• Journal of Ginseng Research
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• 제39권3호
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• pp.189-198
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• 2015

Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase $A_2$ ($PLA_2$), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, $PLA_2$, and transcription factors (nuclear factor-${\kappa}B$ and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the $Ca^{2+}$ influx, protein kinase C, and $PLA_2$, which are propagated by Syk activation upon allergic stimulation of mast cells.

• Journal of Ginseng Research
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• 제33권4호
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• pp.316-323
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• 2009

인삼 사포닌은 면역계에 다양한 약리 효과를 발휘한다. 20(S)-프로토파낙사다이올 (PPD) 및 20(S)- 프로토파낙사트리올 (PPT)은 장내 세균에 의하여 생성되는 인삼 대사체의 일종이며 생체 내 투여 시 순환계에서 탐지된다. 활성화된 비만 세포로부터의 염증 매개체 유리에 미치는 20(S)-프로토파낙사다이올 (PPD) 및 20(S)-프로토파낙사트리올 (PPT)의 영향을 평가하였다. 인삼 사포닌 대사체를 처치 후, 히스타민 유리는 활성화된 해명 폐 비만세포에서 평가하였으며, 인터루킨-4, 인터루킨-8, 및 종양괴사인자-알파 유리는 HMC-1 비만세포에서 평가하였다. 결과는 다음과 같다. PPT는 최고 $100\;{\mu}M$ 농도에서 PMA에 의하여 자극된 HMC-1 세포로부터의 인터루킨-4 유리를 완전히 차단하였다. 또한, 이는 HMC-1 세포로부터의 인터루킨-8의 유리를, PMA와 DMSO동시 처치 시얻어진 수치를 기준으로 대략 40-50% 정도 억제하였다. PPD는 최고 $100\;{\mu}M$ 농도에서 해명 폐 비만세포로부터의 히스타민 유리를 초래하였으나 통계적 유의성은 없었다. PPD는 HMC-1 세포에 PMA와 DMSO 동시 처치 시 얻어진 수치를 기준으로 할 때, 인터루킨-4의 유리를 대략 89% 정도 억제하였으나, 인터루킨-8의 유리에는 유의적인 효과를 초래하지 않았다. 그러나 PPD 및 PPT 모두, PMA에 의하여 자극된 HMC-1 세포로부터의 종양괴사 인자-알파의 유리에는 전혀 효과를 나타내지 않았다. 그러므로 본 연구 결과는 PPD와 PPT가 경구로 투여된 인삼 추출물의 면역조절 작용을 담당하는 장내 인삼 대사체 중의 한 종류임을 제시한다.

• Journal of Ginseng Research
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• 제44권5호
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• pp.690-696
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• 2020

Background: As the main metabolites of ginsenosides, 20(S, R)-protopanaxadiol [PPD(S, R)] and 20(S, R)-protopanaxatriol [PPT(S, R)] are the structural basis response to a series of pharmacological effects of their parent components. Although the estrogenicity of several ginsenosides has been confirmed, however, the underlying mechanisms of their estrogenic effects are still largely unclear. In this work, PPD(S, R) and PPT(S, R) were assessed for their ability to bind and activate human estrogen receptor α (hERα) by a combination of in vitro and in silico analysis. Methods: The recombinant hERα ligand-binding domain (hERα-LBD) was expressed in E. coli strain. The direct binding interactions of ginsenosides with hERα-LBD and their ERα agonistic potency were investigated by fluorescence polarization and reporter gene assays, respectively. Then, molecular dynamics simulations were carried out to simulate the binding modes between ginsenosides and hERα-LBD to reveal the structural basis for their agonist activities toward receptor. Results: Fluorescence polarization assay revealed that PPD(S, R) and PPT(S, R) could bind to hERα-LBD with moderate affinities. In the dual luciferase reporter assay using transiently transfected MCF-7 cells, PPD(S, R) and PPT(S, R) acted as agonists of hERα. Molecular docking results showed that these ginsenosides adopted an agonist conformation in the flexible hydrophobic ligand-binding pocket. The stereostructure of C-20 hydroxyl group and the presence of C-6 hydroxyl group exerted significant influence on the hydrogen bond network and steric hindrance, respectively. Conclusion: This work may provide insight into the chemical and pharmacological screening of novel therapeutic agents from ginsenosides.

• 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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• 제47권1호
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• pp.74-80
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• 2023

Background: Although many studies have evaluated the efficacy and pharmacokinetics of Korean Red Ginseng (KRG) components (Rg1, Rb1, Rg3, Rd, etc.), few have examined the in vivo pharmacokinetics of the radiolabeled components. This study investigated the pharmacokinetics of ginsenosides and their metabolite compound K (CK), 20(s)-protopanaxadiol (PPD), and 20(s)-protopanaxatriol (PPT) using radioisotopes in rat oral administration. Methods: Sprague-Dawley rats were dosed orally once with 10 mg/kg of the tritium(3H) radiolabeled samples, and then the blood was collected from the tail vein after 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 96, and 168 h. Radioactivity in the organs, feces, urine, and carcass was determined using a liquid scintillation counter (LSC) and a bio-imaging analyzer system (BAS). Results and conclusion: After oral administration, as the ³H-labeled ginsenosides were converted to metabolites, C_max and half-life increased, and T_max decreased. Interestingly, Rb1 and CK showed similar values, and after a single oral administration of components, the cumulative excretion ratio of urine and feces was 88.9%-92.4%. Although most KRG components were excreted within 96-168 h of administration, small amounts of components were detected in almost all tissues and mainly distributed to the liver except for the digestive tract when observed through autoradiography. This study demonstrated that KRG components were distributed to various organs in the rats. Further studies could be conducted to prove the bioavailability and transmission of KRG components to confirm the mechanism of KRG efficacy.

• Journal of Ginseng Research
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• 제47권3호
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• pp.479-491
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• 2023

Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.