• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.169-183
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• 1984

인삼의 주된 사포닌으로서 Rg,과 Rb,을 흰쥐에 투여하였을 경우에 이들 물질이 흰쥐의 장기에 흡수 또는 분포되는 상태와 배설에 대하여 연구하였다. 진세노사이드 $Rg_{1}$은 경구 투여량의 약 $1.9{\%}$가 소화관의 상부에서 흡수되었으며, 투여한지 30분 후에 최고 혈중 농도에 이르렀고 조직에서는 1.5시간 걸렸다. 그러나 뇌에서는 확인되지 않았으며 뇨와 당즙에는 2 : 5의 비로 배설되었다. $Rb_{1}$을 100mg/kg 경구투여한 결과, 소화관에서는 거의 흡수가 되지 않았으며, 한편 정맥주사(5mg/kg)의 경우는 혈중 $Rb_{1}$의 농도가 지수적으로 감소하였으며, B-phase의 반감기는 14.5시간이었다. 정맥주사후 혈청과 조직에 장시간 잔존은 활성을 나탄내는 혈청단백과의 결합과 관련이 있는 것으로 사료되며 시간에 따라 뇨로 배설되나 담즙에서는 확인되지 않았다. $Rg_{1}$과 $Rb_{1}$을 경구투여한 후 TLC와 $^{13}C$-NMR을 이용하여 위와 대장에서의 분해 상태를 연구한 결과 위에서 $Rg_{1}$의 일부가 분해, 6종류의 분해 산물이 r-everse phase TLC상에서 관찰되었고 이들 분해 산물은 약산성 (0.1N HCl, $37^{\circ}C$) 조건하에서 $Rg_{1}$의 가수분해산물과 동일하였다. 한편, $Rb_{1}$ 경구투여후 위장에서 얻은 시료중에서 미확인 분해산물이 관찰되었으며, 이 분해산물은 약산성 조건하에서 $Rb_{1}$의 가수분해산물과는 상이하다는 사실을 확인하였다. 대장에서, $Rg_{1}$은 미생물 tetracycline-susceptible bacteria와 tetracycline-resist bacteria에 의해 $Rb_{1}$과 $F_{1}$으로 분해되었으며, $Rb_{1}$은 장내의 효소와 tetracycline-resistantant bacteria에 의해 Rd와 2 종류의 미확인 물질로 분해되었다.

• Journal of Ginseng Research
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• v.22 no.2
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• pp.133-139
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• 1998

We have studied an activation mechanism of $pp60^{c-src}$ protein tyroslne kinase (PTK) by ginsenoside-$Rg_1$ (G-$Rg_1$ ) in NIH(pMcsrc/foc)B c-src overexpressor cells. It was previously reported that G--$Rg_1$ stimulated the activation of c-src kinase at 20 pM with a 18 hr-incubation, increasing the activity by 2-4-fold over that of untreated control, and this effect was blocked by treatments of in- hibitors of either protein synthesis (cycloheximide) or RNA synthesis (actinomycin D) (Hong, H.Y. et at. Arch. Pharm. Res. 16, 114 (1993)). However, an amount of c-src protein itself in wild-type cells was not changed by G-$Rg_1$. When the cells mutated at one or two tyrosine residue(s) (Y416/527) that are important sites to regulate the kinase activity were treated with G-$Rg_1$, increases both in the activity of c-src kinase and in the expression of the protein were not observed. In addition, removal of extracellular calcium ion by EGTA or inhibition of PKC by H-7 canceled the G-$Rg_1$-induced activation of the kinase. Although the activation was little affected by G-$Rg_1$ with a calcium ionophore A23187, it was synergistically stimulated by treatment of G-Rgl and PMA, a PKC activator. Taken together, these results suggest that the activation of c-src kinase by G-$Rg_1$ is caused by an increase in the specific activity of the kinase, but not in amount of it, and is involved with both collular calcium ion and PKC. Further the increase in the specific activity of c-src kinase may result from altered phosphorylation at tyro-416 and -527.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.375-381
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• 2016

Background: We evaluated the drug interaction profile of Red Ginseng (RG) with respect to the activities of major cytochrome P450 (CYP) enzymes and the drug transporter P-glycoprotein (P-gp) in healthy Korean volunteers. Methods: This article describes an open-label, crossover study. CYP probe cocktail drugs, caffeine, losartan, dextromethorphan, omeprazole, midazolam, and fexofenadine were administered before and after RG supplementation for 2 wk. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data using analysis of variance after RG administration versus before RG administration. Results: Fourteen healthy male participants were evaluated, none of whom were genetically defined as poor CYP2C9, 2C19, and CYP2D6 metabolizers based on genotyping. Before and after RG administration, the geometric least-square mean metabolic ratio (90% CI) was 0.870 (0.805-0.940) for caffeine to paraxanthine (CYP1A2), 0.871 (0.800-0.947) for losartan (CYP2C9) to EXP3174, 1.027 (0.938-1.123) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.373 (0.864-2.180) for dextromethorphan to dextrorphan (CYP2D6), and 0.824 (0.658-1.032) for midazolam (CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time ($AUC_{last}$) for fexofenadine (P-gp) was 0.963 (0.845-1.098). Administration of concentrated RG for 2 wk weakly inhibited CYP2C9 and CYP3A4 and weakly induced CYP2D6. However, no clinically significant drug interactions were observed between RG and CYP and P-gp probe substrates. Conclusion: RG has no relevant potential to cause CYP enzyme- or P-gp-related interactions.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.415-422
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• 2016

Background: Rare ginsenosides in Panax quinquefolius L. have strong bioactivities. The fact that it is hard to obtain large amounts of rare ginsenosides seriously restricts further research on these compounds. An easy, fast, and efficient method to obtain different kinds of rare ginsenosides simultaneously and to quantify each one precisely is urgently needed. Methods: Microwave-assisted extraction (MAE) was used to extract nine kinds of rare ginsenosides from P. quinquefolius L. In this article, rare ginsenosides [20(S)-Rh1, 20(R)-Rh1, Rg6, F4, Rk3, 20(S)-Rg3, 20(R)-Rg3, Rk1, and Rg5] were identified by high performance liquid chromatography (HPLC)-electrospray ionization-mass spectrometry. The quantity information of rare ginsenosides was analyzed by HPLC-UV at 203 nm. Results: The optimal conditions for MAE were using water as solvent with the material ratio of 1:40 (w/v) at a temperature of $145^{\circ}C$, and extracting for 15 min under microwave power of 1,600 W. Seven kinds of rare ginsenosides [20(S)-Rh1, 20(R)-Rh1, Rg6, F4, Rk3, Rk1, and Rg5] had high extraction yields, but those of 20(S)-Rg3 and 20(R)-Rg3 were lower. Compared with the conventional method, the extraction yields of the nine rare ginsenosides were significantly increased. Conclusion: The results indicate that rare ginsenosides can be extracted effectively by MAE from P. quinquefolius L. in a short time. Microwave radiation plays an important role in MAE. The probable generation process of rare ginsenosides is also discussed in the article. It will be meaningful for further investigation or application of rare ginsenosides.

• Journal of Ginseng Research
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• v.34 no.1
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• pp.1-7
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• 2010

The quality attributes of coffee treated with different concentrations of white ginseng extract were examined. Increased concentration of white ginseng extract was associated with higher color values (Hunter L. a, b scale). The crude saponin contents of untreated roasted coffee beans (control) and those coated with $5^{\circ}$ Brix (WGC-1) and $20^{\circ}$ Brix white ginseng extract (WGC-2) were 8.29%, 8.74%, and 8.93%, respectively. The total ginsenoside contents of WGC-1 and WGC-2 were 0.3 mg/g and 0.6 mg/g, respectively. In the case of major ginsenosides, the contents of ginsenosides $Rg_1,\;Rg_2,\;Rb_1,\;Rb_2,\;Rg_2,\;Rh_1$, and $Rg_3$ increased directly with the concentration of white ginseng extract. Total sugar and acidic polysaccharide contents also increased directly with the concentration of white ginseng extract. The coffee beans coated with ginseng extract scored significantly higher ginseng taste scores than the control (p<0.005) in sensory evaluation. In terms of coffee taste, WGC-2 had significantly lower scores than the commercial coffee bean. In the consumer sensory evaluation, overall preference did not differ significantly among the treatments.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.470-475
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• 2018

Background: It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. Methods: Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 ("MrgprA3/TRPA1"), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. Results: CQ-induced $Ca^{2+}$ influx was strongly inhibited by KRGE ($10{\mu}g/mL$) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced $Ca^{2+}$ influx in MrgprA3/TRPA1. Moreover, both KRGE ($10{\mu}g/mL$) and Rg3 ($100{\mu}M$) suppressed CQ-induced $Ca^{2+}$ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: $274.0{\pm}51.47$ (control) vs. $104.7{\pm}17.39$ (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: $216.8{\pm}33.73$ (control) vs.$115.7{\pm}20.94$ (Rg3)]. Conclusion: The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.78-84
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• 2017

Background: In the present study, metabolite profiles of ginsenosides Rk1 and Rg5 from red ginseng or red notoginseng in zebrafish were qualitatively analyzed with ultraperformance liquid chromatography/quadrupole-time-of-flight MS, and the possible metabolic were pathways proposed. Methods: After exposing to zebrafish for 24 h, we determined the metabolites of ginsenosides Rk1 and Rg5. The chromatography was accomplished on UPLC BEH C18 column using a binary gradient elution of 0.1% formic acetonitrile-0.1% formic acid water. The quasimolecular ions of compounds were analyzed in the negative mode. With reference to quasimolecular ions and MS2 spectra, by comparing with reference standards and matching the empirical molecular formula with that of known published compounds, and then the potential structures of metabolites of ginsenosides Rk1 and Rg5 were acquired. Results: Four and seven metabolites of ginsenoside Rk1 and ginsenoside Rg5, respectively, were identified in zebrafish. The mechanisms involved were further deduced to be desugarization, glucuronidation, sulfation, and dehydroxymethylation pathways. Dehydroxylation and loss of C-17 residue were also metabolic pathways of ginsenoside Rg5 in zebrafish. Conclusion: Loss of glucose at position C-3 and glucuronidation at position C-12 in zebrafish were regarded as the primary physiological processes of ginsenosides Rk1 and Rg5.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.50-57
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• 2020

Background: The cellular senescence of primary cultured cells is an irreversible process characterized by growth arrest. Restoration of senescence by ginsenosides has not been explored so far. Rg3(S) treatment markedly decreased senescence-associated β-galactosidase activity and intracellular reactive oxygen species levels in senescent human dermal fibroblasts (HDFs). However, the underlying mechanism of this effect of Rg3(S) on the senescent HDFs remains unknown. Methods: We performed a label-free quantitative proteomics to identify the altered proteins in Rg3(S)-treated senescent HDFs. Upregulated proteins induced by Rg3(S) were validated by real-time polymerase chain reaction and immunoblot analyses. Results: Finally, 157 human proteins were identified, and variable peroxiredoxin (PRDX) isotypes were highly implicated by network analyses. Among them, the mitochondrial PRDX3 was transcriptionally and translationally increased in response to Rg3(S) treatment in senescent HDFs in a time-dependent manner. Conclusion: Our proteomic approach provides insights into the partial reversing effect of Rg3 on senescent HDFs through induction of antioxidant enzymes, particularly PRDX3.

• Applied Biological Chemistry
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• v.23 no.4
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• pp.222-227
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• 1980

Ginsenosides in two parts (central fart and epidermis-cortex) of main body of Korea ginseng root (purple stem variety) were analyzed by high performance liquid chromatography in relation to purple color intensity on stem. Pattern similarity of saponin by simple correlation of ginsenosides between the same or different parts of root in the same or different group showed that stem color was not associated with saponin pattern in two parts. Saponin pattern was slightly different between different parts regardless of stem color. The order of each ginsenoside content was $Rg_1>Re>Rb_1>Rb_2>Rc>Rg_2{\geq}Rd>Rf$ in epidermis-cortex while $Rg_1>Re{\geq}Rg_2{\geq}Rb_1{\gg}Rb_2>Rc{\geq}Rd>Rf$ in central part.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.550-561
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• 2019

Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.