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.

Background: Pulmonary Fibrosis (PF) is an interstitial lung disease characterized by excessive accumulation of extracellular matrix in the lungs, which disrupts the structure and gas exchange of the alveoli. There are only two approved therapies for PF, nintedanib (Nib) and pirfenidone. Therefore, the use of Chinese medicine for PF is attracting attention. Tianlongkechuanling (TL) is an effective Chinese formula that has been applied clinically to alleviate PF, which can enhance lung function and quality of life.Purpose: The potential effects and specific mechanisms of TL have not been fully explored, yet. In the present study, proteomics was performed to explore the therapeutic protein targets of TL on Bleomycin (BLM)-induced Pulmonary Fibrosis.Method: BLM-induced PF mice models were established. Hematoxylineosin staining and Masson staining were used to analyze histopathological changes and collagen deposition. To screen the differential proteins expression between the Control, BLM, BLM + TL and BLM + Nib (BLM + nintedanib) groups, quantitative proteomics was performed using tandem mass tag (TMT) labeling with nanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein–protein interactions (PPI) were established by STRING. Expressions of α-smooth muscle actin (α-SMA), Collagen I (Col1a1), Fibronectin (Fn1) and enzymes in arginase-ornithine pathway were detected by Western blot or RT-PCR.Result: TL treatments significantly ameliorated BLM-induced collagen deposition in lung tissues. Moreover, TL can inhibit the protein expressions of α-SMA and the mRNA expressions of Col1a1 and Fn1. Using TMT technology, we observed 253 differentially expressed proteins related to PPI networks and involved different KEGG pathways. Arginase-ornithine pathway is highly significant. The expression of arginase1 (Arg1), carbamoyltransferase (OTC), carbamoy-phosphate synthase (CPS1), argininosuccinate synthase (ASS1), ornithine aminotransferase (OAT) argininosuccinate lyase (ASL) and inducible nitric oxide synthase (iNOS) was significantly decreased after TL treatments.Conclusion: Administration of TL in BLM-induced mice resulted in decreasing pulmonary fibrosis. Our findings propose that the down regulation of arginase-ornithine pathway expression with the reduction of arginase biosynthesis is a central mechanism and potential treatment for pulmonary fibrosis with the prevention of TL.

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an acute respiratory failure syndrome characterized by progressive arterial hypoxemia and dyspnea. Qingfei Litan (QFLT) decoction, as a classic prescription for the treatment of acute respiratory infections, is effective for the treatment of ALI/ARDS. In this study, the compounds, hub targets, and major pathways of QFLT in ALI/ARDS treatment were analyzed using Ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) and systemic pharmacology strategies. UHPLC-MS identified 47 main components of QFLT. To explore its anti-inflammatory and anti-oxidative mechanisms, gene ontology (Go) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and network pharmacological analysis were conducted based on the main 47 components. KEGG enrichment analysis showed that TNF signaling pathway and Toll-like receptor signaling pathway may be the key pathways of ALI/ARDS. We explored the anti-inflammatory and anti-oxidative pharmacological effects of QFLT in treatment of ALI/ARDS in vivo and in vitro. QFLT suppressed the levels of proinflammatory cytokines and alleviated oxidative stress in LPS-challenged mice. In vitro, QFLT decreased the levels of TNF-α, IL-6, IL-1β secreted by LPS-activated macrophages, increased GSH level and decreased the LPS-activated reactive oxygen species (ROS) in lung epithelial A549 cells. This study suggested that QFLT may have anti-inflammatory and anti-oxidative effects on ALI/ARDS, combining in vivo and in vitro experiments with systemic pharmacology, providing a potential therapeutic strategy option.