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Polydatin Attenuates Sepsis-Induced Lung Injury by Inhibiting Neutrophil Extracellular Traps Formation via Nrf2/HO-1
Hongkai Dai1,2, Cheng Li1,2, Bin Yang1,2
1Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
Biomedicines
|May 4, 2026
Summary
Polydatin (PD) protects against sepsis-induced acute lung injury (ALI) by reducing neutrophil extracellular traps (NETs). This protective effect is mediated by the Nrf2/HO-1 antioxidant pathway, suggesting PD as a potential therapeutic agent for ALI.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pharmacology
Background:
- Sepsis-induced acute lung injury (ALI) presents a critical unmet medical need with limited treatment options.
- Neutrophil extracellular traps (NETs) play a significant role in the development of ALI.
- Polydatin (PD) is explored for its potential therapeutic benefits in managing ALI.
Purpose of the Study:
- To investigate the protective effects of polydatin (PD) against sepsis-induced ALI.
- To determine if PD inhibits NET formation through the Nrf2/HO-1 pathway.
- To validate the therapeutic potential of PD for ALI.
Main Methods:
- Established a cecal ligation and puncture (CLP)-induced ALI mouse model and an LPS-stimulated neutrophil model.
- Assessed lung injury using histology, lung wet/dry ratio, BALF protein, and inflammatory cytokines.
- Examined endothelial junction proteins, NETs markers, and Nrf2/HO-1 pathway activation, including experiments with the ML385 inhibitor.
Main Results:
- Polydatin (PD) dose-dependently reduced lung injury and preserved endothelial junction proteins in vivo.
- PD suppressed NET formation in both in vivo and in vitro models.
- PD activated the Nrf2/HO-1 pathway, promoted Nrf2 nuclear translocation, reduced ROS, and inhibited NETs, with effects confirmed by ML385.
Conclusions:
- Polydatin (PD) effectively mitigates sepsis-induced ALI by inhibiting NET formation.
- The mechanism involves the activation of the Nrf2/HO-1 antioxidant pathway.
- PD demonstrates promise as a potential therapeutic candidate for treating sepsis-induced ALI.
