Myricetin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Pyroptosis via Activation of the Nrf2/HO-1/NQO1 Signaling Pathway.
Cao Jing, Jia Zaixing, He Kun, Song Beibei, Chao Lingshan, Wang Boli, Qi Qian, Chen Zixiao, Xu Haibo
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.
Key Findings
- Myricetin significantly mitigates LPS-induced acute lung injury by reducing histopathological damage and pulmonary edema.
- Myricetin activates the Nrf2/HO-1/NQO1 signaling pathway, enhancing antioxidant defenses such as increased SOD and GSH activities and reducing ROS and MDA levels.
- Myricetin suppresses NLRP3 inflammasome activation and pyroptosis, as shown by decreased Caspase-1 and GSDMD-NT levels, with these protective effects dependent on Nrf2 activation.
Clinical Significance
Myricetin shows potential as a therapeutic agent for acute lung injury by activating Nrf2-mediated antioxidant pathways and inhibiting inflammasome-driven pyroptosis, suggesting a novel approach to managing inflammatory lung diseases.
Citation
Cao Jing, Jia Zaixing, He Kunet al.. Myricetin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Pyroptosis via Activation of the Nrf2/HO-1/NQO1 Signaling Pathway. Archives of biochemistry and biophysics. 2026-May-16.