Abstract：
BACKGROUND: Acute respiratory distress syndrome (ARDS) is an acute respiratory disease characterized by bilateral chest radiolucency and severe hypoxemia. Quzhou Fructus Aurantii ethyl acetate extract (QFAEE), which is prepared from the traditional Chinese respiratory anti-inflammatory natural herb Quzhou Fructus Arantii, has the potential to alleviate ARDS. In this work, we aimed to investigate the potential and mechanism underlying the action of QFAEE on ARDS and how QFAEE modulates the STING pathway to reduce type I interferon release to alleviate the inflammatory response.
METHODS: Lipopolysaccharide (LPS), a potential proinflammatory stimulant capable of causing pulmonary inflammation with edema after nasal drops, was employed to model ARDS in vitro and in vivo. Under QFAEE intervention, the mechanism of action of QFAEE to alleviate ARDS was explored in this study. TREX1-/- mice were sued as a research model for the activation of the congenital STING signaling pathway. The effect of QFAEE on TREX1-/- mice could explain the STING-targeted effect of QFAEE on alleviating the inflammatory response. Our explorations covered several techniques, Western blot, histological assays, immunofluorescence staining, transcriptomic assays and qRT-PCR to determine the potential mechanism of action of QFAEE in antagonizing the inflammatory response in the lungs, as well as the mechanism of action of QFAEE in targeting the STING signaling pathway to regulate the release of type I interferon.
RESULTS: QFAEE effectively alleviates ARDS symptoms in LPS-induced ARDS. We revealed that the mechanism underlying LPS-induced ARDS is the STING-TBK1 signaling pathway and further elucidated the molecular mechanism of QFAEE in the prevention and treatment of ARDS. QFAEE reduced the release of type I interferons by inhibiting the STING-TBK1-IRF3 axis, thus alleviating LPS-induced pneumonia and lung cell death in mice. Another key finding is that activation of the STING pathway by activators or targeted knockdown of the TREX1 gene can also induce ARDS. As expected, QFAEE was found to be an effective protective agent in alleviating ARDS and the antagonistic effect of QFAEE on ARDS was achieved by inhibiting the STING signaling pathway.
CONCLUSIONS: The main anti-inflammatory effect of QFAEE was achieved by inhibiting the STING signaling pathway and reducing the release of type I interferons. According to this mechanism of effect, QFAEE can effectively alleviate ARDS and can be considered a potential therapeutic agent. In addition, the STING pathway plays an essential role in the development and progression of ARDS, and it is a potential target for ARDS therapy.
METHODS: Lipopolysaccharide (LPS), a potential proinflammatory stimulant capable of causing pulmonary inflammation with edema after nasal drops, was employed to model ARDS in vitro and in vivo. Under QFAEE intervention, the mechanism of action of QFAEE to alleviate ARDS was explored in this study. TREX1-/- mice were sued as a research model for the activation of the congenital STING signaling pathway. The effect of QFAEE on TREX1-/- mice could explain the STING-targeted effect of QFAEE on alleviating the inflammatory response. Our explorations covered several techniques, Western blot, histological assays, immunofluorescence staining, transcriptomic assays and qRT-PCR to determine the potential mechanism of action of QFAEE in antagonizing the inflammatory response in the lungs, as well as the mechanism of action of QFAEE in targeting the STING signaling pathway to regulate the release of type I interferon.
RESULTS: QFAEE effectively alleviates ARDS symptoms in LPS-induced ARDS. We revealed that the mechanism underlying LPS-induced ARDS is the STING-TBK1 signaling pathway and further elucidated the molecular mechanism of QFAEE in the prevention and treatment of ARDS. QFAEE reduced the release of type I interferons by inhibiting the STING-TBK1-IRF3 axis, thus alleviating LPS-induced pneumonia and lung cell death in mice. Another key finding is that activation of the STING pathway by activators or targeted knockdown of the TREX1 gene can also induce ARDS. As expected, QFAEE was found to be an effective protective agent in alleviating ARDS and the antagonistic effect of QFAEE on ARDS was achieved by inhibiting the STING signaling pathway.
CONCLUSIONS: The main anti-inflammatory effect of QFAEE was achieved by inhibiting the STING signaling pathway and reducing the release of type I interferons. According to this mechanism of effect, QFAEE can effectively alleviate ARDS and can be considered a potential therapeutic agent. In addition, the STING pathway plays an essential role in the development and progression of ARDS, and it is a potential target for ARDS therapy.
摘要：
背景：急性呼吸窘迫综合征（ARDS）是一种急性呼吸道疾病，其特征是双侧胸部射线不透和严重的低氧血症。衢州樟脑乙酸乙酯提取物（QFAEE），这是由中国传统的呼吸抗炎天然中药衢州益母草，有可能减轻ARDS。在这项工作中,我们旨在研究QFAEE对ARDS的潜在作用和潜在机制,以及QFAEE如何调节STING通路以减少I型干扰素释放从而减轻炎症反应.
方法：脂多糖(LPS)，一种潜在的促炎兴奋剂，能够引起肺部炎症，滴鼻后水肿，用于体外和体内模拟ARDS。在QFAEE的干预下，本研究探讨了QFAEE缓解ARDS的作用机制。TREX1-/-小鼠作为先天性STING信号通路激活的研究模型。QFAEE对TREX1-/-小鼠的作用可以解释QFAEE对减轻炎症反应的STING靶向作用。我们的探索涵盖了几种技术，蛋白质印迹,组织学检测,免疫荧光染色，转录组学分析和qRT-PCR确定QFAEE拮抗肺部炎症反应的潜在作用机制，以及QFAEE靶向STING信号通路调节I型干扰素释放的作用机制。
结果：QFAEE可有效缓解LPS诱导的ARDS症状。我们揭示了LPS诱导ARDS的机制是STING-TBK1信号通路，并进一步阐明了QFAEE预防和治疗ARDS的分子机制。QFAEE通过抑制STING-TBK1-IRF3轴来减少I型干扰素的释放，从而减轻LPS诱导的小鼠肺炎和肺细胞死亡。另一个关键发现是通过TREX1基因的激活剂或靶向敲低对STING途径的激活也可以诱导ARDS。不出所料,发现QFAEE是缓解ARDS的有效保护剂，QFAEE对ARDS的拮抗作用是通过抑制STING信号通路实现的。
结论：QFAEE的主要抗炎作用是通过抑制STING信号通路和减少I型干扰素的释放来实现的。根据这种作用机制,QFAEE可以有效缓解ARDS，可以被认为是一种潜在的治疗药物。此外,STING通路在ARDS的发生发展中起着至关重要的作用，是ARDS治疗的潜在靶点。
方法：脂多糖(LPS)，一种潜在的促炎兴奋剂，能够引起肺部炎症，滴鼻后水肿，用于体外和体内模拟ARDS。在QFAEE的干预下，本研究探讨了QFAEE缓解ARDS的作用机制。TREX1-/-小鼠作为先天性STING信号通路激活的研究模型。QFAEE对TREX1-/-小鼠的作用可以解释QFAEE对减轻炎症反应的STING靶向作用。我们的探索涵盖了几种技术，蛋白质印迹,组织学检测,免疫荧光染色，转录组学分析和qRT-PCR确定QFAEE拮抗肺部炎症反应的潜在作用机制，以及QFAEE靶向STING信号通路调节I型干扰素释放的作用机制。
结果：QFAEE可有效缓解LPS诱导的ARDS症状。我们揭示了LPS诱导ARDS的机制是STING-TBK1信号通路，并进一步阐明了QFAEE预防和治疗ARDS的分子机制。QFAEE通过抑制STING-TBK1-IRF3轴来减少I型干扰素的释放，从而减轻LPS诱导的小鼠肺炎和肺细胞死亡。另一个关键发现是通过TREX1基因的激活剂或靶向敲低对STING途径的激活也可以诱导ARDS。不出所料,发现QFAEE是缓解ARDS的有效保护剂，QFAEE对ARDS的拮抗作用是通过抑制STING信号通路实现的。
结论：QFAEE的主要抗炎作用是通过抑制STING信号通路和减少I型干扰素的释放来实现的。根据这种作用机制,QFAEE可以有效缓解ARDS，可以被认为是一种潜在的治疗药物。此外,STING通路在ARDS的发生发展中起着至关重要的作用，是ARDS治疗的潜在靶点。
