Ginsenoside Rh2 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Regulating the TLR4/PI3K/Akt/mTOR, Raf-1/MEK/ERK, and Keap1/Nrf2/HO-1 Signaling Pathways in Mice

Hsieh, Ying‐Hen; Deng, Jeng-Shyan; Chang, Yuan‐Shiun; Huang, Guan-Jhong

doi:10.3390/nu10091208

Cited by 79 publications

(31 citation statements)

References 43 publications

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“…Hu et al [ 28 ] demonstrate that the Nrf2-Keap1-antioxidant response element (ARE) signaling pathway can eliminate oxidative stress and its associated inflammation to improve traumatic lung injury-related pathology, and a Keap1-Nrf2 inhibitor designed by Zhang et al is expected to be a novel protective agent of ALI [ 29 ]. In addition, it has been reported that some drugs and compounds can alleviate lung injury by regulating Keap1-Nrf2 pathways, such as ginsenoside Rh2 [ 30 ], sinomenine [ 31 ], and panaxydol [ 32 ]. However, whether sevoflurane attenuates oxidative stress and subsequent inflammation responses via the Keap1-Nrf2 pathway has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane reduces lipopolysaccharide-induced apoptosis and pulmonary fibrosis in the RAW264.7 cells and mice models to ameliorate acute lung injury by eliminating oxidative damages

Zheng

Zhang

et al. 2022

Redox Report

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Objectives Sevoflurane is identified as an effective candidate drug for acute lung injury (ALI) treatment, but its curing effects and detailed mechanisms have not been fully disclosed. The present study was designed to resolve this academic issue. Methods The ALI mice models were established, and Hematoxylin-eosin staining assay was performed to examine tissue morphologies. Cell viability was determined by CCK-8 assay, and Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The expression levels of proteins were determined by performing Western Blot analysis and immunofluorescence staining assay. ROS levels were examined by using DCFH-DA staining assay. Results In this study, we investigated this issue and the ALI models were respectively established by treating the BALB/c mice and the murine macrophage cell line RAW264.7 with different concentrations of lipopolysaccharide (LPS) in vivo and in vitro, which were subsequently subjected to sevoflurane co-treatment. The results showed that sevoflurane reduced LPS-induced ALI in mice and suppressed LPS-triggered oxidative stress and apoptotic cell death in the RAW264.7 cells. Interestingly, we evidenced that the elimination of reactive oxygen species (ROS) by N-acetyl-L-cysteine (NAC) reversed LPS-induced cell apoptosis in RAW264.7 cells. Then, we verified that sevoflurane suppressed oxidative damages to restrain LPS-induced apoptotic cell death in the RAW264.7 cells through activating the anti-oxidant Keap1/Nrf2 pathway. Mechanistically, sevoflurane down-regulated Keap1 and upregulated Nrf2 in nucleus to activate the downstream anti-oxidant signaling cascades, which further ameliorated LPS-induced cell apoptosis and lung injury by eliminating oxidative damages. Discussion Taken together, our study illustrated that the sevoflurane attenuates LPS-induced ALI by inhibiting oxidative stress-mediated apoptotic cell death and inflammation, and the Keap1/Nrf2 pathway played an important role in this process.

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Section: Introductionmentioning

confidence: 99%

Sevoflurane reduces lipopolysaccharide-induced apoptosis and pulmonary fibrosis in the RAW264.7 cells and mice models to ameliorate acute lung injury by eliminating oxidative damages

Zheng

Zhang

et al. 2022

Redox Report

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“…Hsieh et al. ( 2018 ) suggested that Rh2 ameliorated lipopolysaccharide (LPS)‐induced oxidative stress by regulating signaling pathways (HO‐1/Trx‐1/KAP‐1/Nrf2) in mice. In another study, Rh2 suppressed oxidative stress, had antioxidant activity in vivo, and restored the balance of the antioxidant defense system (Qi et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rh2 administration produces crucial antidepressant‐like effects in a CUMS‐induced mice model of depression

Shi

Liu

et al. 2022

Brain and Behavior

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Introduction The most striking feature of depression is sadness and a loss of interest in activities, which represents a major cause of disability globally. Therefore, it is necessary to identify novel antidepressants for clinical practice. Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides that can be extracted from Panax ginseng and has been demonstrated to improve both memory and learning. The purpose of this study was to provide broad insight into the mechanisms underlying depression and gain greater insights into antidepressant therapy. Methods In this study, we first established an effective and feasible depression animal model of chronic unpredictable mild stress (CUMS) and behavioral testing was evaluated by the forced swim test (FST), the tail suspension test (TST) and the sucrose preference test. Following pretreatment with Rh2 (10 and 20 mg/kg), the immobility time of mice was reduced without affecting locomotor activity in both the FST and TST. Western blotting and immunofluorescence were used to investigate the activation of the hippocampal BDNF signaling pathway and hippocampal neurogenesis. Results Different concentrations of Rh2 significantly reduced depressive‐like symptoms in CUMS‐induced mice and downregulated the effects of the BDNF signaling cascade and neurogenesis in the hippocampus. Furthermore, the administration of K252a completely prevented the antidepressant‐like activity of Rh2 in mice. Conclusion The results indicated that Rh2 possesses the antidepression action via the positive regulation of the BDNF‐TrkB pathway.

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“…QE was demonstrated to mediate the expression of Nrf2 and the activity of antioxidant response element (ARE)-reporter gene, thus regulating Nrf2/ARE-mediated antioxidant defense mechanism [ 43 ]. Previously, in LPS-induced lung injury in mice, the protein level of Cytosol Nrf2 was reduced after LPS treatment, while it was partially restored after GRh2 treatment, which indicated that GRh2 showed antioxidant effects by inhibiting Nrf2 nuclear translocation [ 44 ]. In the present study, we discovered that Cytosol Nrf2 was reduced, while Nucleus Nfr2 was elevated after CSE treatment, which suggested that CSE induced oxidative stress and the subsequent Nrf2 nuclear translocation.…”

Section: Discussionmentioning

confidence: 99%

Quercitrin protects human bronchial epithelial cells from oxidative damage

Wang

et al. 2022

Open Medicine

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Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking (CS), with oxidative stress being one key component during its pathogenesis. This study aimed to investigate the effects of quercitrin (QE) on cigarette smoke extract (CSE)-induced cell apoptosis and oxidative stress in human bronchial epithelial cells (HBECs) and its underlying mechanism. HBECs were treated with 2% CSE for 24 h to establish in vitro COPD cellular models. CCK-8 assay and flow cytometry analysis were performed to evaluate cell viability and apoptosis, respectively. Western blotting was applied to examine protein levels and ELISA kits were used to examine contents of the indicated oxidant/antioxidant markers. The results demonstrated that CSE promoted apoptosis and suppressed viability of HBECs and QE reversed these effects. CSE caused increase in T-AOC, superoxide dismutase, and glutathione (GSH) peroxidase contents and decrease in MDA, reactive oxygen species , and GSH contents in HBECs, which were rescued by QE treatment. The CSE-induced Nrf2 nuclear translocation and elevation of NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression were also reversed by QE in HBECs. The mitogen-activated protein kinase (MAPK) signaling was activated by CSE and further suppressed by QE in HBECs. Collectively, QE exerts a protective role in HBECs against cell apoptosis and oxidative damage via inactivation of the Nrf2/HO-1/NQO1 pathway and the MAPK/ERK pathway.

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Ginsenoside Rh2 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Regulating the TLR4/PI3K/Akt/mTOR, Raf-1/MEK/ERK, and Keap1/Nrf2/HO-1 Signaling Pathways in Mice

Cited by 79 publications

References 43 publications

Sevoflurane reduces lipopolysaccharide-induced apoptosis and pulmonary fibrosis in the RAW264.7 cells and mice models to ameliorate acute lung injury by eliminating oxidative damages

Sevoflurane reduces lipopolysaccharide-induced apoptosis and pulmonary fibrosis in the RAW264.7 cells and mice models to ameliorate acute lung injury by eliminating oxidative damages

Ginsenoside Rh2 administration produces crucial antidepressant‐like effects in a CUMS‐induced mice model of depression

Quercitrin protects human bronchial epithelial cells from oxidative damage

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