Synergistic protection of Schizandrin B and Glycyrrhizic acid against bleomycin-induced pulmonary fibrosis by inhibiting TGF-β1/Smad2 pathways and overexpression of NOX4

Zhang, Di; Liu, Bin; Cao, Bo; Wei, Fei; Yu, Xin; Li, Guofeng; Chen, Hong; Wei, Luqing; Wang, Pei-lan

doi:10.1016/j.intimp.2017.04.024

Cited by 42 publications

(20 citation statements)

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“…This medicine increases the expression of the antioxidant-related genes Gclc and Ec-sod, both in vivo and in vitro, by increasing the transcription of oxidative-related genes, including Rac1 and Nox4. Zhang et al(D Zhang et al, 2017) also showed the overexpression of NOX4 in a bleomycin-induced lung injury model and reported that schizandrin B and glycyrrhizic acid are effective inhibitors of the TGF-β1/Smad3 signaling pathway in this model. Lee et al(SH Lee et al, 2017) measured plasma EphA2 levels in a prospective study of patients who were admitted to an ICU because of sepsis and had their disease severity determined based on acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores to examine the correlation between SOFA score and EphA2 level.…”

Section: Discussionmentioning

confidence: 87%

NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

Lee

Shin

Leem

et al. 2020

Preprint

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BackgroundFor patients with acute respiratory distress syndrome (ARDS), a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 in lung injury using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model.MethodsWild-type male C57BL/6J mice and NOX4 KO male mice were divided into five groups: (1) control group: wild-type (WT) mice + non-ventilator; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group: NOX4 KO + non-ventilator; (4) NOX4 KO with HTV group: NOX4 KO mice + HTV; (5) NOX4 inhibitor group: WT mice + HTV + post-treatment (anti-GKT 137831 inhibitor). In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.ResultsCell counts from BALFs were significantly lower (p<0.01) in the NOX4 KO with HTV group compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO mouse group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (both, p<0.001). In patients with respiratory disease, NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit.ConclusionsIn the VILI model, NOX4 expression is significantly associated with Eph-ephrin signaling. It may be possible to block VILI using NOX4 antibodies.

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Section: Discussionmentioning

confidence: 87%

NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

Lee

Shin

Leem

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This medicine increases the expression of the antioxidant-related genes Gclc and Ec-sod, both in vivo and in vitro, by increasing the transcription of oxidative-related genes, including Rac1 and Nox4. Zhang et al 24 also showed the overexpression of NOX4 in a bleomycin-induced lung injury model and reported that schizandrin B and glycyrrhizic acid are effective inhibitors of the TGF-β1/Smad3 signaling pathway in this model. Lee et al 25 measured plasma EphA2 levels in a prospective study of patients who were admitted to an ICU because of sepsis and had their disease severity determined based on acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores to examine the correlation between SOFA score and EphA2 level.…”

Section: Discussionmentioning

confidence: 89%

NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

Lee

Shin

Leem

et al. 2021

Preprint

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For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. We investigated the role of NOX4 in a ventilator-induced lung injury (VILI) model.Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p<0.001). NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the ICU.In the VILI model, it may be possible to block VILI using NOX4 antibodies.

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“…A total of 10 random microscopic images were acquired for each section, and the fields were scored blindly by two pathologists and averaged. After the lung injury scores were assessed, Q value was used to evaluate the synergistic protective effect (19). Q value was calculated as E A+B /(E A +E B -E A •E B ).…”

Section: Methodsmentioning

confidence: 99%

Synergistic protection of matrine and lycopene against lipopolysaccharide‑induced acute lung injury in mice

Wang

Cao

et al. 2019

Mol Med Report

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Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA. The expressions of IκBα and NF-κB p65 were examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL-6, TNF-α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF-κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS-induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI.

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Synergistic protection of Schizandrin B and Glycyrrhizic acid against bleomycin-induced pulmonary fibrosis by inhibiting TGF-β1/Smad2 pathways and overexpression of NOX4

Cited by 42 publications

References 20 publications

NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

Synergistic protection of matrine and lycopene against lipopolysaccharide‑induced acute lung injury in mice

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Synergistic protection of Schizandrin B and Glycyrrhizic acid against bleomycin-induced pulmonary fibrosis by inhibiting TGF-β1/Smad2 pathways and overexpression of NOX4

Cited by 42 publications

References 20 publications

NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

NADPH Oxidase 4 Signaling in a Ventilator-Induced Lung Injury Mouse Model

NADPH&nbsp;Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

Synergistic protection of matrine and lycopene against lipopolysaccharide‑induced acute lung injury in mice

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NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model