• Journal of Ginseng Research
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• v.37 no.4
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• pp.451-456
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• 2013

Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was $8.35{\pm}3.19$ ng/mL, which was significantly higher than that of ginsenoside Rb1 ($3.94{\pm}1.97$ ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.68-74
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• 2018

Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.

• Analytical Science and Technology
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• v.26 no.4
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• pp.221-227
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• 2013

A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the investigation of the ginsenoside Rg1 in human plasma. After addition of internal standard (digoxin), plasma was diluted with acetone and methanol (80:20), the supernatant was concentrated and analyzed by LC-MS/MS. The optimal chromatographic separation was achieved on an Agilent Eclipse XDB-C18 column ($4.6{\times}150mm$, $5{\mu}m$) with a mobile phase of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.9 mL/min gradient mode. The standard calibration curve for ginsenoside Rg1 was linear ($r^2=0.9995$) over the concentration range 1~500 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of ginsenoside Rg1 was lower than 7.53% (correlation of variance, CV), and accuracy exceeded 98.28%. This LC-MS/MS assay of ginsenoside Rg1 in human plasma is applicable for quantifying in the pharmacokinetic study.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.114-114
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• 2003

Ginseng is a medicinal herb widely used in Asian countries, and its pharmacological effects has been demonstrated in various systems such as cardiovascular, central nervous, and endocrine systems. Its effects are mainly attributed to the ginsenosides. We hypothesize that a component of Panax ginseng, ginsenoside-Rbl, acts by binding to estrogen receptor. We have investigated the estrogenic activity of ginsenoside-Rbl in a transient transfection system using estrogen receptors ${\alpha}$ or ${\beta}$ with estrogen -responsive luciferase plasmids in COS monkey kidney cells. Ginsenoside-Rbl activated both estrogen receptors ${\alpha}$ and ${\beta}$ in a dose-dependent manner (0.5 -100 M ). Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of ginsenoside-Rbl is estrogen receptor dependent. Next, we evaluated the ability of ginsenoside-Rbl to induce estrogen-responsive progesterone receptor gene by semi-quantitative RT-PCR assays. MCF-7 cells treated with l7${\beta}$-estradiol or ginsenoside- Rb1 exhibited an increased expression of progesterone receptor mRNA. However, ginsenoside-Rbl failed to displace the specific binding of ［3H］17${\beta}$-estradiol to estrogen receptor in MCF-7 cells as examined by whole cell ligand binding assays, suggesting that there is no direct interaction of ginsenoside-Rbl with estrogen receptor. Our results indicate that estrogen-like activity of ginsenoside-Rbl is independent of direct estrogen receptor association.

• Korean Journal of Plant Resources
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• v.17 no.1
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• pp.7-13
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• 2004

We have investigated the optimal conditions for the growth and ginsenoside production in adventitious root of “Chunpoong” (Panax ginseng C.A. Meyer). Ginseng adventitous roots induced from the embryo of “Chunpoong” were cultured in various plant media supplemented with several growth hormones. The best growth rate and high ginsenoside contents were obtained in B5 medium supplemented with IBA (2 mg/L) and kinetin (0.1 mg/L). The supplement of 2.5 mM KH$_2$PO$_4$ was good for high growth rate of the adventitious roots, but the accumulation of ginsenosides was increased by reducing the KH$_2$PO$_4$ concentration to 1.25 mM. We have established the effective liquid culture system for the optimal growth and ginsenoside production of “Chunpoong” adventitious roots.

• Journal of Ginseng Research
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• v.29 no.4
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• pp.159-166
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• 2005

Ginsenosides, a group of Panax ginseng saponins, exert the lowering effects of plasma cholesterol levels in animals. We had reported earlier that ginsenoside Rb2 upregulate low-density lipoprotein receptor (LDLR) expression via a mechanism that is dependent of the activation of sterol response element binding protein 2 (SREBP-2) expression. This study was conducted to determine the effects of ginsenoside Rb2 on the expression of the hepatic LDLR expression at cellular levels using HepG2 cells, and to evaluate whether the sterol response element binding protein 1 (SREBP-l) was involved in the regulation of LDLR expression. Incubation of HepG2 cells in serum-free medium supplemented with cholesterol $(10{\mu}g/ml)$ for 8 hours decreased the mRNAs of LDLR mRNA by $12\%$ and SREBP-l mRNA by $35\%$. Ginsenoside Rb2 antagonized the repressive effects of cholesterol and increased both LDLR and SREBP-l mRNA expression to 1.5- and 2-fold, respectively. Furthermore, Western blot and confocal microscopic analyses with SREBP-l polyclonal antibody revealed that ginsenoside Rb2 enhanced the maturation of the SREBP-1 from the inactive precursor form in ER membrane to the active transcription factor form in nucleus. These results suggest that ginsenoside Rb2 upregulates LDLR expression via a mechanism that is dependent of the activation of not only SREBP-2 expression, but also SREBP-1 expression and maturation, and also indicate that the pharmacological value of ginsenoside Rb2 may be distinguished from that of lovastatin which is reported that it upregulate LDLR through SREBP-2 only, not through SREBP-1.

• Preventive Nutrition and Food Science
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• v.14 no.3
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• pp.201-207
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• 2009

In an effort to improve ginsenoside bioavailability, the ginsenosides of fermented red ginseng were examined with respect to bioavailability and physiological activity. The results showed that the fermented red ginseng (FRG) had a high level of ginsenoside metabolites. The total ginsenoside contents in non-fermented red ginseng (NFRG) and FRG were 35715.2 ${\mu}g$/mL and 34822.9 ${\mu}g$/mL, respectively. However, RFG had a higher content (14914.3 ${\mu}g$/mL) of ginsenoside metabolites (Rg3, Rg5, Rk1, CK, Rh1, F2, and Rg2) compared to NFRG (5697.9 ${\mu}g$/mL). The skin permeability of RFG was higher than that of NFRG using Franz diffusion cells. Particularly, after 5 hr, the skin permeability of RFG was significantly (p<0.05) higher than that of NFRG. Using everted instestinal sacs of rats, RFG showed a high transport level (10.3 mg of polyphenols/g sac) compared to NFRG (6.67 of mg of polyphenols/g sac) after 1 hr. After oral administration of NFRG and FRG to rats, serum concentrations were determined by HPLC. Peak concentrations of Rk1, Rh1, Rc, and Rg5 were approximately 1.64, 2.35, 1.13, and 1.25-fold higher, respectively, for FRG than for NFRG. Furthermore, Rk1, Rh1, and Rg5 increased more rapidly in the blood by the oral administration of FRG versus NFRG. FRG had dramatically improved bioavailability compared to NFRG as indicated by skin permeation, intestinal permeability, and ginsenoside levels in the blood. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.58-63
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• 2003

Ginseng has been recommended to alleviate the menopausal symptoms, which indicates that components of ginseng very likely contain estrogenic activity. We have examined the possibility that a component of Panax ginseng, $ginsenoside-R_{b1}$ acts by binding to estrogen receptor. We have investigated the estrogenic activity of $ginsenoside-R_{b1}$ in a transient transfection system using estrogen-responsive luciferase plasmids in MCF-7 cells. $ginsenoside-R_{b1}$ activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 $\mu$M. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of $ginsenoside-R_{b1}$ is estrogen receptor dependent. Next, we evaluated the ability of $ginsenoside-R_{b1}$ to induce the estrogen-responsive gene c-fos by semi-quantitative RT-PCR assays and Western analyses. $ginsenoside-R_{b1}$ increased c-fos both at mRNA and protein levels. However, $ginsenoside-R_{b1}$ failed to activate the glucocorticoid receptor, the retinoic acid receptor, or the androgen receptor in CV-1 cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that $ginsenoside-R_{b1}$ acts a weak phytoestrogen, presumably by binding and activating the estrogen receptor.

• Korean Journal of Plant Tissue Culture
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• v.27 no.6
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• pp.461-468
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• 2000

For the enhancement of ginsenoside production in hairy roots cultures of Panax ginseng, the uptake rate of inorganic elements and ginsenoside contents were investigated by different concentrations of about phosphorus (P $O_{4}$$^{[-10]}$ ) and nitrogen (N $H_{4}$$^{+}$, N $O_{3}$$^{[-10]}$ ) sources. According to increased phosphorus and nitrogen sources, the uptake rate of $Mg^{2+}$ and F $e^{2+}$ in ginseng hairy roots were significantly increased. The uptake rate of F $e^{2+}$ in 5.15 mM N $H_{4}$$^{+}$ was higher at 47.5% than that in 20.6 mM, whereas that of C $u^{2+}$ in 10.3 mM were higher at 123.1% than that in 41.2 mM. These results indicated that phosphorus and nitrogen sources act not only elevated growth of hairy roots but also the uptake-enhancement of the irons and other ions. The optimum concentration of phosphorus and nitrogen sources for the contents of free sugars were different to kinds of free sugars. The optimum concentration of phosphorus and nitrogen sources for the ginsenoside formation in ginseng hairy roots cultures were highest at the most low concentration of all. The contents of ginsenoside-R $b_2$and -Rc in 0.31 mM P $O_{4}$$^{[-10]}$ were increased to 44.7% and 29.9% than that in 0.62 mM P $O_{4}$$^{[-10]}$ , respectively. The contents of ginsenoside-R $b_2$ and -Rc in 5.15 mM N $H_{4}$$^{+}$ were increased to 21.7% and 31.9% than that in 10.30 mM N $H_{4}$$^{+}$, respectively. The contents of ginsenoside-R $b_2$and -Rc in 4.7 mn N $O_{3}$$^{[-10]}$ were also increased to 17.6% and 25.5% than that in 9.4 mM N $O_{3}$$^{[-10]}$ , respectively. These results indicate that enhancement of the ginsenoside formation in ginseng hairy roots was feasible by new medium modulation of concentration of phosphorus and nitrogen sources.rogen sources.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.11
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• pp.1660-1665
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• 2010

To obtain data for the standardization of manufacturing method of red ginseng extract pouch products, saponin and physico-chemical properties of 44 Korean red ginseng extract pouch products were analyzed. The concentration of total ginsenoside contents were 5.5~185.7 mg/100 mL. Distribution of the contents of ginsenoside $Rg_3$, $Rg_2$, $Rh_1$, and $Rh_2$ known to have anticancer effect are as follows: $Rg_3$ is 1.6~46.3 mg/100 mL, $Rg_2$ is 0~22.0 mg/100 mL, $Rh_1$ is 0~4.3 mg/100 mL and that of $Rh_2$ is 0~20.4 mg/100 mL, respectively. The anti-diabetic effect of ginsenoside $Rb_2$ and Re distribution of contents were 0~10.8 mg/100 mL and 0~7.0 mg/100 mL, respectively. Among the other saponins, exhibited content to distribution of ginsenoside $Rb_1$ was 0~25.2 mg/100 mL, Rc was 0~12.5 mg/100 mL, Rd was 0~11.3 mg/100 mL, Rf was 0~5.9 mg/100 mL and $Rg_1$ was 0~4.4 mg/100 mL. Results of physicochemical characterization showed total sugar content of 226.6~3,102.9 mg/100 mL, total soluble solids content $1.4\sim9.5^{\circ}Bx$, turbidity 82.2~100.0%, pH in the range of 4.1 to 5.0, respectively. In approximately 50% of collected domestic ginseng extract pouch products (21~24 items), ginsenoside $Rb_1$, $Rb_2$, Rc, Rd, Re and $Rg_1$ were not detected, and saponin content of each product appears to differ greatly. Results indicated that standardization of production methods and standards set for red ginseng extract pouch products in Korea is needed.