Korean Red Ginseng Water Extract Research Articles

Korean red ginseng water extract produces antidepressant-like effects through involving monoamines and brain-derived neurotrophic factor in rats

BackgroundGinseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. MethodsThe antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. ResultsKGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. ConclusionOur results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

Korean Red Ginseng water extract inhibits cadmium-induced lung injury via suppressing MAPK/ERK1/2/AP-1 pathway

BackgroundFew studies reported the therapeutic effect of Korean Red Ginseng (KRG) in lung inflammatory diseases. However, the anti-inflammatory role and underlying molecular in cadmium-induced lung injury have been poorly understood, directly linked to chronic lung diseases (CLDs): chronic obstructive pulmonary disease (COPD), cancer etc. Therefore, in this study we aim to investigate the therapeutic activities of water extract of KRG (KRG-WE) in mouse cadmium-induced lung injury model. MethodThe anti-inflammatory roles and underlying mechanisms of KRG-WE were evaluated in vitro under cadmium-stimulated lung epithelial cells (A549) and HEK293T cell line and in vivo in cadmium-induced lung injury mouse model using semi-quantitative polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), luciferase assay, immunoblotting, and FACS. ResultsKRG-WE strongly ameliorated the symptoms of CdSO4-induced lung injury in mice according to total cell number in bronchoalveolar lavage fluid (BALF) and severity scores as well as cytokine levels. KRG-WE significantly suppressed the upregulation of inflammatory signaling comprising mitogen-activated protein kinases (MAPK) and their upstream enzymes. In in vitro study, KRG-WE suppressed expression of interleukin (IL)-6, matrix metalloproteinase (MMP)-2, and IL-8 while promoting recovery in CdSO4-treated A549 cells. Similarly, KRG-WE reduced phosphorylation of MAPK and c-Jun/c-Fos in cadmium-exposed A549 cells. ConclusionKRG-WE was found to attenuate symptoms of cadmium-induced lung injury and reduce the expression of inflammatory genes by suppression of MAPK/AP-1-mediated pathway.

Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE2 pathways

BackgroundAsthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). MethodsKorean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. ResultsKRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE2 pathways. ConclusionKRGWE is a promising drug for asthma treatment.

Korean red ginseng water extract alleviates atopic dermatitis-like inflammatory responses by negative regulation of mitogen-activated protein kinase signaling pathway in vivo

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Korean red ginseng is a Korean traditional medicine. In this study, we estimated the effects of Korean red ginseng water extract (RGE) in the 1-chloro-2,4-dinitrobenzene (DNCB)-induced BALB/c mouse model which develops AD-like lesions. After RGE administration (100, 200, and 400 mg/kg) to DNCB-induced mice there were improvements in the dermatitis score and skin pH, a decrease in trans-epidermal water loss, and improved skin hydration. RGE also significantly inhibited eosinophil infiltration, increased filaggrin protein levels, and decreased serum IgE levels, epidermal thickness, mast cell infiltration, and ceramidase release. Compared with that in DNCB-induced mice, RGE effectively decreased the mRNA expression levels of interleukin-6 (IL-6), thymic stromal lymphopoietin (TSLP), and tumor necrosis factor-α (TNF-α), as well as the protein level of thymus and activation-regulated chemokine (TARC). These inhibitory RGE effects are mediated by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Furthermore, we confirmed that RGE suppresses interferon-γ (IFN-γ) and TNF-α-induced expression of macrophage-derived chemokine (MDC) and TARC genes in human keratinocyte (HaCaT) cells. Taken together, these results demonstrate that RGE may exert anti-atopic related to responses by suppression the expression of inflammatory mediators, cytokines, and chemokines via downregulation of MAPK signaling pathways, suggesting that RGE may be an effective therapeutic approach for prevention of AD-like disease.

Korean Red Ginseng extract and ginsenoside Rg3 have anti-pruritic effects on chloroquine-induced itch by inhibition of MrgprA3/TRPA1-mediated pathway

BackgroundIt was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. MethodsIntracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 (“MrgprA3/TRPA1”), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. ResultsCQ-induced Ca2+ influx was strongly inhibited by KRGE (10 μg/mL) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced Ca2+ influx in MrgprA3/TRPA1. Moreover, both KRGE (10 μg/mL) and Rg3 (100 μM) suppressed CQ-induced Ca2+ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: 274.0 ± 51.47 (control) vs. 104.7 ± 17.39 (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: 216.8 ± 33.73 (control) vs. 115.7 ± 20.94 (Rg3)]. ConclusionThe present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.

Korean red ginseng improves testicular ineffectiveness in aging rats by modulating spermatogenesis-related molecules

Korean red ginseng (Panax ginseng Meyer) is known to rejuvenate testicular effectiveness and the sperm maturation process by regulating redox proteins in aged rats. This study was performed to investigate the effect of Korean red ginseng water extract (KRG-WE) on the expression level of spermatogenesis-related key biomolecules and sex hormone receptors as well as enzymes regulating oxidation, histone deacetylation, and growth-related activities in aged rat testis. KRG-WE (200mg/kg) mixed with a regular pellet diet was administered to 12-month-old rats for 6months (KRG-AC), whereas the young (YC, 2months) and aged (AC, 12months) controls received the vehicle only. The results showed that the expression levels of spermatogenesis-related key biomolecules (inhibin-α, nectin-2, and cyclic adenosine monophosphate [cAMP] responsive element binding protein [CREB]-1), sex hormone receptors (androgen, luteinizing- and follicle-stimulating hormone receptors [AR, LHR, and FSHR, respectively]), and antioxidant enzymes (glutathione S-transferase mu [GSTm]-5, glutathione peroxidase [GPx]-4, peroxiredoxin [PRx]-3), as well as histone deactylation (silent mating type information regulation 2 homolog 1, SIRT1) and growth-related (mammalian target of rapamycin complex 1, mTORC1) molecules were significantly altered in the AC group rat testes compared with those of the YC group. However, KRG-WE treatment of the AC group significantly (p<0.05) attenuated these molecular changes. From these results, it can be concluded that long-term administration of KRG-WE significantly delayed the aging-induced testicular dysfunction.

Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells

BackgroundAlthough numerous studies of the anticancer activities of Korean Red Ginseng (KRG) have been performed, the therapeutic effect of KRG on leukemia has not been fully elucidated. In this study, we investigated the antileukemia activities of KRG and its cellular and molecular mechanisms. MethodsAn established leukemia tumor model induced by xenografted T cell lymphoma (RMA cells) was used to test the therapeutic activity of KRG water extract (KRG-WE). Direct cytotoxic activity of KRG-WE was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory activities of KRG-WE were verified by immunohistochemistry, nitric oxide production assay. The inhibitory effect of KRG-WE on cell survival signaling was also examined. ResultsOrally administered KRG-WE reduced the sizes of tumor masses. Levels of apoptosis regulatory enzymes and cleaved forms of caspases-3 and -8 were increased by this extract. In addition, expression of matrix metalloproteinase-9, a metastasis regulatory enzyme, was decreased by KRG-WE treatment. The proportion of CD11c+ cells was remarkably increased in the KRG-treated group compared to the control group. However, KRG-WE did not show significant direct cytotoxicity against RMA cells. ConclusionOur results strongly suggest that the KRG might have antileukemia activity through CD11c+ cell-mediated antitumor immunity.

Korean Red Ginseng improves atopic dermatitis-like skin lesions by suppressing expression of proinflammatory cytokines and chemokines in vivo and in vitro

BackgroundThe prevalence of allergic inflammatory diseases such as atopic dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and complete recovery is difficult. Korean Red Ginseng, which is the heat-processed root of Panax ginseng Meyer, is widely and frequently used as a traditional medicine in East Asia. In this study, we investigated whether Korean Red Ginseng water extract (RGE) regulates the expression of proinflammatory cytokines and chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa B (NF-κB) pathway in allergic inflammation. MethodsCompound 48/80-induced anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin lesion mice models were used to investigate the antiallergic effects of RGE. Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to clarify the effects of RGE on the expression of proinflammatory cytokines and chemokines. ResultsAnaphylactic shock and DNFB-induced AD-like skin lesions were attenuated by RGE administration through reduction of serum immunoglobulin E (IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the production of proinflammatory cytokines including IL-1β, IL-6, and IL-8, and expression of chemokines such as IL-8, thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE decreased the release of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-8 as well as expressions of chemokines including macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC-1 cells. Furthermore, our data demonstrated that these inhibitory effects occurred through blockage of the MAPK and NF-κB pathway. ConclusionRGE may be a useful therapeutic agent for the treatment of allergic inflammatory diseases such as AD-like dermatitis.

Effects of Korean Red Ginseng extract on hepatic lipid accumulation in HepG2 cells.

In this study, we investigated the effects of Korean red ginseng water extract (KRGE) on hepatic lipid accumulation in HepG2 cells. KRGE decreased hepatic triglyceride and cholesterol levels. Further, KRGE suppressed expression of fatty acid synthase (FAS) and 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase. These results suggest that KRGE may reduce hepatic lipid accumulation by inhibition of FAS and HMG-CoA reductase expression in HepG2 cells.

Effect of Korean Red Ginseng water extract on the hepatic fatty acid and cholesterol synthesis in HepG2 cells

Korean Ginseng, the root Panax ginseng CA Meyer, has been widely used as a traditional herbal medicine in East Asian countries. In this study, we investigated the effects of Korean Red Ginseng water extract (KRGE) on hepatic lipid accumulation in HepG2 cells. First, we investigated the cytotoxic effects of KRGE on HepG2 cells. Cytotoxicity was unaffected in the concentrations of 1–50 μg/ml of KRGE.Intracellular lipid accumulation was assessed by the quantification of intracellular triglyceride and cholesterol contents. KRGE decreased hepatic triglyceride and cholesterol levels. Moreover, KRGE suppressed expression of fatty acid synthase (FAS) and 3‐hydroxy‐3‐methyl glutaryl coenzyme A (HMG‐CoA) reductase, a rate‐limiting enzyme in hepatic cholesterol synthesis. These results suggest that KRGE may reduce hepatic lipid accumulation by inhibition of FAS and HMG‐CoA reductase expression in HepG2 cells. Consequently, KRGE may be beneficial as a functional food ingredient to improve various hepatic diseases by reducing hepatic lipid accumulation.

Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation

BackgroundKorean red ginseng (KRG) is a traditional herbal medicine made by steaming and drying the fresh ginseng, leading to chemical transformation of some components by heat. It ameliorates various inflammatory diseases and strengthens the endocrine, immune, and central nervous systems. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumorigenesis. PurposeIn this study we examined the effects and the mechanism underlying Korean red ginseng water extract (KRG-WE) inhibition of hypoxia-induced COX-2 in human distal lung epithelial A549 cells. Study designThe effect of the KRG on suppression of hypoxia-induced COX-2 in A549 cells were determined by Western blot and/or qRT-PCR. The anti-invasive effect of KRG-WE was evaluated on A549 cells using matrigel invasion assay. The activation of glucocorticoid receptor (GR) and sirtuin1 (Sirt1) was examined by using specific inhibitors. ResultsWe first observed that hypoxia induced COX-2 protein and mRNA levels and promoter activity were suppressed by KRG-WE. Second, we observed that hypoxia-induced cell migration is dramatically reduced by KRG-WE. Third, we found that the effect of KRG-WE was not antagonized by the GR antagonist RU486 implying that the effect is mediated other than GR pathway. Finally, we demonstrated that inhibition of Sirt1 abolished the effect of KRG-WE on hypoxia-induced COX-2 suppression and cell-invasion indicating that the suppression is mediated by Sirt1. ConclusionTaken together, KRG-WE inhibits the hypoxic induction of COX-2 expression and cell invasion through Sirt1 activation. Our results imply that KRG-WE could be effective for suppression of inflammation under hypoxia.

Induction of Thioredoxin Reductase 1 by Korean Red Ginseng Water Extract Regulates Cytoprotective Effects on Human Endothelial Cells.

Korean Red Ginseng is a popular herbal medicine and is widely used in many food products. KRG has biological benefits related to vascular diseases including diabetes, hypertension, atherosclerosis, and other cardiac diseases and KRG has antioxidant and anti-hyperlipidemic actions. KRG decreases the level of oxidative stress and suppresses proinflammatory cytokines and cell adhesion molecules, thus protecting endothelial dysfunction. Mammalian Thioredoxin reductase 1 is an NADPH-dependent selenoprotein, essential for antioxidant defense and DNA synthesis and repair, that regulates the redox system by modulating redox-sensitive transcription factors and thiol-containing proteins. Here, we show that KRG water extract increases the expression of TrxR1 in human umbilical vein endothelial cells via the p38 and PKC-δ signaling pathways. The induction of TrxR1 expression by KRG was confirmed by Western blot analysis and reverse transcription polymerase chain reaction. However, the increase in TrxR1 expression was abolished by specific silencing of the p38 and PKC-δ genes. In addition, we demonstrated that auranofin, a TrxR1 inhibitor, weakens the protective effect of KRG against H2O2-induced cell death as measured by the terminal transferase dUTP nick end labeling assay. These results suggest that KRG may have protective effects in vascular diseases by upregulating TrxR1 in endothelial cells, thereby inhibiting the generation of reactive oxygen species and cell death.

ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract

Ethnopharmacological relevanceKorean Red Ginseng (KRG) is one of the representative traditional herbal medicines prepared from Panax ginseng Meyer (Araliaceae) in Korea. It has been reported that KRG exhibits a lot of different biological actions such as anti-aging, anti-fatigue, anti-stress, anti-atherosclerosis, anti-diabetic, anti-cancer, and anti-inflammatory activities. Although systematic studies have investigated how KRG is able to ameliorate various inflammatory diseases, its molecular inhibitory mechanisms had not been carried out prior to this study. Materials and methodsIn order to investigate these mechanisms, we evaluated the effects of a water extract of Korean Red Ginseng (KRG-WE) on the in vitro inflammatory responses of activated RAW264.7 cells, and on in vivo gastritis and peritonitis models by analyzing the activation events of inflammation-inducing transcription factors and their upstream kinases. ResultsKRG-WE reduced the production of nitric oxide (NO), protected cells against NO-induced apoptosis, suppressed mRNA levels of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interferon (IFN)-β, ameliorated EtOH/HCl-induced gastritis, and downregulated peritoneal exudate-derived NO production from lipopolysaccharide (LPS)-injected mice. The inhibition of these inflammatory responses by KRG-WE was regulated through the suppression of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1) and by subsequent inhibition of activating transcription factor (ATF)-2, cAMP response element-binding protein (CREB), and IRF-3 activation. Of ginsensides included in this extract, interestingly, G-Rc showed the highest inhibitory potency on IRF-3-mediated luciferase activity. ConclusionThese results strongly suggest that the anti-inflammatory activities of KRG-WE could be due to its inhibition of the p38/JNK/TBK1 activation pathway.

Antiatherosclerotic Effect of Korean Red Ginseng Extract Involves Regulator of G-Protein Signaling 5

Regulator of G-protein signaling 5 (RGS5), an inhibitor of Gα(q) and Gα(i) activation, has been reported to have antiatherosclerosis. Previous studies showed antiatherosclerotic effect of Korean red ginseng water extract (KRGE) via multiple signaling pathways. However, potential protective effect of KRGE through RGS5 expression has not been elucidated. Here, we investigated the antiatherosclerotic effect of KRGE in vivo and in vitro and its role on RGS5 mRNA expression. Elevated levels of total cholesterol, lactate dehydrogenase (LDH), and triglyceride (TG) in western diet groups of low-density lipoprotein receptor deficient LDLr−/− mice were reversed by oral administration of KRGE. KRGE suppressed transcriptional activity of tumor necrotic factor alpha (TNF-α), interleukin-6 (IL-6), and leptin in adipose tissue. It also potently repressed western diet-induced atheroma formation in aortic sinus. While KRGE showed reduced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells, it enhanced mRNA expression of RGS5. Moreover, RGS5 siRNA transfection of microglia cells pretreated with KRGE reversed its inhibitory effect on the expression of iNOS, COX-2, and IL-1β mRNA. In conclusion, KRGE showed antiatherosclerotic and anti-inflammatory effects in western diet fed LDLr−/− mice and this effect could partly be mediated by RGS5 expression.

Korean red ginseng water extract restores impaired endothelial function by inhibiting arginase activity in aged mice.

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young (10±3 weeks) and aged (55±5 weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.

Korean Red Ginseng water extract inhibits COX-2 expression by suppressing p38 in acrolein-treated human endothelial cells

Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other α,β-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an α,β-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG) water extract suppressed acrolein-induced cyclooxygenase (COX)-2 expression in human umbilical vein endothelial cells (HUVECs). Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin V–propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

Korean red ginseng inhibits arginase and contributes to endothelium-dependent vasorelaxation through endothelial nitric oxide synthase coupling

Korean red ginseng water extract (KG-WE) has known beneficial effects on the cardiovascular system via inducting nitric oxide (NO) production in endothelium. Endothelial arginase inhibits the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion, thereby reducing NO bioavailability and contributing to vascular diseases including hypertension, aging, and atherosclerosis. In the present study, we demonstrate that KG-WE inhibits arginase activity and negatively regulates NO production and reactive oxygen species generation in endothelium. This is associated with increased dimerization of eNOS without affecting the protein expression levels of either arginase or eNOS. In a vascular tension assay, when aortas isolated from wild type mice were incubated with KG-WE, NO-dependent enhanced vasorelaxation was observed. Furthermore, KG-WE administered via by drinking water to atherogenic model mice being fed high cholesterol diet improved impaired vascular function. Taken together, these results suggest that KG-WE may exert vasoprotective effects through augmentation of NO signaling by inhibiting arginase. Therefore, KG-WE may be useful in the treatment of vascular diseases derived from endothelial dysfunction, such as atherosclerosis.

Panax ginseng reduces oxidative stress and restores antioxidant capacity in aged rats

Nutritional antioxidants interact with cells in an active mode, including retrieving and sparing one another, to diminish oxidative stress. However, the intracellular balance of prooxidants and antioxidants becomes unbalanced, favoring prooxidants during the aging process. One hypothesis is that an aging-associated increase in oxidative stress is the primary cause of aging. Hence, the research hypothesis for this study is that Korean red ginseng reduces oxidative stress in vivo. Therefore, we investigated the efficacy of Korean red ginseng water extract (GWE) in reducing aging-associated oxidative stress by measuring lipid peroxidation and antioxidant levels in older rats compared with young rats. We observed a significant increase in the markers for oxidative damage (eg, lipid peroxidation) and markers for vital organ damage (eg, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels) in aged rats. The oxidative damage was accompanied by a significant decrease in enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase, and nonenzymatic antioxidants such as reduced glutathione, vitamin E, and vitamin C. Aged rats fed a diet supplemented with Korean red ginseng water extract had significantly less oxidative damage, possibly by enhancing the enzymatic and nonenzymatic antioxidants status. Our data suggest that consumption of Korean red ginseng reduces lipid peroxidation and restores antioxidant capacity by suppressing oxidative stress in rats.

Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on H2O2-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2- mediated HO-1 induction in human endothelial cell by inhibition of cell death.

Korean Red Ginseng Up-regulates C21-Steroid Hormone Metabolism via Cyp11a1 Gene in Senescent Rat Testes

Ginseng (Panax ginseng Meyer) has been shown to have anti-aging effects in animal and clinical studies. However, the molecular mechanisms by which ginseng exerts these effects remain unknown. Here, the anti-aging effect of Korean red ginseng (KRG) in rat testes was examined by system biology analysis. KRG water extract prepared in feed pellets was administered orally into 12 month old rats for 4 months, and gene expression in testes was determined by microarray analysis. Microarray analysis identified 33 genes that significantly changed. Compared to the 2 month old young rats, 13 genes (Rps9, Cyp11a1, RT1-A2, LOC365778, Sv2b, RGD1565959, RGD1304748, etc.) were up-regulated and 20 genes (RT1-Db1, Cldn5, Svs5, Degs1, Vdac3, Hbb, LOC684355, Svs5, Tmem97, Orai1, Insl3, LOC497959, etc.) were down-regulated by KRG in the older rats. Ingenuity Pathway Analysis of untreated aged rats versus aged rats treated with KRG showed that the affected most was Cyp11a1, responsible for C21-steroid hormone metabolism, and the top molecular and cellular functions are organ morphology and reproductive system development and function. When genes in young rat were compared with those in the aged rat, sperm capacitation related genes were down-regulated in the old rat. However, when genes in the old rat were compared with those in the old rat treated with KRG, KRG treatment up-regulated C21-steroid hormone metabolism. Taken together, Cyp11a1 expression is decreased in the aged rat, however, it is up-regulated by KRG suggesting that KRG seems enhance testes function via Cyp11a1.