• Journal of Ginseng Research
• /
• v.31 no.2
• /
• pp.69-73
• /
• 2007

Since chemical structures of ginsenoside as active ingredient of Panax ginseng are known, accumulating evidence have shown that ginsenoside is one of bio-active ligands through the diverse physiological and pharmacological evaluations. Chemical structures of ginsenoside could be divided into three parts depending on diol or triol ginsenoside: Steroid- or cholesterol-like backbone structure, carbohydrate portions, which are attached at the carbon-3, -6 or -20, and aliphatic side chain coupled to the backbone structure at the carbon-20. Ginsenosides also exist as stereoisomer at the carbon-20. Bioactive ligands usually exhibit the their structure-function relationships. In ginsenosides, there is little known about the relationship of chemical structure and biological activity. Recent reports have shown that ginsenoside $Rg_3$, one of active ginsenosides, exhibits its differential physiological or pharmacological actions depending on its chemical structure. This review will show how ginsenoside $Rg_3$, as a model compound, is functionally coupled to voltage-gated ion channel or ligand-gated ion channel regulations in related with its chemical structure.

• Journal of Ginseng Research
• /
• v.45 no.5
• /
• pp.610-616
• /
• 2021

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

• Korean Journal of Biological Psychiatry
• /
• v.12 no.1
• /
• pp.42-61
• /
• 2005

Objectives:The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. Methods:SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1($80{\mu}M$, $40{\mu}M$, $20{\mu}M$). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. Results:Treatment of SH-SY5Y cells with $80{\mu}M$ ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(${\geq}$3 fold) in Rg1 treated cells and 40 genes were up-regulated(${\geq}$2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1-group. Conclusion:Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

• Journal of Ginseng Research
• /
• v.40 no.3
• /
• pp.237-244
• /
• 2016

Background: Ginsenoside Rg3 and arginine-fructose (Arg-Fru) are known as the hypotensive compounds of Panax ginseng; however, their efficacy on antihypertension has not been reported yet to our best knowledge. Thus, hypotensive components-enriched fraction of red ginseng (HCEF-RG) was prepared from fine root concentrate (FR) and their antihypertensive effects were investigated in spontaneously hypertensive rats (SHR). Methods: Male SHRs were divided into six groups: control (Wistar Kyoto, SHR); FR 500; FR 1,000; HCEF-RG 500; and HCEF-RG 1,000; samples (mg/kg body weight) were orally administered every day for 8 wk. Blood pressure was monitored at 1 wk, 2 wk, 3 wk, 4 wk, 6 wk, and 8 wk by tail cuff method. At 8 wk after samples administration, mice were killed for the measurement of renin activity (RA), angiotensin-I converting enzyme inhibition, angiotensin II, and nitric oxide (NO) levels in plasma. Results: HCEF-RG with four-fold more Rg3 and 24-fold more Arg-Fru contents was successfully prepared from reacted mixtures of FR and persimmon vinegar (12 times against FR, v/v) at $80^{\circ}C$ for 18 h. Both FR 1,000 and HCEF-RG 1,000 showed lowered systolic blood pressure than SHR control group and HCEF-RG 1,000 group exhibited a significant decrease in diastolic blood pressure. RA was significantly lowered in all treated groups, while angiotensin II did not affect by FR and HCEF-RG treatment. However, angiotensin-I converting enzyme inhibition and NO in FR 1,000 and HCEF-RG 1,000 were significantly increased compared with SHR control group. Conclusion: HCEF-RG is more effective and useful for alleviating hypertension than FR, implying the health benefit of Rg3 and Arg-Fru.

• IMMUNE NETWORK
• /
• v.16 no.1
• /
• pp.75-84
• /
• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• Journal of Ginseng Research
• /
• v.45 no.3
• /
• pp.420-432
• /
• 2021

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.4
• /
• pp.1021-1027
• /
• 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.

• The Korean Journal of Food And Nutrition
• /
• v.23 no.3
• /
• pp.405-410
• /
• 2010

The effect of microwave treatment on Korean ginseng was studied by measuring the changes in moisture, crude lipid, crude ash, crude protein, total dietary fiber and saponin contents, as well as changes in density, color and microstructure. Korean ginseng was treated with 100 or 200 watts of microwaves for 1 or 3 hrs, respectively, followed by drying using an oven at $60^{\circ}C$ for 96 hrs. The moisture contents decreased to 13.12~10.77% from an initial 76.26%. The amounts of lipid and ash were reduced in proportion to the time of microwave treatment and level of microwave power. The amount of protein in ginseng after microwave treatment did not significantly change. The amount of total dietary fiber increased after microwave treatment and the color of dried ginseng became dark. The amounts of ginsenoside-$Rb_1$, $Rb_2+Rb_3$, Rc, Rd, Re, Rf, $Rg_1$, $Rg_2+Rh_1$ and $Rg_3$ were reduced after treatment with 100 watts of microwave radiation for 1 and 3. The amounts of ginsenoside-$Rb_1$, Rd, Re, Rf, $Rg_1$, $Rg_2+Rh_1$ and $Rg_3$ after treatment with 200 watts of microwave radiation for 1 and 3 hr also reduced. On the other hand, the amounts of ginsenoside-$Rb_2+Rb_3$ and Rc after treatment of ginseng with 200 watts of microwave radiation for 1 and 3 hrs were increased.

• Molecular & Cellular Toxicology
• /
• v.5 no.2
• /
• pp.126-132
• /
• 2009

The usage and types of chemicals are advancing, specializing, large-scaled increasing, and new chemical exposed workers are concerning to occupational disease. The generation of reactive oxygen in the body from carcinogen, mutation and DNA damage in cancer is protected by natural antioxidants (phytochemicals) with antimutagenic effect. There were many reports of ginsenoside Rb$_1$, Rg$_1$ grievances of the genetic mutation to suppress the effect confirm the genetic toxicity test with chromosomal aberration test and the Comet (SCGE) assay confirmed the suppression effect occurring chromosomal DNA damage. We had wanted to evaluate the compatibility and sensitivity between the chromosomal aberration (CA) test and the Comet assay. We used the CA test and Comet assay to evaluate the anti-genotoxicity of ginsenoside Rb$_1$ and Rg$_1$, in CHO-K1 (Chinese hamster ovary fibroblast) cell in vitro, composed negative control (solvent), positive control (benzo[a]pyrene), test group (carcinogen+variety concentration of ginsenoside) group. The positive control was benzo[a]pyrene (50 $\mu$M), well-known carcinogen, and the negative control was the 1 % DMSO solvent. The test group was a variety concentration of ginsenoside Rb$_1$, Rg$_1$ with 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10%. In chromo-somal aberration test, we measured the number of cells with abnormally structured chromosome. In Comet assay, the Olive tail moment (OTM) and Tail length (TL) values were measured. The ratio of cell proliferation was increased 8.3% in 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10% Rb$_1$ treated groups, and increased 10.4% in 10$^{-10}$%, 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1% Rg$_1$ treated groups. In the CA test, the number of chromosomal aberration was decreased all the Rb$_1$ and Rg$_1$ treated groups. In the Comet assay, the OTM values were decreased in all the Rb$_1$ and Rg$_1$ treated groups. To evaluate the compatibility between CA and Comet assay, we compared the reducing ratio of chromosomal abnormalities with its OTM values, it was identified the antimutagenicity of ginsenoside, but it was more sensitive the CA test than the Comet assay. Ginsenoside Rb$_1$ and Rg$_1$ significantly decrease the number of cells with chromosomal aberration, and decrease the extent of DNA migration. Therefore, ginsenoside Rb$_1$, Rg$_1$ are thought as an antioxidant phytochemicals to protect mutagenicity. The in vitro Comet assay seems to be less sensitive than the in vitro chromosomal aberration test.

• Archives of Pharmacal Research
• /
• v.28 no.10
• /
• pp.1164-1169
• /
• 2005

Brain microglia are phagocytic cells that are the major inflammatory response cells of the central nervous system and widely held to play important pathophysiologic roles in Alzheimer's disease (AD) in both potentially neurotoxic responses and potentially beneficial phagocytic responses. In the study, we examined whether ginsonoside Rg3, a by-product of red ginseng, enhances the microglial phagocytosis of $A{\beta}$. We found that Rg3 promoted $A{\beta}$ uptake, internalization, and digestion. Increased maximal $A{\beta}$ uptake was observed at 4 and 8 h after Rg3 pretreatment (25 ${\mu}g/mL$), and the internalized $A{\beta}$ was almost completely digested from cells within 36 h when pretreated with Rg3 comparing with single non-Rg3-treated groups. The expression of MSRA (type A MSR) was also up-regulated by Rg3 treatment in a dose- and time-dependent manner which was coincidently identified in western blots for MSRA proteins in cytosol. These results indicate that microglial phagocytosis of $A{\beta}$ may be enhanced by Rg3 and the effect of Rg3 on promoting clearance of $A{\beta}$ may be related to the MSRA-associated action of Rg3. Thus, stimulation of the MSRA might contribute to the therapeutic potentials of Rg3 in microglial phagocytosis and digestion in the treatment of AD.