Frontiers in Pharmacology (Jun 2023)
Administration of protopine prevents mitophagy and acute lung injury in sepsis
- Zhong Xiao,
- Zhong Xiao,
- Zhong Xiao,
- Juan Long,
- Juan Long,
- Juan Long,
- Jie Zhang,
- Jie Zhang,
- Jie Zhang,
- Zhimin Qiu,
- Zhimin Qiu,
- Zhimin Qiu,
- Chen Zhang,
- Chen Zhang,
- Chen Zhang,
- Hongbing Liu,
- Hongbing Liu,
- Hongbing Liu,
- Xinyong Liu,
- Xinyong Liu,
- Xinyong Liu,
- Kang Wang,
- Kang Wang,
- Kang Wang,
- Yahui Tang,
- Yahui Tang,
- Yahui Tang,
- Longwang Chen,
- Longwang Chen,
- Longwang Chen,
- Zhongqiu Lu,
- Zhongqiu Lu,
- Zhongqiu Lu,
- Guangju Zhao,
- Guangju Zhao,
- Guangju Zhao
Affiliations
- Zhong Xiao
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Zhong Xiao
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Zhong Xiao
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Juan Long
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Juan Long
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Juan Long
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Jie Zhang
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Jie Zhang
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Jie Zhang
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Zhimin Qiu
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Zhimin Qiu
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Zhimin Qiu
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Chen Zhang
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Chen Zhang
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Chen Zhang
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Hongbing Liu
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Hongbing Liu
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Hongbing Liu
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Xinyong Liu
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Xinyong Liu
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Xinyong Liu
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Kang Wang
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Kang Wang
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Kang Wang
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Yahui Tang
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Yahui Tang
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Yahui Tang
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Longwang Chen
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Longwang Chen
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Longwang Chen
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Zhongqiu Lu
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Zhongqiu Lu
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Zhongqiu Lu
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- Guangju Zhao
- Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Guangju Zhao
- Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China
- Guangju Zhao
- The Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), Wenzhou, China
- DOI
- https://doi.org/10.3389/fphar.2023.1104185
- Journal volume & issue
-
Vol. 14
Abstract
Introduction: Sepsis is a severe life-threatening infection that induces a series of dysregulated physiologic responses and results in organ dysfunction. Acute lung injury (ALI), the primary cause of respiratory failure brought on by sepsis, does not have a specific therapy. Protopine (PTP) is an alkaloid with antiinflammatory and antioxidant properties. However, the function of PTP in septic ALI has not yet been documented. This work sought to investigate how PTP affected septic ALI and the mechanisms involved in septic lung damage, including inflammation, oxidative stress, apoptosis, and mitophagy.Methods: Here, we established a mouse model induced by cecal ligation and puncture (CLP) and a BEAS-2B cell model exposed to lipopolysaccharide (LPS).Results: PTP treatment significantly reduced mortality in CLP mice. PTP mitigated lung damage and reduced apoptosis. Western blot analysis showed that PTP dramatically reduced the expression of the apoptosis-associated protein (Cleaved Caspase-3, Cyto C) and increased Bcl-2/Bax. In addition, PTP decreased the production of inflammatory cytokines (IL-6, IL-1β, TNF-α), increased glutathione (GSH) levels and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) levels. Meanwhile, PTP significantly reduced the expression of mitophagy-related proteins (PINK1, Parkin, LC-II), and downregulated mitophagy by transmission electron microscopy. Additionally, the cells were consistent with animal experiments.Discussion: PTP intervention reduced inflammatory responses, oxidative stress, and apoptosis, restored mitochondrial membrane potential, and downregulated mitophagy. The research shows that PTP prevents excessivemitophagy and ALI in sepsis, suggesting that PTP has a potential role in the therapy of sepsis.
Keywords
