Ding Qi, Zhu Wenxiang, Diao Yirui, Xu Gonghao, Wang Lu, Qu Sihao, Shi Yuanyuan
School of Life Science, Beijing University of Chinese Medicine, Beijing, China.
Shenzhen Research Institute, Beijing University of Chinese Medicine, Shenzhen, China.
Front Pharmacol. 2021 Jan 20;11:611794. doi: 10.3389/fphar.2020.611794. eCollection 2020.
Acute respiratory distress syndrome (ARDS) is a complex cascade that develops from acute lung injury (ALI). Ginseng can be used to treat ALI/ARDS. Studies have shown that some of ingredients in ginseng had anti-inflammation, antioxidative, and immune regulation effects and can protect alveolar epithelial cells in mice. However, the potential targets, biological processes, and pathways related to ginseng against ALI/ARDS have not been investigated systematically. We employed network pharmacology, molecular docking, and animal experiments to explore the therapeutic effects and underlying mechanism of action of ginseng against ALI/ARDS. We identified 25 compounds using ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry and their 410 putative targets through database analyses. Sixty-nine of them were considered to be key targets of ginseng against ALI/ARDS according to overlapping with ALI/ARDS-related targets and further screening in a protein-protein interaction (PPI) network. The phosphatidylinositol 3-kinase-protein kinase B (PI3K-AkT) and mitogen-activated protein kinase (MAPK) pathways were recognized to have critical roles for ginseng in ALI/ARDS treatment. Signal transducer and activator of transcription (STAT) 3, vascular endothelial growth factor A (VEGFA), fibroblast growth factor (FGF) 2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), MAPK1, and interleukin (IL) 2 were the top six nodes identified by analyses of a compound-target-pathway network. Molecular docking showed that most of the ingredients in ginseng could combine well with the six nodes. Ginseng could reduce the pathologic damage, neutrophil aggregation, proinflammatory factors, and pulmonary edema in vivo and inhibit the PI3K-Akt signaling pathway and MAPK signaling pathway through downregulating expressions of STAT3, VEGFA, FGF2, PIK3CA, MAPK1, and IL2. Our study provides a theoretical basis for ginseng treatment of ALI/ARDS.
急性呼吸窘迫综合征（ARDS）是一种由急性肺损伤（ALI）发展而来的复杂级联反应。人参可用于治疗ALI/ARDS。研究表明，人参中的一些成分具有抗炎、抗氧化和免疫调节作用，可保护小鼠肺泡上皮细胞。然而，人参抗ALI/ARDS的潜在靶点、生物学过程和通路尚未得到系统研究。我们采用网络药理学、分子对接和动物实验来探索人参抗ALI/ARDS的治疗效果及其潜在作用机制。通过超高效液相色谱Q-轨道阱质谱法鉴定了25种化合物，并通过数据库分析确定了它们的410个潜在靶点。根据与ALI/ARDS相关靶点的重叠情况以及在蛋白质-蛋白质相互作用（PPI）网络中的进一步筛选，其中69个被认为是人参保肺抗ARDS的关键靶点。磷脂酰肌醇3激酶-蛋白激酶B（PI3K-Akt）和丝裂原活化蛋白激酶（MAPK）通路被认为在人参治疗ALI/ARDS中起关键作用。信号转导和转录激活因子（STAT）3、血管内皮生长因子A（VEGFA）、成纤维细胞生长因子（FGF）2、磷脂酰肌醇-4,5-二磷酸3激酶催化亚基α（PIK3CA）、MAPK1和白细胞介素（IL）2是通过化合物-靶点-通路网络分析确定的前六个节点。分子对接表明，人参中的大多数成分能与这六个节点良好结合。人参可减轻体内病理损伤、中性粒细胞聚集、促炎因子和肺水肿，并通过下调STAT3、VEGFA、FGF2、PIK3CA、MAPK1和IL2的表达来抑制PI3K-Akt信号通路和MAPK信号通路。我们的研究为人参治疗ALI/ARDS提供了理论依据。
