• Journal of Ginseng Research
• /
• v.41 no.4
• /
• pp.548-555
• /
• 2017

Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ($[Ca^{2+}]_i$) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and $[Ca^{2+}]_i$ mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

• Journal of Ginseng Research
• /
• v.46 no.1
• /
• pp.138-146
• /
• 2022

Background: Red Ginseng has been used for many years to treat diseases. Ginsenoside Rg3 has documented therapeutic effects, including anticancer and anti-inflammatory activities. However, the anticancer effect of Rg3-enriched red ginseng extract (Rg3-RGE) and its underlying mechanisms have not been fully explored. We investigated whether Rg3-RGE plays an anti-tumor role in lung cancer cells. Methods: To examine the effect of Rg3-RGE on lung cancer cells, we performed cell viability assays, flow cytometry, western blotting analysis, and immunofluorescence to monitor specific markers. Results: Rg3-RGE significantly inhibited cell proliferation and induced mitochondria-dependent apoptosis. Furthermore, Rg3-RGE also increased expression of mitophagy-related proteins such as PINK1 and Parkin. In addition, treatment with Rg3-RGE and mitophagy inhibitors stimulated cell death by inducing mitochondria dysfunction. Conclusions: Rg3-RGE could be used as a therapeutic agent against lung cancer.

• Biomolecules & Therapeutics
• /
• v.18 no.2
• /
• pp.219-225
• /
• 2010

We tested whether ginsenosides $Rg_3$-standardized ginseng extract (RGE) has anti-stress effects in restraint-stressed animals. RGE increased time spent in the open arms and open arm entries in the elevated plus-maze test. In addition, RGE blocked the reduction of center zone distance and stereotypes behaviors in the open-field test. RGE also increased head dips in stressed mice, indicating anxiolytic-like effects. Stress decreased movement distance and duration, burrowing, and rearing frequency but increased face washing and grooming. RGE significantly reversed burrowing and rearing activity in stressed mice. In addition, we measured sleep architecture in restraint stressed rats using EEG recorder. Stress increased rapid eye movement (REM) sleep, but total sleep and non-rapid eye movement (NREM) sleep were not changed. RGE did not affect sleep architecture in stressed rats. These behavioral experiments suggest that RGE has anti-stress effects in restraint-stressed animal models.

• Journal of Ginseng Research
• /
• v.43 no.3
• /
• pp.421-430
• /
• 2019

Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.429-439
• /
• 2023

Background: The incidence and clinical importance of nonalcoholic fatty liver disease (NAFLD) has emerged. However, effective therapeutic strategies for NAFLD have yet to be found. Panax ginseng (P. ginseng) is a traditional herb in Eastern Asia with therapeutic effects in many chronic disorders. However, the precise effects of ginseng extract on NAFLD are currently unknown. In present study, the therapeutic effects of Rg3-enriched red ginseng extract (Rg3-RGE) on the progression of NAFLD were explored. Methods: Twelve-week-old C57BL/6 male mice were fed a chow or western diet supplemented with high sugar water solution with or without Rg3-RGE. Histopathology, immunohistochemistry, immunofluorescence, serum biochemistry, western blot analysis, and quantitative RT-PCR were used for in vivo experiment. Conditionally immortalized human glomerular endothelial cell (CiGEnC) and primary liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Results: Eight weeks of Rg3-RGE treatment significantly attenuated the inflammatory lesions of NAFLD. Furthermore, Rg3-RGE inhibited the inflammatory infiltrate in liver parenchyma and the expression of adhesive molecules to LSECs. Moreover, the Rg3-RGE exhibited similar patterns on the in vitro assays. Conclusion: The results demonstrate that Rg3-RGE treatment ameliorates NAFLD progression by inhibiting chemotaxis activities in LSECs.

• Preventive Nutrition and Food Science
• /
• v.15 no.2
• /
• pp.105-112
• /
• 2010

Thirty-four strains of Lactobacillus species were isolated from soil and eight of these isolates (M1-4 and P1-4) were capable of growing on red ginseng agar. The M1 and P2 strains were determined to be L. plantarum and other strains (M2, M3, M4, P1, P3 and P4) were determined to be L. brevis. Fermentation of red ginseng extract (RGE) with strains M1, M2, P2 and P4 resulted in a low level of total carbohydrate content (174.3, 170.0, 158.8 and 164.8 mg/mL, respectively). RGE fermented by M3 showed a higher level of uronic acid than the control. The polyphenol levels in RGE fermented by M1, P1 and P2 (964.9, 941.7 and $965.3\;{\mu}g/mL$, respectively) were higher than the control ($936.8\;{\mu}g/mL$). Total saponin contents in fermented RGE (except M1) were higher than the control. RGE fermented by M2 and M3 had the highest levels of total ginsenosides (31.7 and 32.7 mg/mL, respectively). The levels of the ginsenoside Rg3 increased from 2.6 mg/mL (control) to 3.0 mg/mL (M2) or 3.1 mg/mL (M3). RGE fermented by M2 and M3 also had the highest levels of Rg5+Rk1 (7.7 and 8.3 mg/mL, respectively). Metabolite contents of ginsenoside (sum of CK, Rh1, Rg5, Rk1, Rg3 and Rg2) of M2 (13.0 mg/mL) and M3 (13.9 mg/mL) were also at a high level among the fermented RGE. Protopanaxadiol and protopanaxatriol content of ginsenoside of M2 (10.9 and 5.4 mg/mL, respectively) and M3 (11.0 and 5.7 mg/mL, respectively) were at higher levels than other fermented RGE.

• Korean Journal of Food Science and Technology
• /
• v.41 no.1
• /
• pp.106-110
• /
• 2009

In order to reduce the bitter taste and improve the bioavailability of red ginseng extract(RGE), inclusion complexes (RGE-CD) of the extract with ${\alpha}-,\;{\beta}-,\;{\gamma}$-cyclodextrin were prepared and studied for their sensory quality and bioavailability compared to RGE. By complexation, the bitter taste-reducing efficacies of ${\alpha}$-CD and ${\beta}$-CD were much lower than that of ${\gamma}$-CD. In comparative sensory analysis for the bitter taste, RGE-${\gamma}$-CD10, prepared using 10%(w/w) of ${\gamma}$-CD, showed a score of 1.93(decreased by about 78%) compared to RGE as the control. In addition, in sensory analysis for flavor, RGE-${\gamma}$-CD10showed a score of 5.60. Upon increasing the amount of ${\gamma}$-CD to 15%(w/w) and 20%(w/w), respectively, the bitter taste of RGE-${\gamma}$-CD was removed and the flavor of RGE disappeared(scores of 2.67 and 1.67, respectively). Therefore RGE-${\gamma}$-CD10 was chosen as an optimum. The same dosages of RGE and RGE-${\gamma}$-CD10 were orally administered to SD(Sprague-Dawley) rats on a saponin basis, and the plasma concentrations of ginsenoside Rg1 and Rb1 were measured over time to estimate the average AUC(area under the plasma concentration versus time curve) of the ginsenosides. After the oral administration, there were no significant differences in the AUC values of the RGE and RGE-${\gamma}$-CD 10 groups for ginsenoside Rg1. However, AUC values for ginsenoside Rb1 were $25.8{\mu}g{\cdot}hr/mL$ in the RGE group and $81.5{\mu}g{\cdot}hr/mL$ in the RGE-${\gamma}$-CD 10 group, respectively. Therefore, the bioavailability of ginsenoside Rb1 in the RGE-${\gamma}$-CD 10 group was significantly higher by up to 315% compared with that in the RGE group(p = 0.0029). These results show that the bitter taste of RGE can be simultaneously removed by the complexation of RGE and ${\gamma}$-CD(RGE-${\gamma}$-CD) along with increased bioavailability.

• Journal of Ginseng Research
• /
• v.48 no.1
• /
• pp.31-39
• /
• 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 the Korean Applied Science and Technology
• /
• v.33 no.4
• /
• pp.751-761
• /
• 2016

In order to reduce the bitter taste of red ginseng extract(RGE), inclusion complexes(RGE-CD) of the extract with ${\alpha}$-, ${\beta}$-, ${\gamma}$-cyclodextine after acetic acid treatment at the steam process were prepared and studied for their taste by an electronic tongue. By complexation, the bitter taster- reducing efficacies of ${\alpha}$-CD and ${\beta}$-CD were much lower than that of ${\gamma}$-CD. This study suggested that by processing red ginseng with acetic acid it is possible to enhance the yield of both ginsenoside $Rg_3$ and nonpolar ginsenosides. Taste such as bitterness, sourness, saltiness, umami and sweetness of the red ginseng extract with different amounts of ${\alpha}$-CD, ${\beta}$-CD and ${\gamma}$-CD were checked using an electronic tongue. As a result, REG-${\gamma}$-CD10, prepared using 10%(w/w), showed significantly lower bitter taste than those of the other samples.

• Korean Journal of Plant Resources
• /
• v.34 no.5
• /
• pp.433-442
• /
• 2021

The fermented red ginseng by microorganism is known to increase pharmacological activity in vivo. To evaluate the bioavailablity of red ginseng fermented by probiotics, we conducted the pharmacokinetic study of ginsenoside Rb1, Rd and total ginsenosides (TG, ginsenosides Rb1 + Rd + Rg1 + F2 + Rg3 + compound K) in BALB/C mice. The AUC value of ginsenoside Rb1 in mice serum administered with 600mg/kg drugs showed 21.93 ± 14.68 ng·h/mL (RGw, water extract), 275.211 ± 110.04 ng·h/mL (RGe, 50% ethanol extract) and 404.91 ± 162.57 ng·h/mL (fRGe, fermented red ginseng extract). Analysis of ginsenoside Rd also showed a higher ACU value in fRGe than in RGw or RGe. And the AUC value of total ginsenosides in mice serum treated with 600 mg/kg were observed 42.12 ± 23.44 ng·h/mL (RGw), 321.44 ± 133.5 ng·h/mL (RGe) and 537.33 ± 229.01 ng·h/mL (fRGe), respectively. C_max value of ginsenoside Rb1 in mice administered with 600mg/kg were observed 3.67 ± 3.34 ng/mL (RGw), 23.27 ± 8.81 ng/mL (RGe) and 25.52 ± 7.29 ng/mL (fRGe). These results can be considered that the fermented red ginseng has more bioavailability than that of unfermented red ginseng. In quantitative analysis of the inflammation-related cytokines IL-1β and TNF, no significant difference was found between the fermented red ginseng (fRGe) and the red ginseng (RGe).