ArticleJournal of inflammation (London, England)2022
5-Methoxyflavone alleviates LPS-mediated lung injury by promoting Nrf2-mediated the suppression of NOX4/TLR4 axis in bronchial epithelial cells and M1 polarization in macrophages.
Article in Journal of inflammation (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 20 citations in OpenAlex.
- Implications of Protein Posttranslational Modifications in Sepsis-Induced Acute Lung Injury and Acute Respiratory Distress Syndrome.Shock (Augusta, Ga.) · 2025Review
- Elucidating the Neuroprotective Mechanism of 5,7-Dimethoxyflavone and 5,7',4'-Trimethoxyflavone Through In Silico Target Prediction and in Memory-Impaired Mice.Neurochemical research · 2025Article
- Naringenin Accelerates Diabetic Wound Healing via Regulating Macrophage M2 Polarization and Efferocytosis.Food science & nutrition · 2025Article
- Natural Compounds Regulate Macrophage Polarization and Alleviate Inflammation Against ALI/ARDS.Biomolecules · 2025Review
- Ag85B-induced M1 Macrophage Polarization via the TLR4/TRAF6/NF-κB Axis Leading to Bronchial Epithelial Cell Damage and TH17/Treg Imbalance.Current molecular medicine · 2025Article
- Macrophage‑driven pathogenesis in acute lung injury/acute respiratory disease syndrome: Harnessing natural products for therapeutic interventions (Review).Molecular medicine reports · 2025Review
- Article
- Potential for Drug Repositioning of Midazolam as an Inhibitor of Inflammatory Bone Resorption.International journal of molecular sciences · 2024Article
- Valsartan attenuates LPS-induced ALI by modulating NF-κB and MAPK pathways.Frontiers in pharmacology · 2024Article
- Macrophage Polarization: An Important Candidate Regulator for Lung Diseases.Molecules (Basel, Switzerland) · 2023Review
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9 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute lung injury (ALI) arises from sepsis or bacterial infection, which are life-threatening respiratory disorders that cause the leading cause of death worldwide. 5-Methoxyflavone, a methylated flavonoid, is gaining increased attention for its various health benefits. In the current study, we investigated the potential effects of 5-methoxyflavone against LPS-mediated ALI and elucidated the corresponding possible mechanism.
methodsA mouse model with ALI was established by intratracheal instillation of LPS, and lung pathological changes, signaling pathway related proteins and apoptosis in lung tissues were estimated by H&E staining, immunofluorescence and TUNEL assay, respectively. Cell viability was evaluated by MTT assay; protein levels of pro-inflammatory mediators were measured by ELISA assay; levels of ROS and M1 macrophage polarization were assayed by flow cytometry; the expression of Nrf2 signaling, NOX4/TLR4 axis and P-STAT1 were detected by western blotting.
resultsOur results showed that 5-methoxyflavone treatment inhibited LPS-induced expression of NOX4 and TLR4 as well as the activation of downstream signaling (NF-κB and P38 MAPK), which was accompanied by markedly decreased ROS levels and pro-inflammatory cytokines (IL-6, TNF-α, MCP-1, and IL-8) in BEAS-2B cells. Moreover, we revealed that these effects of 5-methoxyflavone were related to its Nrf2 activating property, and blockade of Nrf2 prevented its inhibitory effects on NOX4/TLR4/NF-κB/P38 MAPK signaling, thus abrogating the anti-inflammatory effects of 5-methoxyflavone. Besides, the Nrf2 activating property of 5-methoxyflavone in RAW264.7 cells led to inhibition of LPS/IFN-γ-mediated STAT1 signaling, resulting in suppression of LPS/IFN-γ-induced M1 macrophage polarization and the repolarization of M2 macrophages to M1. In a mouse model of LPS-induced ALI, 5-methoxyflavone administration ameliorated LPS-mediated lung pathological changes, the increased lung index (lung/body weight ratio), and epithelial cell apoptosis. Meanwhile, we found 5-methoxyflavone effectively suppressed the hyperactive signaling pathways and the production of excessive pro-inflammatory mediators. Moreover, 5-methoxyflavone reduced LPS-mediated M1 macrophage polarization associated with elevated P-STAT1 activation in the lung tissues. In addition, 5-methoxyflavone improved the survival of LPS-challenged mice.
conclusionThese results indicated that 5-methoxyflavone might be suitable for the development of a novel drug for ALI therapeutic.
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