{"title":"黄曲醇通过平衡ACE-Ang II-AT1R和ACE2-Ang (1-7)-Mas,抑制NLRP3,减轻lps诱导的急性肺损伤。","authors":"Yan Wu, Xin Yang, Yuanyuan Ju, Fei Zhao","doi":"10.1080/13880209.2022.2067571","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>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.</p><p><strong>Objectives: </strong>This study investigates the ALI therapeutic effect and mechanisms of fraxinol.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Discussion and conclusion: </strong>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.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"979-989"},"PeriodicalIF":3.9000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122403/pdf/","citationCount":"3","resultStr":"{\"title\":\"Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3.\",\"authors\":\"Yan Wu, Xin Yang, Yuanyuan Ju, Fei Zhao\",\"doi\":\"10.1080/13880209.2022.2067571\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>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.</p><p><strong>Objectives: </strong>This study investigates the ALI therapeutic effect and mechanisms of fraxinol.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Discussion and conclusion: </strong>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.</p>\",\"PeriodicalId\":19942,\"journal\":{\"name\":\"Pharmaceutical Biology\",\"volume\":\"60 1\",\"pages\":\"979-989\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122403/pdf/\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13880209.2022.2067571\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2022.2067571","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
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: 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.
期刊介绍:
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.