Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3
Context Acute lung injury (ALI) is a serious heterogenous pulmonary disorder. Fraxinol was selected for this study since it is a simple coumarin compound, not previously investigated in ALI.Objectives This study investigates the ALI therapeutic effect and mechanisms of fraxinol.Materials and methods...
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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/10.1080/13880209.2022.2067571 |
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| author | Yan Wu Xin Yang Yuanyuan Ju Fei Zhao |
| author_facet | Yan Wu Xin Yang Yuanyuan Ju Fei Zhao |
| author_sort | Yan Wu |
| collection | DOAJ |
| description | Context Acute lung injury (ALI) is a serious heterogenous pulmonary disorder. Fraxinol was selected for this study since it is a simple coumarin compound, not previously investigated in ALI.Objectives This study investigates the ALI therapeutic effect and mechanisms of fraxinol.Materials and methods Male BALB/c mice were treated with fraxinol (20, 40, and 80 mg/kg) following intranasal injection of lipopolysaccharide (LPS; 10 μg in 50 μL). The mice in control group were intratracheally injected with 50 μL phosphate buffered saline (PBS). Raw264.7 cells were treated with fraxinol by 100 ng/mL LPS for 6 h, then treated by different concentrations of fraxinol (5, 10, and 25 μM) for 48 h. Cells in control group were treated with PBS.Results Fraxinol with doses of 20, 40, and 80 mg/kg significantly attenuated LPS-induced lung injury in mice (lung injury score, 10.4, 31.2, 50.3%). Fraxinol attenuated the apoptosis and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) activation induced by LPS (apoptosis, 18.3, 30.2, 55.6%; NLRP3, 30.0, 47.7, 63.6%). The anti-apoptosis and anti-inflammation effects of fraxinol were also confirmed in Raw264.7 cells (apoptosis, 38.8, 55.3, 68.9%; NLRP3, 20.6, 55.7, 73.9%).Discussion and conclusion The anti-ALI effects of fraxinol maybe by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas axis and inhibiting NLRP3 inflammasome. Our research provides a candidate drug in the treatment of ALI. |
| first_indexed | 2024-04-14T00:21:37Z |
| format | Article |
| id | doaj.art-2ba5976e547d4ca9bd3be9dbd8ee0646 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-14T00:21:37Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-2ba5976e547d4ca9bd3be9dbd8ee06462022-12-22T02:22:55ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-0160197998910.1080/13880209.2022.2067571Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3Yan Wu0Xin Yang1Yuanyuan Ju2Fei Zhao3Department of Pediatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Pediatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Pediatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Pediatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaContext Acute lung injury (ALI) is a serious heterogenous pulmonary disorder. Fraxinol was selected for this study since it is a simple coumarin compound, not previously investigated in ALI.Objectives This study investigates the ALI therapeutic effect and mechanisms of fraxinol.Materials and methods Male BALB/c mice were treated with fraxinol (20, 40, and 80 mg/kg) following intranasal injection of lipopolysaccharide (LPS; 10 μg in 50 μL). The mice in control group were intratracheally injected with 50 μL phosphate buffered saline (PBS). Raw264.7 cells were treated with fraxinol by 100 ng/mL LPS for 6 h, then treated by different concentrations of fraxinol (5, 10, and 25 μM) for 48 h. Cells in control group were treated with PBS.Results Fraxinol with doses of 20, 40, and 80 mg/kg significantly attenuated LPS-induced lung injury in mice (lung injury score, 10.4, 31.2, 50.3%). Fraxinol attenuated the apoptosis and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) activation induced by LPS (apoptosis, 18.3, 30.2, 55.6%; NLRP3, 30.0, 47.7, 63.6%). The anti-apoptosis and anti-inflammation effects of fraxinol were also confirmed in Raw264.7 cells (apoptosis, 38.8, 55.3, 68.9%; NLRP3, 20.6, 55.7, 73.9%).Discussion and conclusion The anti-ALI effects of fraxinol maybe by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas axis and inhibiting NLRP3 inflammasome. Our research provides a candidate drug in the treatment of ALI.https://www.tandfonline.com/doi/10.1080/13880209.2022.2067571Inflammationapoptosisrenin-angiotensin system |
| spellingShingle | Yan Wu Xin Yang Yuanyuan Ju Fei Zhao Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3 Pharmaceutical Biology Inflammation apoptosis renin-angiotensin system |
| title | Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3 |
| title_full | Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3 |
| title_fullStr | Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3 |
| title_full_unstemmed | Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3 |
| title_short | Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3 |
| title_sort | fraxinol attenuates lps induced acute lung injury by equilibrating ace ang ii at1r and ace2 ang 1 7 mas and inhibiting nlrp3 |
| topic | Inflammation apoptosis renin-angiotensin system |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2022.2067571 |
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