Red Ginseng Extract Research Articles

Korean Red Ginseng extract reduces hypoxia-induced epithelial-mesenchymal transition by repressing NF-κB and ERK1/2 pathways in colon cancer

BackgroundThe incidence of colorectal cancer (CRC) is increasing, with metastasis of newly diagnosed CRC reported in a large proportion of patients. However, the effect of Korean Red Ginseng extracts (KRGE) on epithelial to mesenchymal transition (EMT) in CRC is unknown. Therefore, we examined the mechanisms by which KRGE regulates EMT of CRC in hypoxic conditions. MethodsHuman CRC cell lines HT29 and HCT116 were incubated under hypoxic (1% oxygen) and normoxic (21% oxygen) conditions. Western blot analysis and real-time PCR were used to evaluate the expression of EMT markers in the presence of KRGE. Furthermore, we performed scratched wound healing, transwell migration, and invasion assays to monitor whether KRGE affects migratory and invasive abilities of CRC cells under hypoxic conditions. ResultsKRGE-treated HT29 and HCT116 cells displayed attenuated vascular endothelial growth factor (VEGF) mRNA levels and hypoxia-inducible factor-1α (HIF-1α) protein expression under hypoxic conditions. KRGE repressed Snail, Slug, and Twist mRNA expression and integrin αVβ6 protein levels. Furthermore, hypoxia-repressed E-cadherin was restored in KRGE-treated cells; KRGE blocked the invasion and migration of colon cancer cells by repressing NF-κB and ERK1/2 pathways in hypoxia. ConclusionsKRGE inhibits hypoxia-induced EMT by repressing NF-κB and ERK1/2 pathways in colon cancer cells.

Effects of Red or Black Ginseng Extract in a Rat Model of Inflammatory Temporomandibular Joint Pain

Effects of Red or Black Ginseng Extract in a Rat Model of Inflammatory Temporomandibular Joint Pain

Effective of Red Ginseng Extract on Ameliorate Adipogenesis 3t3-L1 by Decreasing P38 and Erk Phosphorylation

Effective of Red Ginseng Extract on Ameliorate Adipogenesis 3t3-L1 by Decreasing P38 and Erk Phosphorylation

Subacute oral toxicity and bacterial mutagenicity study of Korean Red Ginseng oil

BackgroundRed ginseng oil (RGO) is produced by supercritical CO2 extraction of secondary products derived from Korean Red Ginseng extract. As the use of RGO has increased, product safety concerns have become more important. MethodsIn the present study, the subacute oral toxicity and bacterial reverse mutagenicity of RGO were evaluated. Sprague–Dawley rats were orally administered with RGO for 28 d by gavage. Daily RGO dose concentrations were 0 mg/kg body weight (bw), 500 mg/kg bw, 1,000 mg/kg bw, or 2,000 mg/kg bw per day. Bacterial reverse mutation tests included five bacterial strains (Escherichia coli WP2 and Salmonella typhimurium TA98, TA100, TA1535, and TA1537), which were used in the presence or absence of metabolic activation. The plated incorporation method for mutation test was used with RGO concentrations ranging from 312.5 μg to 5,000 μg per plate. ResultsThe subacute oral toxicity test results did not reveal any marked changes in clinical characteristics. There were no toxicological changes related to RGO administration in hematological and serum biochemical characteristics in either control or treatment animals. Furthermore, no gross or histopathological changes related to RGO treatment were observed. The bacterial reverse mutation test results did not reveal, at any RGO concentration level and in all bacterial strains, any increase in the number of revertant colonies in the RGO treatment group compared to that in the negative control group. ConclusionThe no-observed-adverse-effect level of RGO is greater than 2,000 mg/kg bw and RGO did not induce genotoxicity related to bacterial reverse mutations.

Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation

BackgroundKorean 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. MethodsTo examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ([Ca2+]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. ResultsWe found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and [Ca2+]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. ConclusionThese data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

Effects of processing method on the pharmacokinetics and tissue distribution of orally administered ginseng

BackgroundThe use of different methods for the processing of ginseng can result in alterations in its medicinal properties and efficacy. White ginseng (WG), frozen ginseng (FG), and red ginseng (RG) are produced using different methods. WG, FG, and RG possess different pharmacological properties. MethodsWG, FG, and RG extracts and pure ginsenosides were administered to rats to study the pharmacokinetics and tissue distribution characteristics of the following ginsenosides—Rg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the plasma and tissues were determined using UPLC-MS/MS. ResultsThe rate and extent of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different methods used in processing the ginseng samples. The areas under the plasma drug concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re, Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and Rb1 were significantly (p<0.05) higher in the tissues than those of the pure ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were significantly higher than those from the WG and FG extracts in the heart, lungs, and kidneys of the rats. ConclusionOur results show that the use of different methods to process ginseng might affect the pharmacokinetics and oral bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd, and Rb1.

Simultaneous quantification of twenty-one ginsenosides and their three aglycones in rat plasma by a developed UFLC–MS/MS assay: Application to a pharmacokinetic study of red ginseng

To track the pharmacokinetic features of red ginseng (RG), a rapid and sensitive ultra fast liquid chromatographic coupled with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC–MS/MS) method was developed for simultaneous quantification of twenty-one ginsenosides and their three aglycones, including 18 prototype compounds (ginsenosides Rb1, Rb2, Rc, Rd, Re, Rg1, Rg5, Rh4, Rk1, Rk3, 20(S)-Rf, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(R)-Rh1, 20(S)-NG-R2), and 6 metabolites (ginsenosides 20(S)-Rh2 and Rh3, 20(S)-protopanaxadiol (PPD), 20(S)-protopanaxatriol (PPT), 20(R)-PPT, ginseng saponin compound K) of RG in rat plasma after oral administration of RG water extract at a single dose of 4g/kg body weight to rats. All analytes with internal standard (digoxin) were detected by multiple reaction monitoring in negative ionization mode and separated on an ACQUITY UPLC® BEH RP-C18 column (1.7μm, 100×2.1mm). This established method was well validated in terms of linearity, sensitivity, intra- and inter-day precisions, accuracy, recovery, matrix effect, stability, and had a lower limit of quantification at the concentration range of 0.12–8.12ng/mL for all of analytes. This UFLC–MS/MS approach was successfully applied to the pharmacokinetic study for RG water extract in rats. We firstly proposed that Rb1, Rb2, Rc, Rd, Rg1, Rg5, 20(S)-Rg3, 20(S)-Rh2, and 20(S)-PPD measured in rat plasma were suitable pharmacokinetic markers of RG extract in rats due to their high systemic exposure levels. Thus, this specific and reliable method will be useful for future applications to pharmacokinetic studies for various sources of ginsenoside samples and Panax herbs in vivo.

Oral Administration of Red Ginseng Extract Promotes Neurorestoration after Compressive Spinal Cord Injury in Rats.

Red ginseng and its active ingredients have been shown to decrease neuron death after brain ischemia in experimental animals. However, little is known about the effects of orally administered ginseng extract on spinal cord injury. We orally gave red ginseng extract (RGE) to rats with compressed spinal cord injury (SCI). Open-field locomotor scores were measured as indices of motor function. Histopathological changes and cytokine expressions in situ after SCI were evaluated. Compared to vehicle treatment, RGE treatment (350 mg/kg/day) significantly improved locomotor score up to levels close to those pre-SCI, prevented neuron loss, and facilitated the restoration of white matter in the spinal cord at 14 days after SCI. Treatment with RGE caused less aggregation of Iba-1-positive microglia in grey and white matter at 7 days after SCI, upregulated the expression levels of VEGF and Bcl-xL, and reduced IL-1β and TNFα expressions in the spinal cord at 7 and 14 days after SCI. We concluded that oral administration of RGE facilitates almost complete functional recovery from motor and behavioral abnormalities in rats with SCI and prevents neuron death in situ, possibly through inhibition of inflammation and upregulation of neuroprotective factors in the injured spinal cord.

WITHDRAWN: Cold-water extract of Korean Red Ginseng exhibits potent inhibitory effects against cholesteryl ester transfer protein activity and fructose-mediated glycation along with lipid-lowering activity in hyperlipidemic zebrafish

Abstract Background Red ginseng (RG) is widely used to treat complications of diabetes and atherosclerosis because of its antioxidative and anti-inflammatory activities. Methods In order to investigate the antiatherosclerotic and antisenescence activities of water extracts of RG powder, the lyophilized extract was treated to human macrophage, dermal cells, and brain glioma cells, and supplemented to hyperlipidemic zebrafish. Results Aqueous extracts of RG showed potent inhibitory activity against fructose-mediated glycation and protective effect against low-density lipoprotein (LDL) oxidation. RG extracts also showed potent antiatherogenic activities, demonstrated inhibitory activity against cholesteryl ester transfer protein (CETP), and inhibited cellular uptake of oxidized LDL into macrophages. As in vivo test, zebrafish consumed a high cholesterol diet (HCD) [final, 4% in diet (wt/wt)] with or without RG [final, 10% or 20% (wt/wt)]. The 10% and 20% RG groups showed reductions of 5% and 3%, respectively, in weight and height compared to the HCD group. Plasma total cholesterol level was significantly reduced in both the 10% and 20% RG groups, and glutamic–pyruvic transaminase activity was reduced in the 20% RG group compared to the HCD group. Finally, plasma from zebrafish that consumed 20% RG showed the lowest plasma CETP activity with the least hepatic inflammation and fatty liver change. Conclusion Aqueous extracts of RG suppressed the incidence of atherosclerosis via strong antioxidant potential, prevention of apolipoprotein A-I glycation, uptake of oxLDL, and inhibition of CETP activity. Consumption of RG in hyperlipidemic zebrafish model exhibited potent lipid-lowering and atheroprotective activities with the least fatty liver change.

Effects of ingredients of Korean brown rice cookies on attenuation of cholesterol level and oxidative stress in high-fat diet-fed mice.

BACKGROUND/OBJECTIVESOwing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik, was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies.MATERIALS/METHODSGinseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis.RESULTSThe plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group (P < 0.05). In addition, nuclear factor-kappaB (NF-κB) expression in the GBRD group was significantly lower than that in the RCD group.CONCLUSIONSGBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti-inflammatory status in HFD-fed mice via CAT and GPx upregulation and NF-κB downregulation. These effects were significantly higher than those of RCD.

Investigation of Herb-Drug Interactions between Korean Red Ginseng Extract and five CYP Substrates by LC-MS/MS

Investigation of Herb-Drug Interactions between Korean Red Ginseng Extract and five CYP Substrates by LC-MS/MS

Therapeutic Effects of Korean Red Ginseng Extract in a Murine Model of Atopic Dermatitis: Anti-pruritic and Anti-inflammatory Mechanism.

Korean red ginseng (KRG) and ginsenosides exhibit diverse biological effects, including anti-inflammatory and anti-allergic. We aimed to investigate the therapeutic effect of KRG in a murine model of atopic dermatitis (AD) is mediated whether by diminishing the pruritus or by suppressing the inflammation. Thirty NC/Nga mice were randomly divided to 5 groups. AD-like skin lesions were induced by percutaneous challenge with 2,4,6-trinitro-1-chrolobenzene (TNCB) on the ears and backs of NC/Nga mice. KRG extract, evening primrose oil, cyclosporine, and phosphate-buffered saline were administered orally by a gastric tube. Each study group was also divided into scratching-permitted and scratching-restricted subgroups to evaluate the impact of scratching behavior on AD. The effects of KRG and the other agents were assessed by measuring the clinical severity score, ear thickness, extent of transepidermal water loss (TEWL), number of scratching movements, total systemic immunoglobulin E (IgE) and interleukin (IL)-31 levels, histologic changes of cutaneous lesions, and mRNA expression levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin (TSLP), and IL-31. KRG exerts therapeutic effects against AD by inhibiting the T helper 2 (Th2) mediated inflammation as well as by diminishing the itching sensation. Moreover, restricting scratching behavior suppresses the vicious cycle of itching and scratching, thus reducing clinical and systemic inflammation in our murine model of AD.

Ginsenoside Composition and Change of Taste Quality in Red Ginseng Extract by Acid treatment and Complexation with Cyclodextrin

Ginsenoside Composition and Change of Taste Quality in Red Ginseng Extract by Acid treatment and Complexation with Cyclodextrin

Neuroprotective effect of Korea Red Ginseng extract on 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 Cells

ABSTRACTBackground: Korean Red Ginseng (KRG) is a valuable herb in Asian countries that is used as a crude substance to inhibit inflammation and to enhance vitality, longevity and immunity. The protective effects of KRG against the toxicity of 1-methyl-4-phenylpyridinium (MPP+) were investigated in vitro in the present study.Methods: PC12 cells were pretreated with the water extract of KRG for 24 h, then incubated with MPP+ for 24 h. The growth of the cells was assessed using a live cell viability assay, the ratio of apoptotic cells was measured using flow cytometry and morphology of the apoptotic cells was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The expressions of caspase-3 and -9 were measured by quantitative real-time PCR.Results: Pretreatment of the KRG extract increased cell viability significantly when compared with that of only MPP+-treated cells (p < .01). KRG-pretreated cells revealed reductions of Annexin V-FITC and propidium iodide double staining cells (p < .01), TUNEL-positive cells (p < .01), and caspase-3 and -9 activities (p < .01) when compared with only MPP+-treated cells.Conclusion: These results indicate that KRG treatment suppresses MPP+-induced apoptosis in PC12 cells by regulating caspase cascades, suggesting a possible role for KRG in the prevention and treatment of Parkinson’s disease.

Nonsaponin fractions of Korean Red Ginseng extracts prime activation of NLRP3 inflammasome

BackgroundKorean Red Ginseng extracts (RGE) have been suggested as effective immune modulators, and we reported that ginsenosides possess anti-inflammasome properties. However, the properties of nonsaponin components of RGE have not been well studied. MethodsTo assess the roles of nonsaponin fractions (NS) in NLRP3 inflammasome activation, we treated murine macrophages with or without first or second inflammasome activation signals with RGE, NS, or saponin fractions (SF). The first signal was nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated transcription of pro-interleukin (IL)-1β and NLRP3 while the second signal triggered assembly of inflammasome components, leading to IL-1β maturation. In addition, we examined the role of NS in IL-6 production and IL-1β maturation in mice. ResultsNS induced IL-1β and NLRP3 transcription via toll-like receptor 4 signaling, whereas SF blocked expression. During the second signal, SF attenuated NLRP3 inflammasome activation while NS did not. Further, NS-injected mice presented increased IL-1β maturation and IL-6 production. ConclusionSF and NS of RGE play differential roles in the NLRP3 inflammasome activation. Hence, RGE can be suggested as an NLRP3 inflammasome modulator.

Korean Red Ginseng extract induces angiogenesis through activation of glucocorticoid receptor

BackgroundOur previous studies have demonstrated that ginsenoside-Rg1 can promote angiogenesis in vitro and in vivo through activation of the glucocorticoid receptor (GR). Furthermore, microRNA (miRNA) expression profiling has shown that Rg1 can modulate the expression of a subset of miRNAs to induce angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of a different pathway. These studies highlight the important functions of miRNAs on ginseng-regulated physiological processes. The aim of this study was to determine the angiogenic properties of Korean Red Ginseng extract (KGE). Methods and ResultsCombining in vitro and in vivo data, KGE at 500 μg/mL was found to induce angiogenesis. According to the miRNA sequencing, 484 differentially expressed miRNAs were found to be affected by KGE. Among them, angiogenic-related miRNAs; miR-15b, -23a, -214, and -377 were suppressed by KGE. Meanwhile, their corresponding angiogenic proteins were stimulated, including vascular endothelial growth factor, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and MET transmembrane tyrosine kinase. The miRNAs-regulated signaling pathways of KGE were then found by Cignal 45-Pathway Reporter Array, proving that KGE could activate GR. ConclusionKGE was found capable of inducing angiogenesis both in vivo and in vitro models through activating GR. This study provides a valuable insight into the angiogenic mechanisms depicted by KGE in relation to specific miRNAs.

홍삼의 지용성 성분을 이용한 발효홍삼 농축액 알갱이의 흡습방지 효과

홍삼의 지용성 성분을 이용한 발효홍삼 농축액 알갱이의 흡습방지 효과

Morphine dependence is attenuated by red ginseng extract and ginsenosides Rh2, Rg3, and compound K

BackgroundRed ginseng and ginsenosides have shown plethoric effects against various ailments. However, little is known regarding the effect of red ginseng on morphine-induced dependence and tolerance. We therefore investigated the effect of red ginseng extract (RGE) and biotransformed ginsenosides Rh2, Rg3, and compound K on morphine-induced dependence in mice and rats. MethodsWhile mice were pretreated with RGE and then morphine was injected intraperitoneally, rats were infused with ginsenosides and morphine intracranially for 7 days. Naloxone-induced morphine withdrawal syndrome was estimated and conditioned place preference test was performed for physical and psychological dependence, respectively. Western blotting was used to measure protein expressions. ResultsWhereas RGE inhibited the number of naloxone-precipitated jumps and reduced conditioned place preference score, it restored the level of glutathione in mice. Likewise, ginsenosides Rh2, Rg3, and compound K attenuated morphine-dependent behavioral patterns such as teeth chattering, grooming, wet-dog shake, and escape behavior in rats. Moreover, activated N-methyl-D-aspartate acid receptor subunit 1 and extracellular signal-regulated kinase in the frontal cortex of rats, and cultured cortical neurons from mice were downregulated by ginsenosides Rh2, Rg3, and compound K despite their differential effects. ConclusionRGE and biotransformed ginsenosides could be considered as potential therapeutic agents against morphine-induced dependence.

The Effect of Red Ginseng Extract Intake on Ischemic Flaps

ABSTRACTRed ginseng is well known for its angiogenic effects and its effect of increasing expression of vascular endothelial growth factors (VEGFs), but little experimental evidence has been published. In this study, we examined the effect of red ginseng using an ischemic flap model. Twenty male Sprague-Dawley rats were divided into two groups of 10. One group drank red ginseng solution from 7 days prior to surgery to 7 days after, whereas the other group drank distilled water. We created a local flap on the back of each rat. We analyzed the surviving area of the flap for 10 days after surgery and measured the blood flow of the flap. Ten days after the operation, CD31-positive vessels and VEGF expression were examined by immunohistochemistry. The percentages of surviving areas of the flap were 76 ± 3% for the experimental group and 39 ± 5% for the control group (P = 0.0002). Blood flow in the experimental group increased for 10 days after the surgery. The number of newly generated capillaries in the experimental group was 14.0 ± 3.5, which was significantly higher than 5.7 ± 1.9 in the control group. The expression of VEGF in the experimental group was significantly higher than in the control group (p = 0.0003). Administration of red ginseng extract increases the survival of ischemic flaps via angiogenesis and elevated blood flow. Further clinical studies are warranted to apply the effect shown in this current investigation to various ischemic conditions.

Use of Gold Nanoparticle Fertilizer Enhances the Ginsenoside Contents and Anti-Inflammatory Effects of Red Ginseng.

Red ginseng, a steamed and sun-dried ginseng, is a popular health-promoting food in Korea and other Asian countries. We introduced nanofertilizer technology using gold nanoparticles in an effort to develop red ginseng with an elevated level of ginsenosides, the main active compounds of ginseng. Shoots of 6-year-old ginseng plants were fertilized three times with colloidal gold nanoparticle sprays. Red ginseng extract was prepared from the main roots. The concentrations of gold and ginsenosides were measured following gold nanoparticle treatment. To evaluate the anti-inflammatory effects, mouse peritoneal macrophages of male BALB/c mouse were stimulated with lipopolysaccharide plus interferon-γ in the presence of extracts from red ginseng with or without gold nanoparticle treatment. The content of ginsenosides, such as Rg1, Re, Rf, and Rb1, increased in ginseng treated with gold nanofertilizer whereas the steaming process increased only the levels of Rd and Rg3. The levels of nitric oxide, inducible nitric oxide synthase, and interleukin-6, but not tumor necrosis factor-α, were more suppressed in macrophages treated with extract from gold nanoparticle-treated red ginseng. Our results show that the use of a colloidal gold nanoparticle fertilizer improved the synthesis of ginsenosides in ginseng and enhanced the anti-inflammatory effects of red ginseng. Further research is required to elucidate the causal factors for the gold-induced change in ginsenoside synthesis and to determine the in vivo effect of gold nanoparticle-treated ginseng.