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

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.

Quantitative Proteomics Reveal the Protective Effects of the Combined Chinese Herbal Extracts Against Alzheimer's Disease via Modulating the Expression of Synapse-associated Proteins in Mouse Model

“…The Vina score (a nity (kcal/mol)) indicates the binding activity between the receptor and ligand. The more negative the value of binding free energy, the more stable between ligand and receptor [19]. Most of the compounds had good binding activity with PPP3CC, SNAPIN, PKA and P38MAPK (Supplementary Table 3).…”

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

“…Pharmacological effects of ginseng preparations at various levels of regulation of homeostasis have been studied [ 26 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]; however, network pharmacology studies [ 26 , 33 , 34 , 35 , 36 , 37 , 38 ] at the transcriptomic level of regulation of cellular homeostasis are limited [ 38 ].…”

The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

“…Acute lung injury (ALI), the most severe form of the complex cascade of acute respiratory distress dyndrome (ARDS) continues to leave its mark as the prime cause of death in critically ill individuals 1,2 . ALI is characterized by acute hypoxemia thereby leading to respiratory failure 2,3 . Despite improved diagnostic and treatment measures, so far no significant up‐gradation in the prognosis of ALI has been achieved yet.…”