Quercetin Confers Protection against Sepsis-Related Acute Respiratory Distress Syndrome by Suppressing ROS/p38 MAPK Pathway.
10.1007/s11655-025-3927-5
- Author:
Wei-Chao DING
1
;
Juan CHEN
2
;
Quan LI
3
;
Yi REN
2
;
Meng-Meng WANG
2
;
Wei ZHANG
2
;
Xiao-Hang JI
2
;
Xin-Yao WU
2
;
Shi-Nan NIE
2
;
Chang-Bao HUANG
4
;
Zhao-Rui SUN
5
,
6
Author Information
1. Department of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221002, China.
2. Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
3. Intensive Care Unit, Suqian First Hospital, Suqian, Jiangsu Province, 223800, China.
4. Department of Emergency Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, 241000, China.
5. Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China. sunzhr84@
6. com.
- Publication Type:Journal Article
- Keywords:
acute respiratory distress syndrome;
cell apoptosis;
inflammation;
oxidative stress;
quercetin;
reactive oxygen species/p38 mitogen-activated protein kinase pathway;
sepsis
- MeSH:
Animals;
Sepsis/drug therapy*;
Quercetin/therapeutic use*;
Respiratory Distress Syndrome/enzymology*;
p38 Mitogen-Activated Protein Kinases/metabolism*;
Mice, Inbred C57BL;
Reactive Oxygen Species/metabolism*;
Apoptosis/drug effects*;
Male;
Oxidative Stress/drug effects*;
MAP Kinase Signaling System/drug effects*;
Lung/drug effects*;
Mice;
Lipopolysaccharides;
Macrophages, Alveolar/pathology*;
Inflammation/pathology*;
Protective Agents/therapeutic use*
- From:
Chinese journal of integrative medicine
2025;31(11):1011-1020
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS).
METHODS:In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro.
RESULTS:Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01).
CONCLUSION:Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
