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. 2025 Aug;398(8):10261-10272.
doi: 10.1007/s00210-025-03889-3. Epub 2025 Feb 17.

Wogonin attenuates inflammation and oxidative stress in acute lung injury via regulating PPARα, AKT, and NRF2

Hui Yang #  1   2 , Yunran Hu #  2   3 , Long Cheng  1 , Yuan Xiong  3 , Yuan Xu  2 , Changxing Gao  4 , Ming Qian  5 , Lin Zhou  6   7
Affiliations

Wogonin attenuates inflammation and oxidative stress in acute lung injury via regulating PPARα, AKT, and NRF2

Hui Yang et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug.

Abstract

The study aims to clarify the therapeutic effect and underlying mechanisms of wogonin (WOG) against acute lung injury (ALI). Lipopolysaccharide-induced in vivo ALI mice model and in vitro RAW264.7 cell model were established. Lung histopathologic changes were assessed by H&E staining. Inflammatory cell infiltration in lung tissues and bronchoalveolar lavage fluid (BALF) was determined using H&E staining and flow cytometry. Inflammatory cytokines, reactive oxygen species (ROS), and antioxidant mediators were quantified. Potential targets of WOG were identified by bioinformatics and network pharmacology and further verified by Western blotting. WOG treatment (10 mg/kg, 20 mg/kg, 40 mg/kg) alleviated lung injury of ALI mice by ameliorating infiltration of inflammatory cells in lung tissues and BALF, inhibiting inflammatory cytokines, elevating antioxidant mediator levels, and attenuating lung edema. In RAW264.7 cells, WOG treatment (10 μM, 20 μM, 40 μM) also suppressed inflammatory response and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα), protein kinase B (AKT), and nuclear factor erythroid 2-related factor 2 (NRF2) were predicted to be the targets of WOG against ALI by integrating the network pharmacology database and the GSE1871 dataset. Interestingly, WOG markedly promoted the expression and activation of PPARα and NRF2, while it inhibited the expression and phosphorylation of AKT both in vivo and in vitro. We provided a comprehensive insight into investigating the therapeutic effect of WOG against ALI via ameliorating inflammation and oxidative stress through regulating PPARα, AKT, and NRF2.

Keywords: Acute lung injury; Inflammation; Oxidative stress; Wogonin.

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Conflict of interest statement

Declarations. Ethics approval: All animal experiments were approved by the Animal Experimentation of the Nanjing Drum Tower Hospital and the Animal Ethics Committee of that institution with the application approval number 2024AE01040 and complied with ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. Consent for publication: The details of any images can be published. Competing interests: The authors declare no competing interests. Declaration of generative AI in scientific writing: No generative artificial intelligence (AI) and AI-assisted technology have been used in the writing process.

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