Transcriptome expression profile of compound-K-enriched red ginseng extract (DDK-401) in Korean volunteers and its apoptotic properties

Ginseng and ginsenosides have been reported to have various pharmacological effects, but their efficacies depend on intestinal absorption. Compound K (CK) is gaining prominence for its biological and pharmaceutical properties. In this study, CK-enriched fermented red ginseng extract (DDK-401) was prepared by enzymatic reactions. To examine its pharmacokinetics, a randomized, single-dose, two-sequence, crossover study was performed with eleven healthy Korean male and female volunteers. The volunteers were assigned to take a single oral dose of one of two extracts, DDK-401 or common red ginseng extract (DDK-204), during the initial period. After a 7-day washout, they received the other extract. The pharmacokinetics of DDK-401 showed that its maximum plasma concentration (Cmax) occurred at 184.8 +/- 39.64 ng/mL, Tmax was at 2.4 h, and AUC(0-12h) was 920.3 +/- 194.70 ng h/mL, which were all better than those of DDK-204. The maximum CK absorption in the female volunteers was higher than that in the male volunteers. The differentially expressed genes from the male and female groups were subjected to a KEGG pathway analysis, which showed results in the cell death pathway, such as apoptosis and necroptosis. In cytotoxicity tests, DDK-401 and DDK-204 were not particularly toxic to normal (HaCaT) cells, but at a concentration of 250 mu g/mL, DDK-401 had a much higher toxicity to human lung cancer (A549) cells than DDK-204. DDK-401 also showed a stronger antioxidant capacity than DDK-204 in both the DPPH and potassium ferricyanide reducing power assays. DDK-401 reduced the reactive oxygen species production in HaCaT cells with induced oxidative stress and led to apoptosis in the A549 cells. In the mRNA sequence analysis, a signaling pathway with selected marker genes was assessed by RT-PCR. In the HaCaT cells, DDK-401 and DDK-204 did not regulate FOXO3, TLR4, MMP-9, or p38 expression; however, in the A549 cells, DDK-401 downregulated the expressions of MMP9 and TLR4 as well as upregulated the expressions of the p38 and caspase-8 genes compared to DDK-204. These results suggest that DDK-401 could act as a molecular switch for these two cellular processes in response to cell damage signaling and that it could be a potential candidate for further evaluations in health promotion studies.

Automated summary

In this study, a CK-enriched fermented red ginseng extract was prepared and its pharmacokinetics were studied. The extract showed better pharmacokinetic properties and exhibited higher antioxidant capacity and toxicity against lung cancer cells in vitro.