotein complex triggers the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and initiates pyroptosis, an inflammatory form of programmed cell death. The NLRP3 inflammasome fuels both chronic and acute inflammatory conditions and is critical in the emergence of inflammaging. Recent advances have highlighted that various metabolic pathways converge as potent regulators of the NLRP3 inflammasome. This review focuses on our current understanding of the metabolic regulation of the NLRP3 inflammasome activation, and the contribution of the NLRP3 inflammasome to inflammaging.

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Section: Cell Stress and Redox Regulationmentioning

confidence: 99%

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

Meyers

Zhu

2020

Cells

132

100

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“…The qRT-PCR was performed, which was described in detail. 17 The primers of GLP-1 were listed below: GLP-1 forward, 5′-GAGGACCCTGATGAGATGAATG-3′; and reverse, 5′-GGAGTCCAGGTATTTGCTGTAG-3′.…”

Section: Mrna Of Glp-1mentioning

confidence: 99%

<p>Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells</p>

Ma¹,

Cao²,

Ye³

et al. 2020

DMSO

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Purpose: Glucagon-like peptide-1 (GLP-1) is secreted from the intestinal L-cells to stimulate insulin secretion in the blood glucose control. Our previous study indicates that Sennoside A (SA) can increase the plasma GLP-1 level in a mouse model of type 2 diabetes. However, the mechanism of SA activity remains largely unknown. This issue was explored in this study. Materials and Methods: C57BL/6 mice were randomly divided into four groups: a control group without drug treatment, and the other groups with different SA dosages, respectively. Blood glucose was assayed by oral glucose tolerance test (OGTT). Plasma GLP-1 and insulin were investigated. Colon tissues were collected for mRNA or Western blot analysis. Immunofluorescence staining assays were performed to evaluate the number of β-cells and L-cells. In NCI-H716 cells, extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors were employed to investigate the SA-induced GLP-1 secretion mechanism. Results: In this work, the SA was found to improve OGTT in mice. Plasma GLP-1 and insulin were markedly elevated by SA at the dosage of 45 mg/kg/day. Meanwhile, the increased phosphorylation status of EKR1/2 and prohormone convertase 1/3 (PC1/3) proteins were observed in the colon of SA-treated mice. The number of L-cells exhibited no change in each group. In the NCI-H716 cells, GLP-1 secretion induced by SA was blocked by the ERK1/2 inhibitor. Conclusion: The present study provides a direct evidence for the interaction between SA and L cells for induction of GLP-1 secretion. These data suggest that GLP-1 secretion induced by SA is dependent on the ERK1/2 signaling pathway. Therefore, the SA is a new drug candidate for the type 2 diabetes treatment by induction of GLP-1 secretion.

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“…HO-1 and CO might be possible candidates to initiate intestinal barrier-restorative effects due to their anti-inflammation and antioxidative damage properties [ 27 , 28 ]. However, they often used a kind of middle mechanism (e.g., the nuclear factor erythroid-2-related factor 2 (Nrf 2 )/HO-1/CO pathway) for regulating the intestinal barrier dysfunction [ 29 , 30 ], and the direct effect of the HO-1-CO axis on intestinal barrier injury is poorly understood. Our data indicated that intestinal mucosal injury, TNF- α production, and TJ disruption are markedly attenuated by exogenous upregulation of HO-1 (CoPP) or endogenous supplement CO (CORM-2) after chronic CCl 4 injection.…”

Section: Discussionmentioning

confidence: 99%

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1^-/- Mice

Zhang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. Materials and Methods. We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. Results. Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. Conclusion. HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.

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Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signaling

Cited by 54 publications

References 37 publications

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

<p>Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells</p>

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1^-/- Mice

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Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signaling

Cited by 54 publications

References 37 publications

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

<p>Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells</p>

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1-/- Mice

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HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1^-/- Mice