ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Obstetric and Pediatric Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1542743
This article is part of the Research TopicNew Therapies in Neonatal and Perinatal Care: Shooting for the MoonView all articles
Aerosol inhalation of dimeric artesunate phospholipid-conjugated liposomes ameliorates inflammation, fibrosis, and ferroptosis in neonatal mice with hyperoxia-induced lung injury
Provisionally accepted- nanjing medical university, nanjing, China
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Objective: Bronchopulmonary dysplasia (BPD), a chronic lung disease affecting preterm infants, causes irreversible lung injury with few effective treatments. Artemisinin, derived from Artemisia annua, shows potent anti-inflammatory and anti-fibrotic effects against acute lung injuries, but its role in BPD remains unclear. This study investigates the therapeutic potential and mechanisms of dimeric artesunate phospholipid-conjugated liposomes (Di-ART-GPC) in BPD.Methods:In vivo: Forty-eight male neonatal C57BL/6 mice were randomized into four groups: normoxia (NC), normoxia + Di-ART-GPC (NA), hyperoxia (HO), and hyperoxia + Di-ART-GPC (HA). HO and HA groups received 95% O₂ for 7 days; NC and NA groups were kept in normoxia (21% O₂). On day 8, HO/HA mice were treated with Di-ART-GPC (0.5 mg/day, inhalation) or saline (NC/NA) for 3 days. On postnatal day 10, lungs were analyzed via HE staining (alveolar structure, RAC counts), Masson staining (fibrosis), IHC/RT-qPCR (TGF-β1, α-SMA), ELISA (TNF-α, IL-6), and assays for SOD, MDA, GSH, and GPX4.In vitro: RAW264.7 macrophages were exposed to 95% O₂ for 24 hours with/without Di-ART-GPC (1.25 µM). Supernatants were tested for TNF-α, IL-6, TGF-β1 (ELISA), and cells for GPX4 (Western blot/RT-qPCR).Results:In vivo**: HO mice showed alveolar simplification (reduced RAC, p<0.05), inflammation/fibrosis (elevated TNF-α, IL-6, TGF-β1, α-SMA, p<0.05), oxidative stress (decreased SOD, GSH, GPX4, p<0.05). Di-ART-GPC treatment significantly improved these parameters (p<0.05).In vitro: Hyperoxia increased TNF-α, IL-6, TGF-β1, and reduced GPX4 in RAW264.7 cells; Di-ART-GPC reversed these changes (p<0.05).Conclusion: Di-ART-GPC protects against hyperoxia-induced BPD by reducing inflammation, fibrosis, and macrophage ferroptosis, highlighting its potential as a therapeutic strategy for BPD.
Keywords: Bronchopulmonary Dysplasia, Hyperoxia, Inflammation, Fibrosis, ferroptosis, Macrophages
Received: 10 Dec 2024; Accepted: 09 Jul 2025.
Copyright: © 2025 Guan, Yu, Yu, Yu, Chen, Jia, Wang, Cheng and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhaofang Tian, nanjing medical university, nanjing, China
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