Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis‐Mediated Lung Injury
- 1School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin People's Republic of China
- 2Department of Pharmaceutical Chemistry School of Pharmacy, College of Health Sciences University of Ghana Accra Ghana
Abstract
Sepsis is a systemic inflammatory response syndrome triggered by an uncontrolled host response to infection, which causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Baicalein (Bai) is one of the major active components of Scutellariae Radix for treating pulmonary diseases. However, its specific underlying molecular mechanism is unknown for treating sepsis‐mediated ALI. Herein, we found that Bai inhibited the nuclear factor kappa B (NF‐κB) pathway to suppress inflammation and oxidative stress in vitro and in vivo, alleviating the course of lung injury. Affinity chromatography revealed that Bai directly bound to eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) through hydrogen bond interaction with Q108 and D110, exhibiting a dissociation constant (K d) of 336 nM. Mechanistically, Bai blocked the interaction between eEF1A1 and peroxiredoxin 4 (Prdx4) to inhibit ring finger protein 14 (RNF14)‐mediated ubiquitin‐dependent degradation of Prdx4 based on APEX2 and Co‐IP experiments. Moreover, eEF1A1 knockdown could repress inflammation, whereas its overexpression exerted an opposite effect in the in vitro experiments. Notably, Bai did not display any additional protective effect in LPS‐mediated eEF1A1 knockdown cells, while its effect was weakened in LPS‐mediated eEF1A1 overexpression cells. In addition, our study revealed that the course of sepsis‐mediated lung injury was alleviated in vivo by eEF1A1 knockdown, and no extra effects were exhibited by Bai in sepsis‐mediated eEF1A1 knockdown mice. These findings collectively suggested that targeting eEF1A1 represented a promising therapeutic strategy against sepsis‐associated lung injury through dual anti‐inflammatory and antioxidant mechanisms, particularly via Bai's role as a direct blocker disrupting eEF1A1‐Prdx4 interactions.
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BibTeX
@article{chang2026targeting,
title = {{Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis‐Mediated Lung Injury}},
author = {Jing Chang and Hui‐Lin Zhang and Qi‐Meng Zhu and Si‐Wen Hui and Xin‐Rong Xu and Mahmood Brobbey Oppong and Yan‐Li Feng and Juan Zhang and Cheng‐Peng Sun and Feng Qiu},
journal = {Exploration},
year = {2026},
month = aug,
doi = {10.1002/exp2.70206},
url = {https://doi.org/10.1002/exp2.70206},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis‐Mediated Lung Injury
AU - Jing Chang
AU - Hui‐Lin Zhang
AU - Qi‐Meng Zhu
AU - Si‐Wen Hui
AU - Xin‐Rong Xu
AU - Mahmood Brobbey Oppong
AU - Yan‐Li Feng
AU - Juan Zhang
AU - Cheng‐Peng Sun
AU - Feng Qiu
PY - 2026
DA - 2026/08/24
JO - Exploration
DO - 10.1002/exp2.70206
UR - https://doi.org/10.1002/exp2.70206
AB - Sepsis is a systemic inflammatory response syndrome triggered by an uncontrolled host response to infection, which causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Baicalein (Bai) is one of the major active components of Scutellariae Radix for treating pulmonary diseases. However, its specific underlying molecular mechanism is unknown for treating sepsis‐mediated ALI. Herein, we found that Bai inhibited the nuclear factor kappa B (NF‐κB) pathway to suppress inflammation and oxidative stress in vitro and in vivo, alleviating the course of lung injury. Affinity chromatography revealed that Bai directly bound to eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) through hydrogen bond interaction with Q108 and D110, exhibiting a dissociation constant (K d) of 336 nM. Mechanistically, Bai blocked the interaction between eEF1A1 and peroxiredoxin 4 (Prdx4) to inhibit ring finger protein 14 (RNF14)‐mediated ubiquitin‐dependent degradation of Prdx4 based on APEX2 and Co‐IP experiments. Moreover, eEF1A1 knockdown could repress inflammation, whereas its overexpression exerted an opposite effect in the in vitro experiments. Notably, Bai did not display any additional protective effect in LPS‐mediated eEF1A1 knockdown cells, while its effect was weakened in LPS‐mediated eEF1A1 overexpression cells. In addition, our study revealed that the course of sepsis‐mediated lung injury was alleviated in vivo by eEF1A1 knockdown, and no extra effects were exhibited by Bai in sepsis‐mediated eEF1A1 knockdown mice. These findings collectively suggested that targeting eEF1A1 represented a promising therapeutic strategy against sepsis‐associated lung injury through dual anti‐inflammatory and antioxidant mechanisms, particularly via Bai's role as a direct blocker disrupting eEF1A1‐Prdx4 interactions.
SN - 2766-8509
SN - 2766-2098
ER -