Total terpenoids of Inula japonica activated the Nrf2 receptor to alleviate the inflammation and oxidative stress in LPS-induced acute lung injury

Zhang, Juan; Zhang, Min; Zhang, Wenhao; Zhu, Qi-Meng; Ning, Jing; Huo, Xiaokui; Xiao, Haitao; Sun, Cheng‐Peng

doi:10.1016/j.phymed.2022.154377

Cited by 10 publications

(12 citation statements)

References 56 publications

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“…The ALI pathogenesis is characterized by severe damage of alveolar capillary endothelial cells, impaired blood–air barrier, extensive infiltration of inflammatory cells and inflammatory factors, and alveolar and interstitial lung edema, eventually leading to ARDS [ 30 ]. Lipopolysaccharide (LPS) can be used to induce ALI and is relatively simple to perform [ 31 ]. However, using bacterial infection with ALI is closer to the clinic and can better simulate the pathological changes of clinical ALI.…”

Section: Discussionmentioning

confidence: 99%

Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways

Zhang

Zeng

et al. 2023

Biomol Biomed

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Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI.

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Section: Discussionmentioning

confidence: 99%

Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways

Zhang

Zeng

et al. 2023

Biomol Biomed

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“…MAPK signaling is a classic pathway in various inflammatory diseases such as ALI, which is characterized by the phosphorylation of ERK, JNK and p38 [ 39 ]. Previous studies have shown that the pharmacological blockade of MAPK markedly reduces LPS-induced inflammatory responses and ameliorates lung pathology deterioration in LPS-stimulated ALI mice [ 31 , 40 ]. Similarly, the present findings suggested that pretreatment with echinatin inhibited the phosphorylation of ERK, JNK and p38, which contributing to relieve the LPS-induced inflammatory response in RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

Luo,

Wang,

Xiong

et al. 2024

PLoS ONE

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Echinatin is an active ingredient in licorice, a traditional Chinese medicine used in the treatment of inflammatory disorders. However, the protective effect and underlying mechanism of echinatin against acute lung injury (ALI) is still unclear. Herein, we aimed to explore echinatin-mediated anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated ALI and its molecular mechanisms in macrophages. In vitro, echinatin markedly decreased the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated murine MH-S alveolar macrophages and RAW264.7 macrophages by suppressing inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression. Furthermore, echinatin reduced LPS-induced mRNA expression and release of interleukin-1β (IL-1β) and IL-6 in RAW264.7 cells. Western blotting and CETSA showed that echinatin repressed LPS-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways through targeting transforming growth factor-beta-activated kinase 1 (TAK1). Furthermore, echinatin directly interacted with Kelch-like ECH-associated protein 1 (Keap1) and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to enhance heme oxygenase-1 (HO-1) expression. In vivo, echinatin ameliorated LPS-induced lung inflammatory injury, and reduced production of IL-1β and IL-6. These findings demonstrated that echinatin exerted anti-inflammatory effects in vitro and in vivo, via blocking the TAK1-MAPK/NF-κB pathway and activating the Keap1-Nrf2-HO-1 pathway.

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“…Recently, growing interest in Oriental medicine has prompted a surge in research on natural compounds that exhibit potential for treating inflammatory diseases. Inula japonica Thunb, a frequently utilized medicinal plant in traditional Chinese medicine, has gained recognition for its ability to regulate spleen, liver, lung, and stomach function, as well as its potential in preventing abortion. , Britanin (Bri) is a bioactive sesquiterpene lactone mainly found in plants like Inula britannica, Inula japonica, and Inula lineariifolia Turcz., and it belongs to the category of pharmacologically active phytochemicals. , Inula britannica extract has shown antioxidant and hepatoprotective properties in vitro . Moreover, Wu et al reported that Britanin functions as a protective phytochemical against ischemic brain injury in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) .…”

Section: Introductionmentioning

confidence: 99%

Integrated Pharmaco-Bioinformatics Approaches and Experimental Verification To Explore the Effect of Britanin on Nonalcoholic Fatty Liver Disease

Dou,

Zhu,

Xie

et al. 2024

ACS Omega

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Nonalcoholic fatty liver disease (NAFLD) is a prevalent global liver disorder, posing substantial health risks. Britanin, a bioactive sesquiterpene lactone extracted from Inula japonica, has demonstrated antidiabetic, hypolipidemic, and hepatoprotective attributes. Nonetheless, the precise impact of Britanin on NAFLD and the intricate biological mechanisms underpinning this interaction remain unexplored. We integrated computer-aided methods to unearth shared biological targets and signaling pathways associated with both Britanin and NAFLD. A network was constructed by compiling putative targets associated with Britanin and NAFLD, followed by a stringent screening of key targets and mechanisms through protein–protein interaction analysis along with GO and KEGG pathway enrichment analyses. Molecular docking was integrated as an evaluation tool, culminating in the identification of HO-1 as the pivotal therapeutic target, showcasing a satisfactory binding affinity. The primary mechanism was ascribed to biological processes and pathways linked to oxidative stress, as evidenced by the outcomes of enrichment analyses. Of these, the AMPK/SREBP1c pathway assumed centrality in this mechanism. Furthermore, in vivo experiments substantiated that Britanin effectively curtailed NAFLD development by ameliorating liver injury, modulating hyperlipidemia and hepatic lipid accumulation, and alleviating oxidative stress and apoptosis. In summary, this study demonstrates the potential of Britanin as a promising therapeutic drug against NAFLD.

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Total terpenoids of Inula japonica activated the Nrf2 receptor to alleviate the inflammation and oxidative stress in LPS-induced acute lung injury

Cited by 10 publications

References 56 publications

Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways

Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

Integrated Pharmaco-Bioinformatics Approaches and Experimental Verification To Explore the Effect of Britanin on Nonalcoholic Fatty Liver Disease

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