Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (1): 61-69.doi: 10.12092/j.issn.1009-2501.2025.01.007

Previous Articles     Next Articles

Plumbagin ameliorates pulmonary fibrosis by modulating TGF-β1/Smad2 and Nrf2/NOX4 pathways

LI Hui1, HU Hengzhao2, YU Tingting1, HU Huixian3, WANG Jiale4, WU Jing4, HAO Wei1   

  1. 1 Department of Functional Experimental Training Center, Basic Medical College, Wannan Medical College, Wuhu 241002, Anhui, China; 2 School of Anesthesiology, Wannan Medical College, Wuhu 241002, Anhui, China; 3 School of Medical Imaging, Wannan Medical College, Wuhu 241002, Anhui, China; 4 School of pharmacy, Wannan Medical College, Wuhu 241002, Anhui, China
  • Received:2023-10-12 Revised:2023-11-14 Online:2025-01-26 Published:2025-01-02

Abstract:

AIM: To investigate the protective effect 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 hydroxyproline (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 nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)  positive cell expression in mouse lung tissue. The expression levels of α-smooth muscle actin (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 interstitial injury and extracellular matrix deposition in mice, reduced HYP content (P<0.01, P<0.05), decreased protein expression of α-SMA, collagen I and 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 inflammatory responses and collagen deposition and improve the body's antioxidant capacity.

Key words: plumbagin, pulmonary fibrosis, TGF-β1/Smad2 signalling pathway, Nrf2/NOX4 signalling pathway

CLC Number: