CK absorption in Korean Volunteers from DDK-401

Ginseng and ginsenosides has been reported for various pharmacological effects, its efficacies is highly dependent on intestinal absorption of ginsenosides. Moreover, compound K (CK) is getting prominence due to its biological and pharmaceutical properties. In this study, CK enriched fermented red ginseng extract (DDK 401) were prepared by enzymatic reactions. For pharmacokinetics study, in randomized, single dose, two sequence, crossover study was performed in eleven healthy Korean male and female volunteers. The volunteers were assigned to one of the two extracts as a single oral dose of DDK 401 or DDK 204 in first period. After 7 day washout, alternative sequence treatment was performed. The pharmacokinetics of DDK 401 showed the maximum plasma concentration was two and half hours. Moreover, the CK absorption was showed a maximum in the female volunteers than male volunteers. In addition, the total differential expressed genes from male and female groups were subjected to KEGG pathway which resulted the cell death pathway such as apoptosis and necroptosis. Furthermore, cytotoxicity effect of DDK 401 and DDK 204 are less toxic in HaCat cells whereas at higher concentration in human lung cancer (A549) cells, DDK 401 had much higher toxicity than DDK 204 which lead to apoptosis cancer cells. The DDK 401 showed stronger antioxidant capacity compared to DDK 204 in both the DPPH and potassium ferricyanide reducing power assays. In ROS generation, DDK 401 reduced ROS production in normal cell (HaCat) induced oxidative stress also could lead to apoptosis in lung cancers (A549 cell line). According to RNA sequences analysis, investigating of signaling pathway with selected marker genes was assessed by RTPCR. In the HaCat cells, DDK 401 and DDK 204 did not regulate of FOXO3, TLR4, MMP9, and p38 expressions, whereas in the lung cancer A549 cells, DDK 401 downregulated of the expression of the MMP9 and TLR4 while upregulated expression of the p38 and caspase 8 genes compared to DDK 201. The results suggesting that DDK 401 could act as molecular switches for these two cellular processes in response to cell damage signaling and potential candidate for further evaluation related to health promotion studies.