Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis
Context Ferulic acid (FA) has antioxidative and anti-inflammatory effects, and is a promising drug to treat sepsis.Objective To study the therapeutic effect of FA in sepsis-induced acute lung injury (ALI) and its underlying mechanisms.Materials and methods The caecal ligation and puncture (CLP) mano...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2022.2147549 |
| _version_ | 1811304237586448384 |
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| author | Xianming Tang Jiqiang Liu Shuo Yao Jianfei Zheng Xun Gong Bing Xiao |
| author_facet | Xianming Tang Jiqiang Liu Shuo Yao Jianfei Zheng Xun Gong Bing Xiao |
| author_sort | Xianming Tang |
| collection | DOAJ |
| description | Context Ferulic acid (FA) has antioxidative and anti-inflammatory effects, and is a promising drug to treat sepsis.Objective To study the therapeutic effect of FA in sepsis-induced acute lung injury (ALI) and its underlying mechanisms.Materials and methods The caecal ligation and puncture (CLP) manoeuvre was applied to establish a murine model of sepsis-induced ALI, and female BALB/c mice (6 mice per group) were subjected to 100 mg/kg FA or 0.8 mg/kg ferrostatin-1 (Fer-1, ferroptosis inhibitor) treatment to clarify the role of FA in preserving alveolar epithelial barrier function and inhibiting ferroptosis. Lipopolysaccharide (LPS; 500 ng/mL)-induced cell models were prepared and subjected to FA (0.1 μM), sh-Nrf2, and Fe (Fe-citrate, ferroptosis inducer; 5 M) treatment to study the in vitro effect of FA on LPS-induced alveolar epithelial cell injury and the role of the Nrf2/HO-1 pathway.Results We found that FA decreased the lung injury score (48% reduction), lung wet/dry weight ratio (33% reduction), and myeloperoxidase activity (58% reduction) in sepsis-induced ALI. Moreover, FA inhibited ferroptosis of alveolar epithelial cells and improved alveolar epithelial barrier dysfunction. The protective role of FA against alveolar epithelial barrier dysfunction could be reversed by the ferroptosis inducer Fe-citrate, suggesting that FA alleviates alveolar epithelial barrier dysfunction by inhibiting ferroptosis. Mechanistically, we found that FA inhibited ferroptosis of alveolar epithelial cells by activating the Nrf2/HO-1 pathway.Conclusion Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment. |
| first_indexed | 2024-04-13T08:02:21Z |
| format | Article |
| id | doaj.art-50056ff46b274688aaee12054f5898c1 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-13T08:02:21Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-50056ff46b274688aaee12054f5898c12022-12-22T02:55:15ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-016012286229410.1080/13880209.2022.2147549Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosisXianming Tang0Jiqiang Liu1Shuo Yao2Jianfei Zheng3Xun Gong4Bing Xiao5Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, P. R. ChinaDepartment of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, P. R. ChinaDepartment of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, P. R. ChinaDepartment of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, P. R. ChinaDepartment of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, P. R. ChinaDepartment of Emergency Medicine, The Second Xiangya Hospital of Central South University, Emergency and Difficult Diseases Institute of Central South University, Changsha, P. R. ChinaContext Ferulic acid (FA) has antioxidative and anti-inflammatory effects, and is a promising drug to treat sepsis.Objective To study the therapeutic effect of FA in sepsis-induced acute lung injury (ALI) and its underlying mechanisms.Materials and methods The caecal ligation and puncture (CLP) manoeuvre was applied to establish a murine model of sepsis-induced ALI, and female BALB/c mice (6 mice per group) were subjected to 100 mg/kg FA or 0.8 mg/kg ferrostatin-1 (Fer-1, ferroptosis inhibitor) treatment to clarify the role of FA in preserving alveolar epithelial barrier function and inhibiting ferroptosis. Lipopolysaccharide (LPS; 500 ng/mL)-induced cell models were prepared and subjected to FA (0.1 μM), sh-Nrf2, and Fe (Fe-citrate, ferroptosis inducer; 5 M) treatment to study the in vitro effect of FA on LPS-induced alveolar epithelial cell injury and the role of the Nrf2/HO-1 pathway.Results We found that FA decreased the lung injury score (48% reduction), lung wet/dry weight ratio (33% reduction), and myeloperoxidase activity (58% reduction) in sepsis-induced ALI. Moreover, FA inhibited ferroptosis of alveolar epithelial cells and improved alveolar epithelial barrier dysfunction. The protective role of FA against alveolar epithelial barrier dysfunction could be reversed by the ferroptosis inducer Fe-citrate, suggesting that FA alleviates alveolar epithelial barrier dysfunction by inhibiting ferroptosis. Mechanistically, we found that FA inhibited ferroptosis of alveolar epithelial cells by activating the Nrf2/HO-1 pathway.Conclusion Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment.https://www.tandfonline.com/doi/10.1080/13880209.2022.2147549MLE-12 cellscell deathcaecal ligation and punctureferrostatin-1 |
| spellingShingle | Xianming Tang Jiqiang Liu Shuo Yao Jianfei Zheng Xun Gong Bing Xiao Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis Pharmaceutical Biology MLE-12 cells cell death caecal ligation and puncture ferrostatin-1 |
| title | Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis |
| title_full | Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis |
| title_fullStr | Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis |
| title_full_unstemmed | Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis |
| title_short | Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis |
| title_sort | ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis induced acute lung injury by activating the nrf2 ho 1 pathway and inhibiting ferroptosis |
| topic | MLE-12 cells cell death caecal ligation and puncture ferrostatin-1 |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2022.2147549 |
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