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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1552251
Gui-Zhi-Fu-Ling-Wan alleviates bleomycin-induced pulmonary fibrosis through inhibiting epithelial-mesenchymal transition and ferroptosis
Provisionally accepted
Ziyong Chen 1
Mengmeng Ma 1 Qingqing Zhang 1 Yongxia Guo 1 Meiling Xie 1 Yingli Wang 1 Kui Liu 1 Lifang Cao 1
Lin Fu 2* Yalin Jiang 1*- 1 Bozhou People's Hospital, Bozhou, Anhui, China
- 2 Anhui Medical University, Hefei, China
Background: Idiopathic pulmonary fibrosis (IPF) has a higher morbidity and poor prognosis. Gui-Zhi-Fu-Ling-Wan (GFW) is a traditional Chinese herbal formula which exerts anti-inflammatory and anti-oxidative effects. The goal was to determine the protective effect of GFW on bleomycin (BLM)-induced pulmonary fibrosis.Methods: One hundred and twenty-four mice were randomly divided into eight groups, and orally supplemented with GFW (1 g/kg) in one week ago and continuing to one week later of single BLM intratracheal injection (5.0 mg/kg). Lung tissues were collected in 7 days and 21 days after BLM injection. BEAS-2B cells were pretreated with GFW (100 μg/mL) for 3 consecutive days before BLM (10 μg/mL) exposure. Cells were harvested in 12 or 24 h after BLM co-culture.Results: GFW supplementation alleviated BLM-induced alveolar structure destruction and inflammatory cell infiltration in mice lungs. BLM-incurred collagen deposition was attenuated by GFW. In addition, GFW pretreatment repressed BLM-evoked downregulation of E-cadherin, and elevation of N-cadherin and Vimentin in mouse lungs. Besides, BLM-excited GPX4 reduction, ferritin increases, lipid peroxidation, and free iron overload were significantly relieved by GFW pretreatment in mouse lungs and BEAS-2B cells. Notably, BLM-provoked mitochondrial reactive oxygen species (mtROS) excessive production, elevation of mitochondrial stress markers, such as HSP70 and CLPP, and mitochondrial injury, were all abolished in mouse lungs and BEAS-2B cells by GFW pretreatment.GFW supplementation attenuated BLM-evoked lung injury and pulmonary fibrosis partially through repressing EMT and mtROS-mediated ferroptosis in pulmonary epithelial cells.
Keywords: gui-zhi-fu-ling-wan, Pulmonary Fibrosis, Bleomycin, Epithelial-Mesenchymal Transition, ferroptosis, Mitochondrial reactive oxygen species
Received: 27 Dec 2024; Accepted: 31 Mar 2025.
Copyright: © 2025 Chen, Ma, Zhang, Guo, Xie, Wang, Liu, Cao, Fu and Jiang. 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:
Lin Fu, Anhui Medical University, Hefei, China
Yalin Jiang, Bozhou People's Hospital, Bozhou, Anhui, China
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