Elucidation of the Mechanism of Action of Ginseng Against Acute Lung Injury/Acute Respiratory Distress Syndrome by a Network Pharmacology-Based Strategy.

Qi Ding,Yirui Diao,Yuanyuan Shi,Sihao Qu,Gonghao Xu,Wenxiang Zhu,Lu Wang

doi:10.3389/fphar.2020.611794

Qi Ding, Yirui Diao + Show 5 more

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https://doi.org/10.3389/fphar.2020.611794

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Abstract

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.

Highlights

Acute respiratory distress syndrome (ARDS) is a complex process which develops from acute lung injury (ALI)
Expression of p-STAT3, PIK3CA, and protein kinase (MAPK) 1 (p-MAPK1) in lung tissue was detected by Western blotting. (D–F) Expression of IL-2, vascular endothelial growth factor A (VEGFA), and FGF2 in lung tissue was measured by Enzyme-Linked Immunosorbent Assay (ELISA)
Our in vivo experiments showed that ginseng could significantly reduce the pathologic damage, infiltration of proinflammatory factors, and pulmonary edema induced by LPS and downregulate the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway through suppressing expression of PIK3CA, IL2, FGF2, and VEGFA in lung tissue

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a complex process which develops from acute lung injury (ALI). In China, ∼20% of coronavirus disease 2019 (COVID-19) patients have the severe disease form of disease, which can develop rapidly into ALI/ARDS (Wu and McGoogan, 2020). ALI/ARDS is one of the most common diseases that seriously threatens the lives of patients (Sweeney and McAuley, 2016). Antiinflammatory, antioxidative, and anticoagulant agents, surfactants, and neuromuscular blockers have been used to treat ALI/ARDS (Fan et al, 2018). None of these treatments have been approved by the US Food and Drug Administration, European Medicines Agency, or the Chinese National Medical Products Administration because of weak efficacy or serious side effects

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