Erchentang Ameliorates SiO2-induced Lung Injury by Regulating Oxidative Stress and Metabolic Disorders via Nrf2/HO-1 Signaling Pathway
10.13422/j.cnki.syfjx.20260307
- VernacularTitle:二陈汤通过Nrf2/HO-1信号通路调节氧化应激和代谢紊乱改善SiO2诱导的肺损伤
- Author:
Jun LU
1
;
Xinyi ZHU
1
;
Ziyi LIU
1
;
Jixia HU
1
;
Jialu CHEN
2
;
Rong XIAO
3
;
Zhibin WANG
4
;
Chang LIU
1
;
Fangguo LU
1
Author Information
1. Medical School， Hunan University of Chinese Medicine， Changsha 410208， China
2. School of Traditional Chinese Medicine， Hunan University of Chinese Medicine， Changsha 410208， China
3. Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine， Changsha 410006， China
4. School of Integrated Chinese and Western Medicine， Hunan University of Chinese Medicine， Changsha 410208， China
- Publication Type:Journal Article
- Keywords:
Erchentang;
SiO2;
lung injury;
nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway;
oxidative stress;
metabolic disorders
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(13):32-42
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO2-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL-1 SiO2 suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg-1·d-1 and 9 g·kg-1·d-1， respectively） ECT， and dexamethasone （0.2 mg·kg-1·d-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO2-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO2-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO2-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.
