• Journal of Ginseng Research
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• 제46권3호
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• pp.418-425
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• 2022

Background: Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3 signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3) have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and to examine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafenib-resistant hepatoma.

• 한국미생물·생명공학회지
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• 제45권4호
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• pp.305-310
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• 2017

발효식품으로부터 분리한 젖산균 중 ${\alpha}$-rhamnosidase 효소활성을 보유한 젖산균 12점을 선별하였다. 효소활성이 우수한 Weissella confuse 1점, L. pentosus 1점과 효소활성이 우수하였던 4점의 L. plantarum 균주를 사용하여 진세노사이드 Rb1과 Re를 Rg1, Rg5로 각각 생물전환하였다. L. plantarum MBE/L2990 균주를 사용한 생물전환반응에서 Rg1과 Rg5의 함량이 각각 0.58 mg, 0.24 mg 가량 증가하였으며, 대조구로 사용한 L. plantarum KCTC21004 균주에 비해 약 56% 및 42% 우수한 생물전환 효율이었다. L. plantarum MBE/L2990 균주는 한국미생물자원센터에 KCTC18529P로 기탁하였다.

• 대한화장품학회지
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• 제49권4호
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• pp.323-330
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• 2023

피부의 장벽 구조는 표피의 각질 형성세포의 분화과정에 의해서 생성된다. 이 구조는 케라틴 단백질로 구성되는 각질세포와 그 사이를 채우고 있는 세포간 지질로 구성된다. 이때 표피의 기저층의 세포의 막을 이루던 인지질 등의 성분은 분해되어 없어지고, 세라마이드 등이 성분이 신규로 합성되어 각질층의 세포간 지질을 구성한다. 본 연구에서는 피부 장벽의 세포간 지질 구조의 패킹과 장벽기능에 진세노사이드 Rg3성분이 미치는 영향을 확인하였다. 이를 위해 3D피부 세포의 분화과정에 Rg3성분을 처리하였다. 3D피부를 대상으로 FT-IR 및 TEWL를 분석한 결과, 각질 세포간 지질의 orthorhombic패킹이 강화되고 장벽기능이 강화되는 것을 확인하였다. 또한 HaCaT세포에 Rg3를 처리한 경우, 긴 체인 길이의 지질을 합성하는 EVOL1 및 EVOL4의 발현 증가와 짧은 길이의 세라마이드의 합성을 당하는 CERS6의 감소 그리고 피토스핑고신을 사용하는 세라마이드를 분해시키는 ACER6의 증가를 검출하였다. 이를 통해 Rg3가 표피 분화 과정 중 지질의 합성에 영향을 주어 장벽 기능 변화를 가져올 가능성을 제시하였다.

• Journal of Chest Surgery
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• 제31권6호
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• pp.567-575
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• 1998

최근 심장 분야 수술의 발달로 여러 가지 고난도의 심장 수술과 심장 이식술의 시행이 증가하고 있으며, 술 후 예후에 크게 영향을 주는 심장의 심근 손상 방지에 대한 다각적인 연구가 행해지고 있는데, 수술 및 이식 전후의 허혈기와 재관류시 발생할 수 있는 심근 손상을 최소화하고, 술 후 심근 기능의 조속한 회복을 위한 목적으로 여러 약제 및 방법을 제시하고 있다. 한편 한국에서는 오래 전 부터 만병 통치의 영약으로 전해져 오고 있는 인삼을 이용한 동물 실험 및 임상 경험을 통해 성분 효과에 대한 여러 결과가 보고되고 있고, 심장 기능에 대한 효과도 약리학적 측면에서 많은 결과가 발표되었다. 그런데 여러 분획 추출물 중 ginsenoside Rg1 mixtures에 대해서는 그 결과가 다소 미비한 상태이고 ginsenoside Rb1과의 이원 작용에 대한 결과가 흥미로울 것으로 판단되었으며 여러 저자들의 결과에 차이가 있어 ginsenoside Rg1을 이용하여 심근의 허혈 후 재관류 시행 10분 및 지속적 관류 상태에서의 심근 손상에 대한 심근 보호 정도를 혈역학적 지표 및 관상 혈류를 통한 관류액의 효소치를 측정하여 실험한 결과 심근 허혈 및 재관류 후 심근 손상 방지와 심근 기능 회복에 효과가 있다고 판단되며 향후 약제의 투여 용량에 따른 심근 보호 정도에 관한 실험이 필요할 것으로 사료되고, 인삼 성분 각 분획의 복합 투여에 의한 결과도 재차 확인하여야 할 것으로 생각된다.

• Journal of Ginseng Research
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• 제42권4호
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• pp.412-418
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• 2018

Background: Ginsenoside Rg3(S) and compound K (C-K) are pharmacologically active components of ginseng that promote human health and improve quality of life. The aim of this study was to produce Rg3(S) and C-K from ginseng extract using recombinant Lactococcus lactis. Methods: L. lactis subsp. cremoris NZ9000 (L. lactis NZ9000), which harbors ${\beta}$-glucosidase genes (BglPm and BglBX10) from Paenibacillus mucilaginosus and Flavobacterium johnsoniae, respectively, was reacted with ginseng extract (protopanaxadiol-type ginsenoside mixture). Results: Crude enzyme activity of BglBX10 values comprised 0.001 unit/mL and 0.003 unit/mL in uninduced and induced preparations, respectively. When whole cells of L. lactis harboring pNZBglBX10 were treated with ginseng extract, after permeabilization of cells by xylene, Rb1 and Rd were converted into Rg3(S) with a conversion yield of 61%. C-K was also produced by sequential reactions of the permeabilized cells harboring each pNZBgl and pNZBglBX10, resulting in a 70% maximum conversion yield. Conclusion: This study demonstrates that the lactic acid bacteria having specific ${\beta}$-glucosidase activity can be used to enhance the health benefits of Panax ginseng in either fermented foods or bioconversion processes.

• Journal of Ginseng Research
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• 제42권3호
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• pp.298-303
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• 2018

Background: Panax ginseng is one of the most commonly used medicinal herbs worldwide for a variety of therapeutic properties including neurocognitive effects. Ginsenoside Rg1 is one of the most abundant active chemical constituents of this herb with known neuroprotective, anxiolytic, and cognition improving effects. Methods: We investigated the effects of Rg1 on the medial prefrontal cortex (mPFC), a key brain region involved in cognition, information processing, working memory, and decision making. In this study, the effects of systemic administration of Rg1 (1 mg/kg, 3 mg/kg, or 10 mg/kg) on (1) spontaneous firing of the medial prefrontal cortical neurons and (2) long-term potentiation (LTP) in the hippocampal-medial prefrontal cortical (HP-mPFC) pathway were investigated in male Sprague-Dawley rats. Results: The spontaneous neuronal activity of approximately 50% the recorded pyramidal cells in the mPFC was suppressed by Rg1. In addition, Rg1 attenuated LTP in the HP-mPFC pathway. These effects were not dose-dependent. Conclusion: This report suggests that acute treatment of Rg1 impairs LTP in the HP-mPFC pathway, perhaps by suppressing the firing of a subset of mPFC neurons that may contribute to the neurocognitive effects of Rg1.

• 생약학회지
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• 제47권4호
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• pp.352-359
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• 2016

The purpose of this study is to develop a new preparation process of ginseng leaf and stem extracts having high concentrations of ginsenoside Rg2, Rg3, Rg5, Rh1, a special component of red and black ginseng. Chemical transformation from ginseng saponin glycosides to prosapogenin was analyzed by the HPLC. Extracts of ginseng (Panax ginseng) leaf and stem were processed under several treatment conditions including ultrasonication treatments. The content of total saponin reached their heights at 17 hr (UGL-17) of ultrasonication treatment, followed by 16 hr (UGL-16) and 7 hr (UGL-7) of ultrasonication treatment at $100^{\circ}C$. UGL-17 findings show that the ginseng leaf and stem that had been processed with ultrasonication for 17 hours peaked in the level of Rg2, Rg3 and Rh1. In addition, UGL-16 contained ginsenoside Rg5 at high concentrations. It is thought that such results provide basic information in preparing ginseng leaf and stem extracts with functionality enhanced.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.182-189
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• 1998

Administration of ginsenosides, a mixture of saponin extracted from Panax ginseng, decreased blood pressure in rat. Previous studies have shown that ginsenosides caused endothelium-dependent relaxation, which was associated with the formation of cyclic GMP, suggested that ginsenosides caused release of nitric oxide (NO) from the vascular endothelium. The aim of the present study was to characterize the endothelium-independent relaxation to ginsenosides in the isolated rat aorta. Ginsenosides caused a concentration-dependent relaxation of rat aortic rings without endothelium constricted with 25 mM KCI but affected only minimally those constricted with 60 mM KCI. Ginsenoside Rg3 (Rg3) was a more potent vasorelaxing agonist than total ginsenoside mixture and also the ginsenoside PPT and PPD groups. Relaxation to ginsenosides were markedly reduced by TEA, but not by glibenclamide. Rg3 significantly inhibited Cal'-induced concentration-contraction curves and the "50a2'influx in aortic rings incubated in 25 mM KCI whereas those responses were not affected in 60 mM KCI. Rg3 caused efflux of $"Rb in aortic rings that was inhibited by tetraethy- lammonium (TEA), an inhibitor of Ca"-dependent K'channels, but not by glibenclamide, an inhibitor of AfP-dependent K'channels. These findings indicate that ginsenosides may induce vasorelaxation via activation of Ca2'-dependent K'channels resulting in hyperpolarization of the vas- cular smooth muscle with subsequent inhibition of the opening of voltage-dependent Caf'channels. These effects could contribute to explain the red ginseng-associated vasodilation and the beneficial effect on the cardiovascular system.

• 대한약침학회지
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• 제13권2호
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• pp.33-49
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• 2010

Objectives: The aim of this experiment is to provide an objective differentiation of cultivated ginseng, mountain ginseng through component analysis, and to know the change of gin senoside components in the process of heating and fermentation Methods: Comparative analyses of ginsenoside $Rb_1$, $Rb_2$, Rc, Rd, Re, Rf, $Rg_1$, $Rg_3$, $Rh_1$, and $Rh_2$, from the cultivated ginseng 4 and 6 years, and mountain cultivated ginseng were conducted using HPLC (High Performance Liquid Chromatography, hereafter HPLC). And the same analyses were conducted in the process of heating and fermentation using mixed Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium lactis for 7 days. Results: The change of ginsenosides to the process of red ginseng and fermentation, cultivated ginseng and mountain cultivated ginseng were showed another results. Mountain ginseng showed a lot of change compared with cultivated ginsengs. In the 7 days of fermentation, mountain ginseng showed that ginsenoside $Rg_1$, $Rb_1$, $Rb_2$, Rc, and Rd were decreased and increased ginsenoside Re, Rf, $Rg_3$ and $Rh_1$ were increased compared with cultivated ginseng Conclusions: It seemed that ginsenosides of mountain cultivated ginseng was better resolved than cultivated ginseng because the difference of structure or distribution of ginsenosides in the condition of fermentation.

• Journal of Ginseng Research
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• 제47권2호
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• pp.237-245
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• 2023

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.