• Journal of Ginseng Research
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• 제33권4호
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• pp.294-304
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• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of various symptoms in South Korea. The neuroprotective effects of ginsenoside $Rg_3$ (G-$Rg_3$) on cholesterol-oxide-(CO)-induced neurotoxicity were investigated through the analyses of rat brains. The recently accumulated reports show that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, the neuroprotective effects of G-$Rg_3$ on CO-induced hippocampal excitotoxicity were examined in vivo. The in-vitro studies using rat cultured hippocampal neurons revealed that G-$Rg_3$ treatment significantly inhibited CO-induced hippocampal cell death. G-$Rg_3$ treatment not only significantly reduced CO-induced DNA damage but also attenuated CO-induced apoptosis. The in-vivo studies that were conducted revealed that the intracerebroventricular (i.c.v.) pre-administration of G-$Rg_3$ significantly reduced i.c.v. CO-induced hippocampal damage in rats. To examine the mechanisms underlying the in-vitro and in-vivo neuroprotective effects of G-$Rg_3$ against CO-induced hippocampal excitotoxicity, the effect of G-$Rg_3$ on the CO-induced elevations of the apoptotic cells in cultured hippocampal cells was examined, and it was found that G-$Rg_3$ treatment inhibited CO-induced apoptosis. The histopathological evaluation demonstrated that G-$Rg_3$ significantly diminished the apoptosis in the hippocampus and also spared the hippocampal CA1, CA3, and dentate gyrus neurons. G-$Rg_3$ also significantly improved the CO-caused behavioral impairment. G-$Rg_3$ itself had no effect, however, on the CO-induced inhibition of succinate dehydrogenase activity (data not shown). These results collectively indicate the G-$Rg_3$-induced neuroprotection against CO in rat hippocampus. With regard to the wide use of G-$Rg_3$, this agent is potentially beneficial in treating CO-induced brain injury.

• Journal of Ginseng Research
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• 제44권2호
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• pp.247-257
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• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Journal of Ginseng Research
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• 제46권5호
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• pp.636-645
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• 2022

Background: Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity. Methods: RNA-seq and survival data from The Cancer Genome Atlas (TCGA)-PAAD and Genotype-Tissue Expression (GTEx) were used for in-silicon analysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used for in vitro analysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth in vivo. Results: Ginsenoside Rg3 reduced ZFP91 expression in PAAD cells in a dose-dependent manner. ZFP91 upregulation was associated with significantly shorter survival of patients with PAAD. ZFP91 overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment. ZFP91 depletion sensitized PANC-1/GR cells to gemcitabine treatment. ZFP91 interacted with Testis-Specific Y-Encoded-Like Protein 2 (TSPYL2), induced its poly-ubiquitination, and promoted proteasomal degradation. Ginsenoside Rg3 treatment weakened ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforced TSPYL2 expression increased gemcitabine sensitivity of PAAD cells and partly reversed induced gemcitabine resistance in PANC-1/GR cells. Conclusion: Ginsenoside Rg3 can increase gemcitabine sensitivity of pancreatic adenocarcinoma at least via reducing ZFP91 mediated TSPYL2 destabilization.

• IMMUNE NETWORK
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• 제16권1호
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• Journal of Ginseng Research
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• 제34권1호
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• pp.1-7
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• 2010

본 논문은 백삼 추출물의 코팅 처리에 의한 인삼 커피의 품질 특성에 대한 것으로 주요 내용은 다음과 같다. 백삼 추출물 (WGC-2)의 농도에 따라 커피의 품질 속성을 실험하였다. 대조군과 $5^{\circ}$ Brix (WGC-1)와 $20^{\circ}$ Brix의 사포닌 농도는 8.29%, 8.74%와 8.93% 였고, WGC-1과 WGC-2의 총 진세노사이드 농도는 0.3 mg/g과 0.6 mg/g 였다. 특히 주요 진세노사이드 $Rg_1,\;Rg_2,\;Rb_1,\;Rb_2,\;Rg_2,\;Rh_1$와 $Rg_3$ 함량은 백삼 추출물의 농도에 따라 증가하였다. 커피 맛은 WGC-2가 상업적 커피콩보다 유의하게 낮았고, 소비자 관능 평가에서는 별 차이가 없다는 내용이다.

• 한국미생물·생명공학회지
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• 제50권3호
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• pp.414-421
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• 2022

식물 공생 미생물은 기주 식물과 함께 공생하는 미생물로 생장 촉진, 면역력 증진, 대사체 생성 등의 역할을 수행하며 식물 발달에 영향을 준다. 본 연구를 통해 30년근 산삼에서 분리 동정한 미생물인 W. ginsengihumi LGHNH (KCTC 14462BP)은 식물 생장 촉진 호르몬인 indole-3-acetic acid (IAA)을 1.38 ㎍/ml에서 2.22 ㎍/ml 수준으로 분비함을 확인하였다. 또한 발효 전, 후의 진세노사이드 함량 비교를 통해 진세노사이드 전환능이 있음을 확인하였다. 전환된 저분자 진세노사이드인 Rg2(R), Rg4, Rg6, Rg3(S), Rg3(R), Rk1, Rg5, Rh1(R), Rk3, Rh4 등은 생체 이용률이 높고 다양한 피부 효능을 갖는다고 알려져 있다. 배양물로 제조한 W. ginsengihumi LGHNH (W. ginsengihumi LGHNH Cultured product, WCP)의 항노화 소재로서 가능성을 탐색하기 위해 미토콘드리아의 막전위와 ATP 생합성량을 측정하여 기능 저하 억제 여부를 확인하였다. 노화를 발생시키는 인자인 UVB를 조사한 HaCaT 세포 내 미토콘드리아 막전위 값을 측정한 결과, 미조사군 대비 39.3%로 감소하나 WCP 0.001% (v/v), 0.01% (v/v)에 의해 각각 57.3%, 58.1% 수준까지 회복함을 확인하였다. 또한 미토콘드리아의 ATP 생합성량 측정 결과, UVB 조사에 의해 미조사군 대비 94.3% 수준으로 감소하나 WCP를 0.001% (v/v), 0.01% (v/v) 처리한 군에서 각 각 105.3%, 105.7%로 증가하여 미토콘드리아 기능을 정상으로 회복하는데 도움을 줄 수 있다고 판단된다. 따라서, 본 연구를 통해 확보한 30년근 산삼의 공생 미생물은 항노화 관련 생물 자원으로서 산업적 활용 가능성이 높다.

• Journal of Ginseng Research
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• 제43권4호
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• pp.625-634
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• 2019

Background: Ginsenoside Rg3, a derivative of steroidal saponins abundant in ginseng, has a range of effects on cancer cells, including anti-cell proliferation and anti-inflammation activity. Here, we investigate two long noncoding RNAs (lncRNAs), STXBP5-AS1 and RFX3-AS1, which are hypomethylated and hypermethylated in the promoter region by Rg3 in MCF-7 cancer cells. Methods: The lncRNAs epigenetically regulated by Rg3 were mined using methylation array analysis. The effect of the lncRNAs on the apoptosis and proliferation of MCF-7 cells was monitored in the presence of Rg3 or Korean Red Ginseng (KRG) extract after deregulating the lncRNAs. The expression of the lncRNAs and their target genes was examined using qPCR and Western blot analysis. The association between the expression of the target genes and the survival rate of breast cancer patients was analyzed using the Kaplan-Meier Plotter platform. Results: STXBP5-AS1 and RFX3-AS1 exhibited anti- and pro-proliferation effects, respectively, in the cancer cells, and the effects of Rg3 and KRG extract on apoptosis and cell proliferation were weakened after deregulating the lncRNAs. Of the genes located close to STXBP5-AS1 and RFX3-AS1 on the chromosome, STXBP5, GRM1, RFX3, and SLC1A1 were regulated by the lncRNAs on the RNA and protein level. Breast cancer patients that exhibited a higher expression of the target genes of the lncRNAs had a higher metastasis-free survival rate. Conclusion: The current study is the first to identify lncRNAs that are regulated by the presence of Rg3 and KRG extract and that subsequently contribute to inhibiting the proliferation of cancer cells.

• 동의생리병리학회지
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• 제32권1호
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• pp.43-50
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• 2018

Korean Red Ginseng (RG) are used as a traditional treatment for improve blood circulation. This experimental study was designed to investigate the inhibitory effects of Korean red ginseng on lipid metabolism in high fat/cholesterol diet (HFCD)-induced hypertriglyceridemia. Sprague Dawley rats were fed the HFCD diet with/without fluvastatin (Flu, positive control) 3 mg/kg/day, and RG 125 or 250 mg/kg/day, respectively. All groups received regular diet or HFCD diet, respectively, for 13 weeks. The last three groups treatment of Flu and RG 125, and RG 250 orally for a period of 9 weeks. Group 1, reular diet; group 2, HFCD diet; group 3, Flu + HFCD diet; group 4, RG 125 + HFCD diet; group 5, RG 250 + HFCD diet. As a result, treatment with low or high doses of RG markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. RG and Flu also led to an increase in lipoprotein lipase activity in the HFCD group. On the other hand, RG and Flu led to an decrease in fatty acid synthase and free fatty acid activity in the HFCD group. Treatment with RG suppressed increased expressions of $PPAR-{\alpha}$ and AMPK in HFCD rat liver or muscle. In addition, the RG attenuated triglyceridemia by inhibition of $PPAR-{\gamma}$ and FABP protein expression levels and LXR and SREBP-1 gene expression in liver or muscle. The RG significantly prevented the development of the metabolic disturbances such as hypertriglyceridemia and hyperlipidemia. Taken together, the administration of RG improves hypertriglyceridemia through the alteration in suppression of triglyceride synthesis and accentuated of triglyceride decomposition. These results suggested that RG is useful in the prevention or treatment of hypertriglyceridemia.

• Natural Product Sciences
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• 제27권2호
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• pp.86-98
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• 2021

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K⁺, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and N^ω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na⁺ and Ca²⁺ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca²⁺ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT₁-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.

• 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.