Abstract: Background: Ginseng, the root of Panax ginseng, has been extensively used in traditional oriental medicine and is a modern pharmaceutical reagent for the prevention of various human diseases, including cancer. Ginsenosides are the major active component of ginseng and exhibit immunomodulatory effects. However, the mechanism and function underlying such effects have not been fully elucidated, especially in human monocytes and dendritic cells (DCs).Methods: We investigated the immunomodulatory effect of ginsenosides from the root of Panax ginseng on CD14+ monocytes purified from human adult peripheral blood mononuclear cells (PBMC) and differentiation into DCs that affect CD4+ T cell activity.Results: The results showed that tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 increased in monocytes upon treatment with ginsenoside fractions through phosphorylation of ERK1/2 (pERK1/2) and JNK, but not p38 MAP kinase. Interestingly, TNF-α production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes upon treatment with ginsenoside fractions. Next, we confirmed that DCs derived from CD14+ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the co-stimulatory molecules, CD80 and CD86. In the presence of ginsenoside fractions, expression of these co-stimulatory molecules decreased in LPS-treated DCs compared with LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, Gin-DCs treated with LPS could not induce proliferation and IFN-γ production of CD4+ T cells at co-culture of Gin-DCs with CD4+ T cells.Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of DCs treated with LPS, resulting in the down-regulation of CD4+ T cells.

Abstract: Background: Korean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white or red ginseng, accordance to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in mouse model of acute asthma.Methods: To produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. White and red ginseng extracts (WG and RG) were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific IgE, IgG1, and IgG2a in serum were investigated. Cytokine productions by lymphocytes isolated from peribronchial lymph nodes and histopathological changes also examined.Results: In OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG treated OVA-sensitized mice than in OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG and RG treated OVA mice than in OVA controls.Conclusion: In this study, WG and RG showed anti-asthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

Abstract: Background: Many glaucoma patients have difficulty in using anti-glaucoma eye drops due to dry eye symptom. In this prospective, randomized, double-blind, placebo-controlled study, we evaluated the effect of Korean red ginseng on dry eye syndrome in glaucoma patients treated with anti-glaucoma eye drops.Methods: Forty nine participants were allocated to the Korean red ginseng (3 g/day; n = 24) or placebo (n = 25) groups for 8 weeks. Tear film stability, fluorescein corneal staining, conjunctival hyperemia, tear production, the grade of meibomian gland dysfunction, and dry eye questionnaire (Ocular Surface Disease Index) were evaluated at baseline and on completion of the treatment.Results: Nearly all subjects displayed dry eye symptoms and signs at baseline. After the 8-week intervention, Korean red ginseng supplementation significantly improved the tear film stability and total Ocular Surface Disease Index score, as compared to placebo (p < 0.01).Conclusion: Korean red ginseng supplementation may provide an additional treatment option for dry eye and glaucoma patients using anti-glaucoma eye drops.

Abstract: Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model.Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by AOM/DSS, was established and the effects of oral American ginseng were evaluated. The contents of representative ginseng saponins in the extract were determined.Results: Our data demonstrated that American ginseng significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated AOM/DSS-induced colon carcinogenesis by reducing colon tumor number and tumor load. The ginseng also effectively suppressed DSS induced pro-inflammatory cytokines activation using ELISA array, in which 12 pro-inflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time PCR data.Conclusion: Our results suggested that American ginseng, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.

Abstract: Background: Glucocorticoids (GCs) are commonly used in many chemotherapeutic protocols and play an important role in the normal regulation of bone remodeling. However, the prolonged use of GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. In this study, effects of Korean Red Ginseng (KRG) of a GC-treated murine osteoblastic MC3T3-E1 cells and a GC-induced osteoporosis mouse model were investigated.Methods: MC3T3-E1 cells were exposed to dexamethasone (Dex) with or without KRG and cell viability was measured by MTT assay. Real-time PCR was done to evaluate the apoptotic gene expression, osteogenic gene expression and ALP activity were also measured. Western blotting was performed to evaluate the MAPK proteins. Glucocorticoid-induced osteoporosis animal model was used for in vivo study.Results: and conclusion: MTT assay revealed that KRG prevents a loss of cell viability against dexamethasone (Dex) induced apoptosis in MC3T3E1 cells. Real-time polymerase chain reaction (PCR) data showed that groups treated with both Dex and KRG exhibited lower mRNA levels of caspase-3 and -9, whereas the mRNA levels of Bcl2, IAPs and XIAP increased. Moreover, groups treated with both Dex and KRG demonstrated increased mRNA levels of ALP, RUNX2, and BMPs as well as increased ALP activity in MC3T3-E1 cells compared to cells only treate with Dex. In addition, KRG increased AKT phosphorylation and decreased JNK phosphorylation. Also, Micro-CT analysis of the femurs showed that GC implantation caused trabecular bone loss. However, a significant reduction of bone loss was observed in the KRG-treated group. These results suggest that the molecular mechanism of KRG in the GC-induced apoptosis may lead to the development of therapeutic strategies to prevent and/or delay osteoporosis.

Abstract: Background: The present study is designed to prepare and find the optimum active preparation or fraction from Korea Red Ginseng inhibiting matrix metalloproteinase-13 (MMP-13) expression, since MMP-13 is a pivotal enzyme to degrade the collagen matrix of the joint cartilage.Methods: From total red ginseng ethanol extract, n-BuOH fraction (total ginsenoside-enriched fraction), ginsenoside diol-type-enriched fraction (GDF) and ginsenoside triol-type-enriched fraction (GTF) were prepared, and ginsenoside diol type-/F4-enriched fraction (GDF/F4) was obtained from Panax ginseng leave extract.Results and Conclusion: When their effects on MMP-13 expression were compared, the n-BuOH fraction, GDF, and GDF/F4 clearly inhibited MMP-13 expression against IL-1β-treated SW1353 cells (human chondrosarcoma), whereas the total extract and GTF did not. In particular, GDF/F4, the most prominent inhibitor, blocked the activation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun-activated protein kinase (JNK), and signal transducer and activator of transcription-1/2 (STAT-1/2) among the signal transcription pathways involved. Further, GDF/F4 also inhibited the glycosaminoglycan release from IL-1α-treated rabbit cartilage culture (30.6% inhibition at 30 μg/ml). Therefore, it is suggested that some preparation from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as a new therapeutic agent.

Abstract: Background: Ginseng has been shown to exert anti-stress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. In this study, we investigated how Korean Red inseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of PI3K/AKT and estrogen receptor β signaling.Methods: Human neuroblastoma SK-N-SH cells were pre-treated with KRG and subsequently exposed to H2O2. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined by western blot analysis. The roles of ER-β, PI3K, and p-AKT signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists.Results: Pre-treating SK-N-SH cells with KRG decreased expression of the pro-apoptotic proteins p-p53 and caspase-3, but increased expression of the anti-apoptotic protein BCL2. KRG pre-treatment was also associated with increased ERβ, PI3K, and p-AKT expression. Conversely, ER-β inhibition with siRNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-AKT expression. Moreover, inhibition of PI3K/AKT signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression.Conclusion: Collectively, our data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/AKT signaling via up-regulation of ER-β expression.

Abstract: Background: Identifying suitable sites for growing mountain-cultivated ginseng are an area of concern for ginseng producers. This study was conducted to evaluate the soil properties of cultivation sites for mountain-cultivated ginseng in Hamyang-gun, which is known to be one of the most famous areas for mountain-cultivated ginseng in Korea.Methods: The sampling plots from 30 sites were randomly selected on or near the center of the ginseng growing sites in July and August 2009. Soil samples for the soil property analysis were collected through the top 20 cm at five randomly selected points.Results: Mountain-cultivated ginseng was grown in soils that varied greatly in soil properties on coniferous, mixed, and deciduous broadleaved stand sites of elevations between > 200 m and < 1,000 m. The soil bulk density was higher in Pinus densiflora than in Larix leptolepis stand sites and higher in the 700 m sites. Soil pH was unaffected by the type of stand sites (pH 4.35–4.55), while the high-elevation sites of > 700 m were strongly acidified, with pH 4.19. The organic carbon and total nitrogen content were lower in the P. densiflora stand sites than in the deciduous broadleaved stand sites. Available phosphorus was low in all of the stand sites. The exchangeable cation was generally higher in the mixed and low-elevation sites than in the P. densiflora and high-elevation sites, respectively.Conclusion: These results indicate that mountain-cultivated ginseng in Korea is able to grow in very acidic, nutrient-depleted forest soils.

Abstract: Background: Ginsenoside Rp1 (G-Rp1) is a novel ginsenoside derived from ginsenoside Rk1. This compound was reported to have anti-cancer, anti-platelet, and anti-inflammatory activities. In this study, we examined the molecular target of G-Rp1’s anti-proliferative and pro-apoptotic activities.Methods: To examine the effects of G-Rp1, cell proliferation assays, propidium iodine staining, proteomic analysis by two-dimensional gel electrophoresis, immunoblotting analysis, and a knockdown strategy were employed.Results: G-Rp1 dose-dependently suppressed the proliferation of colorectal cancer LoVo cells and also increased the apoptosis of these cells. Interestingly, G-Rp1 remarkably up-regulated the protein level of apolipoprotein (Apo)-A1 in LoVo, SNU-407, DLD-1, SNU-638, AGS, KPL-4, and SK-BR-3 cells. The knockdown of Apo-A1 by its siRNA increased the levels of cleaved poly(ADP-ribose) polymerase (c-PARP) and p53 and diminished the proliferation of LoVo cells.Conclusion: These results suggest that G-Rp1 may act as an anti-cancer agent by strongly inhibiting cell proliferation and enhancing cell apoptosis through the up-regulation of Apo-A1.

Abstract: Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anti-cancer, anti-atherosclerosis, anti-diabetic, and anti-inflammatory activities. Since only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activities, in this study we aimed to investigate the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2)], and downregulated the mRNA expression of their corresponding genes [inducible NO synthase (iNOS), TNF-α, and cyclooxygenase (COX)-2], without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated EtOH/HCl-induced gastritis via suppression of phospho-JNK2 levels. Therefore, these results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TBK1-linked pathways and their corresponding transcription factors (ATF2/IRF3).