Taohe Chengqi decoction inhibits PAD4-mediated neutrophil extracellular traps and mitigates acute lung injury induced by sepsis.
10.1016/S1875-5364(25)60874-0
- Author:
Mengting XIE
1
;
Xiaoli JIANG
1
;
Weihao JIANG
1
;
Lining YANG
1
;
Xiaoyu JUE
1
;
Yunting FENG
1
;
Wei CHEN
2
;
Shuangwei ZHANG
1
;
Bin LIU
1
;
Zhangbin TAN
3
,
4
;
Bo DENG
4
,
5
;
Jingzhi ZHANG
6
Author Information
1. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
2. The First Clinical School of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510260, China.
3. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. Electronic address: doctorzjz@
4. com.
5. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. Electronic address: dengbotjmu@
6. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. Electronic address: 249880441@qq.com.
- Publication Type:Journal Article
- Keywords:
Acute lung injury;
Cecum ligation and puncture;
Neutrophil extracellular traps;
PAD4
- MeSH:
Extracellular Traps/immunology*;
Acute Lung Injury/immunology*;
Animals;
Sepsis/immunology*;
Drugs, Chinese Herbal/pharmacology*;
Mice;
Neutrophils/immunology*;
Male;
Protein-Arginine Deiminase Type 4/genetics*;
Mice, Inbred C57BL;
Humans;
Disease Models, Animal;
Cytokines/metabolism*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(10):1195-1209
- CountryChina
- Language:English
-
Abstract:
Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
