Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3.

IF 3.9 3区医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pharmaceutical Biology Pub Date : 2022-12-01 DOI:10.1080/13880209.2022.2067571

Yan Wu, Xin Yang, Yuanyuan Ju, Fei Zhao

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引用次数: 3

Abstract

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.

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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。

背景:急性肺损伤(ALI)是一种严重的异质性肺疾病。本研究选择黄曲霉醇是因为它是一种简单的香豆素化合物，以前没有在ALI中研究过。目的:探讨黄曲醇治疗ALI的疗效及作用机制。材料与方法:雄性BALB/c小鼠经鼻注射脂多糖(LPS)后，分别给予20、40、80 mg/kg的黄曲醇;10 μg (50 μL)。对照组小鼠气管内注射50 μL磷酸缓冲盐水(PBS)。用100 ng/mL LPS对Raw264.7细胞处理6 h，然后用不同浓度(5、10、25 μM)的黄蜡醇处理48 h。对照组细胞用PBS处理。结果:20、40、80 mg/kg剂量的曲辛醇显著减轻lps诱导的小鼠肺损伤(肺损伤评分分别为10.4%、31.2、50.3%)。曲蜡醇可减弱LPS诱导的细胞凋亡和核苷酸结合寡聚结构域样受体家族pyrin结构域-3 (NLRP3)激活(凋亡，18.3%，30.2%，55.6%;Nlrp3, 30.0, 47.7, 63.6%)。黄曲醇在Raw264.7细胞中的抗凋亡和抗炎症作用也得到证实(凋亡，38.8%，55.3,68.9%;Nlrp3, 20.6, 55.7, 73.9%)。讨论与结论:黄曲醇的抗ali作用可能通过平衡ACE-Ang II-AT1R和ACE2-Ang (1-7)-Mas轴，抑制NLRP3炎性体发挥作用。我们的研究提供了一种治疗ALI的候选药物。

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来源期刊

Pharmaceutical Biology 医学-药学

CiteScore

6.70

自引率

2.60%

发文量

191

审稿时长

1 months

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.