• Journal of Ginseng Research
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• v.41 no.4
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• pp.548-555
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• 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
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• v.45 no.2
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• pp.228-235
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• 2021

Backgroud: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK-OCMC Nps), which enhance the aqueous solubility and stability of GK. Methods: The GK-OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK-OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK-OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK-OCMC Nps. Results: The GK-OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK-OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK-OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK-OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. Conclusion: GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.666-674
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• 2022

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.202-210
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• 1989

The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

• Korean Journal of Microbiology
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• v.49 no.4
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• pp.369-376
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• 2013

We isolated the ${\beta}$-glucosidase producing bacteria (BGB) in ginseng root system (rhizosphere soil, rhizoplane, inside of root). Phylogenetic analysis of the 28 BGB based on the 16S rRNA gene sequences, BGB from rhizosphere soil belong to genus Stenotrophomonas (3 strains), Bacillus (1 strain), and Pseudoxanthomonas (1 strain). BGB isolates from rhizoplane were Stenotrophomonas (16 strains), Streptomyces (1 strain) and Microbacterium (1 strain). BGB from inside of root were categorized into Stenotrophomonas (3 strains) and Lysobacter (2 strains). Especially, Stenotrophomonas comprised the largest portion (approximately 90%) of total isolates and Stenotrophomonas was a dominant group of the ${\beta}$-glucosidase producing bacteria. We selected strain 4KR4, which had high ${\beta}$-glucosidase activity (108.17 unit), could transform ginsenoside Rb1 into Rd, Rg3, and Rh2 ginsenosides. In determining its relationship on the basis of 16S rRNA sequence, 4KR4 strain was most closely related to Stenotrophomonas rhizophila e-$p10^T$ (AJ293463) (99.62%). Therefore, on the basis of these polyphasic taxonomic evidence, the ginsenoside Rb1 converting bacteria 4KR4 was identified as Stenotrophomonas sp. 4KR4 (=KACC 17635).

• Journal of Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.790-798
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• 2020

Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.

• Korean Journal of Medicinal Crop Science
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• v.28 no.2
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• pp.152-166
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• 2020

Background: Ginsenosides, which have various physiological activities, are known to be abundant in the leaves and roots of ginseng. Ginseng sprouts can be used as a fresh vegetable and roots, stems, and leaves of ginseng can be consumed. This study aimed to investigate the effect of carbon dioxide treatment and the modified atmosphere (MA) packaging method in suppressing quality deterioration during the distribution of ginseng sprouts. Methods and Results: Ginseng sprouts were packed using Styrofoam, barrier film + non gas treatment, barrier film + gas treatment, 15 ㎛ polyamide (PA) double film + non gas treatment, 15 ㎛ PA double film + gas treatment, 25 ㎛ PA film + non gas treatment, or 25 ㎛ PA film + gas treatment. Quality parameters including gas composition, relative humidity, chlorophyll SPAD (Soil Plant Analysis Development) value, firmness, and rate of quality loss in ginseng sprouts were monitored at the following temperatures: 20℃, and 10℃. Ginseng sprouts packaged with 25 ㎛ PA film showed loss in quality because of wilting owing to low relative humidity within the film. Chlorophyll and firmness did not differ between film and gas treatments. The time point at which the combined loss from softening and decay owing to fungal, and bacterial infection and wilt reached 20% was considered the limit of distribution. At 20℃, the packaging not included in the 20% distribution loss rate limit or up to 7 days was 15 ㎛ PA double film + gas treatment. At 10℃, the packaging not included in the 20% distribution loss rate limit for up to 18 days were barrier film + gas treatment and 15 ㎛ PA double film + gas treatment. Conclusions: The film packaging suitable for the distribution of ginseng sprouts was found to be the barrier film and PA film with low gas permeability and maintaining hygroscopicity at 95% relative humidity. To prevent the loss in quality of ginseng sprouts, gas treatment (8% of O₂ and 18% of CO₂) in the film was found to be more suitable than no gas treatment for inhibition of decay.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.221-225
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• 2004

The root of Panax ginseng C. A. Meyer has been used as a traditional anti-aging and anti-wrinkle agent in the Orient. However, it is still unknown which component of ginseng is effective at suppressing wrinkle formation. Recently at least twenty ginsenosides regarded as the main active ingredients of ginseng have been isolated. Among them, we examined the effect of ginsenoside Rg3 on dermal ECM metabolism to elucidate the mechanism of anti-wrinkle by ginseng. In our study, to investigate the anti-wrinkle effect of the ginsenoside Rg3, ECM component and growth factor in dennis were evaluated by ELISA assay. Ginsenoside Rg3 was found to stimulate type I procollagen and fibronectin (FN) biosynthesis in a dose-dependent manner in normal human fibroblast culture (p < 0.05, n =3), and dose-dependently enhance TGF- ${\beta}$1 level (p < 0.05, n =3). In RT-PCR analysis mRNA level of c-Jun, a member of AP-1 transcription factor, was reduced by ginsenoside Rg3 in normal human fibroblast culture. These results indicate that ginsenoside Rg3 stimulates type I collagen and FN synthesis through the changes of TGF - ${\beta}$1 and AP-1 expression in fibroblasts.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.247-256
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• 2017

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.