Korean Red Ginseng Saponin Research Articles

Korean Red Ginseng Saponins Play an Anti-Inflammatory Role by Targeting Caspase-11 Non-Canonical Inflammasome in Macrophages.

We previously reported that Korean red ginseng (KRG) exerts an anti-inflammatory role through inhibiting caspase-11 non-canonical inflammasome in macrophages; however, the components responsible for the anti-inflammatory role remained unclear. This study explored the anti-inflammatory activity of the KRG saponin fraction (KRGSF) in caspase-11 non-canonical inflammasome-activated macrophages. KRGSF inhibited pyroptosis, pro-inflammatory cytokine secretion, and inflammatory mediator production in caspase-11 non-canonical inflammasome-activated J774A.1 cells. A mechanism study revealed that KRGSF-induced anti-inflammatory action was mediated via suppressing the proteolytic activation of caspase-11 and gasdermin D (GSDMD) in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Moreover, KRGSF increased the survival of lethal septic mice. Taken together, these results reveal KRGSF-mediated anti-inflammatory action with a novel mechanism, by inhibiting caspase-11 non-canonical inflammasome in macrophages.

Korean Red Ginseng saponin fraction exerts anti-inflammatory effects by targeting the NF-κB and AP-1 pathways

BackgroundAlthough ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. MethodsThe ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E2 (PGE2) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. ResultsHPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. ConclusionRGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

Korean Red Ginseng Suppresses the Expression of Oxidative Stress Response and NLRP3 Inflammasome Genes in Aged C57BL/6 Mouse Ovaries.

Female infertility and subfertility have been increasing in prevalence worldwide. One contributing factor is ovarian function, which is highly age-dependent. Korean red ginseng is widely used as an herbal medicine and has many beneficial properties. We aimed to determine the effect of the Korean red ginseng saponin fraction (KRGSF) on ovarian function in female C57BL/6 mice. Ovaries were isolated from 6- and 12-month-old female mice and treated with KRGSF, and then RNA was extracted and microarray analysis was performed. The expression of key genes was subsequently verified using quantitative RT-PCR. Aging markedly increased the expression of genes encoding oxidative stress factors and NLRP3 inflammasome components, but the expression of these genes was significantly reduced by KRGSF treatment. Thus, the reduction in ovarian health with age is associated with greater oxidative stress response and inflammation, but KRGSF treatment may limit these age-related changes.

A Combination of Korean Red Ginseng Extract and Glycyrrhiza glabra L. Extract Enhances Their Individual Anti-Obesity Properties in 3T3-L1 Adipocytes and C57BL/6J Obese Mice.

Anti-obesity activities of Korean red ginseng saponin fraction (RGS) and/or Glycyrrhiza glabra L. extract (GG) were investigated in 3T3-L1 adipocytes and high-fat diet-induced C57BL/6J obese mice. RGS and GG extracts were mixed at a mass ratio of 3:1 (SG31), 1:1 (SG11), or 1:3 (SG13). SG31 showed the highest anti-obesity activity among the three different mass ratios of RGS and GG extracts. SG31 showed higher inhibition efficiency on triglyceride (TG) accumulation than either single extract in 3T3-L1 adipocytes and without any cytotoxicity. It also decreases the expression of adipogenic and lipogenic genes such as C/EBPα and SREBP-1c (sterol regulatory element-binding protein 1c). In the obese induced mouse model, SG31 significantly reduced white adipose tissue weight and body weight, attenuated dyslipidemia, and decreased serum TG levels. In some indices, the activity of SG31 was even higher compared with Garcinia Cambogia water extract, a positive control. The possible mechanism by which SG31 causes the above results was by activating the AMP-activated protein kinase (AMPK) pathway and stimulating the secretion of adiponectin in adipose tissue to regulate energy metabolism balance, inhibit TG formation, and promote β-oxidation of fatty acids. Therefore, SG31 may have efficacy as an anti-obesity functional food or raw material if the results can be confirmed in human studies.

Specific activity of Korean red ginseng saponin and non-saponin fractions in ageing-induced rat testicular dysfunction

Korean red ginseng (Panax ginseng Meyer, KRG) is a functional food with multiple therapeutic benefits. This study evaluated the fraction-specific effects of KRG in ageing-induced testicular dysfunction rat model. KRG water extract (KRG-WE; 200mg/kg), crude saponin (CS; 20mg/kg), and non-saponin (NS; 180mg/kg) fractions were administered orally for six months. Body weight increments, blood chemistry, histological parameters, sperm kinematics, expression levels of key spermatogenesis molecules and anti-oxidative enzyme status were determined in vehicle treated young and aged control groups. KRG-WE, CS and NS fractions significantly (p<0.05) ameliorated the ageing-induced testicular damage in all the parameters tested. Although total KRG-WE outperformed the tested activities, both CS and NS fractions also exhibited distinct effects in improving ageing-induced testicular dysfunction in rats. The potential non-saponin active constituents in combination with CS fraction might be responsible for such synergistic effect. More detailed study on the KRG-NS fraction active constituents is quite essential.

Korean Red Ginseng saponin fraction modulates radiation effects on lipopolysaccharide-stimulated nitric oxide production in RAW264.7 macrophage cells

BackgroundIn previous work, we reported that Korean Red Ginseng saponin fraction (RGSF) showed anti-inflammatory activities in vitro and in vivo. MethodsThe present study investigated the radioprotective properties of RGSF by examining its effects on ionizing radiation (IR)-enhanced and lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophage cells. ResultsRGSF induced strong downregulation of IR-enhanced and LPS-induced proinflammatory responses such as nitric oxide (NO) production (Inhibitory Concentration 50 (IC50) = 5.1 ± 0.8 μM) and interleukin-1β levels. RGSF was found to exert its radioprotective effects by inhibition of a signaling cascade that activated checkpoint kinase 2–nuclear factor-κB. In addition, RGSF strongly inhibited IR-enhanced LPS-induced expression of hemoxyganase-1, implying that the latter may be a potential target of RGSF. ConclusionTaken together, our data suggest that RGSF can be considered and developed for use as an effective radioprotective agent with minimal adverse effects.

Korean red ginseng saponin fraction rich in ginsenoside-Rb1, Rc and Rb2 attenuates the severity of mouse collagen-induced arthritis.

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3+/CD69+, CD4+/CD25+, CD8+ T-cell, CD19+, B220/CD23+ B-cell, MHCII+/CD11c+, and Gr-1+/CD11b+ cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1β, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.

Korean Red Ginseng Saponin Fraction Downregulates Proinflammatory Mediators in LPS Stimulated RAW264.7 Cells and Protects Mice against Endotoxic Shock

Korean red ginseng has shown therapeutic effects for a number of disease conditions. However, little is known about the antiinflammatory effect of Korean red ginseng saponin fraction (RGSF) in vitro and in vivo. Therefore, in this study, we showed that RGSF containing 20(S)-protopanaxadiol type saponins inhibited nitric oxide production and attenuated the release of tumor necrotic factor (TNF)-α, interleukin (IL)-6, granulocyte monocyte colony stimulating factor (GMCSF), and macrophage chemo-attractant protein-1 in lipopolysaccharide (LPS) stimulated murine macrophage RAW264.7 cells. Moreover, RGSF down-regulated the mRNA expressions of inducible nitric oxide synthase, cyclooxyginase-2, IL-1β, TNF-α, GMCSF, and IL-6. Furthermore, RGSF reduced the level of TNF-α in the serum and protected mice against LPS mediated endotoxic shock. In conclusion, these results indicated that ginsenosides from RGSF and their metabolites could be potential sources of therapeutic agents against inflammation.

Effects of topically applied Korean red ginseng and its genuine constituents on atopic dermatitis-like skin lesions in NC/Nga mice

Ginseng (the root of Panax ginseng C.A. Meyer, family Araliaceae) possesses various biological activities, including anti-inflammatory and anti-tumor actions. However, their topical effect on atopic dermatitis (AD) has not been studied yet. The aim of this study was to examine the therapeutic effects of topical Korean red ginseng saponin fraction (KRGS) and its genuine constituents on AD-like skin lesions in an AD mouse model. The therapeutic effect of topical KRGS and ginsenosides in 2-chloro-1,3,5-trinitrobenzene (TNCB)-treated NC/Nga mice was assessed by measuring the skin severity scores, ear thickness, histological changes of lesional skin including mast cell count, tissue tumor necrosis factor (TNF)-α, interleukin (IL)-4, and interferon (IFN)-γ mRNA expression, and total serum IgE. Topical administration of 0.1% KRGS, 0.1% Rh2 and 0.1% Rh2+0.1% Rg3 significantly reduced the clinical skin severity scores, ear thickness and mast cell infiltration in the TNCB-induced AD-like skin lesions. Topical application of KRGS and its constituents significantly reduced TNCB-induced increase in ear TNF-α and IL-4 mRNA expression, but not IFN-γ mRNA expression. There was little change of serum total IgE level by topical KRGS and its constituents. In this study, topical KRGS and ginsenosides Rh2 and Rg3 were found to exert an anti-inflammatory effect in vivo and proved to be beneficial in an animal model of AD. Our results suggest that KRGS and its ginsenosides Rh2 and Rg3 have potential as a topical agent for the treatment of AD.

The Combination Effect of Korean Red Ginseng Saponins with Kanamycin and Cefotaxime against Methicillin-Resistant Staphylococcus aureus

Korean red ginseng saponins (ginsenosides) have been reported as having various biological properties, but the combinational effects with commercial antibiotics and the mode of action of ginsenosides remain mostly unknown. In this study, saponins were isolated from Korean red ginseng, and the antibacterial effects of ginsenosides were investigated. Ginsenosides showed antibacterial activities toward pathogenic Gram-positive and Gram-negative bacteria. To elucidate the antibacterial mode of action of ginsenosides, we measured the release of the fluorescent marker calcein from negatively charged PC/PG (1 : 1, w/w) liposomes, which mimic bacterial membranes. The results suggest that ginsenosides may exert antibacterial activity by disrupting the cell membrane. To estimate the general combination effects of ginsenosides and commercial antibiotics, such as kanamycin and cefotaxime, on antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains that were clinically isolated from an infected patient, the fraction inhibitory concentration (FIC) indexes were determined by a checkerboard study. The FIC indexes showed synergistic or additive effects between the ginsenosides and antibiotics tested.

In Vitro Candidacidal Action of Korean Red Ginseng Saponins against Candida albicans

Korean red ginseng saponins (ginsenosides) have been reported as having various biological properties, but the antifungal effects and the mode of action of ginsenosides remain mostly unknown. In this study, saponins were isolated from Korean red ginseng, and the antifungal effects of ginsenosides were investigated. Ginsenosides showed fungicidal effects toward pathogenic fungi tested. To elucidate the antifungal mode of action of ginsenosides, flow cytometry analysis and the change in membrane dynamics using 1,6-diphenyl-1,3,5-hexatriene (DPH), as a plasma membrane probe, were performed with Candida albicans. The results suggest that ginsenosides may exert antifungal activity by disrupting the structure of cell membrane. The present study indicates that ginsenosides have considerable antifungal activity, deserving further investigation for clinical applications.

The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3AReceptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on <TEX>$5-HT_{3A}$</TEX> receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human <TEX>$5-HT_{3A}$</TEX> receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with <TEX>$H_2O\;and\;5-HT_{3A}$</TEX> receptor cRNA. In oocytes injected with <TEX>$5- HT_{3A}$</TEX> receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current <TEX>$(I_{5-HT})$</TEX> than CK with dose-dependent and reversible manner. The half-inhibitory concentrations <TEX>$(IC_{50})$</TEX> of CK and M4 were <TEX>$36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$</TEX>, respectively. The inhibition of <TEX>$I_{5-HT}$</TEX> by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate <TEX>$5-HT_{3A}$</TEX> receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by <TEX>$51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$</TEX> during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of <TEX>$5-HT_{3A}$</TEX> receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice

The effects of two ginseng saponins having a different ratio of protopanaxadiol (PD) and protopanaxatriol saponins (PT) on the learning impairment induced by scopolamine, and learning and memory in mice were investigated in a passive avoidance task and a Morris water maze task. The ratio of PD and PT was 1.24 and 1.46, respectively. Before training, the ginseng saponins were administered intraperitoneally at doses of 50 and 100 mg/kg. The two saponins improved the scopolamine-induced learning impairment at different dosages in mice, 50 and 100 mg/kg, respectively. However, the two saponins did not show a favorable effect on learning and memory in normal mice. Korean red ginseng saponin with a low PD/PT ratio had an improving effect on spatial working memory, but the saponin with a high PD/PT ratio did not. This finding suggests that the PD/PT ratio of the ginseng saponins may be an important factor in the pharmacological role of red ginseng as a medicinal herb.

Anticomplementary activity of ginseng saponins and their degradation products

The anticomplementary activity of ginseng saponins and their degradation products obtained by chemical treatment of Korean red ginseng saponins was investigated. The total saponin and its major components showed strong anticomplementary activity and their structure-activity relationship was evaluated.