Myricetin attenuates lipopolysaccharide-induced acute lung injury by suppressing pyroptosis via activation of the Nrf2/HO-1/NQO1 signaling pathway

  • Arch Biochem Biophys. 2026 Aug:782:110848. doi: 10.1016/j.abb.2026.110848.
Jing Cao  1 ,  Zaixing Jia  1 ,  Kun He  1 ,  Beibei Song  1 ,  Lingshan Chao  1 ,  Boli Wang  1 ,  Qian Qi  2 ,  Zixiao Chen  3 ,  Haibo Xu  4
Affiliations
  • 1. The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, Shijiazhuang, Hebei, 050000, China.
  • 2. Hebei Key Laboratory of Forensic Medicine, College of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
  • 3. Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101100, China. Electronic address: [email protected].
  • 4. The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, Shijiazhuang, Hebei, 050000, China. Electronic address: [email protected].
PMID: 42144067 DOI: 10.1016/j.abb.2026.110848
Abstract

Objective: To investigate the protective role and underlying mechanisms of Myricetin (Myr) in lipopolysaccharide (LPS)-induced acute lung injury (ALI), with emphasis on its modulation of oxidative stress and Pyroptosis.

Methods: LPS-induced ALI in mice and an in vitro alveolar type II epithelial cell (AT2) model were employed to assess Myr's effects on lung pathology, oxidative stress, Nrf2/HO-1/NQO1 signaling, and NLRP3 inflammasome-associated Pyroptosis. Evaluations included HE staining, lung wet-to-dry weight ratio, measurements of oxidative stress biomarkers (GSH, MDA, and SOD), Western blotting, ELISA, TUNEL assay, and related techniques.

Results: Myr markedly mitigated LPS-induced histopathological injuries in lung tissue (P<0.001), attenuated pulmonary edema, and lowered concentrations of IL-1β and IL-18. Enhanced activities of SOD and GSH, alongside suppression of ROS and MDA production, were observed via activation of the Nrf2/HO-1/NQO1 axis (P<0.01). Concurrently, Myr suppressed NLRP3 inflammasome activity, as evidenced by reduced levels of Caspase-1 and GSDMD-NT (P<0.01), leading to diminished Pyroptosis. Notably, the protective effects of Myr were completely reversed following Nrf2 knockdown or ML385 treatment, confirming that Nrf2 mediates the crosstalk between antioxidant defense and Pyroptosis inhibition.

Conclusion: Myr could alleviate LPS-induced ALI through activation of the Nrf2 pathway, enhancing antioxidant defense and repressing NLRP3 inflammasome-driven Pyroptosis, indicating its therapeutic potential in managing ALI.

Keywords
Acute lung injury (ALI); Myricetin; NLRP3 inflammasome; Oxidative stress; Pyroptosis Nrf2/HO-1/NQO1 signaling pathway.
Products