Imrecoxib Inhibits Paraquat-Induced Pulmonary Fibrosis through the NF-κB/Snail Signaling Pathway

Huang, Jin

doi:10.1155/2020/6374014

Cited by 7 publications

(7 citation statements)

References 23 publications

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“…A previous study reported that activation of the NF-κB signaling pathway occurs in the lung tissue of patients with IPF and mice with pulmonary fibrosis ( 46 ). The results of the present study demonstrated that the protein expression levels of p-NF-κB were significantly increased in TGF-β1-induced MRC-5 cells, which was consistent with previous studies ( 45 , 46 ). Notably, PG or PG-derived components increase AMP-activated protein kinase (AMPK) signaling in numerous types of cell, such as macrophages and lung carcinoma cells, hepatocellular carcinoma cells ( 47 – 49 ).…”

Section: Discussionsupporting

confidence: 93%

“…The NF-κB pathway is commonly regarded as a pro-inflammatory signaling pathway ( 43 , 44 ). Moreover, NF-κB is involved in the development and progression of fibrosis via regulation of transcription factors associated with fiber growth, such as platelet-derived growth factor and TGF-β1 ( 45 ). A previous study reported that activation of the NF-κB signaling pathway occurs in the lung tissue of patients with IPF and mice with pulmonary fibrosis ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

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Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Tang

Huang

et al. 2022

Mol Med Rep

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Platyconic acid A (PA), the active component of Platycodi radix-derived saponin, exerts ameliorating effects on liver fibrosis. Platycodon grandiflorum is used to treat lung disease. Therefore, the present study evaluated the effects of PA on pulmonary fibrosis. Transforming growth factor-β1 (TGF-β1) was used to induce MRC-5 cells to establish an in vitro pulmonary fibrosis model. The viability of MRC-5 cells in the presence or absence of TGF-β1 induction was examined using a Cell Counting Kit-8 assay and the results demonstrated that PA markedly decreased viability of TGF-β1-induced MRC-5 cells in a dose-dependent manner. Wound healing analysis, immunofluorescent staining and western blotting were performed to determine the levels of cell migration and expression of α-smooth muscle actin and extracellular matrix (ECM)-associated proteins. The results of the present study demonstrated that PA significantly suppressed the migration and ECM deposition of TGF-β1-induced MRC-5 cells. Furthermore, results obtained from ELISA and western blotting demonstrated that PA exerted suppressive effects on the inflammation of MRC-5 cells following TGF-β1 stimulation. The mRNA and protein expression levels of protein phosphatase Mg2 + /Mn2 + -dependent 1A (PPM1A) before and after transfection were assessed using reverse transcription-quantitative PCR and western blotting and the results demonstrated that the mRNA and protein expression levels of PPM1A were significantly decreased following transfection with small interfering RNA targeting PPM1A. Moreover, following PPM1A knockdown, PA significantly inhibited the proliferation, migration, inflammation and ECM deposition of TGF-β1-induced MRC-5 cells via activation of the SMAD/ β-catenin signaling pathway. In conclusion, PA activated PPM1A to ameliorate TGF-β1-elicited lung fibroblast injury via modulating SMAD/β-catenin signaling.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Tang

Huang

et al. 2022

Mol Med Rep

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“…40 rats were randomly divided into 5 groups ( n = 8 per group) and treated as previously described [ 24 , 25 ]: (1) control group, rats received no PQ but saline; (2) PQ group, rats were intragastric administration with 30 mg/kg PQ; (3) 8 mg/kg GC group, rats received 8 mg/kg GC after administration of 30 mg/kg PQ; (4) 16 mg/kg GC group, rats received 16 mg/kg GC after administration of 30 mg/kg PQ; and (5) 32 mg/kg GC group, rats received 32 mg/kg GC after administration of 30 mg/kg PQ. The GC groups received intraperitoneal injections of GC at the same time every day for 5 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

“…RLE-6TN cells were randomly divided into 5 groups ( n = 8 per group) and treated as previously described [ 24 , 25 ]: (1) control group, cells were cultured in DMEM; (2) PQ group, cells were treated with 20 μ M PQ for 4 h; (3) 1 μ M GC group, cells were incubated with 1 μ M GC for 24 h after PQ treatment; (4) 10 μ M GC group, cells were incubated with 10 μ M GC for 24 h after PQ treatment; and (5) 100 μ M GC group, cells were incubated with 100 μ M GC for 24 h after PQ treatment.…”

Section: Methodsmentioning

confidence: 99%

Ginkgolide C Alleviates Acute Lung Injury Caused by Paraquat Poisoning via Regulating the Nrf2 and NF-κB Signaling Pathways

Zhang

Zhao

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Paraquat (PQ), a highly toxic herbicide and primary attack for lung, results in severe acute lung injury (ALI) appeared as evident oxidative stress, inflammation, and apoptosis. Increasing evidence elucidates that nuclear factor erythroid-2-related factor 2 (Nrf2) and its associated nuclear factor-κB (NF-κB) exhibit many merits for protection of ALI by coordinating a fine-turned response to oxidative stress, inflammation, and apoptosis. Ginkgolide C (GC) has been reported to be a safe and potent therapeutic agent against ALI. However, whether GC could protect ALI induced by PQ poisoning and the possible underlining mechanisms have remained not to be fully elucidated. A rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury constructed by exposure to PQ were applied to discuss the protective effect of GC. Furthermore, Nrf2 gene silencing RLE-6TN cells were used to discuss the exact mechanism. We confirmed that GC significantly ameliorated the histopathological damages, ultrastructural changes, lung injury score, W/D ratio, and Hyp activity of lung tissue and inhibited polymorphonuclear neutrophil (PMN) infiltration after PQ poisoning. Further results revealed that GC remarkably activated Nrf2-based cytoprotective system and inhibited NF-κB-induced inflammatory injury as well as apoptosis. Taken together, we concluded that GC preserved protection of PQ-induced ALI via the Nrf2-NF-κB dependent signal pathway, which may provide us novel insights into the treatment strategies for PQ poisoning.

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“…These studies suggest that imrecoxib has a noninferior analgesic efficacy to celecoxib with good tolerance. In addition, imrecoxib can alleviate pulmonary fibrosis caused by paraquat poisoning through the NF-κB/snail signaling pathway (Jin, 2020).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of imrecoxib on mRNA and protein expression of CYP2C11 enzyme in rats

Dong

et al. 2022

Biomedical Chromatography

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To evaluate the effect of imrecoxib on CYP2C11 enzyme activity, mRNA, and protein expression, a UPLC method was established. Tolbutamide was selected as the CYP2C11 enzyme‐specific probe drug and incubated with imrecoxib in rat liver microsomes. The yield of 4‐hydroxytolbutamide was measured using UPLC to investigate the effect of imrecoxib on CYP2C11 enzyme activity. Imrecoxib (10 mg/kg) was administered intragastrically twice daily. After 1, 7, and 14 days of administration, the liver tissues were analyzed. The expression of CYP2C11 enzyme mRNA was determined using reverse transcription‐polymerase chain reaction, and its protein expression was determined using Western blot analysis. Imrecoxib concentration was inversely proportional to the production of 4‐hydroxytolbutamide in liver microsomes. Imrecoxib demonstrated a dose‐dependent inhibitory effect on CYP2C11 activity with IC50 = 74.77 μM. After administration, reverse transcription‐polymerase chain reaction showed CYP2C11 enzyme mRNA expressions were 65% (P < 0.05), 35%, and 34% of the control group, respectively (P < 0.01). Western blot analysis showed CYP2C11 enzyme protein expressions were 80, 37, and 34% of the control group, respectively (P < 0.01). Imrecoxib can reduce mRNA and protein expression of CYP2C11 enzyme in rat liver and inhibit the activity of CYP2C11 enzyme in a dose‐dependent manner. However, it does not produce clinically significant drug interactions.

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Imrecoxib Inhibits Paraquat-Induced Pulmonary Fibrosis through the NF-κB/Snail Signaling Pathway

Cited by 7 publications

References 23 publications

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Ginkgolide C Alleviates Acute Lung Injury Caused by Paraquat Poisoning via Regulating the Nrf2 and NF-κB Signaling Pathways

Inhibition of imrecoxib on mRNA and protein expression of CYP2C11 enzyme in rats

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