Network Pharmacology-Based Prediction and Verification of Ginsenoside Rh2-Induced Apoptosis of A549 Cells via the PI3K/Akt Pathway

Ginsenoside Rh2 (G-Rh2), a rare protopanaxadiol (PPD)-type triterpene saponin, from Panax ginseng has anti-proliferation, anti-invasion, and anti-metastatic activity. However, the mechanisms by which G-Rh2 induces apoptosis of lung cancer cells are unclear. In the present work, a G-Rh2 target-lung cancer network was constructed and analyzed by the network pharmacology approach. A total of 91 compound-targets of G-Rh2 was obtained based on the compound-target network analysis, and 217 targets were identified for G-Rh2 against lung cancer by PPI network analysis. The 217 targets were significantly enriched in 103 GO terms with FDR <0.05 as threshold in the GO enrichment analysis. In KEGG pathway enrichment analysis, all the candidate targets were significantly enriched in 143 pathways, among of which PI3K-Akt signaling pathway was identified as one of the top enriched pathway. Besides, G-Rh2 induced apoptosis in human lung epithelial (A549) cells was verified in this work. G-Rh2 significantly inhibited the proliferation of A549 cells in a dose-dependent manner, and the apoptosis rate significantly increased from 4.4% to 78.7% using flow cytometry. Western blot analysis revealed that the phosphorylation levels of p85, PDK1, Akt and IκBα were significantly suppressed by G-Rh2. All the experimental findings were consistent with the network pharmacology results. Research findings in this work will provide potential therapeutic value for further mechanism investigations.