Gao Hejun, Yuan Ziyi, Liang Haoxuan, Liu Youtan
Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Front Pharmacol. 2024 Mar 22;15:1261772. doi: 10.3389/fphar.2024.1261772. eCollection 2024.
Patients with sepsis are at an incremental risk of acute lung injury (ALI). Baiqian, also known as rhizoma et radix (Csrer), has anti-inflammatory properties and is traditionally used to treat cough and phlegm. This study aimed to demonstrate the multicomponent, multitarget, and multi-pathway regulatory molecular mechanisms of Csrer in treating lipopolysaccharide (LPS)-induced ALI. The bioactive components of Csrer were identified by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). Active targets predicted from PharmMapper. DrugBank, OMIM, TTD, and GeneCards were used to identify potential targets related to ALI. Intersection genes were identified for Csrer against ALI. The PPI network was analysed to identify prime targets. GO and KEGG analyses were performed. A drug-compound-target-pathway-disease network was constructed. Molecular docking and simulations evaluated the binding free energy between key proteins and active compounds. The protective effect and mechanism of Csrer in ALI were verified using an ALI model in mice. Western blot, Immunohistochemistry and TUNEL staining evaluated the mechanisms of the pulmonary protective effects of Csrer. Forty-six bioactive components, one hundred and ninety-two potential cross-targets against ALI and ten core genes were identified. According to GO and KEGG analyses, the PI3K-Akt, apoptosis and p53 pathways are predominantly involved in the "Csrer-ALI" network. According to molecular docking and dynamics simulations, ten key genes were firmly bound by the principal active components of Csrer. The "Csrer-ALI" network was revealed to be mediated by the p53-mediated apoptosis and inflammatory pathways in animal experiments. Csrer is a reliable source for ALI treatment based on its practical components, potential targets and pathways.
脓毒症患者发生急性肺损伤（ALI）的风险增加。白前，又称根茎（Csrer），具有抗炎特性，传统上用于治疗咳嗽和祛痰。本研究旨在阐明Csrer治疗脂多糖（LPS）诱导的ALI的多成分、多靶点和多途径调节分子机制。通过超高效液相色谱Q-轨道阱质谱（UPLC-Q-Orbitrap MS）鉴定Csrer的生物活性成分。利用PharmMapper、DrugBank、OMIM、TTD和GeneCards预测的活性靶点来识别与ALI相关的潜在靶点。确定Csrer针对ALI的交集基因。分析蛋白质-蛋白质相互作用（PPI）网络以识别主要靶点。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。构建药物-化合物-靶点-途径-疾病网络。分子对接和模拟评估关键蛋白与活性化合物之间的结合自由能。使用小鼠ALI模型验证Csrer在ALI中的保护作用及机制。蛋白质免疫印迹法、免疫组织化学和TUNEL染色评估Csrer肺保护作用的机制。鉴定出46种生物活性成分、192个针对ALI的潜在交叉靶点和10个核心基因。根据GO和KEGG分析，PI3K-Akt、凋亡和p53途径主要参与“Csrer-ALI”网络。根据分子对接和动力学模拟，Csrer的主要活性成分与10个关键基因紧密结合。在动物实验中，“Csrer-ALI”网络被揭示由p53介导的凋亡和炎症途径介导。基于其实际成分、潜在靶点和途径，Csrer是治疗ALI的可靠药物来源。
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