2. Academic Validation
  3. Dendrobine attenuates lipopolysaccharide-induced acute lung injury by modulating FAM134B-mediated endoplasmic reticulum autophagy and mitochondrial function

Dendrobine attenuates lipopolysaccharide-induced acute lung injury by modulating FAM134B-mediated endoplasmic reticulum autophagy and mitochondrial function

  • Phytomedicine. 2025 Aug:144:156952. doi: 10.1016/j.phymed.2025.156952.
Jia Zhou 1,  Sanzhong Li 2,  Zhiguo Hu 3,  Shuying Huang 4,  Yuting Yang 3,  Chaoqi Zhou 3,  Shichao Zhang 1,  Kaihang Luo 1,  Cheng Wang 3,  Cheng Qing 5,  Zhenguo Zeng 6
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Medical Center of Anesthesiologyand Pain, The First Affliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang 330006, PR China; Jiangxi Institute of Respiratory Disease, Nanchang 330052, PR China.
  • 2 Department of Blood Transfusion, The First Affliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang 330006, PR China.
  • 3 Department of Critical Care Medicine, Medical Center of Anesthesiologyand Pain, The First Affliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang 330006, PR China; Key Laboratory of Critical Care Medicine, Nanchang, 330000, PR China.
  • 4 Department of Reproductive Medicine, The First Affliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang 330006, PR China.
  • 5 Department of Critical Care Medicine, Medical Center of Anesthesiologyand Pain, The First Affliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang 330006, PR China; Key Laboratory of Critical Care Medicine, Nanchang, 330000, PR China. Electronic address: ncicu2023@126.com.
  • 6 Department of Critical Care Medicine, Medical Center of Anesthesiologyand Pain, The First Affliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang 330006, PR China; Key Laboratory of Critical Care Medicine, Nanchang, 330000, PR China. Electronic address: zengzhenguo@ncu.edu.cn.
PMID: 40532488 DOI: 10.1016/j.phymed.2025.156952
Abstract

Background: Macrophage-mediated excessive inflammatory responses play a pivotal role in sepsis progression, particularly in the lungs. Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, also contribute to the development of acute lung injury (ALI). Dendrobine is a natural alkaloid known to alleviate ERS in various diseases; however, its specific role in sepsis-associated ALI is not yet fully understood.

Objective: This study investigates the protective effects of dendrobine against ALI and elucidates the underlying mechanisms.

Methods: We assessed the protective effects of dendrobine using LPS-induced THP-1 cells and a murine model of sepsis. Techniques included HE staining for lung tissue damage, TUNEL staining for pulmonary Apoptosis, flow cytometry for intracellular Reactive Oxygen Species (ROS) levels and Apoptosis, transmission electron microscopy for ER Autophagy and changes in mitochondria-associated ER membranes (MAMs), and confocal microscopy for ER Autophagy flux, mitochondrial membrane potential, and mitochondrial calcium ion levels.

Results: Dendrobine significantly alleviated LPS-induced ALI and inflammatory responses in mice by reducing the expression of ERS-related and pro-apoptotic proteins. It enhanced ER Autophagy by upregulating FAM134B, inhibiting its ubiquitination and degradation, and promoting its interaction with LC3B. Dendrobine partially restored LPS-induced mitochondrial dysfunction by reducing MAM formation. Conversely, FAM134B knockdown reversed the protective effects of dendrobine.

Conclusion: This study demonstrates that dendrobine alleviates LPS-induced ERS and mitochondrial dysfunction through FAM134B-mediated ER Autophagy and MAM reduction, thereby protecting lung tissue. These findings highlight the potential of dendrobine as a therapeutic agent against sepsis-induced ALI.

Keywords

Dendrobine; Endoplasmic reticulum autophagy; Endoplasmic reticulum stresses; FAM134B; Mitochondria-associated endoplasmic reticulum membranes; Septic lung injuries.

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