• Journal of Ginseng Research
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• 제43권3호
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• pp.460-474
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• 2019

Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

• Journal of Ginseng Research
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• 제45권2호
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• pp.228-235
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• 2021

Backgroud: 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. Methods: 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. Results: 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. Conclusion: GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

• Journal of Ginseng Research
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• 제35권1호
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• pp.60-68
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• 2011

The chemical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity changes of ginsenoside $Rb_1$-glycine and ginsenoside $Rg_1$-glycine mixtures by Maillard reaction were investigated to identify the role of Maillard reaction in the increased antioxidant activity of ginseng by heat-processing. The DPPH radical scavenging activity of $Rg_1$-glycine mixture was more strongly increased by heat-processing than that of $Rb_1$-glycine mixture. From the analyses of ginsenosides, $Rb_1$ was gradually changed into 20(S)-$Rg_3$, 20(R)-$Rg_3$, $Rk_1$ and $Rg_5$ by heat-processing. $Rg_1$ was gradually changed into 20(S)-$Rh_1$, 20(R)-$Rh_1$, $Rk_3$ and $Rh_4$ by heat-processing. However, the generation of these less-polar ginsenosides was not related to the increased DPPH radical scavenging activity of $Rb_1$-glycine and $Rg_1$-glycine mixtures because their DPPH radical scavenging activities were already significantly increased when dried at $50^{\circ}C$, which temperature induce no structural changes of ginsenosides. In the comparison of browning compound levels of $Rg_1$-glycine and $Rb_1$-glycine mixtures, the extents of Maillard reaction were positively correlated with their increased free radical scavenging activities. Based on the chemical and DPPH radical scavenging activity changes of $Rg_1$-glycine and $Rb_1$-glycine mixtures by heat-processing, we clearly identified that the increased free radical scavenging activity of ginsenoside is mediated by the Maillard reaction between sugar moiety of ginsenoside and amino acid.

• Archives of Pharmacal Research
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• 제26권10호
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• pp.868-873
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might playa role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside $Rg_{2-}$, CK-, or M4-induced regulation of $\alpha3\beta4$ nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current ($I_{Ach}$) in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor. Co-treatment of ginsenoside $Rg_2$, CK, or M4 with ACh inhibited IAch in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and co-treatment of ginsenoside $Rg_2$ or M4 but not CK with ACh inhibited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites.

• Journal of Ginseng Research
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• 제37권4호
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• pp.457-467
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• 2013

A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides.

• Natural Product Sciences
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• 제25권4호
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• pp.317-325
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• 2019

Here, we designed to examine the anti-inflammatory effects on RAW264.7 cells and the immunosuppressive effects by evaluating interleukin-2 (IL-2) production in Jurkat T cells using a MeOH extract of Panax notoginseng roots. The results showed that the MeOH extract inhibited the synthesis of nitric oxide (NO) in a dose-dependent manner (IC₅₀ value of 7.08 ㎍/mL) and displayed effects on T cell activation at a concentration of 400 ㎍/mL. In efforts to identify the potent compounds, bioactivity-guided fractionation of the MeOH extract and chemical investigation of its active CH₂Cl₂-, EtOAc-, and butanol-soluble fractions led to the successful isolation and identification of eleven compounds, including two polyacetylenes (1, 2), a steroid saponin (3), seven dammarane-type ginsenosides (4 - 10), and an oleanane-type ginsenoside (11). Among them, compound 11 was isolated from this plant for the first time. Compound 2 exhibited potent inhibitory effects on NO synthesis and an immunosuppressive effect with IC₅₀ values of 2.28 and 65.57 μM, respectively.

• Journal of Ginseng Research
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• 제47권1호
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• pp.167-167
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• 2023

• Journal of Ginseng Research
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• 제33권4호
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• pp.268-277
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• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in South Korea. The anti-ischemic effects of compound K (CK), a metabolite of ginsenoside Rb1, on ischemia-induced isolated rat hearts were investigated through the analyses of the changes in the hemodynamics (blood pressure, aortic flow, coronary flow, and cardiac output) and the measurement of the infarct region. The subjects in this study were divided into four groups: the normal control, the CK-alone group, the ischemia-induced group without any treatment, and the ischemia-induced group treated with CK. No significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output were found between the groups before ischemia was induced. The oxygen and buffer supply was stopped for 30 min to induce ischemia 60 min after reperfusion in the isolated rat hearts, and the CK was administered 5 min before ischemia induction. The CK treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, the hemodynamics (except for the heart rate) of the group treated with CK significantly recovered 60 min after reperfusion, unlike in the control group. CK significantly limited the infarct. These results suggest that CK treatment has distinct anti-ischemic effects in an exvivo model of an ischemia-reperfusion-induced rat heart.

• Journal of Ginseng Research
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• 제41권3호
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• pp.298-306
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• 2017

Background: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. Methods: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes. Results: Compound K induced cell cluster formation through cell-cell adhesion, cell migration, and phagocytic activity, but it suppressed cell-tissue interactions in U937 and RAW264.7 cells. Compound K also upregulated the surface expression of the cell adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release of reactive oxygen species and induced messenger RNA expression of proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor-alpha by enhancing the nuclear translocation and transcriptional activities of nuclear factor kappa-B and activator protein-1. Conclusion: Our results suggest that CK has an immunomodulatory role in innate immune responses through regulating various cellular events mediated by monocytes and macrophages.

• Journal of Ginseng Research
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• 제32권1호
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• pp.57-61
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• 2008

Ginseng (the root of Panax ginseng CA Meyer, family Araliacease), which is used in Korea, China and Japan as a herbal medicine, was fermented with Ganoderma lucidum (GL) and their antiallergic effects were investigated. Of GLs used for fermentation, KCTC 6283 potently produced ginsenoside Rh2, followed by KFRI M101. KCTC 6532, and ginsenoside Rd, followed by KFRI M101. Oral administration of these fermented ginseng extracts inhibited allergic reactions, passive cutaneous anaphylaxis reaction induced by IgE and scratching behaviors induced by compound 48/80. Of them, the ginseng extract fermented by KCTC 6532 and KFRI M101 potently inhibited allergic reactions compared to that fermented by KCTC 6283. These findings suggest that the fermentation of ginseng with GL can increase its antiallergic activity and the increment of its antiallergic effect may be due to the biotransformation of ginseng saponins to ginsenosides Rd and Rh2.