Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults

Abstract

Red ginseng (RG) and black ginseng (BG, CJ EnerG) were prepared from fresh ginseng using one and nine cycles of steaming and drying, respectively. This process reduces the molecular weight (MW) of ginsenoside-active compounds in ginseng by removing sugar moieties from their dammaranes. We compared the pharmacokinetic characteristics of ginsenosides between BG comprising mainly low-MW ginsenosides (Rg3, Rg5, Rk1, and Rh1) and RG that predominantly contains high-MW ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1). The safety profiles and tolerability were also studied using a randomized, double-blind, single-dose, crossover clinical trial. A combination of Rb1, Rg1, and Rg3, well-known representative and functional RG components, exhibited a 1 h faster absorption rate (Tmax) and 58% higher exposure (24 h area under the concentration-time curve, AUC24) in BG than in RG. Furthermore, the combination of Rg3, Rg5, and Rk1, the major and most efficient components in BG, displayed 824% higher absorption (AUC24) in BG than in RG. The total ginsenoside showed a 5 h rapid intestinal absorption (Tmax) and 79% greater systemic exposure (AUC24) in BG than in RG. No clinically significant findings were observed in terms of safety or tolerability. Thus, BG extract was more effective than RG extract.

Keywords: black ginseng; ginsenosides; pharmacokinetics.

Conflict of interest statement

B.-I.P., Y.K.S., K.K. and D.Y.S. are employees of the CJ CheilJedang Corporation. B.-I.P. analyzed and visualized RG and BG ginsenosides. She also wrote the figure legend (Figure 1). Y.K.S., K.K. and D.Y.S. were involved in the conceptualization, validation, and funding acquisition. D.Y.S. also reviewed the manuscript. The other authors declare no conflict of interest.

Figures

Figure 1

Multiple steaming cycles and gut microbial activity reduce the molecular weight (MW) of ginsenosides in ginseng. Ginsenosides are tetracyclic triterpene (dammarane)-type saponins and are divided into protopanaxadiol (PPD) type (e.g., Rb1, Rb2, Rc, Rd, Rg3, Rk1, Rg5, CK, Rh2, and PPD) and protopanaxatriol (PPT) type (e.g., Re, Rg1, Rh1, and PPT). Based on their size, ginsenosides are divided into three groups: (1) high molecular weight (HMW) (>800) ginsenosides found in red ginseng (RG) such as Rb1 (MW: 1109), Rb2 (MW: 1079), Rc (MW: 1079), Rd (MW: 1079), Re (MW: 947), and Rg1 (MW: 801); (2) low MW (LMW) (>637,

Figure 2

Chromatograms obtained from high-performance liquid chromatography analysis of ginsenosides in (A) black ginseng and (B) red ginseng extracts. Detection at a wavelength of 203 nm.

Figure 3

Flowchart showing subject disposition.

Figure 4

Mean (± standard error (SE)) plasma concentration–time profiles of ginsenosides after administration of a single dose of 9 g of red ginseng (RG) (red empty symbol and dashed line) and black ginseng (BG) (black filled symbol and solid line) extract. The inserted bar plot showing the mean (±SE) for the 0 to 24 h area under the concentration–time curve (AUC24) of RG (red color) and BG (black color) extract: (A) Rb1; (B) Rb2; (C) Rc; (D) Rd; (E) Rg3; (F) Rg5; (G) Rk1; (H) Rh2; (I) CK; (J) PPD; (K) Re; (L) Rg1; (M) Rh1; (N) PPT. * Statistically significant at p < 0.05.

Figure 5

Pharmacokinetic characteristics of functional ginsenoside groups after the administration of a single dose of red ginseng (RG) (red color) and black ginseng (BG) (black color) extracts: (A–E) Functional ginsenoside group with Rb1, Rg1 and Rg3; (F–J) functional ginsenoside group with Rg3, Rg5, and Rk1; (A,F) mean (± standard error (SE)) plasma concentration–time profile of group 1; (B,G) mean (±SE) for Cmax; (C,H) median (inter-quartile range (IQR)) boxes for Tmax (lines for 1.5 times the IQR and dots for outliers); (D,I) mean (±SE) for area under the concentration–time curve AUC from 0 to 24 h (AUC24); (E,J) mean (±SE) for AUC from 0 to the actual time point relevant to the last concentration above the lower limit of quantification (LLOQ) (AUClast). * Statistically significant at p < 0.05.

Figure 6

Pharmacokinetic characteristics of total ginsenosides after the administration of a single dose of red ginseng (RG) (red color) and black ginseng (BG) (black color) extracts: (A) mean (±standard error (SE)) plasma concentration–time profile; (B) mean (±SE) for Cmax; (C) median (inter-quartile range (IQR)) boxes for Tmax (lines for 1.5 times the IQR and dots for outliers); (D) mean (±SE) for area under the concentration–time curve from 0 to 24 h (AUC24); (E) mean (±SE) for AUC from 0 to the actual point in time with respect to the last concentration above the lower limit of quantification (LLOQ) (AUClast). * Statistically significant at p < 0.05.