• Journal of Microbiology and Biotechnology
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• v.16 no.11
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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.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.75-85
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• 2021

Background: Invasive infections due to foodborne pathogens, including Salmonella enterica serovar Typhimurium, are prevalent and life-threatening. This study aimed to evaluate the effects of ginsenoside Rg3 (Rg3) on the adhesion, invasion, and intracellular survival of S. Typhimurium. Methods: The impacts of Rg3 on bacterial growth and host cell viability were determined using the time kill and the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays, respectively. Gentamicin assay and confocal microscopic examination were undertaken to determine the effects of Rg3 on the adhesive and invasive abilities of S. Typhimurium to Caco-2 and RAW 264.7 cells. Quantitative reverse transcription polymerase chain reaction was performed to assess the expression of genes correlated with the adhesion, invasion, and virulence of S. Typhimurium. Results: Subinhibitory concentrations of Rg3 significantly reduced (p < 0.05) the adhesion, invasion, and intracellular survival of S. Typhimurium. Rg3 considerably reduced (p < 0.05) the bacterial motility as well as the release of nitrite from infected macrophages in a concentration-dependent manner. The expression of genes related to the adhesion, invasion, quorum sensing, and virulence of S. Typhimurium including cheY, hilA, OmpD, PrgK, rsgE, SdiA, and SipB was significantly reduced after Rg3 treatment. Besides, the compound downregulated rac-1 and Cdc-42 that are essential for actin remodeling and membrane ruffling, thereby facilitating Salmonella entry into host cells. This report is the first to describe the effects of Rg3 on "trigger" entry mechanism and intracellular survival S. Typhimurium. Conclusion: Rg3 could be considered as a supplement agent to prevent S. Typhimurium infection.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.662-669
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• 2020

Objective: This study was conducted to evaluate the effect of red glasswort (RG) (Salicornia herbacea L.) curing on the physicochemical, textural and sensory properties of cooked pork loin ham (M. longissimus thoracis et lumborum). Methods: All treatments were cured with different salt and RG powder levels. RG0 treatment was prepared with only 4% NaCl (w/w) as a control, and RG25, 3% NaCl:1% RG (w/w); RG50, 2% NaCl:2% RG (w/w); RG75, 1% NaCl:3% RG (w/w); RG100, 0% NaCl:4% RG (w/w) treatments were prepared sequentially. All samples were individually vacuum packaged in polyethylene bags and stored for 7 d at 3℃±1℃. Results: The results showed that as the rate of RG substitution increased, pH value, redness, myofibrillar protein solubility, and myofibrillar fragmentation index increased (p<0.05), but salt concentration and shear force decreased (p<0.05). However, there were no significant differences in cooking loss and moisture content. In terms of sensory evaluation, RG100 exhibited higher scores in tenderness and juiciness than RG0 (p<0.05). Conclusion: The partial substitution of NaCl by RG could improve the physicochemical properties, textural and sensory characteristics of cooked pork loin. Therefore, it is suggested that RG as a natural salt replacer could be an effective ingredient for developing low-sodium cured hams.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.743-754
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• 2023

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10^-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.304-313
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• 2015

Background: Ginsenoside Rg3 is a promising anticancer agent. It is usually produced by heat treatment of ginseng, in which ginsenoside Rb1 is the major ginsenoside. A kinetic study was conducted to optimize ginsenoside Rg3 production by the heat treatment of ginsenoside Rb1. Methods: Ginsenoside Rb1 was heated using an isothermal machine at $80^{\circ}C$ and $100^{\circ}C$ and analyzed using HPLC. The kinetic parameters were calculated from the experimental results. The activation energy was estimated and used to simulate the process. The optimized parameters of ginsenoside Rg3 production are suggested based on the simulation. Results: The rate constants were $0.013h^{-1}$ and $0.073h^{-1}$ for the degradation of ginsenosides Rb1 and Rg3 at $80^{\circ}C$, respectively. The corresponding rate constants at $100^{\circ}C$ were $0.045h^{-1}$ and $0.155h^{-1}$. The estimated activation energies of degradation of ginsenosides Rb1 and Rg3 were 69.2 kJ/mol and 40.9 kJ/mol, respectively. The rate constants at different temperatures were evaluated using the estimated activation energies, and the kinetic profiles of ginsenosides Rb1 and Rg3 at each temperature were simulated based on the proposed kinetic model of consecutive reaction. The optimum strategies for producing ginsenoside Rg3 from ginsenoside Rb1 are suggested based on the simulation. With increased temperature, a high concentration of ginsenoside Rg3 is formed rapidly. However, the concentration decreases quickly after the reaching the maximal concentration value. Conclusion: The optimum temperature for producing ginsenoside Rg3 should be the highest temperature technically feasible below $180^{\circ}C$, in consideration of the cooling time. The optimum reaction time for heat treatment is 30 min.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.300-307
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• 2020

Background: Emerging evidence suggests that endothelial-to-mesenchymal transition (EndMT) in endothelial dysfunction due to persistent inflammation is a key component and emerging concept in the pathogenesis of vascular diseases. Ginsenoside Rg3 (Rg3), an active compound from red ginseng, has been known to be important for vascular homeostasis. However, the effect of Rg3 on inflammation-induced EndMT has never been reported. Here, we hypothesize that Rg3 might reverse the inflammation-induced EndMT and serve as a novel therapeutic strategy for vascular diseases. Methods: EndMT was examined under an inflammatory condition mediated by the NOD1 agonist, γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), treatment in human umbilical vein endothelial cells. The expression of EndMT markers was determined by Western blot analysis, real-time polymerase chain reaction, and immunocytochemistry. The underlying mechanisms of Rg3-mediated EndMT regulation were investigated by modulating the microRNA expression. Results: The NOD1 agonist, iE-DAP, led to a fibroblast-like morphology change with a decrease in the expression of endothelial markers and an increase in the expression of the mesenchymal marker, namely EndMT. On the other hand, Rg3 markedly attenuated the iE-DAP-induced EndMT and preserved the endothelial phenotype. Mechanically, miR-139 was downregulated in cells with iE-DAP-induced EndMT and partly reversed in response to Rg3 via the regulation of NF-κB signaling, suggesting that the Rg3-miR-139-5p-NF-κB axis is a key mediator in iE-DAP-induced EndMT. Conclusion: These results suggest, for the first time, that Rg3 can be used to inhibit inflammation-induced EndMT and may be a novel therapeutic option against EndMT-associated vascular diseases.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.771-779
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• 2022

Background: As a kind of common complication of the surgery of perianal diseases, perianal ulcer is known as a nuisance. This study aims to develop a kind of 20(S)-ginsenoside Rg3 (Rg3)-loaded hydrogel to treat perianal ulcers in a rat model. Methods: The copolymers PLGA₁₆₀₀-PEG₁₀₀₀-PLGA₁₆₀₀ were synthesized by ring-opening polymerization process and Rg3-loaded hydrogel was then developed. The perianal ulcer rat model was established to analyze the treatment efficacy of Rg3-loaded hydrogel for ulceration healing for 15 days. The animals were divided into control group, hydrogel group, free Rg3 group, Rg3-loaded hydrogel group, and Lidocaine Gel® group. The residual wound area rate was calculated and the blood concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were recorded. Hematoxylin and eosin (H&E) staining, Masson's Trichrome (MT) staining, and tumor necrosis factor α (TNF-α), Ki-67, CD31, ERK1/2, and NF-κB immunohistochemical staining were performed. Results: The biodegradable and biocompatible hydrogel carries a homogenous interactive porous structure with 10 ㎛ pore size and five weeks in vivo degradation time. The loaded Rg3 can be released sustainably. The in vitro cytotoxicity study showed that the hydrogel had no effect on survival rate of murine skin fibroblasts L929. The Rg3-loaded hydrogel can facilitate perianal ulcer healing by inhibiting local and systematic inflammatory responses, swelling the proliferation of nuclear cells, collagen deposition, and vascularization, and activating ERK signal pathway. Conclusion: The Rg3-loaded hydrogel shows the best treatment efficacy of perianal ulcer and may be a candidate for perianal ulcer treatment.

• Journal of Ginseng Research
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• v.45 no.6
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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

• Journal of Ginseng Research
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• v.46 no.3
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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.

• The Journal of Internal Korean Medicine
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• v.39 no.5
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• pp.929-938
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• 2018

Objectives: To report the clinical application and effects of Rg3 ginseng (ginseng radix) pharmacopuncture in patients with dry eye syndrome. Methods: Six patients who suffered from dry eye syndrome were treated with Rg3 ginseng pharmacopuncture for 4 weeks. The Ocular Surface Disease Index (OSDI) was used twice, at the start and end of treatment, to analyze the results. Results: After treatment with Rg3 ginseng pharmacopuncture, OSDI scores were improved in all six patients. Conclusion: Rg3 ginseng pharmacopuncture is an effective treatment for patients with the symptoms of dry eye syndrome.