ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicIron Dysregulation, Oxidative Stress, and Inflammation: Mechanisms and Therapeutic InsightsView all 4 articles
Farrerol inhibits ferroptosis and protects against LPS-induced acute lung injury by targeting the RUNX1/SLC7A11 axis
Provisionally accepted
Ying Xu1,2,3,4*
Yueyan Yang1,2Shihua Deng1,2Teng Liu1,2Min Yang1,2Xintao Zhang1,2Xiaobian Wang1,2Sunhan Zhang1,2
Ting Zhang1,2
Dongming Wu1,2- 1First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- 2Chengdu Medical College, Chengdu, China
- 3Sichuan Clinical Research Center for Radiation and Therapy, Chengdu, China
- 4Clinical IVD Joint Research Center of Chengdu Medical College-Maccura Biotechnology, Chengdu, China
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Introduction: Acute lung injury (ALI) is a critical condition with diverse etiologies, characterized by high mortality rates and a lack of specific therapeutic interventions. Farrerol, a naturally occurring flavonoid isolated from Rhododendron spp., exhibits potent anti-inflammatory and antioxidant activities. Previous studies have indicated that farrerol exerts protective effects against lipopolysaccharide (LPS)-induced ALI; however, the underlying mechanisms remain elusive. This study aimed to elucidate the protective mechanisms of farrerol against LPS-induced ALI. Methods: We evaluated the efficacy of farrerol using both in vitro (LPS-stimulated BEAS-2B cells) and in vivo (LPS-induced ALI in mice) models. The protective mechanism of rhododendron against ALI was investigated using proteomics, cellular thermal shift assays, co-immunoprecipitation, and molecular docking. Results: Pretreatment with farrerol significantly improved cell viability and reduced lactate dehydrogenase release in LPS-induced BEAS-2B cells. In vivo, farrerol effectively alleviated LPS‑ induced pulmonary edema and histopathological damage in mice. Mechanistically, we found that farrerol directly binds to and stabilizes runt-related transcription factor 1 (RUNX1), thereby transcriptionally activating the expression of solute carrier family 7 member 11. Overexpression of RUNX1 mimicked the protective effects of farrerol, while knockdown of RUNX1 abolished these effects. Discussion: Farrerol could directly bind and stabilize the expression of RUNX1, thereby enhancing SLC7A11 transcription and ultimately inhibiting ferroptosis. Thus, farrerol is a potential therapeutic agent for ALI.
Keywords: Acute Lung Injury, Farrerol, ferroptosis, Runx1, SLC7A11
Received: 08 Oct 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Xu, Yang, Deng, Liu, Yang, Zhang, Wang, Zhang, Zhang and Wu. 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: Ying Xu
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