• Journal of Ginseng Research
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• 제48권1호
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• pp.31-39
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• 2024

Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl₂, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl₂-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl₂-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.

• Journal of Ginseng Research
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• 제45권6호
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• pp.654-664
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• 2021

Background: Ginsenoside Rg3, isolated from Panax ginseng, has anti-inflammatory and anti-tumor activities. It is known to reduce inflammation in acute lung injury in mice, and to reduce the expression of inflammatory cytokines and COX-2 in human asthmatic airway epithelium. In this study, we attempted to determine whether ginsenoside Rg3 inhibits airway inflammation, oxidative stress, and airway hyperresponsiveness (AHR) in the lungs of asthmatic mice. We also investigated its effects on oxidative stress and the inflammatory response in tracheal epithelial cells. Methods: Asthma symptoms were induced in female BALB/c mice sensitized with ovalbumin (OVA). Mice were divided into five groups: normal controls, OVA-induced asthmatic controls, and asthmatic mice treated with ginsenoside Rg3 or prednisolone by intraperitoneal injection. Inflammatory BEAS-2B cells (human tracheal epithelial cells) treated with ginsenoside Rg3 to investigate its effects on inflammatory cytokines and oxidative responses. Results: Ginsenoside Rg3 treatment significantly reduced eosinophil infiltration, oxidative responses, airway inflammation, and AHR in the lungs of asthmatic mice. Ginsenoside Rg3 reduced Th2 cytokine and chemokine levels in bronchoalveolar lavage fluids and lung. Inflammatory BEAS-2B cells treated with ginsenoside Rg3 reduced the eotaxin and pro-inflammatory cytokine expressions, and monocyte adherence to BEAS-2B cells was significantly reduced as a result of decreased ICAM-1 expression. Furthermore, ginsenoside Rg3 reduced the expression of reactive oxygen species in inflammatory BEAS-2B cells. Conclusion: Ginsenoside Rg3 is a potential immunomodulator that can ameliorate pathological features of asthma by decreasing oxidative stress and inflammation

• 대한화학회지
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• 제44권3호
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• pp.190-193
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• 2000

M-Rg 및 M-Rg2 (M=Li,Na,Rg=He,Ar) 반데르발스 복합체들에 대한양자화학적계산을 시행하였다. AIl-electron MP2(6-311++G(3df,3pd))에 의하여 계산된 LiHe, LiAr 및 NaAr의 균형 핵간 거리와 결합 에너지는 실험값과 잘 일치하였다. $LiHe_2,\;LiAr_2$ 및 $NaAr_2$에 대하여 계산된 분광학적 성질들도 또한 계산하였다.

• 동의생리병리학회지
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• 제18권4호
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• pp.1021-1027
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• 2004

Panax ginseng has been used as a typical tonic medicine in Asian countries, such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in Panax ginseng increases the proportion of T helper cells in the whole T cells and promotes IL-2 gene expression in murine splenocytes. These studies imply that ginsenoside Rg1 increases the immune activity of CD4+ T cell, however the exact mechanism of ginsenoside Rg1 on helper T cell remains to be verified. The present study tried to elucidate the direct effect of Rg1 on helper T cell s activities and its Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had not mitogenic effects on the unstimulated CD4+ T cell, but augmented CD4+ T cell proliferation upon activating with anti-CD3/anti-CD28 antibodies in a dose dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4+ T cell. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4+ T cells, suggesting Rg1 prefer to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secreting CD4+ T cell under Th2 skewed condition, while decreases IFN-γ secreting cell in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from naive CD4+ T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 might be desirable agent for enhancing CD4+ T cell's activity, as well as the correction of Th1 dominant pathological disorders.

• 산업식품공학
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• 제21권3호
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• pp.225-232
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• 2017

본 연구에서는 홍삼분말 입자크기 $10.00{\mu}m$ 이하의 홍삼분말과 $100.00{\mu}m$ 이상의 홍삼분말 간의 이화학적 특성 및 추출 효율성분 함량을 비교분석하였으며, 분산안정성을 기반으로 가공공정에서 적합한 홍삼분말 입자크기를 조사하였다. 본 연구에 사용된 홍삼분말은 $158.00{\mu}m$, $8.45{\mu}m$, $6.33{\mu}m$ 의 입도크기를 가졌으며, 각각 RG A, RG B, RG C로 표현하였다. 본 연구에서는 홍삼분말(2.6%, w/v)을 증류수에 분산시킨 홍삼용액을 4주 동안 저장 온도 $4^{\circ}C$, $25^{\circ}C$, $40^{\circ}C$에 각각 보관하였으며, 이에 따른 갈색도 및 지방산패도 변화를 확인하였다. 갈색도는 홍삼분말 입자크기와 관계없이 저장온도 및 시간에 따라 갈색도 값이 감소하였으며, 지방산패도(TBA)의 값은 저장온도에 상관없이 4주 동안 유의적으로 증가하였으나 홍삼분말의 지방함량이 낮아 지방산패도 값은 0.1 미만의 낮은 값을 보였다. 분산 안정성을 나타내는 backscatterting 값은 홍삼분말을 이용한 제품 가공시 적합한 입자크기를 알아보기 위하여 측정하였으며, RG A는 RG B 및 RG C와 다르게 분산직후 바로 침전이 되어 용기의 바닥부분에서 높은 backscattering 값을 보였다. RG B는 분산 10시간 이전까지 RG C보다 낮은 TSI 값을 보였으며, 10시간 이후 RG C와 같은 분산안정성을 보였다. RG A, RG B, RG C의 DPPH 및 ABTS 자유 라디칼 소거능의 $IC_{50}$ 값들은 각각 2.74-3.34 mg/mL, 2.77-2.95 mg/mL으로 홍삼분말 입자크기에 따른 유의적인 차이를 보이지 않았다. 일반적으로 홍삼분말의 입자크기 감소는 표면적 증가로 이어져 유효성분 추출 효율성이 증가하지만, 본 실험에서 RG A, RG B, RG C 간의 유효성분 추출에 큰 차이를 보이지 않은 것은 미세한 입자가 열수추출 과정 중 입자간 뭉침현상이 발생하여 표면적 증가와 관련있는 것으로 고려된다. 홍삼분말의 ginsenoside 총 함량은 24.28 mg/g 및 24.53 mg/g로 입자크기에 따른 유의적 차이를 보이지 않았으나, ginsenoside $Rg_1$, Re, $Rh_2$ 함량은 RG C가 RG A보다 유의적으로 높은 값을 가졌다. 따라서 홍삼분말 입자크기는 갈색도, 지방산패도, 항산화 효과에 큰 영향을 미치지 않지만 미세한 입자크기를 가진 홍삼분말이 분산안정성이 좋아 홍삼분말을 이용한 홍삼제품 가공공정에 보다 적합할 것으로 사료된다.

• Journal of Ginseng Research
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• 제34권3호
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• pp.246-253
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• 2010

Ginsenoside $Rg_3$ ($Rg_3$), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents in vitro and antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. In the present study, we examined the neuroprotective effects of $Rg_3$ on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that $Rg_3$ treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cortical neurons, with an $IC_{50}$ value of $28.7{\pm}7.5\;{\mu}m$. Furthermore, the $Rg_3$ treatment not only significantly reduced DNA damage, but also dose-dependently attenuated 24-OH-chol-induced caspase-3 activity. To study the mechanisms underlying the in vitro neuroprotective effects of $Rg_3$ against 25-OH-chol-induced cytotoxicity, we also examined the effect of $Rg_3$ on intracellular $Ca^{2+}$ elevations in cultured neurons and found that $Rg_3$ treatment dose-dependently inhibited increases in intracellular $Ca^{2+}$, with an $IC_{50}$ value of $40.37{\pm}12.88\;{\mu}m$. Additionally, $Rg_3$ treatment dose-dependently inhibited apoptosis with an $IC_{50}$ of $47.3{\pm}14.2\;{\mu}m$. Finally, after confirming the protective effect of $Rg_3$ using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that $Rg_3$ is an active component in ginseng-mediated neuroprotection. These results collectively indicate that $Rg_3$-induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated $Ca^{2+}$ channel. This is the first report to employ cortical neurons to study the neuroprotective effects of $Rg_3$ against 24-OH-chol. In conclusion, $Rg_3$ was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes $Rg_3$ a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.

• Journal of Ginseng Research
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• 제19권2호
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• pp.117-121
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• 1995

We studied the effects of ginsenoside-$Rg_1$ (G-$Rg_1$) extracted from Panax ginseng C.A. Meyer on $p56^{kk}$ kinase and cell proliferation in Jurkat T cells. $p56^{kk}$ was maximally activated within 5 min after the treatment of 16.7 $\mu\textrm{g}$/ml of G-$Rg_1$ increasing the activity by 1.2-2 times relative to untreated control, thereafter its activity was gradually decreased to the level of untreated control. The action of EGTA on the kinase was altered by the addition of G-$Rg_1$, accompanying the band shift of $p56^{kk}$ to $p60^{kk}$. In addition, G-$Rg_1$promoted cell proliferation in a concentration-dependent manner. These results suggest that G-$Rg_1$ may be involved in T cell receptor-CD3 (TCR) signaling via the activation of $p56^{kk}$ and the chance of cellular calcium concentration.

• KSBB Journal
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• 제16권5호
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• pp.486-492
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• 2001

숙지황 물추출물로부터 분리된 fraction(RG-III) 의 항돌연변이원성의 기작을 E. coli GW, B/r 균주를 이용하여 조사하였다. SOS 유도를 반영하는 $\beta$-galactiosidase 활성이 E. coli GW 1060, 1103, 1107, 1105에서 증가되지 않았다. RG-III는 RecA는 단백질의 합성을 증폭시키거나 LexA 산물의 분해를 저해하지 않았으므로 SOS en 기능의 발현이 영향을 미치지 못했다. 따라서 DNA 수복의 경로가 다른 E. coli B.r 변이주를 사용하여 4NQO와 MNNG에 대한 세포내 항돌연변이원성과 생존효과를 조사하였다. ZA159(uvrB, 최)를 제외한 WP2, WP2s, WP67, CM561, CM611에서 RG-III는 4NQO에 대한 생존력을 미약하게나마 증가시켰으나, 이러한 생존력 재활성을 수복모드에 의해 설명할 수 없었다. WP2, WP2s, WP67, CM561, CM611에서 RG-III는 MNNG로 유도된 돌연변이원성과 치사력을 증가시킴에도 불구하고 ZA159(uvr B, chl)에서는 감소시켰다. 4NQO의 변이원성을 두드러지게 억제하였으나 ZA159(uvr B, chl)에서 상승효과가 상대적으로 감소되었다. 이러한 결과들은 RG-III가 4NQO의 변이원성을 방어하는 차단제임을 시시하여, chl 산물의 기능과 유사한 작용을 하는 것으로 사료된다.

• 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.

• Journal of Microbiology and Biotechnology
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• 제16권11호
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• pp.1791-1798
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• 2006

When ginsenoside Rg5, a main component isolated from red ginseng, was incubated with three human fecal microflora for 24 h, all specimens showed hydrolyzing activity: all specimens produced ginsenoside Rh3 as a main metabolite, but a minor metabolite $3{\beta},12{\beta}$-dihydroxydammar-21(22),24-diene (DD) was observed in two specimens. To evaluate the antiallergic effect of ginsenoside Rg5 and its metabolites, the inhibitory effect of ginsenoside Rg5 and its metabolite ginsenoside Rh3 against RBL-2H3 cell degranulation, mouse passive cutaneous anaphylaxis (PCA) reaction induced by the IgE-antigen complex, and mouse ear skin dermatitis induced by 12-O-tetradecanoilphorbol-13-acetate (TPA) were measured. Ginsenosides Rg5 and Rh3 potently inhibited degranulation of RBL-2H3 cells. These ginsenosides also inhibited mRNA expression of proinflammatory cytokines IL-6 and $TNF-{\alpha}$ in RBL-2H3 cells stimulated by IgE-antigen. Orally and intraperitoneally administered ginsenoside Rg3 and orally administered ginsenoside Rg5 to mice potently inhibited the PCA reaction induced by IgE-antigen complex. However, intraperitoneally administered ginsenoside Rg5 nearly did not inhibit the PCA reaction. These ginsenosides not only suppressed the swelling of mouse ears induced by TPA, but also inhibited mRNA expression of cyclooxygenase-2, $TNF-{\alpha}$, and IL-4 and activation of transcription factor NF-kB. These inhibitions of ginsenoside Rh3 were more potent than those of ginsenoside Rg5. These findings suggest that ginsenoside Rg5 may be metabolized in vivo to ginsenoside Rh3 by human intestinal microflora, and ginsenoside Rh3 may improve antiallergic diseases, such as rhinitis and dermatitis.