Plumbagin ameliorates pulmonary fibrosis by modulating TGF-β1/Smad2 and Nrf2/NOX4 pathways
10.12092/j.issn.1009-2501.2025.01.007
- VernacularTitle:白花丹素通过调节TGF-β1/Smad2及Nrf2/NOX4通路改善博来霉素诱导的肺纤维化
- Author:
Hui LI
1
;
Hengzhao HU
;
Tingting YU
;
Huixian HU
;
Jiale WANG
;
Jing WU
;
Wei HAO
Author Information
1. 皖南医学院机能学实验实训中心,芜湖 241002,安徽
- Publication Type:Journal Article
- Keywords:
plumbagin;
pulmonary fibrosis;
TGF-β1/Smad2 signalling pathway;
Nrf2/NOX4 signalling pathway
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(1):61-69
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the protective ef-fect of plumbagin(PL)against pulmonary fibrosis(PF)and its possible mechanisms.METHODS:Sixty male C57BL/6 mice were randomly divided into control,bleomycin group(BLM),low dose PL group(1 mg/kg)and high dose PL group(2 mg/kg).The mice PF model was replicated using intratracheal injection of BLM(3 mg/kg),and then PL(1 or 2 mg/kg)was injected intraperitoneally for 3 weeks and the animals were executed.HE and Masson staining were used to observe morphological changes in lung tissue and collagen deposition.The activities or levels of superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA)and hy-droxyproline(HYP)were measured in mouse lung tissue;ELISA for interleukin-6(IL-6)in mouse lung tissue.Immunohistochemical detection of nuclear factor-related factor 2(Nrf2)and reduced nicotin-amide adenine dinucleotide phosphate oxidase 4(NOX4)positive cell expression in mouse lung tis-sue.The expression levels of α-smooth muscle ac-tin(α-SMA),collagen Ⅰ(Col Ⅰ),collagen Ⅲ(Col Ⅲ),IL-6,transforming growth factor-β1(TGF-β1),p-Smad2,Nrf2 and NOX4 were detected by Western blotting.RESULTS:Compared with the BLM group,PL treatment attenuated lung parenchymal and in-terstitial injury and extracellular matrix deposition in mice,reduced HYP content(P＜0.01,P＜0.05),de-creased protein expression of α-SMA,collagen Ⅰand Ⅲ(P＜0.01,P＜0.05),diminished IL-6 secretion(P＜0.01);improved the body's antioxidant capacity(increased SOD and GSH activity and decreased MDA content,P＜0.01,P＜0.05),significantly down-regulated TGF-β1,p-Smad2 and NOX4-positive cells and protein expression(P＜0.01,P＜0.05)and up-regulated Nrf2-positive cells and protein expression(P＜0.01,P＜0.05).CONCLUSION:PL may slow down the PF process by modulating the TGF-β1/Smad2 and Nrf2/NOX4 pathways to attenuate inflammato-ry responses and collagen deposition and improve the body's antioxidant capacity.
