Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK–OCMC Nps), which enhance the aqueous solubility and stability of GK. The GK–OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK–OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK–OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK–OCMC Nps. The GK–OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK–OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK–OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK–OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. GK–OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

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.