Sophoricoside attenuates lipopolysaccharide-induced acute lung injury by activating the AMPK/Nrf2 signaling axis

Wu, Yaxian; Zeng, Si; Wan, Bin-bin; Wang, Yingying; Sun, Hao; Liu, Gang; Gao, Zhiqi; Chen, Dan; Chen, Yong Q.; Lu, Mengji; Pang, Qingfeng

doi:10.1016/j.intimp.2020.107187

Cited by 28 publications

(22 citation statements)

References 47 publications

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“…Hoogendijk et al [ 52 ] also found that LTA has no significant effect on AMPK phosphorylation in a macrophage cell line. Our previous study showed that the alteration of AMPK phosphorylation was not consistent in RAW264.7 cells and BMDMs upon LPS stimulation [ 53 ]. In addition, the phosphorylation of AMPK was not induced in LPS-induced ALI [ 31 ], but decreased in D-GalN/LPS-induced acute liver failure [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the phosphorylation of AMPK was not induced in LPS-induced ALI [ 31 ], but decreased in D-GalN/LPS-induced acute liver failure [ 54 ]. Regardless of the effects of different stimuli on the phosphorylation of AMPK in macrophages and tissues, AMPK agonists are able to improve the damage to macrophages and tissues under these stimuli [ 31 , 52 , 53 , 54 ], indicating that activation of AMPK might be a vital index for seeking potential candidates with anti-inflammatory activities and improving tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…Bone-marrow-derived macrophages (BMDMs) were isolated from C57BL/6 mice, and mice femurs and tibias were flushed with PBS and cultured in high-glucose DMEM medium (Gibco-BRL, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (Gibco-BRL, Grand Island, NY, USA), 1% penicillin–streptomycin (Gibco-BRL, Grand Island, NY, USA) and macrophage colony-stimulating factor (M-CSF, 10 ng/mL) (PeproTech, Rocky Hill, NJ, USA) for 6 days in an incubator (37 °C, 5% CO 2 ) as we previously described [ 53 ]. Then, cells were harvested and pretreated with DHL for 0.5 h before stimulation with LTA (20 μg/mL) [ 45 ] for the indicated time.…”

Section: Methodsmentioning

confidence: 99%

“…The slides were stained with hematoxylin and eosin (H&E). Subsequently, sections were assessed with a Pannoramic MIDI (3D, HISTECH, Budapest, Hungary) as we described previously [ 53 ]. Ten fields from lung sections were randomly selected to determine lung injury degree, and each field was scored as 0–4 according to the severity of damage as described previously [ 63 ]: grade 0: normal appearance, no injury; grade 1: mild polymorphonuclear leukocyte infiltration (PMN) and interstitial congestion; grade 2: moderate cell infiltration, perivascular edema, and moderate destruction of lung structure; grade 3: massive cell infiltration and moderate lung alveolar damage; grade 4: severe cell infiltration and destruction of lung structure.…”

Section: Methodsmentioning

confidence: 99%

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Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

Jiang

Liu

et al. 2021

IJMS

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Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

Jiang

Liu

et al. 2021

IJMS

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“…The 5 μm thick sections were stained with hematoxylin and eosin (H&E) staining for Journal of Immunology Research analysis of pathological changes. The degree of pathological injury was scored as described previously [22,23].…”

Section: Methodsmentioning

confidence: 99%

Baicalin Magnesium Salt Attenuates Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting of TLR4/NF-κB Signaling Pathway

Zhang

Yang²,

Xie

et al. 2021

Journal of Immunology Research

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Baicalin (BA) magnesium salt (BA-Mg) is a good water-soluble ingredient extracted from Scutellaria baicalensis Georgi, a commonly used traditional Chinese medicine. This study is aimed at investigating whether BA-Mg could exert a better protective effect on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and illuminate the underlying mechanisms in vivo and in vitro. Mice were intraperitoneally administrated with equimolar BA-Mg, BA, and MgSO4 before LPS inducing ALI. Lung tissues and bronchoalveolar lavage fluid were collected for lung wet/dry ratio, histological examinations, cell counts, and biochemical analyses at 48 h post-LPS exposure. Meanwhile, the protein expressions of TLR4/NF-κB signaling pathway and proinflammatory cytokines in lung tissues and lung bronchial epithelial cells (BEAS-2B) were detected. The results showed BA-Mg pronouncedly ameliorated LPS-induced inflammatory response and histopathological damages, elevated antioxidant enzyme activity (SOD), and downregulated myeloperoxidase (MPO) and malonaldehyde (MDA) levels through the inhibition of TLR4/NF-κB signaling pathway activation. Moreover, the effect of BA-Mg was significantly better than that of BA and MgSO4 in ameliorating symptoms. Overall, BA-Mg can effectively relieve inflammatory response and oxidative stress triggered by LPS, indicating it may be a potential therapeutic candidate for treating ALI.

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Nrf2/PHB2 alleviates mitochondrial damage and protects against Staphylococcus aureus‐induced acute lung injury

Jin,

Sun,

Liu

et al. 2023

MedComm

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Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA‐induced ALI (SA‐ALI) remains unclear. In this study, serum samples were collected from SA‐sepsis patients, and a SA‐ALI mouse model was established by grouping WT and Nrf2−/− mice after 6 h of intraperitoneal injection. A cell model simulating SA‐ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA‐sepsis patients, negatively correlated with the severity of ALI. In SA‐ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation‐induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA‐ALI. The p‐Nrf2/total‐Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA‐treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual‐luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA‐ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.

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Sophoricoside attenuates lipopolysaccharide-induced acute lung injury by activating the AMPK/Nrf2 signaling axis

Cited by 28 publications

References 47 publications

Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

Baicalin Magnesium Salt Attenuates Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting of TLR4/NF-κB Signaling Pathway

Nrf2/PHB2 alleviates mitochondrial damage and protects against Staphylococcus aureus‐induced acute lung injury

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