• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.3-3
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• 2018

For centuries, Panax ginseng Meyer (Korean ginseng) has been widely used as a medicinal herb in Korea, China, and Japan. Ginsenosides are a class of triterpene saponins and recognized as the bioactive components in Korean ginseng. Ginsenosides, which can be classified broadly as protopanaxadiols (PPD), protopanaxatriols (PPT), and oleanolic acids, have been shown to flaunt a vast array of pharmacological activities such as immune-modulatory, anti-inflammatory, anti-tumor, anti-diabetic, and antioxidant effects. In recent years, a number of ginseng and ginsenoside researches have increasingly gained wide attention owing to its unique pharmacological properties. Although good efficacies of ginsenosides have been reported, lack of target specific delivery into tumor sites, low solubility, and low bioavailability due to modifications in gastro-intestinal environments limit their biomedical application in clinical trials. As a result to this major challenge, nanotechnology and drug delivery techniques play a significant role to solve this problematic issue. Thus, we reported the preparation of poly-ethylene glycol (PEG) and glycol chitosan (GC) functionalized to ginsenoside (Compound K and PPD) conjugates via hydrolysable ester bonds with improved aqueous solubility and pH-dependent drug release. In vitro cytotoxicity assays revealed that PEG-CK, and PPD-CK conjugates exhibited lower cytotoxicity compared to bare CK and PPD in HT29 cells. However, GC-CK conjugates exhibited higher and similar cytotoxicity in HT29 and HepG2 cells. Furthermore, GC-CK-treated RAW264.7 cells did not exhibit significant cell death at higher concentration of treatment which supports the biocompatibility of the polymer conjugates. They also inhibited nitric oxide production in lipopolysaccharide (LPS)-induced RAW64.7 cells. In addition to polymer-ginsenoside conjugates, silver (AgNps) and gold nanoparticles (AuNps) have been successfully synthesized by green chemistry using different m. The biosynthesized nanoparticles demonstrated antimicrobial efficacy, anticancer, anti-inflammatory, antioxidant activity, biofilm inhibition, and anticoagulant effect. Special interest on the effective delivery methods of ginsenoside to treatment sites is the focus of metal nanoparticle research.In short, nano-sizing of ginsenoside results in an increased water solubility and bioavailability. The use of nano-sized ginsenoside and P. ginseng mediated metallic nanoparticles is expected to be effective on medical platform against various diseases in the future.

• Journal of Ginseng Research
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• 제35권3호
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• pp.375-383
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• 2011

In the previous report, we have demonstrated that ginsenoside Rc, one of major ginsenosides, is a major component for the restoration for normal growth of worms in cholesterol-deprived medium. In the present study, we further investigated the roles of minor ginsenosides, such as ginsenoside $Rh_1$ and $Rh_2$, ginsenoside metabolites such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) and ginsenoside epimers such as 20(R)- and 20(S)-ginsenoside $Rg_3$ in cholesterol-deprived medium. We found that ginsenoside $Rh_1$ almost restored normal growth of worms in cholesterol-deprived medium in F1 generation. However, supplement of ginsenoside $Rh_2$ caused a suppression of worm growths in cholesterol-deprived medium. In addition, CK and PPD also slightly restored normal growth of worms in cholesterol-deprived medium but PPT not. In experiments using ginsenoside epimers, supplement of 20(S)- but not 20(R)-ginsenoside $Rg_3$ in cholesterol-deprived medium also almost restored worm growth. These results indicate that the absence or presence of carbohydrate component at backbone of ginsenoside, the number of carbohydrate attached at carbon-3, and the position of hydroxyl group at carbon-20 of ginsenoside might plays important roles in restoration of worm growth in cholesterol-deprived medium.

• Journal of Ginseng Research
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• 제48권2호
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• pp.190-201
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• 2024

Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.127-132
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• 2013

Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The ${\gamma}$-aminobutyric acid $receptor_C$ ($GABA_C$) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on $GABA_C$ receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant $GABA_C$ receptor (${\rho}$ 1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing $GABA_C$ receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current ($I_{GABA}$). Interestingly, pre-application of M4 inhibited $I_{GABA}$ more potently than CK in a dose- dependent and reversible manner. The half-inhibitory concentration ($IC_{50}$) values of CK and M4 were $52.1{\pm}2.3$ and $45.7{\pm}3.9{\mu}M$, respectively. Inhibition of $I_{GABA}$ by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate $GABA_C$ receptor channel activity in the brain, including in the eyes.

• 디지털융복합연구
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• 제15권11호
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• pp.285-295
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• 2017

본 연구에서는 증폭시킨 홍삼으로부터 분리한 ginsenoside Rh2(Rh2)와 compound K(CK)의 융복합적 항염증 및 항암효과를 연구하여 홍삼 내 유용한 기능성분에 대한 기초 자료를 제공하고자 한다. 이에 Hep3B에서의 세포독성과 IL-6 유도 STAT3 루시퍼라아제 활성, B16F10과 Hacat 세포의 생존 농도를 측정하였고 Apoptosis와 관련된 분자의 발현양상을 확인하기 위해 FAC (fluorescence activated cell sorting) 분석을 수행하였다. 실험결과 Rh2, CK mixture가 10 ug/ml일 때 Hep3B 세포에서 세포독성이 없고 IL-6 감소율이 102%로 항염증 효과가 있는 것으로 나타났다. 또한 Rh2, CK mixture 50 uM에서 melanoma 세포인 B16F10과 human keratinocyte인 Hacat에서 독성을 보여 사멸하는 것을 관찰하였다. FACS 분석 결과 annexin V가 발현되지 않고 흑색종 세포와 keratinocyte가 탈착되면서 사멸되는 것을 확인하였다. 이러한 현상을 통하여 사멸되는 메카니즘이 anoikis 방식의 세포사멸로 인한 것으로 추정할 수 있으며 그것에 대한 명확한 세포사 신호 체계 규명을 위하여 향후 세포부착 단백질의 변화에 대한 연구가 필요할 것으로 판단된다.

• 한국약용작물학회지
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• 제22권3호
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• pp.223-230
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• 2014

This study was performed to enhance contents of low molecular ginsenoside using steaming and fermentation process in low quality fresh ginseng. For increase in contents of Rg2, Rg3, Rh2 and CK in low quality fresh ginseng, a steaming process was applied at $90^{\circ}C$ for 12 hr which was followed by fermentation process at Lactobacillus rhamnosus HK-9 incubated at $36^{\circ}C$ for 72 h. The contents of ginsenoside Rg1, Rb1, Rc, Re and Rd were decreased with the steaming associated with fermentation process but ginsenoside Rg2, Rg3, Rh2 and CK increased after process. It was found that under the steaming associated with fermentation process, low molecule ginsenosides such as Rg2, Rg3, Rh2 and CK were increased as 3.231 mg/g, 2.585 mg/g and 1.955 m/g and 2.478 mg/g, respectively. In addition, concentration of benzo[${\alpha}$]pyrene in extracts of the low quality fresh ginseng treated by the complex process was 0.11 ppm but it was 0.22 ppm when it was treated with the steaming process. This result could be caused by that the most efficiently breakdown of 1,2-glucoside and 1,4-glucoside linkage to backbone of ginsenosides by steaming associated with fermentation process. This results indicate that steaming process and fermenration process can increase in contents of Rg2, Rg3, Rh2 and CK in low quality fresh ginseng.

• 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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• 제42권2호
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• pp.218-224
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• 2018

Background: Compound K (CK) is a ginsenoside, a metabolite of Panax ginseng. There is interest both in increasing skin health and antiaging using natural skin care products. In this study, we explored the possibility of using CK as a cosmetic ingredient. Methods: To assess the antiaging effect of CK, RT-PCR was performed, and expression levels of matrix metalloproteinase-1, cyclooxygenase-2, and type I collagen were measured under UVB irradiation conditions. The skin hydrating effect of CK was tested by RT-PCR, and its regulation was explored through immunoblotting. Melanin content, melanin secretion, and tyrosinase activity assays were performed. Results: CK treatment reduced the production of matrix metalloproteinase-1 and cyclooxygenase-2 in UVB irradiated NIH3T3 cells and recovered type I collagen expression level. Expression of skin hydrating factors-filaggrin, transglutaminase, and hyaluronic acid synthases-1 and -2-were augmented by CK and were modulated through the inhibitor of ${\kappa}B{\alpha}$, c-Jun N-terminal kinase, or extracellular signal-regulated kinases pathway. In the melanogenic response, CK did not regulate tyrosinase activity and melanin secretion, but increased melanin content in B16F10 cells was observed. Conclusion: Our data showed that CK has antiaging and hydrating effects. We suggest that CK could be used in cosmetic products to protect the skin from UVB rays and increase skin moisture level.

• Journal of Ginseng Research
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• 제46권3호
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• pp.496-504
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• 2022

Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

• Journal of Ginseng Research
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• 제43권1호
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• pp.154-160
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• 2019

Background: Compound K (CK) is an active metabolite of ginseng saponin, ginsenoside Rb1, that has been shown to have ameliorative properties in various diseases. However, its role in inflammation and the underlying mechanisms are poorly understood. In this report, the antiinflammatory role of CK was investigated in macrophage-like cells. Methods: The CK-mediated antiinflammatory mechanism was explored in RAW264.7 and HEK293 cells that were activated by lipopolysaccharide (LPS) or exhibited overexpression of known activation proteins. The mRNA levels of inflammatory genes and the activation levels of target proteins were identified by quantitative and semiquantitative reverse transcription polymerase chain reaction and Western blot analysis. Results: CK significantly inhibited the mRNA expression of inducible nitric oxide synthase and tumor necrosis factor-${\alpha}$ and morphological changes in LPS-activated RAW264.7 cells under noncytotoxic concentrations. CK downregulated the phosphorylation of AKT1, but not AKT2, in LPS-activated RAW264.7 cells. Similarly, CK reduced the AKT1 overexpression-induced expression of aldehyde oxidase 1, interleukin-$1{\beta}$, interferon-${\beta}$, and tumor necrosis factor-${\alpha}$ in a dose-dependent manner. Conclusion: Our results suggest that CK plays an antiinflammatory role during macrophage-mediated inflammatory actions by specifically targeting the AKT1-mediated signaling pathway.