Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung...
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| Format: | Article |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1067402/full |
| _version_ | 1811157657310986240 |
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| author | Lejing Lou Min Wang Jingjing He Song Yang Fanxi Meng Shijia Wang Xiao Jin Jihao Cai Chang Cai |
| author_facet | Lejing Lou Min Wang Jingjing He Song Yang Fanxi Meng Shijia Wang Xiao Jin Jihao Cai Chang Cai |
| author_sort | Lejing Lou |
| collection | DOAJ |
| description | Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the link between UA and ferroptosis is unknown. The purpose of this research was to look into the role of UA in regulating LPS-induced ferroptosis in ALI. The current study used LPS to injure two models, one BEAS-2B cell injury model and one ALI mouse model. UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering in vivo lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismutase, catalase, and glutathione depletion. Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe2+ levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced. The Keap1-Nrf2/HO-1 pathway was upregulated by UA, which inhibited LPS-induced ALI and ferroptosis. ML385 inhibited UA’s protective effect against LPS-induced ALI. These findings suggested that UA could be a novel potential therapeutic target for ALI. |
| first_indexed | 2024-04-10T05:09:53Z |
| format | Article |
| id | doaj.art-dc794316cce24f9fb4e07f6cf1910881 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T05:09:53Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-dc794316cce24f9fb4e07f6cf19108812023-03-09T10:31:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.10674021067402Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathwayLejing Lou0Min Wang1Jingjing He2Song Yang3Fanxi Meng4Shijia Wang5Xiao Jin6Jihao Cai7Chang Cai8Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaRenji College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaAcute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the link between UA and ferroptosis is unknown. The purpose of this research was to look into the role of UA in regulating LPS-induced ferroptosis in ALI. The current study used LPS to injure two models, one BEAS-2B cell injury model and one ALI mouse model. UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering in vivo lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismutase, catalase, and glutathione depletion. Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe2+ levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced. The Keap1-Nrf2/HO-1 pathway was upregulated by UA, which inhibited LPS-induced ALI and ferroptosis. ML385 inhibited UA’s protective effect against LPS-induced ALI. These findings suggested that UA could be a novel potential therapeutic target for ALI.https://www.frontiersin.org/articles/10.3389/fphar.2023.1067402/fullurolithin aNrf2ferroptosisacute lung injuryLPS |
| spellingShingle | Lejing Lou Min Wang Jingjing He Song Yang Fanxi Meng Shijia Wang Xiao Jin Jihao Cai Chang Cai Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway Frontiers in Pharmacology urolithin a Nrf2 ferroptosis acute lung injury LPS |
| title | Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway |
| title_full | Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway |
| title_fullStr | Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway |
| title_full_unstemmed | Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway |
| title_short | Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway |
| title_sort | urolithin a ua attenuates ferroptosis in lps induced acute lung injury in mice by upregulating keap1 nrf2 ho 1 signaling pathway |
| topic | urolithin a Nrf2 ferroptosis acute lung injury LPS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1067402/full |
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