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Esculetin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice Via Modulation of the AKT/ERK/NF-κB and RORγt/IL-17 Pathways

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Abstract

Esculetin, a coumarin derivative from various natural plants, has an anti-inflammatory property. In the present study, we examined if esculetin has any salutary effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Acute lung injury (ALI) was induced via the intratracheal administration of LPS, and esculetin (20 and 40 mg/kg) was given intraperitoneally 30 min before LPS challenge. After 6 h of LPS administration, lung tissues were collected for analysis. Pretreatment with esculetin significantly attenuated histopathological changes, inflammatory cell infiltration, and production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, in the lung tissue. Furthermore, esculetin inhibited the protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-κB) pathways and downregulated the expression of RORγt and IL-17 in LPS-induced ALI. Our results indicated that esculetin possesses anti-inflammatory and protective effects against LPS-induced ALI via inhibition of the AKT/ERK/NF-κB and RORγt/IL-17 pathways.

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Funding

This work was supported by grants from the Ministry of Science and Technology (MOST108-2314-B-182A-059-MY2) and Chang Gung Memorial Hospital (CMRPG3G1601-2) to Fu-Chao Liu and the Ministry of Science and Technology (MOST105-2314-B-182A-012-MY3) and Chang Gung Memorial Hospital (CMRPG3H0811-3, CMRPG3H1191-3) to Huang-Ping Yu.

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  1. Hung-Chen Lee and Fu-Chao Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Hung-Chen Lee, Fu-Chao Liu, An-Hsun Chou, Chia-Chih Liao & Huang-Ping Yu

  2. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Hung-Chen Lee, Fu-Chao Liu, An-Hsun Chou, Chia-Chih Liao & Huang-Ping Yu

  3. Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

    Hung-Chen Lee & Chi-Neu Tsai

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Lee, HC., Liu, FC., Tsai, CN. et al. Esculetin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice Via Modulation of the AKT/ERK/NF-κB and RORγt/IL-17 Pathways. Inflammation 43, 962–974 (2020). https://doi.org/10.1007/s10753-020-01182-4

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