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Sample records for ginsenoside rg1 promotes

  1. Long-term ginsenoside Rg1 supplementation improves age-related cognitive decline by promoting synaptic plasticity associated protein expression in C57BL/6J mice.

    PubMed

    Yang, Lumeng; Zhang, Jing; Zheng, Kunmu; Shen, Hui; Chen, Xiaochun

    2014-03-01

    In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.

  2. Protective effects of ginsenoside Rg1 against colistin sulfate-induced neurotoxicity in PC12 cells.

    PubMed

    Jiang, Guo-Zheng; Li, Ji-Chang

    2014-03-01

    The present study aimed to examine the protective effect of ginsenoside Rg1 against colistin-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Ginsenoside Rg1 was shown to elevate cell viability, decrease levels of malondialdehyde and intracellular reactive oxygen species, enhance activity of superoxide dismutase and glutathione, and decrease the release of cytochrome-c, formation of DNA fragmentation in colistin-treated PC12 cells. Ginsenoside Rg1 also reversed the increased caspase-9 and -3 mRNA levels caused by colistin in PC12 cells. These results suggest that ginsenoside Rg1 exerts a neuroprotective effect on colistin-induced neurotoxicity in PC12 cells, at least in part, via the inhibition of oxidative stress, prevention of apoptosis mediated via mitochondria pathway. Co-administration of ginsenoside Rg1 highlights the potential to increase the therapeutic index of colistin.

  3. Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells

    PubMed Central

    Sun, Zhi-gao; Chen, Li-ping; Wang, Fa-wei; Xu, Cheng-yong; Geng, Miao

    2016-01-01

    The active ingredient of ginseng, ginsenosides Rg1, has been shown to scavenge free radicals and improve antioxidant capacity. This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2. Ginsenosides Rg1 at different concentrations (50 and 100 μM) was used to treat H2O2 (150 μM)-injured SH-SY5Y cells. Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5Y cells injured by H2O2, diminished the amount of leaked lactate dehydrogenase, and increased superoxide dismutase activity. Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity, and contributed to heat shock protein 70 gene expression, in a dose-dependent manner. These results indicate that ginsenoside Rg1 has protective effects on SH-SY5Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis. PMID:27630703

  4. Ameliorative Effect of Ginsenoside Rg1 on Lipopolysaccharide-Induced Cognitive Impairment: Role of Cholinergic System.

    PubMed

    Jin, Yang; Peng, Jian; Wang, Xiaona; Zhang, Dong; Wang, Tianyin

    2017-01-11

    Bacterial endotoxin lipopolysaccharide (LPS) can induce systemic inflammation, and therefore disrupt learning and memory processes. Ginsenoside Rg1, a major bioactive component of ginseng, is shown to greatly improve cognitive function. The present study was designed to further investigate whether administration of ginsenoside Rg1 can ameliorate LPS-induced cognitive impairment in the Y-maze and Morris water maze (MWM) task, and to explore the underlying mechanisms. Results showed that exposure to LPS (500 μg/kg) significantly impaired working and spatial memory and that repeated treatment with ginsenoside Rg1 (200 mg/kg/day, for 30 days) could effectively alleviate the LPS-induced cognitive decline as indicated by increased working and spatial memory in the Y-maze and MWM tests. Furthermore, ginsenoside Rg1 treatment prevented LPS-induced decrease of acetylcholine (ACh) levels and increase of acetylcholinesterase (AChE) activity. Ginsenoside Rg1 treatment also reverted the decrease of alpha7 nicotinic acetylcholine receptor (α7 nAChR) protein expression in the prefrontal cortex (PFC) and hippocampus of LPS-treated rats. These findings suggest that ginsenoside Rg1 has protective effect against LPS-induced cognitive deficit and that prevention of LPS-induced changes in cholinergic system is crucial to this ameliorating effect.

  5. Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling

    PubMed Central

    Li, Jun; Liu, Dong; Wu, Jinfeng; Zhang, Daniel; Cheng, Binbin; Zhang, Yani; Yin, Zifei; Wang, Yuan; Du, Juan; Ling, Changquan

    2016-01-01

    Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plant Panax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells). Pretreatment with Rg1 increased the expression of GR and restored Dex responsiveness to inflammation in UVB-irradiated HaCaT cells. Mechanistically, Rg1 rescued UVB-induced HDAC2 degradation. HDAC2 knockdown partially abolished the Rg1-induced up-regulation of GR and the enhancement of GC sensitivity. In addition, Rg1 reduced the production of reactive oxygen species (ROS), which preceded the up-regulation of HDAC2, and consequent sensitization of cells to Dex. Moreover, Rg1 treatment promoted the translocation and activation of Nrf2. Nrf2 knockdown partially abolished the Rg1-induced decrease of ROS production and increase of HDAC2. Rg1 also potentiated the anti-inflammatory effects of Dex in UVB-irradiated mouse skin. In conclusion, we demonstrated that Rg1 attenuated UVB-induced GC insensitivity. Notably, these effects were partially mediated by the Nrf2/HDAC2 pathway. PMID:27982079

  6. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of D-galactose-induced aging.

    PubMed

    Zhu, Jiahong; Mu, Xinyi; Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus.

  7. Ginsenoside Rg1 Prevents Cognitive Impairment and Hippocampus Senescence in a Rat Model of D-Galactose-Induced Aging

    PubMed Central

    Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus. PMID

  8. Vaccine adjuvant ginsenoside Rg1 enhances immune responses against hepatitis B surface antigen in mice.

    PubMed

    Yuan, Ding; Yuan, Qin; Cui, Qianqian; Liu, Chaoqi; Zhou, Zhiyong; Zhao, Haixia; Dun, Yaoyan; Wang, Ting; Zhang, Changcheng

    2016-06-01

    The adjuvant effect of ginsenoside Rg1 on immune responses against hepatitis B surface antigen (HBsAg) in mice was investigated. Female BALB/c mice were subcutaneously injected with saline or HBsAg antigen with or without Rg1 on days 7 and 21. Samples were collected 2 weeks after the boosting for the detection of anti-HBsAg immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced in splenocytes. The innate and adaptive immune responses were measured in mice immunized as described above. The results showed that ginsenoside Rg1 had adjuvant properties in stimulating IgG, splenocyte proliferation, and mRNA expression of cytokines IFN-γ and IL-4, as well as the expression of cell surface marker TLR4 in the HBsAg-immunized mice. These results indicate that Rg1 enhances both Th1 (IgG2b and IFN-γ) and Th2 (IgG1 and IL-4) responses. In addition, the TLR4 signaling pathway is involved in the adjuvant activities of ginsenoside Rg1.

  9. Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice.

    PubMed

    Gao, Yan; Chu, Shifeng; Shao, Qianhang; Zhang, Meijin; Xia, Congyuan; Wang, Yingying; Li, Yueting; Lou, Yuxia; Huang, Huiyong; Chen, Naihong

    2017-01-01

    Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62-Keap1-Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.

  10. The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice

    PubMed Central

    Zhao, Qun; Yang, Min; Deng, Yanping; Yu, Haitao; Wang, Linlin; Teng, Fukang; Cho, Kenka; Ma, Hongmei; Wu, Peng; Li, Xue; Wu, Wanying; Liu, Xuan; Xu, Feng; Jiang, Baohong; Guo, De-An

    2015-01-01

    Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination. PMID:26690140

  11. The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.

    PubMed

    Zhao, Qun; Yang, Min; Deng, Yanping; Yu, Haitao; Wang, Linlin; Teng, Fukang; Cho, Kenka; Ma, Hongmei; Wu, Peng; Li, Xue; Wu, Wanying; Liu, Xuan; Xu, Feng; Jiang, Baohong; Guo, De-An

    2015-12-09

    Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination.

  12. [Research of anti-aging mechanism of ginsenoside Rg1 on brain].

    PubMed

    Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

    2014-11-01

    Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

  13. Characterization of oxygenated metabolites of ginsenoside Rg1 in plasma and urine of rat.

    PubMed

    Wang, Jing-Rong; Tong, Tian-Tian; Yau, Lee-Fong; Chen, Cheng-Yu; Bai, Li-Ping; Ma, Jing; Hu, Ming; Liu, Liang; Jiang, Zhi-Hong

    2016-07-15

    This study describes the characterization of oxygenated metabolites of ginsenoside Rg1 in rat urine and plasma. These in vivo metabolites were profiled by using UHPLC-QTOF MS-based method. On the basis of high-resolution MS/MS data, and comparison with chemically synthesized authentic compounds, nine oxygenated metabolites of Rg1 were characterized as vinaginsenosides 21 and 22 (M1 and M2), vinaginsenoside R15 (M3), 6-O-(β-d-glucopyranosyl)-20-O-(β-d-glucopyranosyl) 3β, 6α, 12β, 20(S)-tetrahydroxy-24ξ-hydroxydammar-25-ene (M4 and M5), floralginsenoside A (M7 and M8), floralginsenoside B (M9) and epoxyginsenoside Rg1 (M13), respectively. Among these metabolites, M4, M5 and M13 are new ginsenosides and others were detected as in vivo metabolites of Rg1 for the first time. In addition, a series of oxygenated metabolites of Rh1 and deglycosylated metabolite of Rg1, were observed and characterized by comparing with compounds synthesized by us, which revealed an association between C-20 configuration and the extent of oxidation metabolism. Appearance of all these metabolites in blood stream and urine after i.v. dosing and oral administration of Rg1 was further examined, which clearly showed that mono-oxygenated metabolites of Rg1 were major circulating metabolites at the early stage after dosing. Characterization of exact chemical structures of these circulating metabolites contribute greatly to our understanding of chemical exposure after consumption of ginseng products, and provide valuable information for explaining multiple bioactivities of ginseng products.

  14. Near-infrared reflectance spectroscopy (NIRS) for rapid determination of ginsenoside Rg1 and Re in Chinese patent medicine Naosaitong pill

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Qu, Zhengyi; Wang, Yingping; Yao, Chunlin; Bai, Xueyuan; Bian, Shuai; Zhao, Bing

    2015-03-01

    Ginsenosides in plant samples have been extensively studied because protopanaxadiol saponins are ubiquitous in Chinese patent medicines, in which they can be used in promoting human health as the main active ingredients. A method for rapid determination of two ginsenosides (Rg1 and Re) in Naosaitong (NST) samples using near-infrared reflectance spectroscopy (NIRS) is studied to determine the contents of ginsenoside Rg1 and Re in this work. Partial least square (PLS) regression was used for building the calibration models, and the effects of spectral preprocessing and variable selection on the models are investigated for optimization of the models. A total of 93 samples were scanned by NIRS, and also by high performance liquid chromatography coupled to a diode array detector to determine the contents of ginsenoside Rg1 and Re. The calibration models for Rg1 and Re had high values of the coefficient of determination (R2) (0.9766 and 0.9764) and low root mean square error of cross validation (RMSECV) (0.0136 and 0.0104), and the values of the standard error of prediction set (SEP) are 0.00764 and 0.0103, which indicate a good correlation between reference values and NIRS predicted values. The overall results show that NIRS could be applied for the rapid determination of the contents of ginsenosides in Ginseng byproducts for pharmaceuticals that develop high-quality Chinese patent medicines.

  15. A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson's Disease

    PubMed Central

    Song, Liang; Xu, Meng-Bei; Zhou, Xiao-Li; Zhang, Dao-pei

    2017-01-01

    To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0.01), two studies for improving the swim-score values (P < 0.01), six studies for improving the level of TH protein expression (P < 0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P < 0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n = 10), antioxidant stress (n = 3), and antiapoptosis (n = 11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials. PMID:28386306

  16. Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection

    PubMed Central

    Cheng, Wendan; Jing, Juehua; Wang, Zhen; Wu, Dongying; Huang, Yumin

    2017-01-01

    This study aimed to assess whether Ginsenoside Rg1 (Rg1) inhibits inflammatory responses in human chondrocytes and reduces articular cartilage damage in a rat model of osteoarthritis (OA). Gene expression and protein levels of type II collagen, aggrecan, matrix metalloproteinase (MMP)-13 and cyclooxygenase-2 (COX-2) were determined in vitro by quantitative real-time-polymerase chain reaction and Western blotting. Prostaglandin E2 (PGE2) amounts in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA). For in vivo assessment, a rat model of OA was generated by anterior cruciate ligament transection (ACLT). Four weeks after ACLT, Rg1 (30 or 60 mg/kg) or saline was administered by gavage once a day for eight consecutive weeks. Joint damage was analyzed by histology and immunohistochemistry. Ginsenoside Rg1 inhibited Interleukin (IL)-1β-induced chondrocyte gene and protein expressions of MMP-13, COX-2 and PGE2, and prevented type II collagen and aggrecan degradation, in a dose-dependent manner. Administration of Ginsenoside Rg1 to OA rats attenuated cartilage degeneration, and reduced type II collagen loss and MMP-13 levels. These findings demonstrated that Ginsenoside Rg1 can inhibit inflammatory responses in human chondrocytes in vitro and reduce articular cartilage damage in vivo, confirming the potential therapeutic value of Ginsenoside Rg1 in OA. PMID:28287423

  17. Purity assessment of ginsenoside Rg1 using quantitative (1)H nuclear magnetic resonance.

    PubMed

    Huang, Bao-Ming; Xiao, Sheng-Yuan; Chen, Ting-Bo; Xie, Ying; Luo, Pei; Liu, Liang; Zhou, Hua

    2017-05-30

    Ginseng herbs comprise a group of the most popular herbs, including Panax ginseng, P. notoginseng and P. quinquefolius (Family Araliaceae), which are used as traditional Chinese medicine (TCM) and are some of the best-selling natural products in the world. The accurate quantification of ginsenoside Rg1 is one of the major aspects of its quality control. However, the purity of the commercial Rg1 chemical reference substance (CRS) is often measured with high-performance chromatography coupled with an ultraviolet detector (HPLC-UV), which is a selective detector with unequal responses to different compounds; thus, this detector introduces probable error to purity assessments. In the present study, quantitative nuclear magnetic resonance (qNMR), due to its absolute quantification ability, was applied to accurately assess the purity of Rg1 CRS. Phenylmethyl phthalate was used as the internal standard (IS) to calibrate the purity of Rg1 CRS. The proton signal of Rg1 CRS in methanol-d4 at 4.37ppm was selected to avoid interfering signals, enabling accurate quantitative analysis. The relaxation delay, number of scans, and NMR windowing were optimized for data acquisition. For post-processing, the Lorentz/Gauss deconvolution method was employed to increase the signal accuracy by separating the impurities and noise in the integrated region of the quantitative proton. The method validation showed that the developed method has acceptable sensitivity, linearity, precision, and accuracy. The purity of the commercial Rg1 CRS examined with the method developed in this research was 90.34±0.21%, which was obviously lower than that reported by the manufacturer (>98.0%, HPLC-UV). The cross-method validation shows that the commonly used HPLC-UV, HPLC-ELSD (evaporative light scattering detector) and even LC-MS (mass spectrometry) methods provide significantly higher purity values of Rg1 CRS compared with the qNMR method, and the accuracy of these LC-based methods largely depend on the

  18. Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cell function for soft tissue regeneration.

    PubMed

    Xu, Fang-Tian; Liang, Zhi-Jie; Li, Hong-Mian; Peng, Qi-Liu; Huang, Min-Hong; Li, De Quan; Liang, Yi-Dan; Chi, Gang-Yi; Li, De Hui; Yu, Bing-Chao; Huang, Ji-Rong

    2016-06-07

    Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering.

  19. Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cells function for soft tissue regeneration

    PubMed Central

    Li, Hong-Mian; Peng, Qi-Liu; Huang, Min-Hong; Li, De-Quan; Liang, Yi-Dan; Chi, Gang-Yi; Li, De-Hui; Yu, Bing-Chao; Huang, Ji-Rong

    2016-01-01

    Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering. PMID:27191987

  20. Ginsenoside Rg1-induced antidepressant effects involve the protection of astrocyte gap junctions within the prefrontal cortex.

    PubMed

    Jin, Can; Wang, Zhen-Zhen; Zhou, Heng; Lou, Yu-Xia; Chen, Jiao; Zuo, Wei; Tian, Man-Tong; Wang, Zhi-Qi; Du, Guo-Hua; Kawahata, Ichiro; Yamakuni, Tohru; Zhang, Yi; Chen, Nai-Hong; Zhang, Dan-Shen

    2017-04-03

    Ginsenoside Rg1 (Rg1) exhibits antidepressant-like activity by increasing neurogenesis and dendritic spine density without discernible side effects. However, the molecular mechanisms underlying Rg1 antidepressant activity remain poorly understood. As the dysfunction of gap junctions between astrocytes in the prefrontal cortex (PFC) is implicated in major depression disorder, the aim of this study was to investigate the effects of Rg1 on astrocyte gap junctions in the PFC. Rats exposed to chronic unpredictable stress (CUS) were administered Rg1 (5, 10, and 20mg/kg) for 28days and analyzed for depressive symptoms using the sucrose preference and forced swimming tests. Functional and morphological changes of gap junction channels in the PFC were evaluated using dye transfer and electron microscopy, respectively. The expression of connexin 43 (Cx43) was analyzed by western blotting. Rg1 markedly alleviated depression-like behavior in rats. Long-term Rg1 treatment of CUS-exposed rats also significantly prevented the decrease in dye diffusion and improved the ultrastructure of astrocyte gap junctions in the PFC, indicating beneficial effects on the functional activity of gap junction channels in the brain. In addition, Rg1 upregulated Cx43 expression in the PFC reduced by CUS exposure, which significantly correlated with its antidepressant-like effects. The results demonstrate that Rg1-induced antidepressant effects are might be mediated, in part, by protecting astrocyte gap junctions within the prefrontal cortex.

  1. Ginsenoside Rg-1 protects retinal pigment epithelium (RPE) cells from cobalt chloride (CoCl2) and hypoxia assaults.

    PubMed

    Li, Ke-Ran; Zhang, Zhi-Qing; Yao, Jin; Zhao, Yu-Xia; Duan, Jing; Cao, Cong; Jiang, Qin

    2013-01-01

    Severe retinal ischemia causes persistent visual impairments in eye diseases. Retinal pigment epithelium (RPE) cells are located near the choroidal capillaries, and are easily affected by ischemic or hypoxia. Ginsenoside Rg-1 has shown significant neuroprotective effects. This study was performed to test the cytoprotective effect of ginsenoside Rg-1 in RPE cells against hypoxia and cobalt chloride (CoCl2) assaults, and to understand the underlying mechanisms. We found that Rg-1 pre-administration significantly inhibited CoCl2- and hypoxia-induced RPE cell death and apoptosis. Reactive oxygen specisis (ROS)-dependent p38 and c-Jun NH(2)-terminal kinases (JNK) MAPK activation was required for CoCl2-induced RPE cell death, and Rg-1 pre-treatment significantly inhibited ROS production and following p38/JNK activation. Further, CoCl2 suppressed pro-survival mTOR complex 1 (mTORC1) activation in RPE cells through activating of AMP-activated protein kinase (AMPK), while Rg-1 restored mTORC1 activity through inhibiting AMPK activation. CoCl2-induced AMPK activation was also dependent on ROS production, and anti-oxidant N-acetylcysteine (NAC) prevented AMPK activation and RPE cell death by CoCl2. Our results indicated that Rg-1 could be further investigated as a novel cell-protective agent for retinal ischemia.

  2. Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats.

    PubMed

    Deng, Yanping; Yang, Min; Xu, Feng; Zhang, Qian; Zhao, Qun; Yu, Haitao; Li, Defang; Zhang, Ge; Lu, Aiping; Cho, Kenka; Teng, Fukang; Wu, Peng; Wang, Linlin; Wu, Wanying; Liu, Xuan; Guo, De-An; Jiang, Baohong

    2015-01-01

    Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.

  3. Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Deng, Yanping; Yang, Min; Xu, Feng; Zhang, Qian; Zhao, Qun; Yu, Haitao; Li, Defang; Zhang, Ge; Lu, Aiping; Cho, Kenka; Teng, Fukang; Wu, Peng; Wang, Linlin; Wu, Wanying; Liu, Xuan; Guo, De-an; Jiang, Baohong

    2015-01-01

    Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury. PMID:26280455

  4. Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

    PubMed Central

    Li, Jian-ping; Gao, Yan; Chu, Shi-feng; Zhang, Zhao; Xia, Cong-yuan; Mou, Zheng; Song, Xiu-yun; He, Wen-bin; Guo, Xiao-feng; Chen, Nai-hong

    2014-01-01

    Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes. PMID:24976156

  5. Ginsenoside Rg1 Protects against Oxidative Stress-induced Neuronal Apoptosis through Myosin IIA-actin Related Cytoskeletal Reorganization

    PubMed Central

    Wang, Yan; Liu, Qian; Xu, Yingqiong; Zhang, Yuanyuan; Lv, Yanni; Tan, Yisha; Jiang, Nan; Cao, Guosheng; Ma, Xiaonan; Wang, Jingrong; Cao, Zhengyu; Yu, Boyang; Kou, Junping

    2016-01-01

    Oxidative stress-induced cytoskeletal dysfunction of neurons has been implicated as a crucial cause of cell apoptosis or death in the central nervous system (CNS) diseases, such as neurodegenerative and psychiatric diseases. The application of neuroprotectants rescuing the neurons from cytoskeletal damage and apoptosis can be a potential treatment for these CNS diseases. Ginsenoside Rg1 (Rg1), one of the major active components of ginseng, has been reported possessing notable neuroprotective activities. However, there is rare report about its effect on cytoskeleton and its undergoing mechanism. The current study is to reveal the regulatory effects of Rg1 on cytoskeletal and morphological lesion in oxidative stress-induced neuronal apoptosis. The results demonstrated that pre-treatment with Rg1 (0.1-10 μM) attenuated hydrogen peroxide (H2O2)-induced neuronal apoptosis and oxidative stress through reducing the intracellular reactive oxygen species (ROS) production and methane dicarboxylic aldehyde (MDA) level. The Rg1 treatment also abolished H2O2-induced morphological changes, including cell rounding, membrane blebbing, neurite retraction and nuclei condensation, which were generated by myosin IIA-actin interaction. These effects were mediated via the down-regulation of caspase-3, ROCK1 (Rho-associated kinase1) activation and myosin light chain (MLC, Ser-19) phosphorylation. Furthermore, inhibiting myosin II activity with blebbistatin partly blocked the neuroprotective effects of Rg1. The computer-aided homology modelling revealed that Rg1 preferentially positioned in the actin binding cleft of myosin IIA and might block the binding of myosin IIA to actin filaments. Accordingly, the neuroprotective mechanism of Rg1 is related to the activity that inhibits myosin IIA-actin interaction and the caspase-3/ROCK1/MLC signaling pathway. These findings put some insights into the unique neuroprotective properties of Rg1 associated with the regulation of myosin IIA

  6. Protective effects of ginsenoside Rg1 on chronic restraint stress induced learning and memory impairments in male mice.

    PubMed

    Wang, Yuchan; Kan, Hongwei; Yin, Yanyan; Wu, Wangyang; Hu, Wen; Wang, Mingming; Li, Weiping; Li, Weizu

    2014-05-01

    Alzheimer's disease (AD) is one of the major neurological diseases of the elderly. Chronic stress, which can induce atrophy and functional impairments in several key brain areas such as the frontal cortex and hippocampus, plays an important role in the generation and progression of AD. Currently, there are no effective drug treatment options for preventing chronic stress induced learning and memory impairments and neuronal damage. Ginsenoside Rg1 (Rg1) is a steroidal saponin abundantly contained in ginseng. This study explored the neuroprotective effects of Rg1 on chronic restraint stress (CRS) induced learning and memory impairments in a mouse model. Our results showed that Rg1 (5mg/kg) significantly protected against learning and memory impairments induced by CRS in a Morris water maze. Besides, Rg1 (2, 5mg/kg) was able to decrease ROS generation and attenuate the neuronal oxidative damage in the frontal cortex and hippocampus CA1 in mice. Additionally, the inhibition of NOX2, p47phox and RAC1 expression is also involved in the action mechanisms of Rg1 in this experimental model. This study provided an experimental basis for the clinical application of Rg1 in chronic stress induced neuronal oxidative damage.

  7. Ginsenoside Rg1 prevents cerebral and cerebellar injury induced by obstructive jaundice in rats via inducing expression of TIPE-2.

    PubMed

    Zhou, Tingting; Zu, Guo; Zhou, Lu; Che, Ningwei; Guo, Jing; Liang, Zhanhua

    2016-01-01

    The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg(-1)d(-1) or 20 mg kg(-1) d(-1)). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats.

  8. Drug-eluting coating of ginsenoside Rg1 and Re incorporated poly(lactic-co-glycolic acid) on stainless steel 316L: Physicochemical and drug release analyses.

    PubMed

    Miswan, Zulaika; Lukman, Siti Khadijah; Abd Majid, Fadzilah Adibah; Loke, Mun Fai; Saidin, Syafiqah; Hermawan, Hendra

    2016-12-30

    Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent.

  9. Characterizing a full spectrum of physico-chemical properties of ginsenosides rb1 and rg1 to be proposed as standard reference materials.

    PubMed

    Kim, Il-Woung; Hong, Hee-Do; Choi, Sang Yoon; Hwang, Da-Hye; Her, Youl; Kim, Si-Kwan

    2011-11-01

    Good manufacturing practice (GMP)-based quality control is an integral component of the common technical document, a formal documentation process for applying a marketing authorization holder to those countries where ginseng is classified as a medicine. In addition, authentication of the physico-chemical properties of ginsenoside reference materials, and qualitative and quantitative batch analytical data based on validated analytical procedures are prerequisites for certifying GMP. Therefore, the aim of this study was to propose an authentication process for isolated ginsenosides Rb1 and Rg1 as reference materials (RM) and for these compounds to be designated as RMs for ginseng preparations throughout the world. Ginsenoside Rb1 and Rg1 were isolated by Diaion HP-20 adsorption chromatography, silica gel flash chromatography, recrystallization, and preparative HPLC. HPLC fractions corresponding to those two ginsenosides were recrystallized in appropriate solvents for the analysis of physico-chemical properties. Documentation of the isolated ginsenosides was made according to the method proposed by Gaedcke and Steinhoff. The ginsenosides were subjected to analyses of their general characteristics, identification, purity, content quantitation, and mass balance tests. The isolated ginsenosides were proven to be a single compound when analyzed by three different HPLC systems. Also, the water content was found to be 0.940% for Rb1 and 0.485% for Rg1, meaning that the net mass balance for ginsenoside Rb1 and Rg1 were 99.060% and 99.515%, respectively. From these results, we could assess and propose a full spectrum of physicochemical properties for the ginsenosides Rb1 and Rg1 as standard reference materials for GMP-based quality control.

  10. Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine-induced learning and memory impairment in mice.

    PubMed

    Wang, Qiong; Sun, Li-Hua; Jia, William; Liu, Xin-Min; Dang, Hai-Xia; Mai, Wen-Li; Wang, Ning; Steinmetz, Andre; Wang, Yu-Qin; Xu, Chang-Jiang

    2010-12-01

    Rg1 and Rb1 are two major active compounds of ginseng that facilitate learning and memory. The present study aimed to compare the nootropic effects of Rg1 and Rb1 in a scopolamine induced dementia mice model. After 6 and 12 mg/kg of Rg1 and Rb1 intraperitoneal administration to mice for 7 days, their effects were assessed using the step-down passive avoidance (SD) and the Morris water maze (MWM) tests, the acetylcholinesterase (AChE) activity, acetylcholine (ACh) content and serotonin (5-HT) level in the hippocampus were analysed after SD and MWM tests. The results showed that Rg1 and Rb1 ameliorated cognition-deficiency in mice with dementia. Rg1 showed stronger effects than Rb1 on escape acquisition in MWM. Both Rg1 and Rb1 increased ACh levels in the hippocampus, but Rg1 inhibited AChE activity while Rb1 had no effect on AChE activity. Both Rg1 and Rb1 inhibited the decrease of 5-HT induced by scopolamine, but Rb1 was more active than the same dose of Rg1. These results demonstrate that multiple administrations of Rg1 and Rb1 are effective in improving memory deficiency induced by scopolamine. Rg1 appears to be more potent than Rb1 in improving acquisition impairment, and the two ginsenosides may act through different mechanisms.

  11. Optimization of combinations of ginsenoside-Rg1, ginsenoside-Rb1, evodiamine and rutaecarpine for effective therapy of mouse migraine.

    PubMed

    Wu, Yanchuan; Pan, Xueqiang; Xu, Yongsong; Lu, Xuran; He, Shida; He, Rui; Gong, Muxin

    2016-04-01

    Wuzhuyu decoction (WZYD) is a classic traditional Chinese medicine (TCM) formula. It has been extensively used for treating migraine for thousands of years in TCM. Four potential active ingredients from WZYD, ginsenoside-Rg1 (Rg1), ginsenoside-Rb1 (Rb1), evodiamine (Ev) and rutaecarpine (Ru), were found to have positive correlations with pharmacodynamic indicators involving mouse migraine in our previous study. To find a better therapeutic effect on migraine, this research was carried out to optimize the combinations of Rg1, Rb1, Ev and Ru using the uniform design method. The results showed that Rb1 and Ev played key roles in improving the therapeutic effect on mouse migraine by strongly ameliorating pharmacodynamic indicators associated with migraine. They significantly increased the contents of 5-hydroxytryptamine, noradrenaline and dopamine in brain tissues, and reduced the content of nitric oxide in brain tissues and the activities of nitric oxide synthase in both brain tissues and blood serum. The optimal concentrations of Rb1 and Ev were 1057.4 mg/L and 312.5 mg/L, respectively. Rg1 and Ru contributed less to the overall desirability, suggesting that they had reverse effects on some pharmacodynamic indicators of this type of migraine. The verification test demonstrated by the immunohistochemical method that the optimal combination inhibited the expression of c-fos and c-jun in periaqueductal gray of mice, and strongly ameliorated pharmacodynamic indicators. These results suggested that the therapeutic effect of the optimal combination of the four ingredients was strong, and the optimal results were proven to be reliable and accurate.

  12. Ginsenoside Rg1 attenuates hypoxia and hypercapnia-induced vasoconstriction in isolated rat pulmonary arterial rings by reducing the expression of p38

    PubMed Central

    Zheng, Mengxiao; Zhao, Meiping; Tang, Lanlan; Zhang, Congcong; Song, Longsheng

    2016-01-01

    Background Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arteriolar resistance. Pulmonary vasoconstriction has been proved to play a significant role in PAH. We previously reported that Panax notoginseng saponins (PNS) might attenuate hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). Methods In the present study, our specific objective was to investigate the role of ginsenoside Rg1, a major component of PNS, in this process and the possible underlying mechanism. The second order pulmonary rings isolated from the Sprague-Dawley rats were treated with different dosage of ginsenoside Rg1 at 8, 40, or 100 mg/L respectively, both before and during the conditions of hypoxia and hypercapnia. Contractile force changes of the rings were detected. Furthermore, SB203580, the selective inhibitor for p38 activation was applied to the rings. Pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and ginsenoside Rg1 was administered to detect the changes induced by p38. Results Under the hypoxic and hypercapnic conditions, we observed a biphasic pulmonary artery contractile response to the second pulmonary artery rings. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by ginsenoside Rg1. This effect was significantly reinforced by SB203580 (P<0.05 or P<0.01). The expression of p38 in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (P<0.05 or P<0.01) and the observed activation was attenuated by ginsenoside Rg1 (P<0.05 or P<0.01). Conclusions Our findings strongly support the significant role of ginsenoside Rg1 in the inhibition of hypoxia and hypercapnia-induced vasoconstriction by the p38 pathway. PMID:27499938

  13. The Beneficial Effect of Ginsenoside Rg1 on Schwann Cells Subjected to Hydrogen Peroxide Induced Oxidative Injury

    PubMed Central

    Ma, Junxiong; Liu, Jun; Wang, Qi; Yu, Hailong; Chen, Yu; Xiang, Liangbi

    2013-01-01

    Ginsenoside Rg1 (GRg1) has been considered to have therapeutic potential in promoting peripheral nerve regeneration and functional recovery after sciatic nerve injuries. However, the mechanism underlying the beneficial effect of GRg1 on peripheral nerve regeneration is currently unclear. The possible effect of GRg1 on Schwann cells (SCs), which were subjected to oxidative injury after nerve injury, might contribute to the beneficial effect of GRg1 on nerve regeneration. The present study was designed to investigate the potential beneficial effect of GRg1 on SCs exposed to oxidative injury. The oxidative injury to SCs was induced by hydrogen peroxide. The effect of GRg1 (50 μM) on SCs exposed to oxidative injury was measured by the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in SCs. The cell number and cell viability of SCs were evaluated through fluorescence observation and MTT assay. The apoptosis of SCs induced by oxidative injury was evaluated by an apoptosis assay. The expression and secretion of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were evaluated using RT-PCR, Western blotting, and an ELISA method. We found that GRg1 significantly up-regulated the level of SOD, GSH and CAT, and decreased the level of MDA in SCs treated with hydrogen peroxide. In addition, GRg1 has been shown to be able to inhibit the proapoptotic effect of hydrogen peroxide, as well as inhibit the detrimental effect of hydrogen peroxide on cell number and cell viability. Furthermore, GRg1 also increased the mRNA levels, protein levels and secretion of NGF and BDNF in SCs after incubation of hydrogen peroxide. Further study showed that preincubation with H89 (a PKA inhibitor) significantly inhibited the effects induced by hydrogen peroxide, indicating that the PKA pathway might be involved in the antioxidant effect and neurotrophic factors (NTFs) promoting effect of GRg1. In addition, a short-term in vivo

  14. Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

    PubMed Central

    Zu, Guo; Guo, Jing; Che, Ningwei; Zhou, Tingting; Zhang, Xiangwen

    2016-01-01

    Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury. PMID:27910952

  15. Protective Effect of Ginsenosides Rg1 and Re on Lipopolysaccharide-Induced Sepsis by Competitive Binding to Toll-Like Receptor 4

    PubMed Central

    Su, Fei; Xue, Yin; Wang, Yuemin; Zhang, Lili; Chen, Wangxue

    2015-01-01

    We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor α, interleukin-1β, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent. PMID:26149990

  16. Mechanism of ginsenoside Rg1 renal protection in a mouse model of d-galactose-induced subacute damage.

    PubMed

    Fan, Yanling; Xia, Jieyu; Jia, Daoyong; Zhang, Mengsi; Zhang, Yanyan; Huang, Guoning; Wang, Yaping

    2016-09-01

    Context Ginseng is a widely used herbal medicine in China but its mechanism of action remains unclear. Objective The objectives of this work were to study the protective effect of ginsenoside Rg1 on subacute murine renal damage induced by d-galactose and its mechanism. Materials and methods C57BL/6J mice were injected with 120 mg/kg/d (sc) d-galactose for 1 week, followed by a combined treatment of Rg1 20 mg/kg/d (ip) and 120 mg/kg/d d-galactose (sc) for 5 weeks. Mice were injected with the 0.9% saline 0.2 mL/d (sc) and 120 mg/kg/d d-galactose (sc) for 6 weeks in the control group and the d-galactose group, respectively. After 6 weeks, urea, creatinine, uric acid, cystatin (Cys-C), senescence-associated β-galactosidase (SA-β-gal) staining positive kidney cells, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG) were measured. Results Treatment with Rg1 ameliorated kidney function and aging state (urea from 17.19 ± 1.09 to 15.77 ± 1.22 mmol·L (-) (1), creatinine from 29.40 ± 5.72 to 22.60 ± 3.97 μmol·L (-) (1), uric acid from 86.80 ± 5.97 to 72.80 ± 10.61 μmol·L (-) (1), Cys-C from 0.23 ± 0.03 to 0.18 ± 0.05 mg·L (-) (1), ROD of SA-β-gal from 56.32 ± 10.48 to 26.78 ± 7.34, SOD from 150.22 ± 19.07 to 190.56 ± 15.83 U·(mg·prot) (-1), MDA from 9.28 ± 1.59 to 3.17 ± 0.82 nmol·(mg·prot) (-1), GSH-PX from 15.68 ± 2.11 to 20.32 ± 2.96 U·(mg·prot) (-1) as well as regulated glomerulus morphology (glomerulus diameter from 775.77 ± 18.41 to 695.04 ± 14.61 μm, renal capsule width from 39.56 ± 3.51 to 31.42 ± 2.70 μm, glomerulus basement membrane from 206.03 ± 16.22 to 157.27 ± 15.70 nm, podocyte slit from 55.21 ± 8.55 to 37.63 ± 6.65 nm). Conclusions Ginsenoside Rg1 can antagonise d

  17. Ginsenoside Rg1 Decreases Aβ1–42 Level by Upregulating PPARγ and IDE Expression in the Hippocampus of a Rat Model of Alzheimer's Disease

    PubMed Central

    Quan, QianKun; Wang, Jue; Li, Xi; Wang, Yi

    2013-01-01

    Background and Purpose The present study was designed to examine the effects of ginsenoside Rg1 on expression of peroxisome proliferator-activated receptor γ (PPARγ) and insulin-degrading enzyme (IDE) in the hippocampus of rat model of Alzheimer's disease (AD) to determine how ginsenoside Rg1 (Rg1) decreases Aβ levels in AD. Experimental Approach Experimental AD was induced in rats by a bilateral injection of 10 µg soluble beta-amyloid peptide 1–42 (Aβ1–42) into the CA1 region of the hippocampus, and the rats were treated with Rg1 (10 mg·kg−1, intraperitoneally) for 28 days. The Morris water maze was used to test spatial learning and memory performance. Hematoxylin-eosin staining was performed to analyze the hippocampal histopathological damage. Immunohistochemistry, western blotting, and real-time PCR were used to detect Aβ1–42, PPARγ, and insulin-degrading enzyme (IDE) expression in the hippocampus. Key Results Injection of soluble Aβ1–42 into the hippocampus led to significant dysfunction of learning and memory, hippocampal histopathological abnormalities and increased Aβ1–42 levels in the hippocampus. Rg1 treatment significantly improved learning and memory function, attenuated hippocampal histopathological abnormalities, reduced Aβ1–42 levels and increased PPARγ and IDE expression in the hippocampus; these effects of Rg1 could be effectively inhibited by GW9662, a PPARγ antagonist. Conclusions and Implications Given that PPARγ can upregulate IDE expression and IDE can degrade Aβ1–42, these results indicate that Rg1 can increase IDE expression in the hippocampus by upregulating PPARγ, leading to decreased Aβ levels, attenuated hippocampal histopathological abnormalities and improved learning and memory in a rat model of AD. PMID:23520555

  18. Effects of Ginsenoside Rg1 on Learning and Memory in a Reward-directed Instrumental Conditioning Task in Chronic Restraint Stressed Rats.

    PubMed

    Kezhu, Wang; Pan, Xu; Cong, Lu; Liming, Dong; Beiyue, Zhang; Jingwei, Lu; Yanyan, Yang; Xinmin, Liu

    2017-01-01

    Ginsenoside Rg1 is one of the major active ingredients of Panax ginseng and has showed notable improving learning and memory effects in several behavioral tasks, such as water maze, shuttle-box, and step-through, based on avoidance. However, there was no report about the role of Rg1 on the performance of reward-directed instrumental conditioning, which could reflect the adaptive capacity to ever-changing environments. Thus, in this study, the reward devaluation test and conditional visual discrimination task were conducted to study the ameliorating effects of Rg1 on cognitive deficits, especially the loss of adaptation capacity in chronic restraint stress (CRS) rat model. Our results showed that rat subjected to CRS became insensitive to the changes in outcome value, and it significantly harmed the rat's performance in conditional visual discrimination task. Moreover, the levels of BDNF, TrkB, and Erk phosphorylation were decreased in the prefrontal cortex of CRS rats. However, these changes were effectively reversed by Rg1 (5 and 10 mg/kg, i.p.). Therefore, it demonstrated that Rg1 has a good ability to improve learning and memory and also ameliorate impaired adaptive capacity induced by CRS. This amelioration effect of Rg1 might be mediated partially by BDNF/TrkB/Erk pathway in prefrontal cortex. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Carbon nanotubes as carriers of Panax ginseng metabolites and enhancers of ginsenosides Rb1 and Rg1 anti-cancer activity

    NASA Astrophysics Data System (ADS)

    Lahiani, Mohamed H.; Eassa, Souzan; Parnell, Charlette; Nima, Zeid; Ghosh, Anindya; Biris, Alexandru S.; Khodakovskaya, Mariya V.

    2017-01-01

    A major benefit to nanomaterial based-medicine is the ability to provide nanosized vehicles for sporadic metabolites. Here, we describe how the conjugation of valuable ginseng secondary metabolites (ginsenoside Rb1 or Rg1) with carbon nanotubes (CNT) can enhance their anti-proliferative and anti-cancer effects. Ginsenoside-CNT conjugate (Rb-CNT or Rg-CNT) permitted the ginsenosides to be used at a low dose, yet achieve a higher incidence of cancer killing. We were able to demonstrate that the ginsenoside-CNT conjugate can decrease cell viability up to 62% in breast cancer cells (MCF-7) and enhance antiproliferation of drug-resistant pancreatic cancer cells (PANC-1) by 61%. The interaction of the ginsenoside-CNT conjugate with breast cancer cells was studied using Raman Spectroscopy mapping. Total transcriptome profiling (Affymetrix platform) of MCF-7 cells treated with the ginsenoside-CNT conjugate shows that a number of cellular, apoptotic and response to stimulus processes were affected. Therefore, our data confirmed the potential use of CNT as a drug delivery system.

  20. Synergistic Use of Geniposide and Ginsenoside Rg1 Balance Microglial TNF-α and TGF-β1 following Oxygen-Glucose Deprivation In Vitro: A Genome-Wide Survey

    PubMed Central

    Wang, Jun; Hou, Jincai; Zhao, Hui; Liu, Jianxun

    2015-01-01

    Ischemia-activated microglia are like a double-edged sword, characterized by both neurotoxic and neuroprotective effects. The aim of this study was to reveal the synergistic effect of geniposide and ginsenoside Rg1 based on tumor necrosis factor- (TNF-) α and transforming growth factor- (TGF-) β1 balance of microglia. BV2 microglial cells were divided into 5 groups: control, model (oxygen-glucose deprivation (OGD)), geniposide-treated, ginsenoside-Rg1-treated, and combination-treated. A series of assays were used to detect on (i) cell viability; (ii) NO content; (iii) expression (content) of TNF-α and TGF-β1; and (iv) gene expression profiles. The results showed that integrated use of geniposide and ginsenoside Rg1 significantly inhibited NO level and protected cell viability, improved the content and expression of TGF-β1, and reduced the content and expression of TNF-α. Separated use of geniposide or ginsenoside Rg1 showed different effects at different emphases. Next-generation sequencing showed that Fcγ-receptor-mediated phagocytosis pathway played a key regulatory role in the balance of TNF-α and TGF-β1 when cotreated with geniposide and ginsenoside Rg1. These findings suggest that synergistic drug combination of geniposide and ginsenoside Rg1 in the treatment of stroke is a feasible avenue for the application. PMID:26693244

  1. Protective Effect of Ginsenoside Rg1 on Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of Caveolin-1 and TGF-β1 Signal Pathway.

    PubMed

    Zhan, Heqin; Huang, Feng; Ma, Wenzhuo; Zhao, Zhenghang; Zhang, Haifang; Zhang, Chong

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and high mortality rate. Panax Notoginseng Saponins (PNS), extracted from Panax Notoginseng as a traditional Asian medicine, displayed a significant anti-fibrosis effect in liver and lung. However, whether Ginsenoside Rg1 (Rg1), an important and active ingredient of PNS, exerts anti-fibrotic activity on IPF still remain unclear. In this study, we investigated the effect of Rg1 on bleomycin-induced pulmonary fibrosis in rats. Bleomycin (5 mg/kg body weight) was intratracheally administrated to male rats. Rg1 (18, 36 and 72 mg/kg) was orally administered on the next day after bleomycin. Lungs were harvested at day 7 and 28 for the further experiments. Histological analysis revealed that bleomycin successfully induced pulmonary fibrosis, and that Rg1 restored the histological alteration of bleomycin-induced pulmonary fibrosis (PF), significantly decreased lung coefficient, scores of alveolitis, scores of PF as well as contents of alpha smooth muscle actin (α-SMA) and hydroxyproline (Hyp) in a dose-dependent manner in PF rats. Moreover, Rg1 increased the expression levels of Caveolin-1 (Cav-1) mRNA and protein, lowered the expression of transforming growth factor-β1 (TGF-β1) mRNA and protein in the lung tissues of PF rats. These data suggest that Rg1 exhibits protective effect against bleomycin-induced PF in rats, which is potentially associated with the down-regulation of TGF-β1 and up-regulation of Cav-1.

  2. Analyses of mRNA Profiling through RNA Sequencing on a SAMP8 Mouse Model in Response to Ginsenoside Rg1 and Rb1 Treatment

    PubMed Central

    Zhang, Shuai; Zhu, Dina; Li, Hong; Zhang, Haijing; Feng, Chengqiang; Zhang, Wensheng

    2017-01-01

    Ginsenoside Rg1 and Rb1 are the major ingredients in two medicines called QiShengLi (Z20027165) and QiShengJing (Z20027164) approved by China. These ingredients are believed to mitigate forgetfulness. Numerous studies have confirmed that GRg1 and GRb1 offer protection against Alzheimer's disease (AD), and our morris water maze (MWM) experiment also indicated that GRg1 and GRb1 may attenuate memory deficits in the 7-month-old SAMP8 mice; however, comprehensive understanding of their roles in AD remains limited. This study systematically explored the mechanism at the genome level of the anti-AD effects of GRg1 and GRb1 in a senescence-accelerated mouse prone 8 (SAMP8) model through deep RNA sequencing. A total of 74,885 mRNA transcripts were obtained. Expression analysis showed that 1,780 mRNA transcripts were differentially expressed in SAMP8 mice compared with the SAMP8+GRg1 mice. Moreover, 1,066 significantly dysregulated mRNA transcripts were identified between SAMP8 and SAMP8+GRb1 mice. Analyses according to gene ontology and the Kyoto Encyclopedia of Genes and Genomes revealed that oral administration of GRg1 and GRb1 improved the learning performance of the SAMP8 mouse model from various aspects, such as nervous system development and mitogen-activated protein kinase signaling pathway. The most probable AD-related transcriptional responses after medication were predicted and discussed in detail. This study is the first to provide a systematic dissection of mRNA profiling in SAMP8 mouse brain in response to GRg1 and GRb1 treatment. We explained their efficacy thoroughly from the source (gene-level explanation). The findings serve as a theoretical basis for the exploration of GRg1 and GRb1 as functional drugs with anti-AD activity. PMID:28289387

  3. Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells.

    PubMed

    Lee, Min Jung; Jang, Minhee; Choi, Jonghee; Chang, Byung Soo; Kim, Do Young; Kim, Sung-Hoon; Kwak, Yi-Seong; Oh, Seikwan; Lee, Jong-Hwan; Chang, Byung-Joon; Nah, Seung-Yeol; Cho, Ik-Hyun

    2016-04-01

    The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1β), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE

  4. Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

    PubMed

    Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan

    2015-09-25

    We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms.

  5. Enhancement of ginsenoside biosynthesis and secretion by Tween 80 in Panax ginseng hairy roots.

    PubMed

    Liang, Yanlong; Wu, Jianjun; Li, Yao; Li, Jian; Ouyang, Yong; He, Zhi; Zhao, Shoujing

    2015-01-01

    We evaluated the effect of Tween 80 permeabilization on ginsenoside secretion in Panax ginseng hairy roots. Tween 80 (1.2%, w/v) had no significant effect on hairy root vitality. After a 25-day treatment with Tween 80, approximately 76% of the total ginsenosides was released into the surrounding medium. In the case of control, the ginsenosides secreted into the medium were negligible. Furthermore, when compared with control, the level of total ginsenosides was enhanced by approximately threefold under Tween treatment. Additionally, secretion of the typical ginsenoside monomers including Rb1 , Rg1 , and Re was analyzed, indicating that the most of them were released into the medium. Moreover, it was observed that dammarenediol synthase, a key enzyme involved in ginsenoside biosynthesis, was upregulated at both gene expression and enzyme activity levels. The expression of genes CYP716A47 and CYP716A53v2 encoding Cyt P450 enzymes catalyzing the formation of protopanaxadiol from dammarenediol and protopanaxatriol from protopanaxadiol, respectively, was slightly upregulated. These results clearly demonstrated that Tween 80 could act not only as an efficient permeabilizer to enhance ginsenoside secretion from the hairy roots, but also as an elicitor to promote the biosynthesis of ginsenoside.

  6. Oral Rg1 supplementation strengthens antioxidant defense system against exercise-induced oxidative stress in rat skeletal muscles

    PubMed Central

    2012-01-01

    Background Previous studies reported divergent results on nutraceutical actions and free radical scavenging capability of ginseng extracts. Variations in ginsenoside profile of ginseng due to different soil and cultivating season may contribute to the inconsistency. To circumvent this drawback, we assessed the effect of major ginsenoside-Rg1 (Rg1) on skeletal muscle antioxidant defense system against exhaustive exercise-induced oxidative stress. Methods Forty weight-matched rats were evenly divided into control (N = 20) and Rg1 (N = 20) groups. Rg1 was orally administered at the dose of 0.1 mg/kg bodyweight per day for 10-week. After this long-term Rg1 administration, ten rats from each group performed an exhaustive swimming, and remaining rats considered as non-exercise control. Tibialis anterior (TA) muscles were surgically collected immediately after exercise along with non-exercise rats. Results Exhaustive exercise significantly (p<0.05) increased the lipid peroxidation of control group, as evidenced by elevated malondialdehyde (MDA) levels. The increased oxidative stress after exercise was also confirmed by decreased reduced glutathione to oxidized glutathione ratio (GSH/GSSG ratio) in control rats. However, these changes were completely eliminated in Rg1 group. Catalase (CAT) and glutathione peroxidase (GPx) activities were significantly (p<0.05) increased by Rg1 in non-exercise rats, while no significant change after exercise. Nevertheless, glutathione reductase (GR) and glutathione S-transferase (GST) activities were significantly increased after exercise in Rg1 group. Conclusions This study provide compelling evidences that Rg1 supplementation can strengthen antioxidant defense system in skeletal muscle and completely attenuate the membrane lipid peroxidation induced by exhaustive exercise. Our findings suggest that Rg1 can use as a nutraceutical supplement to buffer the exhaustive exercise-induced oxidative stress. PMID:22607394

  7. Promotion of hair growth by ginseng radix on cultured mouse vibrissal hair follicles.

    PubMed

    Matsuda, Hideaki; Yamazaki, Miho; Asanuma, Yusuke; Kubo, Michinori

    2003-08-01

    A 70% methanol extract from red ginseng (steamed and dried roots of Panax ginseng C. A. Meyer, a kind of Ginseng Radix) had superior activity to that of white ginseng (peeled and dried root of P. ginseng, another kind of Ginseng Radix) in a hair growth promoting assay using mouse vibrissal follicles in organ culture. Of the major constituents of P. ginseng, ginsenoside-Rb(1) (G-Rb(1)) exhibited activity, but ginsenoside-Rg(1) (G-Rg(1)) and -Ro (G-Ro) were ineffective. Additionally, 20(S)-ginsenoside-Rg(3) (20(S)-G-Rg(3)) formed by the processing of red ginseng from the crude root of P. ginseng also showed hair growth promoting activity. These results indicate that Ginseng Radix possesses hair growth promoting activity, and its bioactive components are partially attributable to the ginseng saponin components mentioned above.

  8. The study of mechanisms of protective effect of Rg1 against arthritis by inhibiting osteoclast differentiation and maturation in CIA mice.

    PubMed

    Gu, Yanqing; Fan, Weimin; Yin, Guoyong

    2014-01-01

    Ginsenoside Rg1 is a natural product extracted from Panax ginseng C.A. Although Rg1 protects tissue structure and functions by inhibiting local inflammatory reaction, the mechanism remains poorly understood. In vitro, Rg1 dose-dependently inhibited TRAP activity in receptor activator of nuclear factor-κB ligand- (RANKL-) induced osteoclasts and decreased the number of osteoclasts and osteoclast resorption area. Rg1 also significantly inhibited the RANK signaling pathway, including suppressing the expression of Trap, cathepsin K, matrix metalloproteinase 9 (MMP9), and calcitonin receptor (CTR). In vivo, Rg1 dramatically decreased arthritis scores in CIA mice and effectively controlled symptoms of inflammatory arthritis. Pathologic analysis demonstrated that Rg1 significantly attenuated pathological changes in CIA mice. Pronounced reduction in synovial hyperplasia and inflammatory cell invasion were observed in CIA mice after Rg1 therapy. Alcian blue staining results illustrated that mice treated with Rg1 had significantly reduced destruction in the articular cartilage. TRAP and cathepsin K staining results demonstrated a significant reduction of numbers of OCs in the articular cartilage in proximal interphalangeal joints and ankle joints in Rg1-treated mice. In summary, this study revealed that Rg1 reduced the inflammatory destruction of periarticular bone by inhibiting differentiation and maturation of osteoclasts in CIA mice.

  9. Angiogenic Rg1 /Sr-Doped TiO2 Nanowire/Poly(Propylene Fumarate) Bone Cement Composites.

    PubMed

    Salarian, Mehrnaz; Xu, William Z; Bohay, Richard; Lui, Edmund M K; Charpentier, Paul A

    2017-02-01

    A new approach is provided for preparing radiopaque and angiogenic poly(propylene fumarate) (PPF) bone cements by integrating Sr-doped n-TiO2 nanowires and ginsenoside Rg1 suitable for treating osteonecrosis. High aspect ratio radiopaque TiO2 -nanowires are synthesized by strontium doping in supercritical CO2 for the first time, showing a new phase, SrTiO3 . PPF is synthesized using a transesterification method by reacting diethyl fumarate and propylene glycol, then functionalized using maleic anhydride to produce terminal carboxyl groups, which are subsequently linked to the nanowires. The strong interfacial adhesion between functionalized PPF and nanowires is examined by scanning electron microscopy, Fourier transform infrared, X-ray photoelectron spectroscopy, thermal analysis, and mechanical testing. An angiogenic modulator, ginsenoside Rg1 , is integrated into the bone cement formulation with the mechanical properties, radiopacity, drug release, and angiogenesis behavior of the formed composites explored. The results show superior radiopacity and excellent release of ginsenoside Rg1 in vitro, as well as a dose-dependent increase in the branching point numbers. The present study suggests this new methodology provides sufficient mechanical properties, radiopacity, and angiogenic activity to be suitable for cementation of necrotic bone.

  10. Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides

    PubMed Central

    Yue, Patrick Ying Kit; Mak, Nai Ki; Cheng, Yuen Kit; Leung, Kar Wah; Ng, Tzi Bun; Fan, David Tai Ping; Yeung, Hin Wing; Wong, Ricky Ngok Shun

    2007-01-01

    In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions. Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K→Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid

  11. Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor β signaling cascades.

    PubMed

    Li, Zheng; Ryu, Seung-Wook; Lee, Jungsul; Choi, Kyungsun; Kim, Sunchang; Choi, Chulhee

    2016-02-19

    Ginsenosides, the major bio-active ingredients included in Panax ginseng, have been known for the hair growth activity and used to treat patients who suffer from hair loss; however, the detailed mechanisms of this action are still largely unknown. This study was conducted to investigate the molecular and cellular mechanisms responsible for hair growth promoting effect of ginsenoside Re (GRe) in vitro and in vivo. Different doses of minoxidil and GRe were administered topically to the back regions of nude mice for up to 45 days, and hair shaft length and hair cycles were determined for hair promoting activities. Topical treatment of GRe significantly increased the hair shaft length and hair existent time, which was comparable to the action of minoxidil. We also demonstrated that GRe stimulated hair shaft elongation in the ex vivo cultures of vibrissa hair follicles isolated from C57BL/6 mouse. Systemic transcriptome analysis by next generation sequencing demonstrated that TGF-β-pathway related genes were selectively down-regulated by treatment of GRe in vivo, and the same treatment suppressed TGF-β-induced phosphorylation of ERK in HeLa cells. The results clearly indicated that GRe is the effective constituent in the ginseng on hair promotion via selective inhibition of the hair growth phase transition related signaling pathways, TGF-β signaling cascades.

  12. Comparison of Ginsenoside Contents in Different Parts of Korean Ginseng (Panax ginseng C.A. Meyer)

    PubMed Central

    Kang, Ok-Ju; Kim, Ji-Sang

    2016-01-01

    The present study was conducted to investigate the ginsenoside profiles of the main root, root hair, and leaf of ginseng in order to demonstrate their possible application in medicine. The total ginsenoside content of the leaf was up to 12 times than that in the main root, and the content of protopanaxadiol groups was higher than that of protopanaxatriol groups in all the samples. The leaf was shown to contain high amounts of ginsenosides Rb3 and Rh1, whereas the main root contained large amounts of ginsenosides Rb1 and Rc. Moreover, Rb2, Rb3, and Rg1 were only detected in the root hair, leaf, and main root, respectively. The ginsenoside Re content of Panax ginseng leaf and root hair was 2.6~4 times higher than that of the main root. Therefore, the results indicate that the ginsenoside content of Panax ginseng is higher in the leaf and root hair, and lower in the main root. PMID:28078264

  13. Effects of Fusarium solani and F. oxysporum Infection on the Metabolism of Ginsenosides in American Ginseng Roots.

    PubMed

    Jiao, Xiaolin; Lu, Xiaohong; Chen, Amanda Juan; Luo, Yi; Hao, Jianjun J; Gao, Weiwei

    2015-06-08

    American ginseng (Panax quinquefolius L.) is a highly valuable herb widely used for medicinal treatments. Its pharmacologically important compounds are the ginsenosides, which are secondary metabolites in American ginseng root. The concentrations of ginsenoside in roots can be changed by fungal infection, but it is unclear what specific root tissues are impacted and whether the change is systemic. In this study, American ginseng roots were inoculated with two fungal pathogens (Fusarium solani or F. oxysporum) and the levels of six ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1) were then measured in the phloem and xylem around the discolored lesions and adjacent healthy areas of the root. Results indicated that the growth of Fusarium spp. was strictly limited to phloem, and correspondingly the ginsenoside concentration was only altered in this infected phloem. The concentration of Rg1, Rd, and Rc significantly changed in phloem tissues where F. solani was inoculated, while only Rg1 and Rd changed significantly after F. oxysporum inoculation. However, no changes of any ginsenoside occurred in either xylem or phloem tissue adjacent to the inoculation point. In addition, when two Fusarium spp. were grown on ginsenoside-amended Czapek medium, the majority of ginsenosides were depleted. Therefore, pathogenic Fusarium spp. may reduce ginsenoside levels by consuming them.

  14. Ginsenoside-free molecules from steam-dried ginseng berry promote ethanol metabolism: an alternative choice for an alcohol hangover.

    PubMed

    Lee, Do Ik; Kim, Seung Tae; Lee, Dong Hoon; Yu, Jung Min; Jang, Su Kil; Joo, Seong Soo

    2014-07-01

    Ethanol metabolism produces harmful compounds that contribute to liver damage and cause an alcohol hangover. The intermediate metabolite acetaldehyde is responsible for alcohol hangover and CYP2E1-induced reactive oxygen species damage liver tissues. In this study, we examined whether ginsenoside-free molecules (GFMs) from steam-dried ginseng berries promote ethanol metabolism and scavenge free radicals by stimulating primary enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, CYP2E1, and catalase) and antioxidant effects using in vitro and in vivo models. The results revealed that GFM effectively scavenged 2,2-diphenyl-1-picrylhydrazyl hydrate radicals and hydroxyl radicals. Notably, GFM significantly enhanced the expression of primary enzymes within 2 h in HepG2 cells. GFM clearly removed the consumed ethanol and significantly reduced the level of acetaldehyde as well as enhancement of primary gene expression in BALB/c mice. Moreover, GFM successfully protected HepG2 cells from ethanol attack. Of the major components identified in GFM, it was believed that linoleic acid was the most active ingredient. Based on these findings, we conclude that GFM holds promise for use as a new candidate for ethanol metabolism and as an antihangover agent.

  15. Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.

    PubMed

    Wu, Chun Fu; Bi, Xiu Li; Yang, Jing Yu; Zhan, Jia Yang; Dong, Ying Xu; Wang, Jin Hui; Wang, Ji Ming; Zhang, Ruiwen; Li, Xian

    2007-03-01

    Ginsenosides, the main active components of ginseng, have been reported to exert neuroprotective effects in the central nervous system. In this report, the effects of ginsenoside-Rd and -Rb2, two protopanaxadiols, and ginsenoside-Rg1 and -Re, two protopanaxatriols, on the production of nitric oxide (NO) and TNF-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated N9 microglial cells were studied. All ginsenosides studied potently suppressed TNF-alpha production in LPS-activated N9 cells. Ginsenoside-Rg1 and -Re, but not ginsenoside-Rb2 and -Rd, inhibited the production of NO in LPS-activated N9 cells. Ginsenosides inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK), c-Jun and extracellular signal-regulated kinase (ERK), The findings herein show that the inhibition of LPS-induced ERK1/2 and JNK activation may be a contributing factor to the main mechanisms by which ginsenosides inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit TNF-alpha and NO induction, the effect of ginsenosides on transcription factor NF-kappaB protein level was also examined. These activities were associated with the down-regulation of inhibitor kappaB (IkappaB). These findings suggest that the inhibition of LPS-induced NO formation and TNF-alpha production in microglia by ginsenosides is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of ginsenosides. The significant suppressive effects of ginsenosides on proinflammatory responses of microglia implicate their therapeutic potential in neurodegenerative diseases accompanied by microglial activation.

  16. Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model

    PubMed Central

    Wang, Meng; Yan, Shi-Ju; Zhang, Hong-Tao; Li, Nan; Liu, Tao; Zhang, Ying-Long ; Li, Xiao-Xiang; Ma, Qiong; Qiu, Xiu-Chun; Fan, Qing-Yu; Ma, Bao-An

    2017-01-01

    The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post-surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T-lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma. PMID:28356946

  17. Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation.

    PubMed

    Cho, Young-Lai; Hur, Sung-Mo; Kim, Ji-Yoon; Kim, Ji-Hee; Lee, Dong-Keon; Choe, Jongeon; Won, Moo-Ho; Ha, Kwon-Soo; Jeoung, Dooil; Han, Sanghwa; Ryoo, Sungwoo; Lee, Hansoo; Min, Jeong-Ki; Kwon, Young-Guen; Kim, Dong-Hyun; Kim, Young-Myeong

    2015-01-02

    Ginsenoside Rg5 is a compound newly synthesized during the steaming process of ginseng; however, its biological activity has not been elucidated with regard to endothelial function. We found that Rg5 stimulated in vitro angiogenesis of human endothelial cells, consistent with increased neovascularization and blood perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in aortic rings isolated from wild type and high cholesterol-fed ApoE(-/-) mice but not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic activity of Rg5 was highly associated with a specific increase in insulin-like growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated phospholipase C/Ca(2+)/eNOS dimerization pathways. The vasodilative activity of Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5-induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1 to its receptor with an IC50 of ∼90 nmol/liter. However, Rg5 did not induce vascular inflammation and permeability. These data suggest that Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature.

  18. Specific Activation of Insulin-like Growth Factor-1 Receptor by Ginsenoside Rg5 Promotes Angiogenesis and Vasorelaxation*

    PubMed Central

    Cho, Young-Lai; Hur, Sung-Mo; Kim, Ji-Yoon; Kim, Ji-Hee; Lee, Dong-Keon; Choe, Jongeon; Won, Moo-Ho; Ha, Kwon-Soo; Jeoung, Dooil; Han, Sanghwa; Ryoo, Sungwoo; Lee, Hansoo; Min, Jeong-Ki; Kwon, Young-Guen; Kim, Dong-Hyun; Kim, Young-Myeong

    2015-01-01

    Ginsenoside Rg5 is a compound newly synthesized during the steaming process of ginseng; however, its biological activity has not been elucidated with regard to endothelial function. We found that Rg5 stimulated in vitro angiogenesis of human endothelial cells, consistent with increased neovascularization and blood perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in aortic rings isolated from wild type and high cholesterol-fed ApoE−/− mice but not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic activity of Rg5 was highly associated with a specific increase in insulin-like growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated phospholipase C/Ca2+/eNOS dimerization pathways. The vasodilative activity of Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5-induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1 to its receptor with an IC50 of ∼90 nmol/liter. However, Rg5 did not induce vascular inflammation and permeability. These data suggest that Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature. PMID:25391655

  19. Ginsenosides, ingredients of the root of Panax ginseng, are not substrates but inhibitors of sodium-glucose transporter 1.

    PubMed

    Gao, Shengli; Kushida, Hirotaka; Makino, Toshiaki

    2017-01-01

    Recent pharmacokinetic studies have revealed that ginsenosides, the major ingredients of ginseng (the roots of Panax ginseng), are present in the plasma collected from subjects receiving ginseng, and speculated that ginsenosides might be actively transported via glucose transporters. We evaluated whether ginsenosides Rb1 and Rg1, and their metabolites from enteric bacteria act as substrates of sodium-glucose cotransporter (SGLT) 1, the major glucose transporter expressed on the apical side of intestinal epithelial cells. First, we evaluated the competing effects of ginseng extract and ginsenosides on the uptake of [(14)C]methyl-glucose, a substrate of SGLT1, by SGLT1-overexpressing HEK293 cells. A boiling water extract of ginseng inhibited SGLT1 in a concentration-dependent manner with an IC50 value of 0.85 mg/ml. By activity-guided fractionation, we determined that the fraction containing ginsenosides displayed an inhibitory effect on SGLT1. Of the ginsenosides evaluated, protopanaxatriol-type ginsenosides were not found to inhibit SGLT1, whereas protopanaxadiol-type ginsenosides, including ginsenosides Rd, Rg3, Rh2, F2 and compound K, exhibited significant inhibitory effects on SGLT1, with ginsenoside F2 having the highest activity with an IC50 value of 23.0 µM. Next, we measured the uptake of ginsenoside F2 and compound K into Caco-2 cells, a cell line frequently used to evaluate the intestinal absorption of drugs. The uptake of ginsenoside F2 and compound K into Caco-2 cells was not competitively inhibited by glucose. Furthermore, the uptake of ginsenoside F2 and compound K into SGLT1-overexpressing HEK293 cells was not significantly higher than into mock cells. Ginsenoside F2 and compound K did not appear to be substrates of SGLT1, although these compounds could inhibit SGLT1. Ginsenosides might be absorbed by passive diffusion through the intestinal membrane or actively transported via unknown transporters other than SGLT1.

  20. Ginsenoside Re Inhibits Osteoclast Differentiation in Mouse Bone Marrow-Derived Macrophages and Zebrafish Scale Model

    PubMed Central

    Park, Chan-Mi; Kim, Hye-Min; Kim, Dong Hyun; Han, Ho-Jin; Noh, Haneul; Jang, Jae-Hyuk; Park, Soo-Hyun; Chae, Han-Jung; Chae, Soo-Wan; Ryu, Eun Kyoung; Lee, Sangku; Liu, Kangdong; Liu, Haidan; Ahn, Jong-Seog; Kim, Young Ock; Kim, Bo-Yeon; Soung, Nak-Kyun

    2016-01-01

    Ginsenosides, which are the active materials of ginseng, have biological functions that include anti-osteoporotic effects. Aqueous ginseng extract inhibits osteoclast differentiation induced by receptor activator of NF-κB ligand (RANKL). Aqueous ginseng extract produces chromatography peaks characteristic of ginsenosides. Among these peaks, ginsenoside Re is a major component. However, the preventive effects of ginsenoside Re against osteoclast differentiation are not known. We studied the effect of ginsenoside Re on osteoclast differentiation, RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, and formation of multinucleated osteoclasts in vitro. Ginsenoside Re hampered osteoclast differentiation in a dose-dependent manner. In an in vivo zebrafish model, aqueous ginseng extract and ginsenoside Re had anti-osteoclastogenesis effects. These findings suggest that both aqueous ginseng extract and ginsenoside Re prevent bone resorption by inhibiting osteoclast differentiation. Ginsenoside Re could be important for promoting bone health. PMID:27927007

  1. Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

    PubMed Central

    Li, Juan; Zhong, Wei; Wang, Weiwei; Hu, Shaoping; Yuan, Jiahui; Zhang, Bing; Hu, Tianhui; Song, Gang

    2014-01-01

    Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production. PMID:24504372

  2. Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways

    PubMed Central

    Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming

    2016-01-01

    Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng’s biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways. PMID:26840295

  3. Biomass and content of ginsenosides and polyacetylenes in American ginseng roots can be increased without affecting the profile of bioactive compounds.

    PubMed

    Christensen, Lars P; Jensen, Martin

    2009-04-01

    Fifty selected roots from a 7-year-old American ginseng (Panax quinquefolium L.) plant population grown in Denmark, with root weights varying from 191 to 490 g fresh weight (FW), were investigated for bioactive ginsenosides and polyacetylenes (PAs) in order to determine the correlation between the content of ginsenosides and PAs and root FW. PAs (falcarinol, panaxydol) and ginsenosides (Rb(1), Rb(2), Rb(3), Rc, Rd, Re, Rg(1)) were extracted from roots by sequential extraction with ethyl acetate and 80% methanol, respectively, and quantified in extracts by reverse-phase high-performance liquid chromatography (HPLC) using photodiode array detection. Total concentrations of PAs and ginsenosides varied between 150 and 780 mg/kg FW and 5,920 and 15,660 mg/kg FW, respectively. No correlation existed between the content of ginsenosides and PAs and root FW or between the total concentration of ginsenosides and PAs. Strong significant correlation was found between total content of ginsenosides and ginsenoside Rb(1) (r = 0.8190, P < 0.0001) and between total content of PAs and falcarinol (r = 0.9904, P < 0.0001). Based on the results of this study, it was concluded that it is possible to select large American ginseng roots for increased biomass production and concentration of bioactive ginsenosides and PAs without affecting the profile of bioactive compounds. Ginsenoside Rb(1) and falcarinol were found to be important selection parameters for identifying superior genotypes with the highest content of bioactive compounds.

  4. Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

    PubMed

    Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

    2016-01-01

    To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

  5. Preparation and characterization of mucoadhesive enteric-coating ginsenoside-loaded microparticles.

    PubMed

    Baek, Jong-Suep; Yeon, Won-Gi; Lee, Cho-A; Hwang, Sung-Joo; Park, Jeong-Sook; Kim, Dong-Chool; Cho, Cheong-Weon

    2015-01-01

    Ginsenoside saponins are phytochemically extracted from red ginseng and have been regarded as the principal components manifesting the pharmacologic activities. Saponins are very soluble in water but poorly absorbed when orally administrated. Moreover, they have some disadvantages including the decomposition in acid medium. The aim of this study was to develop oral formulation of ginsenosides composed of enteric-coating polymer and mucoadhesive polymer considering the low stability in acid medium and the low permeability of saponins. Ginsenoside-loaded microparticles were prepared by spray dryer. The influences of various parameters such as the ratio of saponin to polymer, feed concentration, feed rate, inlet/outlet temperature and additional excipients during spray-drying were investigated. In vitro release profile of ginsenoside-loaded microparticles using additional excipients, ginsenoside saponin Rg1 or Rb1 showed an 18 or 13% release in pH 1.2 when ethyl cellulose was added. Also, ginsenoside-loaded microparticles exhibited mucoadhesive properties in the presence of chitosan. The application of these polymers is being considered as the potential strategy for improvement of bioavailability in saponin delivery, orally.

  6. Changes in the ginsenoside content during the fermentation process using microbial strains

    PubMed Central

    Lee, So Jin; Kim, Yunjeong; Kim, Min-Gul

    2015-01-01

    Background Red ginseng (RG) is processed from Panax ginseng via several methods including heat treatment, mild acid hydrolysis, and microbial conversion to transform the major ginsenosides into minor ginsenosides, which have greater pharmaceutical activities. During the fermentation process using microbial strains in a machine for making red ginseng, a change of composition occurs after heating. Therefore, we confirmed that fermentation had occurred using only microbial strains and evaluated the changes in the ginsenosides and their chemical composition. Methods To confirm the fermentation by microbial strains, the fermented red ginseng was made with microbial strains (w-FRG) or without microbial strains (n-FRG), and the fermentation process was performed to tertiary fermentation. The changes in the ginsenoside composition of the self-manufactured FRG using the machine were evaluated using HPLC, and the 20 ginsenosides were analyzed. Additionally, we investigated changes of the reducing sugar and polyphenol contents during fermentation process. Results In the fermentation process, ginsenosides Re, Rg1, and Rb1 decreased but ginsenosides Rh1, F2, Rg3, and Compound Y (C.Y) increased in primary FRG more than in the raw ginseng and RG. The content of phenolic compounds was high in FRG and the highest in the tertiary w-FRG. Moreover, the reducing sugar content was approximately three times higher in the tertiary w-FRG than in the other n-FRG. Conclusion As the results indicate, we confirmed the changes in the ginsenoside content and the role of microbial strains in the fermentation process. PMID:26869833

  7. Characterization of Panax ginseng UDP-Glycosyltransferases Catalyzing Protopanaxatriol and Biosyntheses of Bioactive Ginsenosides F1 and Rh1 in Metabolically Engineered Yeasts.

    PubMed

    Wei, Wei; Wang, Pingping; Wei, Yongjun; Liu, Qunfang; Yang, Chengshuai; Zhao, Guoping; Yue, Jianmin; Yan, Xing; Zhou, Zhihua

    2015-09-01

    Ginsenosides, the main pharmacologically active natural compounds in ginseng (Panax ginseng), are mostly the glycosylated products of protopanaxadiol (PPD) and protopanaxatriol (PPT). No uridine diphosphate glycosyltransferase (UGT), which catalyzes PPT to produce PPT-type ginsenosides, has yet been reported. Here, we show that UGTPg1, which has been demonstrated to regio-specifically glycosylate the C20-OH of PPD, also specifically glycosylates the C20-OH of PPT to produce bioactive ginsenoside F1. We report the characterization of four novel UGT genes isolated from P. ginseng, sharing high deduced amino acid identity (>84%) with UGTPg1. We demonstrate that UGTPg100 specifically glycosylates the C6-OH of PPT to produce bioactive ginsenoside Rh1, and UGTPg101 catalyzes PPT to produce F1, followed by the generation of ginsenoside Rg1 from F1. However, UGTPg102 and UGTPg103 were found to have no detectable activity on PPT. Through structural modeling and site-directed mutagenesis, we identified several key amino acids of these UGTs that may play important roles in determining their activities and substrate regio-specificities. Moreover, we constructed yeast recombinants to biosynthesize F1 and Rh1 by introducing the genetically engineered PPT-producing pathway and UGTPg1 or UGTPg100. Our study reveals the possible biosynthetic pathways of PPT-type ginsenosides in Panax plants, and provides a sound manufacturing approach for bioactive PPT-type ginsenosides in yeast via synthetic biology strategies.

  8. Simultaneous determination of ginsenosides and polyacetylenes in American ginseng root (Panax quinquefolium L.) by high-performance liquid chromatography.

    PubMed

    Christensen, Lars P; Jensen, Martin; Kidmose, Ulla

    2006-11-29

    A method for simultaneous determination of ginsenosides and polyacetylenes in Panax quinquefolium L. (American ginseng) roots was developed. The ginsenosides Rb1, Rb2, Rc, Rd, Re, Rg1, Ro, malonyl-Rb1, malonyl-Rc, and malonyl-Rd and the polyacetylenes falcarinol and panaxydol were extracted from fresh ginseng roots in a sequential extraction process with 100% methanol followed by 80% aqueous methanol and quantified simultaneously in extracts by high-performance liquid chromatography using diode array detection. Separations were achieved with a phosphate buffer-acetonitrile gradient system using an RP-C18 column. Except for Rd, the present extraction method resulted in similar or significantly higher concentrations of both ginsenosides and polyacetylenes in comparison to commonly used extraction methods for these compounds. The contents of polyacetylenes and ginsenosides were determined in the root hairs, lateral roots, and main roots of 6 year old ginseng plants. The total mean concentrations of ginsenosides and polyacetylenes in root hairs were 31.0 g/kg fresh weight (FW) and 2.6 g/kg FW, respectively, whereas the concentrations of these bioactive compounds in the main roots were significantly lower with total mean concentrations of 17.8 g/kg FW for ginsenosides and 0.6 g/kg FW for polyacetylenes. The concentration of individual and total ginsenosides and polyacetylenes did not differ significantly between main roots of different sizes. Consequently, it is possible to do quantitative screening for ginsenosides and polyacetylenes to breed ginseng roots with higher levels of bioactive compounds.

  9. New Method for Simultaneous Quantification of 12 Ginsenosides in Red Ginseng Powder and Extract: In-house Method Validation.

    PubMed

    In, Gyo; Ahn, Nam-Geun; Bae, Bong-Seok; Han, Sung-Tai; Noh, Kil-Bong; Kim, Cheon-Suk

    2012-04-01

    For quality control of components in Korean red ginseng powder and extract, a new method for simultaneous quantification of 12 ginsenosides (Rg1, Re, Rf, Rh1, Rg2[S], Rg2[R], Rb1, Rc, Rb2, Rd, Rg3[S], and Rg3[R]) was studied. Compared to the official method for quantification of marker substances (ginsenosides Rg1 and Rb1), the proposed methods were guaranteed by in-house method validation. Several criteria such as linearity, specificity, precision and accuracy were evaluated. For red ginseng powder, recovery (averaging 95% to 105%) was calculated, and analysis of variance was carried out to estimate the relative standard deviation (0.20% to 2.12%). For red ginseng extract, the average recovery rate was 90% to 99% and the relative standard deviation was 0.39% to 2.40%. These results indicate that the proposed method could be used in the laboratory for determination of 12 ginsenosides in red ginseng powder and extract. In addition, this method was found to be suitable for quality control of ginseng products and potentially offer time and cost benefits.

  10. PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng

    PubMed Central

    Rahimi, Shadi; Kim, Yu-Jin; Sukweenadhi, Johan; Zhang, Dabing; Yang, Deok-Chun

    2016-01-01

    Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production. PMID:27811076

  11. Simplified ultrasonically- and microwave-assisted solvent extractions for the determination of ginsenosides in powdered Panax ginseng rhizomes using liquid chromatography with UV absorbance or electrospray mass spectrometric detection.

    PubMed

    MacCrehan, William A; White, Christian M

    2013-05-01

    New approaches for the recovery of ginsenosides are presented that greatly simplify the liquid chromatographic (LC) determination of the total content of eight ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2) in powdered Panax ginseng rhizomes. The extraction protocols not only recover the neutral ginsenosides, but also simultaneously incorporate base-catalyzed hydrolysis of the malonyl-ginsenosides using dilute potassium hydroxide added to the methanol-water extractant. This eliminates the need for an independent extraction step followed by acid- or base-catalyzed hydrolysis. Both ultrasonically-assisted and microwave-assisted extraction methods are developed. The optimization of these simplified methods to remove pendant malonate esters, while retaining the glycosidic linkages, was determined by LC through variation of the extraction/hydrolysis time, order of hydrolysis reagent addition, and evaluation of multiple extractions. A comparison of the ginsenoside profiles obtained with and without addition of base to the extractant solution was made using LCMS with positive-mode electrospray ionization (ESI(+)) detection. A number of malonyl-ginsenosides were tentatively identified by their mass spectral fragmentation spectra and indicating that they were converted to the free ginsenosides by the new extraction/hydrolysis procedure.

  12. [Advances in the biosynthesis research of ginsenosides].

    PubMed

    Yang, Jin-Ling; Gao, Li-Li; Zhu, Ping

    2013-02-01

    Ginsenosides are the main active components of medicinal herbs including Panax ginseng and Panax quinquefolium, which have potent effects of anti-tumor, anti-inflammatory, antioxidant and apoptosis inhibition. But the low content of ginsenosides limits its development and usage. At present, how to improve the production of ginsenosides by biological technology has been a new research focus. Some advances in the biosynthesis of ginsenosides by tissue culture and biotransformation have been made in recent years. So far at least twenty genes related to the biosynthesis of ginsenosides from Panax genus plants have been cloned and functionally identified, which has laid a good foundation for the study on the synthetic biology of ginsenosides. This review outlines recent advances in several aspects and is expected to provide a theoretical support to the thorough research of the pathway and regulation of ginsenosides biosynthesis.

  13. Inhibition of autophagy potentiates anticancer property of 20(S)-ginsenoside Rh2 by promoting mitochondria-dependent apoptosis in human acute lymphoblastic leukaemia cells

    PubMed Central

    Wang, Yingnan; Wang, Yuanyuan; Cai, Jianye; Wang, Min; Chen, Qidan; Song, Jia; Yu, Ziqi; Huang, Wei; Fang, Jianpei

    2016-01-01

    Acute lymphoblastic leukaemia (ALL) is the most prevalent childhood malignancy. Although most children with ALL are cured, there is still a group of patients for which therapy fails owing to severe toxicities and drug resistance. Ginsenoside Rh2 (GRh2), a major bioactive component isolated from Panax ginseng, has been shown to have a therapeutic effect on some tumors. However, the molecular mechanisms of cell death induced by 20(S)-GRh2 in ALL cells remains unclear. In this study, we showed that 20(S)-GRh2 inhibited the cell growth and induced mitochondria-dependent apoptosis and autophagy. But it has no cytotoxic effect on human normal blood cells. Furthermore, autophagy plays a protective role in 20(S)-GRh2-induced apoptosis in ALL cell lines and human primary ALL cells. We demonstrated that either genetic or pharmacologic inhibition of autophagy could be more effective in reducing viability and enhancing 20(S)-GRh2-induced toxicity than 20(S)-GRh2 treatment alone. In addition, inhibition of autophagy could aggravate mitochondrial ROS generation and mitochondrial damage, and then accelerate mitochondria-dependent apoptosis. Taken together, these results suggest that inhibition of autophagy can sensitize ALL cells towards 20(S)-GRh2. The appropriate inhibition of autophagy could provide a powerful strategy to increase the potency of 20(S)-GRh2 as a novel anticancer agent for ALL therapy. PMID:27027340

  14. A dual purpose cell line of an Indian congener of ginseng--Panax sikkimensis with distinct ginsenoside and anthocyanin production profiles.

    PubMed

    Biswas, Tanya; Singh, Manju; Mathur, Ajay Kumar; Mathur, Archana

    2015-03-01

    The age-dependent production kinetics of ginsenosides and an anthocyanin pigment in a cell suspension line of Panax sikkimensis was followed in vitro. Highest total saponin content [7.37 mg/g dry weight (DW)] and biomass accumulation (% biomass increase = 209.67) in this line occurred after 3 and 5 weeks of culture, respectively. Accumulation of individual protopanaxatriol (Re, Rg1, and Rg2) and protopanaxadiol (Rb1, Rb2, and Rc) ginsenosides showed a variable pattern of accumulation independent of cell biomass buildup during the 7-week culture cycle. However, total content of triol ginsenosides was always significantly more than the diol group of ginsenosides, being 183.2-, 63.5-, and 72.1-folds at third, fourth, and fifth week stage of cell growth. Interestingly, in addition to these ginsenosides, the cell line also co-accumulated an anthocyanin pigment in vitro. The pigment content increased gradually from 8.66 to 14.29 mg/g DW after first to fifth week followed by a marginal fall to 12.79 and 10.95 mg/g DW during next 2 weeks. Therefore, in terms of total recovery of saponins (77.4 mg/l) and anthocyanin (199.16 mg/l), harvesting of cells after 3 and 5 weeks of growth was most profitable, respectively. The possible utility of this dual purpose cell line in nutraceutical industry is discussed.

  15. COL Application Content Guide for HTGRs: Revision to RG 1.206, Part 1 - Status Report

    SciTech Connect

    Wayne Moe

    2012-08-01

    A combined license (COL) application is required by the Nuclear Regulatory Commission (NRC) for all proposed nuclear plants. The information requirements for a COL application are set forth in 10 CFR 52.79, “Contents of Applications; Technical Information in Final Safety Analysis Report.” An applicant for a modular high temperature gas-cooled reactor (HTGR) must develop and submit for NRC review and approval a COL application which conforms to these requirements. The technical information necessary to allow NRC staff to evaluate a COL application and resolve all safety issues related to a proposed nuclear plant is detailed and comprehensive. To this, Regulatory Guide (RG) 1.206, “Combined License Applications for Nuclear Power Plants” (LWR Edition), was developed to assist light water reactor (LWR) applicants in incorporating and effectively formatting required information for COL application review (Ref. 1). However, the guidance prescribed in RG 1.206 presumes a LWR design proposal consistent with the systems and functions associated with large LWR power plants currently operating under NRC license.

  16. Improved Inflammatory Balance of Human Skeletal Muscle during Exercise after Supplementations of the Ginseng-Based Steroid Rg1

    PubMed Central

    Hou, Chien-Wen; Lee, Shin-Da; Kao, Chung-Lan; Cheng, I-Shiung; Lin, Yu-Nan; Chuang, Sheng-Ju; Chen, Chung-Yu; Ivy, John L.; Huang, Chih-Yang; Kuo, Chia-Hua

    2015-01-01

    The purpose of the study was to determine the effect of ginseng-based steroid Rg1 on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo-controlled crossover trials were performed, separated by a 4-week washout. Healthy young men were randomized into two groups and received capsule containing either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle biopsies were conducted at baseline, immediately and 3 h after a standardized 60-min cycle ergometer exercise. While treatment differences in glycogen depletion rate of biopsied quadriceps muscle during exercise did not reach statistical significance, Rg1 supplementations enhanced post-exercise glycogen replenishment and increased citrate synthase activity in the skeletal muscle 3 h after exercise, concurrent with improved meal tolerance during recovery (P<0.05). Rg1 suppressed the exercise-induced increases in thiobarbituric acids reactive substance (TBARS) and reversed the increased TNF-alpha and decreased IL-10 mRNA of quadriceps muscle against the exercise challenge. PGC-1 alpha and GLUT4 mRNAs of exercised muscle were not affected by Rg1. Maximal aerobic capacity (VO2max) was not changed by Rg1. However, cycling time to exhaustion at 80% VO2max increased significantly by ~20% (P<0.05). Conclusion: Our result suggests that Rg1 is an ergogenic component of ginseng, which can minimize unwanted lipid peroxidation of exercised human skeletal muscle, and attenuate pro-inflammatory shift under exercise challenge. PMID:25617625

  17. Interaction of the ginsenosides with κ-casein and their effects on amyloid fibril formation by the protein: Multi-spectroscopic approaches.

    PubMed

    Chen, Fanbo; Wang, Yunhua; Yang, Miao; Yin, Jianyuan; Meng, Qin; Bu, Fengquan; Sun, Dandan; Liu, Jihua

    2016-07-01

    The interaction of the ginsenosides (GS) including ginsenoside Rg1, Rb1 and Re with κ-casein and the effects of GS inhibiting amyloid fibril formation by κ-casein have been investigated in vitro by fluorescence and ultraviolet spectra. Results showed that Rg1 and Rb1 had dose-dependent inhibitory effects on reduced and carboxymethylated κ-casein (RCMκ-CN) fibril formation, while Re resulted in an increase in the rate of fibril formation. The enhancement in RLS intensity was attributed to the formation of new complex between GS and RCMκ-CN, and the corresponding thermodynamic parameters (ΔH, ΔS and ΔG) were assayed. The steady-state ultraviolet-visible absorption spectra had also been tested to observe if the ground-state complex formed, and it showed the same result as RLS spectra. The binding constants and the number of binding sites between GS and RCMκ-CN at different temperatures had been evaluated from relevant fluorescence data. According to the Förster non-radiation energy transfer theory, the binding distance between RCMκ-CN and GS was calculated. The fluorescence lifetime of RCMκ-CN was longer in the presence of GS than in absence of GS, which was evident that the hydrophobic interaction plays a major role in the binding of GS to RCMκ-CN. From the results of synchronous fluorescence, it could be deduced that the polarity around RCMκ-CN Trp97 residue decreased and the hydrophobicity increased after addition of Rg1 or Rb1. Based on all the above results, it is explained that Rg1 and Rb1 inhibited amyloid fibril formation by κ-casein because the molecular spatial conformation and physical property of κ-casein changed causing by the complex formation between GS and κ-casein.

  18. Pharmacokinetic Compatibility of Ginsenosides and Schisandra Lignans in Shengmai-san: From the Perspective of P-Glycoprotein

    PubMed Central

    Liang, Yan; Zhou, Yuanyuan; Zhang, Jingwei; Rao, Tai; Zhou, Lijun; Xing, Rong; Wang, Qian; Fu, Hanxu; Hao, Kun; Xie, Lin; Wang, Guangji

    2014-01-01

    Background Phytochemical-mediated alterations in P-glycoprotein (P-gp) activity may result in herb-drug interactions by altering drug pharmacokinetics. Shengmai-san, a traditional Chinese herbal medicine composed by Panax Ginseng, Ophiopogon Japonicus, and Schisandra Chinensis, is routinely being used for treating various coronary heart diseases. In our previous studies, Schisandra Lignans Extract (SLE) was proved as a strong P-gp inhibitor, and herein, the compatibility of Shengmai-san was studied by investigating the influence of SLE on the pharmacokinetics of the ginsenosides from the perspective of P-gp. Methodology Pharmacokinetic experiments were firstly performed based on in vitro uptake, efflux and transport experiments in Caco-2, LLC-PK1 wild-type and MDR1-overexpressing L-MDR1 cells. During the whole experiment, digoxin, a classical P-gp substrate, was used as a positive control drug to verify the cells used are the valid models. Meanwhile, the effects of SLE on the pharmacokinetics of ginsenosides were further investigated in rats after single-dose and multi-dose of SLE. Results and Conclusions The efflux ratios of ginsenoside Rb2, Rc, Rg2, Rg3, Rd and Rb1 were found more than 3.5 in L-MDR1 cells and can be decreased significantly by verapamil (a classical P-gp inhibitor). Contrarily, the efflux ratios of other ginsenosides (Rh1, F1, Re, and Rg1) were lower than 2.0 and not affected by verapamil. Then, the effects of SLE on the uptake and transport of ginsenosides were investigated, and SLE was found can significantly enhance the uptake and inhibit the efflux ratio of ginsenoside Rb2, Rc, Rg2, Rg3, Rd and Rb1 in Caco-2 and L-MDR1 cells. Besides, In vivo experiments showed that single-dose and multi-dose of SLE at 500 mg/kg could increase the area under the plasma concentration time curve of Rb2, Rc and Rd significantly without affecting terminal elimination half-time. In conclusion, SLE could enhance the exposure of ginsenosides Rb2, Rc, Rg2, Rg3, Rd and

  19. Functional regulation of ginsenoside biosynthesis by RNA interferences of a UDP-glycosyltransferase gene in Panax ginseng and Panax quinquefolius.

    PubMed

    Lu, Chao; Zhao, Shoujing; Wei, Guanning; Zhao, Huijuan; Qu, Qingling

    2017-02-01

    Panax ginseng (Asian ginseng) and Panax quinquefolius (American ginseng) have been used as medicinal and functional herbal remedies worldwide. Different properties of P. ginseng and P. quinquefolius were confirmed not only in clinical findings, but also at cellular and molecular levels. The major pharmacological ingredients of P. ginseng and P. quinquefolius are the triterpene saponins known as ginsenosides. The P. ginseng roots contain a higher ratio of ginsenoside Rg1:Rb1 than that in P. quinquefolius. In ginseng plants, various ginsenosides are synthesized via three key reactions: cyclization, hydroxylation and glycosylation. To date, several genes including dammarenediol synthase (DS), protopanaxadiol synthase and protopanaxatriol synthase have been isolated in P. ginseng and P. quinquefolius. Although some glycosyltransferase genes have been isolated and identified association with ginsenoside synthesis in P. ginseng, little is known about the glycosylation mechanism in P. quinquefolius. In this paper, we cloned and identified a UDP-glycosyltransferase gene named Pq3-O-UGT2 from P. quinquefolius (GenBank accession No. KR106207). In vitro enzymatic activity experiments biochemically confirmed that Pq3-O-UGT2 catalyzed the glycosylation of Rh2 and F2 to produce Rg3 and Rd, and the chemical structure of the products were confirmed susing high performance liquid chromatography electrospray ionization mass spectrometry (HPLC/ESI-MS). High sequence similarity between Pq3-O-UGT2 and PgUGT94Q2 indicated a close evolutionary relationship between P. ginseng and P. quinquefolius. Moreover, we established both P. ginseng and P. quinquefolius RNAi transgenic roots lines. RNA interference of Pq3-O-UGT2 and PgUGT94Q2 led to reduce levels of ginsenoside Rd, protopanaxadiol-type and total ginsenosides. Expression of key genes including protopanaxadiol and protopanaxatriol synthases was up-regulated in RNAi lines, while expression of dammarenediol synthase gene

  20. Ginsenoside Rd and ginsenoside Re offer neuroprotection in a novel model of Parkinson’s disease

    PubMed Central

    Zhang, Xinmu; Wang, Yingzi; Ma, Cheng; Yan, Yan; Yang, Yang; Wang, Xin; Rausch, Wolf-Dieter

    2016-01-01

    Ginsenosides are the main active constituents of Panax ginseng. Ginsenoside Re is one of the major ginsenosides; whereas hydrolysis products such as Rd appear to have higher biological activity though are present in smaller amounts. Ginsenosides, from their early use in folk medicine to modern studies, appear to exert beneficial actions against aging and even neurodegenerative disorders. Parkinson’s disease is a progressive neurodegenerative movement disorder characterized by a profound loss of midbrain dopamine neurons in the substantia nigra pars compacta. Carbon tetrachloride (CCl4) exerts neurotoxic effects when present as an environmental pollutant. As a model compound it was used here to study the impact on primary nigrostriatal dopaminergic nerve cells and to investigate the neuroprotective potential of ginsenosides Rd and Re against this organic solvent. CCl4 (2.5 mM on day 12 in vitro for 48 h) significantly decreased the number of tyrosine hydroxylase (TH+) cells by 51% compared with untreated control cultures, reduced their neuritic lengths, and led to truncated degenerations of cell morphology. Ginsenosides Rd and Re (10 µM) strongly reduced cell loss and degeneration and significantly protected process lengths and numbers of neurites of TH+ cells. The anti-oxidative and anti-inflammatory potential of the cellular supernatant was lowered by CCl4 exposure. Inclusion of ginsenosides inhibited both oxidative stress and inflammation. Therefore the neuroprotective effects of ginsenosides at least partially depend on lowering oxidative stress and anti-inflammation. PMID:27073742

  1. The Rg1 allele as a valuable tool for genetic transformation of the tomato 'Micro-Tom' model system

    PubMed Central

    2010-01-01

    Background The cultivar Micro-Tom (MT) is regarded as a model system for tomato genetics due to its short life cycle and miniature size. However, efforts to improve tomato genetic transformation have led to protocols dependent on the costly hormone zeatin, combined with an excessive number of steps. Results Here we report the development of a MT near-isogenic genotype harboring the allele Rg1 (MT-Rg1), which greatly improves tomato in vitro regeneration. Regeneration was further improved in MT by including a two-day incubation of cotyledonary explants onto medium containing 0.4 μM 1-naphthaleneacetic acid (NAA) before cytokinin treatment. Both strategies allowed the use of 5 μM 6-benzylaminopurine (BAP), a cytokinin 100 times less expensive than zeatin. The use of MT-Rg1 and NAA pre-incubation, followed by BAP regeneration, resulted in high transformation frequencies (near 40%), in a shorter protocol with fewer steps, spanning approximately 40 days from Agrobacterium infection to transgenic plant acclimatization. Conclusions The genetic resource and the protocol presented here represent invaluable tools for routine gene expression manipulation and high throughput functional genomics by insertional mutagenesis in tomato. PMID:20929550

  2. Cloning and Characterization of Ginsenoside-Hydrolyzing β-Glucosidase from Lactobacillus brevis That Transforms Ginsenosides Rb1 and F2 into Ginsenoside Rd and Compound K.

    PubMed

    Zhong, Fei-Liang; Ma, Rui; Jiang, Mingliang; Dong, Wei-Wei; Jiang, Jun; Wu, Songquan; Li, Donghao; Quan, Lin-Hu

    2016-10-28

    The ginsenoside-hydrolyzing β-glucosidase gene (bgy2) was cloned from Lactobacillus brevis. We expressed this gene in Escherichia coli BL21(DE3), isolated the resulting protein, and then utilized the enzyme for the biotransformation of ginsenosides. The bgy2 gene contains 2,223 bp, and encodes a protein of 741 amino acids that is a member of glycosyl hydrolase family 3. β-Glucosidase (Bgy2) cleaved the outer glucose moieties of ginsenosides at the C-20 position, and the inner glucose at the C-3 position. Under optimal conditions (pH 7.0, 30°C), we used 0.1 mg/ml Bgy2 in 20 mM sodium phosphate buffer (PBS) for enzymatic studies. In these conditions, 1.0 mg/ml ginsenoside Rb1 and ginsenoside F2 were converted into 0.59 mg/ml ginsenoside Rd and 0.72mg/ml compound K, with molar conversion productivities of 69% and 91%, respectively. In pharmaceutical and commercial industries, this recombinant Bgy2 would be suitable for producting ginsenoside Rd and compound K.

  3. Identification and Characterization of a Mucilaginibacter sp. Strain QM49 β-Glucosidase and Its Use in the Production of the Pharmaceutically Active Minor Ginsenosides (S)-Rh1 and (S)-Rg2

    PubMed Central

    Cui, Chang-Hao; Liu, Qing-Mei; Kim, Jin-Kwang; Sung, Bong-Hyun; Kim, Song-Gun

    2013-01-01

    Here, we isolated and characterized a new ginsenoside-transforming β-glucosidase (BglQM) from Mucilaginibacter sp. strain QM49 that shows biotransformation activity for various major ginsenosides. The gene responsible for this activity, bglQM, consists of 2,346 bp and is predicted to encode 781 amino acid residues. This enzyme has a molecular mass of 85.6 kDa. Sequence analysis of BglQM revealed that it could be classified into glycoside hydrolase family 3. The enzyme was overexpressed in Escherichia coli BL21(DE3) using a maltose binding protein (MBP)-fused pMAL-c2x vector system containing the tobacco etch virus (TEV) proteolytic cleavage site. Overexpressed recombinant BglQM could efficiently transform the protopanaxatriol-type ginsenosides Re and Rg1 into (S)-Rg2 and (S)-Rh1, respectively, by hydrolyzing one glucose moiety attached to the C-20 position at pH 8.0 and 30°C. The Km values for p-nitrophenyl-β-d-glucopyranoside, Re, and Rg1 were 37.0 ± 0.4 μM and 3.22 ± 0.15 and 1.48 ± 0.09 mM, respectively, and the Vmax values were 33.4 ± 0.6 μmol min−1 mg−1 of protein and 19.2 ± 0.2 and 28.8 ± 0.27 nmol min−1 mg−1 of protein, respectively. A crude protopanaxatriol-type ginsenoside mixture (PPTGM) was treated with BglQM, followed by silica column purification, to produce (S)-Rh1 and (S)-Rg2 at chromatographic purities of 98% ± 0.5% and 97% ± 1.2%, respectively. This is the first report of gram-scale production of (S)-Rh1 and (S)-Rg2 from PPTGM using a novel ginsenoside-transforming β-glucosidase of glycoside hydrolase family 3. PMID:23811513

  4. Metabolism of ginsenoside Rb1 by human intestinal microflora and cloning of its metabolizing β-D-glucosidase from Bifidobacterium longum H-1.

    PubMed

    Jung, Il-Hoon; Lee, Jeong Hoon; Hyun, Yang-Jin; Kim, Dong-Hyun

    2012-01-01

    To understand the role of intestinal microflora in expressing the pharmacological effect of ginsenoside Rb1, the metabolic activity of ginsenoside Rb1 by 148 fecal specimens was measured and its metabolizing β-glucosidase was cloned. The average activities for p-nitrophenyl-β-D-glucopyranoside and ginsenoside Rb1 were 0.097±0.059 μmol/min/mg and 0.311±0.118 pmol/min/mg, respectively. These enzyme activities were not different between male and female, or between ages. A gene encoding β-D-glucosidase (BglX) was cloned from Bifidobacterium longum H-1, which transformed ginsenoside Rb1 to compound K. The probe for cloning was synthesized from the genes encoding a β-D-glucosidase of previously reported B. longum DJO10A. The sequences of the cloned gene revealed 2364 bp open reading frame (ORF) encoding a protein containing 787 amino acids (molecular weight of 95 kDa). The gene exhibited 99% homology (identities) to that of B. longum. The cloned gene was expressed under T7 promoter of the expression vector, pET-39b(+), in Escherichia coli BL21(DE3), and the expressed enzyme was purified by using HiTrap immobilized metal affinity chromatography (IMAC) HP. The enzyme potently biotransformed ginsenoside Rb1, loganin, arctiin and arbutin to ginsenoside Rd, loganetin, arctigenin and hydroquinone, respectively, but was not active in the case of hesperidin, and kakkalide. This is the first report on cloning and expression of β-D-glucosidase from B. longum. Based on these findings, ginsenoside Rb1 may be metabolized to bioactive compound(s) by exo-β-D-glucosidase(s) produced from the intestinal bacteria and its pharmacological effects may be dependent on intestinal bacterial exo-β-D-glucosidase(s) activity.

  5. Ginsenoside Rg5 Inhibits Succinate-Associated Lipolysis in Adipose Tissue and Prevents Muscle Insulin Resistance

    PubMed Central

    Xiao, Na; Yang, Le-Le; Yang, Yi-Lin; Liu, Li-Wei; Li, Jia; Liu, Baolin; Liu, Kang; Qi, Lian-Wen; Li, Ping

    2017-01-01

    Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue. Succinate promoted IL-1β production through NLRP3 inflammasome activation and then increased cAMP accumulation by impairing PDE3B expression, leading to increased lipolysis. Ginsenoside Rg5 treatment suppressed NLRP3 inflammasome activation, preserved PDE3B expression and then reduced cAMP accumulation, contributing to inhibition of lipolysis. Adipose lipolysis increased FFAs trafficking from adipose tissue to muscle. Rg5 reduced diacylglycerol (DAG) and ceramides accumulation, inhibited protein kinase Cθ translocation, and prevented insulin resistance in muscle. In conclusion, succinate accumulation in hypoxic adipose tissue acts as a metabolic signaling to link ER stress, inflammation and cAMP/PKA activation, contributing to lipolysis and insulin resistance. These findings establish a previously unrecognized role of ginsenosides in the regulation of lipid and glucose homeostasis and suggest that adipose succinate-associated NLRP3 inflammasome activation might be targeted therapeutically to prevent lipolysis and insulin resistance. PMID:28261091

  6. Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides.

    PubMed

    Liu, Can; Zhang, Mian; Hu, Meng-Yue; Guo, Hai-Fang; Li, Jia; Yu, Yun-Li; Jin, Shi; Wang, Xin-Ting; Liu, Li; Liu, Xiao-Dong

    2013-05-01

    Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca2+ concentration. The metabolic inhibitor azide (3 mM), the KATP channel opener diazoxide (340 μM), and the Ca2+ channel blocker nifedipine (20 μM) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion.

  7. Bioavailability of ginsenosides from white and red ginsengs in the simulated digestion model.

    PubMed

    Kim, Eun Ok; Cha, Kwang Hyun; Lee, Eun Ha; Kim, Sang Min; Choi, Sang Won; Pan, Cheol-Ho; Um, Byung-Hun

    2014-10-15

    This study aims to investigate the bioavailability of ginsenosides during simulated digestion of white (WG) and red (RG) ginseng powders. Stability, bioaccessibility, and permeability of ginsenosides present in WG and RG were studied in a Caco-2 cell culture model coupled with oral, gastric, and small intestinal simulated digestion. Most ginsenosides in WG and RG were stable (>90%) during the simulated digestion. Bioaccessibilities of total ginsenosides during in vitro digestion of WG and RG were similar at approximately 85%. However, the bioaccessibility of protopanaxatriol type ginsenosides in the early food phase was greater than that of the protopanaxadiol type. The less polar RG ginsenosides were released later following the jejunum phase. Ginsenosides had low permeability (<1 × 10(-6) cm/s) through Caco-2 cell monolayers. These findings suggest that the WG and RG ginsenoside compositions affect bioaccessibility during digestion and that ginsenosides are poorly absorbed in humans.

  8. The Tomato (Solanum Lycopersicum cv. Micro-Tom) Natural Genetic Variation Rg1 and the DELLA Mutant Procera Control the Competence Necessary to Form Adventitious Roots and Shoots

    PubMed Central

    Peres, Lázaro Eustáquio Pereira

    2012-01-01

    Despite the wide use of plant regeneration for biotechnological purposes, the signals that allow cells to become competent to assume different fates remain largely unknown. Here, it is demonstrated that the Regeneration1 (Rg1) allele, a natural genetic variation from the tomato wild relative Solanum peruvianum, increases the capacity to form both roots and shoots in vitro; and that the gibberellin constitutive mutant procera (pro) presented the opposite phenotype, reducing organogenesis on either root-inducing medium (RIM) or shoot-inducing medium (SIM). Mutants showing alterations in the formation of specific organs in vitro were the auxin low-sensitivity diageotropica (dgt), the lateral suppresser (ls), and the KNOX-overexpressing Mouse ears (Me). dgt failed to form roots on RIM, Me increased shoot formation on SIM, and the high capacity for in vitro shoot formation of ls contrasted with its recalcitrance to form axillary meristems. Interestingly, Rg1 rescued the in vitro organ formation capacity in proRg1 and dgtRg1 double mutants and the ex vitro low lateral shoot formation in pro and ls. Such epistatic interactions were also confirmed in gene expression and histological analyses conducted in the single and double mutants. Although Me phenocopied the high shoot formation of Rg1 on SIM, it failed to increase rooting on RIM and to rescue the non-branching phenotype of ls. Taken together, these results suggest REGENERATION1 and the DELLA mutant PROCERA as controlling a common competence to assume distinct cell fates, rather than the specific induction of adventitious roots or shoots, which is controlled by DIAGEOTROPICA and MOUSE EARS, respectively. PMID:22915742

  9. Determination of ginsenoside content in Panax ginseng C.A. Meyer and Panax quinquefolius L. root materials and finished products by high-performance liquid chromatography with ultraviolet absorbance detection: interlaboratory study.

    PubMed

    Brown, Paula N; Yu, Ronan; Cain, T; Huie, G; Jin, C D; Kababick, J N; Leong, G; LeVanseler, K; Lunetta, S; Ma, Y C; Reif, K; Schaneberg, B; Shevchuk, C; Smith, R; Sullivan, D; Wijewickreme, N; Windust, A

    2013-01-01

    An interlaboratory study was conducted on an HPLC method with UV absorbance detection, previously validated using AOAC single-laboratory validation guidelines, for the determination of the six major ginsenosides (Rg1, Re, Rb1, Rc, Rb2, and Rd) in Panax ginseng C.A. Meyer and Panax quinquefolius L. root materials, extracts, and finished products. Fourteen participating laboratories analyzed five test materials (P. ginseng whole root, P. ginseng powdered extract, P. quinquefolius whole root, P. quinquefolius powdered extract, and P. ginseng powdered extract spiked in a matrix blank) as blind duplicates, and two test materials (P. ginseng powdered whole root tablet and P. quinquefolius powdered extract hard-filled capsule) as single samples. Due to the variability of the ginsenosides (low level concentration of Rb2 in P. quinquefolius raw materials and in P. ginseng spiked matrix blanks, and the possibility of incomplete hydrolysis of the finished products during processing), it was deemed more applicable to analyze total ginsenosides rather than individual ones. Outliers were evaluated and omitted using the Cochran's test and single and double Grubbs' tests. The reproducibility RSD (RSD(R)) for the blind duplicate samples ranged from 4.38 to 5.39%, with reproducibility Horwitz Ratio (HorRat(R)) values ranging from 1.5 to 1.9. For the single replicate samples, the data sets were evaluated solely by their repeatability HorRat (HorRat(r)), which were 2.9 and 3.5 for the capsule and tablet samples, respectively. Based on these results, the method is recommended for AOAC Official First Action for the determination of total ginsenosides in P. ginseng and P. quinquefolius root materials and powdered extracts.

  10. Ginsenoside Rd and ischemic stroke; a short review of literatures☆

    PubMed Central

    Nabavi, Seyed Fazel; Sureda, Antoni; Habtemariam, Solomon; Nabavi, Seyed Mohammad

    2015-01-01

    Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID:26869821

  11. Simultaneous determination of three alkaloids, four ginsenosides and limonin in the plasma of normal and headache rats after oral administration of Wu-Zhu-Yu decoction by a novel ultra fast liquid chromatography-tandem mass spectrometry method: application to a comparative pharmacokinetics and ethological study.

    PubMed

    Xu, Huarong; Li, Qing; Yin, Yidi; Lv, Chunxiao; Sun, Wanyang; He, Bosai; Liu, Ran; Chen, Xiaohui; Bi, Kaishun

    2013-04-01

    A novel, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantitation of eight main active ingredients (evodiamine, rutaecarpine, dehydroevodiamine, limonin, ginsenoside Rb1, Rd, Re and Rg1) in rat plasma after oral administration of Wu-Zhu-Yu (WZY) decoction, which is a celebrated and widely used Traditional Chinese Medicine formula for the treatment of headache. The analytes and internal standard (IS) were separated on a SHIM-PACK XR-ODS II column, and the detection was performed on a UFLC-MS/MS system with turbo ion spray source. The lower limits of quantification were 1.5, 0.5, 1.0, 2.0, 2.0, 1.0, 0.5 and 0.2 ng ml(-1) for evodiamine, rutaecarpine, dehydroevodiamine, limonin, gensenoside Rb1, Rd, Re and Rg1, respectively. Linearity, accuracy, precision and absolute recoveries of the eight analytes were all within satisfaction. The IS-normalized matrix factor was adopted for assessing the matrix effect and accompanied with a satisfactory result. The validated method has been successfully applied to compare pharmacokinetic profiles of the eight active ingredients in rat plasma between normal and headache rats after administration. Exact pharmaceutical effect of WZY decoction on headache was demonstrated by the ethological response of headache rats induced by nitric oxide donor after administration. The results indicated that the absorption of evodiamine, rutaecarpine, gensenoside Rb1, Re and Rg1 in headache group were significantly higher than those in normal group with similar concentration-time curves while no significant differences existed in limonin and ginsenoside Rd between the two groups.

  12. A chimeric 18L1-45RG1 virus-like particle vaccine cross-protects against oncogenic alpha-7 human papillomavirus types.

    PubMed

    Huber, Bettina; Schellenbacher, Christina; Jindra, Christoph; Fink, Dieter; Shafti-Keramat, Saeed; Kirnbauer, Reinhard

    2015-01-01

    Persistent infection with oncogenic human papillomaviruses (HPV) types causes all cervical and a subset of other anogenital and oropharyngeal carcinomas. Four high-risk (hr) mucosal types HPV16, 18, 45, or 59 cause almost all cervical adenocarcinomas (AC), a subset of cervical cancer (CxC). Although the incidence of cervical squamous cell carcinoma (SCC) has dramatically decreased following introduction of Papanicolaou (PAP) screening, the proportion of AC has relatively increased. Cervical SCC arise mainly from the ectocervix, whereas AC originate primarily from the endocervical canal, which is less accessible to obtain viable PAP smears. Licensed (bivalent and quadrivalent) HPV vaccines comprise virus-like particles (VLP) of the most important hr HPV16 and 18, self-assembled from the major capsid protein L1. Due to mainly type-restricted efficacy, both vaccines do not target 13 additional hr mucosal types causing 30% of CxC. The papillomavirus genus alpha species 7 (α7) includes a group of hr types of which HPV18, 45, 59 are proportionally overrepresented in cervical AC and only partially (HPV18) targeted by current vaccines. To target these types, we generated a chimeric vaccine antigen that consists of a cross-neutralizing epitope (homologue of HPV16 RG1) of the L2 minor capsid protein of HPV45 genetically inserted into a surface loop of HPV18 L1 VLP (18L1-45RG1). Vaccination of NZW rabbits with 18L1-45RG1 VLP plus alum-MPL adjuvant induced high-titer neutralizing antibodies against homologous HPV18, that cross-neutralized non-cognate hr α7 types HPV39, 45, 68, but not HPV59, and low risk HPV70 in vitro, and induced a robust L1-specific cellular immune response. Passive immunization protected mice against experimental vaginal challenge with pseudovirions of HPV18, 39, 45 and 68, but not HPV59 or the distantly related α9 type HPV16. 18L1-45RG1 VLP might be combined with our previously described 16L1-16RG1 VLP to develop a second generation bivalent vaccine

  13. Inhibition of influenza A virus infection by ginsenosides

    PubMed Central

    Leon, Alberto J.; Kelvin, David J.

    2017-01-01

    Influenza viruses cause mild to severe respiratory infections in humans. Due to efficient means of transmission, the viruses infect human population on a large scale. Apart from vaccines, antiviral drugs are used to control infection; neuraminidase inhibitors are thought to be the first choice of treatment, particularly for severe cases. Rapidly evolving and emerging influenza viruses with increased frequency of viral resistance to these drugs stress the need to explore novel antiviral compounds. In this study, we investigated antiviral activity of ginseng extract and ginsenosides, the ginseng-derived triterpene and saponin compounds, against 2009 pandemic H1N1 virus in vitro and in vivo. Our data showed that treatment of mice with ginsenosides protected the animals from lethal 2009 pandemic H1N1 infection and lowered viral titers in animal lungs. Mechanistic studies revealed that ginsenosides interact with viral hemagglutinin protein and prevent the attachment of virus with α 2–3’ sialic acid receptors present on host cell surfaces. The interference in the viral attachment process subsequently minimizes viral entry into the cells and decreases the severity of the viral infection. We also describe that sugar moieties present in ginsenosides are indispensible for their attachment with viral HA protein. On the basis of our observations, we can say that ginsenosides are promising candidates for the development of antiviral drugs for influenza viruses. PMID:28187149

  14. Treatment of stress urinary incontinence by ginsenoside Rh2.

    PubMed

    Chen, Yung-Hsiang; Lin, Yu-Ning; Chen, Wen-Chi; Hsieh, Wen-Tsong; Chen, Huey-Yi

    2014-01-01

    Stress urinary incontinence (SUI) is a common disorder in middle-aged women and the elderly. Although surgical treatment of SUI has progressed, there are no effective pharmacological therapies without a side effect. We studied the effect of ginsenoside Rh2 against SUI. Here, we studied the effect of ginsenoside Rh2 on the contractile force of the urethra and blood vessels in an ex vivo organ bath assay. We further investigated the mechanisms and effects of Rh2 in cell culture and animal models. Ginsenoside Rh2 dose-dependently reduced lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. In the vaginal distension (VD)-induced SUI mouse model, ginsenoside Rh2 significantly reversed the VD-induced SUI physical signs and reduced blood pressure. The modulation of several SUI-related proteins, including myosin, survival motor neuron (SMN) protein, α-adrenergic receptor 1a (AdR1a), and superoxide dismutase 3 (SOD3), may play some crucial roles in the therapeutic approaches against SUI. In conclusion, the ginsenoside Rh2 may offer therapeutic potential against SUI.

  15. Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction

    NASA Astrophysics Data System (ADS)

    Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin

    2016-03-01

    Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.

  16. Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction.

    PubMed

    Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin

    2016-03-02

    Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.

  17. Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin.

    PubMed

    Im, Dong-soon; Nah, Seung-yeol

    2013-11-01

    Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine as a tonic herb that provides many beneficial effects. Pharmacologic studies in the last decades have shown that ginsenosides (ginseng saponins) are primarily responsible for the actions of ginseng. However, the effects of ginseng are not fully explained by ginsenosides. Recently, another class of active ingredients called gintonin was identified. Gintonin is a complex of glycosylated ginseng proteins containing lysophosphatidic acids (LPAs) that are the intracellular lipid mitogenic mediator. Gintonin specifically and potently activates the G protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics. In the present review, we evaluate the pharmacology of ginseng with the traditional viewpoint of Yin and Yang components. Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs.

  18. Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation

    PubMed Central

    Zhang, Li-ping; Jiang, Yi-chuan; Yu, Xiao-feng; Xu, Hua-li; Li, Min

    2016-01-01

    Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1β in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1β in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation. PMID:28105061

  19. Selection of Reference Genes for Quantitative Real-Time RT-PCR Studies in Tomato Fruit of the Genotype MT-Rg1

    PubMed Central

    González-Aguilera, Karla L.; Saad, Carolina F.; Chávez Montes, Ricardo A.; Alves-Ferreira, Marcio; de Folter, Stefan

    2016-01-01

    Quantitative real-time RT-PCR (qRT-PCR) has become one of the most widely used methods for accurate quantification of gene expression. Since there are no universal reference genes for normalization, the optimal strategy to normalize raw qRT-PCR data is to perform an initial comparison of a set of independent reference genes to assess the most stable ones in each biological model. Normalization of a qRT-PCR experiment helps to ensure that the results are both statistically significant and biologically meaningful. Tomato is the model of choice to study fleshy fruit development. The miniature tomato (Solanum lycopersicum L.) cultivar Micro-Tom (MT) is considered a model system for tomato genetics and functional genomics. A new genotype, containing the Rg1 allele, improves tomato in vitro regeneration. In this work, we evaluated the expression stability of four tomato reference genes, namely CAC, SAND, Expressed, and ACTIN2. We showed that the genes CAC and Exp are the best reference genes of the four we tested during fruit development in the MT-Rg1 genotype. Furthermore, we validated the reference genes by showing that the expression profiles of the transcription factors FRUITFULL1 and APETALA2c during fruit development are comparable to previous reports using other tomato cultivars. PMID:27679646

  20. Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3

    PubMed Central

    Song, Jae-Hyoung; Choi, Hwa-Jung; Song, Hyuk-Hwan; Hong, Eun-Hye; Lee, Bo-Ra; Oh, Sei-Ryang; Choi, Kwangman; Yeo, Sang-Gu; Lee, Yong-Pyo; Cho, Sungchan; Ko, Hyun-Jeong

    2014-01-01

    Background Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of 100 μg/mL. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at 100 μg/mL. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection. PMID:25378991

  1. Optimization of medium composition for keratinase production on feather by Bacillus licheniformis RG1 using statistical methods involving response surface methodology.

    PubMed

    Ramnani, Priya; Gupta, Rani

    2004-10-01

    A 3.5-fold increase in keratinase production by Bacillus licheniformis RG1 was achieved by using statistical methods involving Plackett-Burman design and response surface methodology. Eight variables were screened using Plackett-Burman design. Of these, glucose, peptone and glutathione were found to affect the response signal positively, whereas CaCl(2) had a negative effect. Further interaction of these factors, along with phosphate and incubation time, was studied using response surface methodology. An optimum keratinase production of 1295 units/mg dry weight was obtained with the following medium composition: 1% glucose, 1% peptone, 1% phosphate, 0.05% glutathione, 0.5% feather and 2% inoculum under shaking at 250 rev./min with an incubation period of 72 h at 37 degrees C. Keratinase production was found to be a function of biomass and maximum production occurred during the stationary phase.

  2. Changes in the Ginsenoside Content During Fermentation Using an Appliance for the Preparation of Red Ginseng.

    PubMed

    Lee, So Jin; Ha, Na; Kim, Yunjeong; Kim, Min-Gul

    2016-01-01

    The total amount of ginsenoside in fermented red ginseng (FRG) is increased by microbial fermentation. The aim of this study was to evaluate whether fermentation time and temperature affect the ginsenoside content during fermentation using an appliance for the preparation of red ginseng. The FRG and fermented red ginseng extracts (FRG-e) were prepared using an appliance for the preparation of red ginseng. The temperature was recorded and time points for sampling were scheduled at pre-fermentation (0[Formula: see text]h) and 18, 36, 48, 60 and 72[Formula: see text]h after the addition of the microbial strains. Samples of FRG and FRG-e were collected to identify changes in the ginsenoside contents at each time point during the fermentation process. The ginsenoside content was analyzed using high performance liquid chromatography (HPLC). The levels of ginsenoside Rh1, Rg3, and compound Y, which are known to have effective pharmacological properties, increased more than three-fold in the final products of FRG relative to samples prior to fermentation. Although the ginsenoside constituents of FRG-e decreased or increased and then decreased during fermentation, the total amount of ginsenoside in FRG-e was even higher than those in FRG; the total amounts of ginsenoside in FRG-e and FRG were 8282.8 and 738.0[Formula: see text]mg, respectively. This study examined the changes in composition of ginsenosides and suggests a method to manufacture high-content total ginsenosides according to the fermentation temperature and process time. Reducing the extraction time is expected to improve the decrease of ginsenosides in FRG-e as a function of the fermentation time.

  3. Ginsenoside-Rg{sub 1} induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a

    SciTech Connect

    Kwok, Hoi-Hin; Chan, Lai-Sheung; Poon, Po-Ying; Yue, Patrick Ying-Kit; Wong, Ricky Ngok-Shun

    2015-09-15

    Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg{sub 1} (Rg{sub 1}), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of non-coding RNAs, as important regulators of angiogenesis, but the role of microRNAs in Rg{sub 1}-induced angiogenesis has not been fully explored. In this report, we found that stimulating endothelial cells with Rg{sub 1} could reduce miR-23a expression. In silico experiments predicted hepatocyte growth factor receptor (MET), a well-established mediator of angiogenesis, as the target of miR-23a. Transfection of the miR-23a precursor or inhibitor oligonucleotides validated the inverse relationship of miR-23a and MET expression. Luciferase reporter assays further confirmed the interaction between miR-23a and the MET mRNA 3′-UTR. Intriguingly, ginsenoside-Rg{sub 1} was found to increase MET protein expression in a time-dependent manner. We further demonstrated that ginsenoside-Rg{sub 1}-induced angiogenic activities were indeed mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression, as confirmed by gain- and loss-of-function angiogenic experiments. In summary, our results demonstrated that ginsenoside-Rg{sub 1} could induce angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a. This study has broadened our understanding of the non-genomic effects of ginsenoside-Rg{sub 1,} and provided molecular evidence that warrant further development of natural compound as novel angiogenesis-promoting therapy. - Highlights: • Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. • Ginsenoside-Rg{sub 1} (Rg{sub 1}) has been demonstrated as an angiogenesis-stimulating compound. • We found that Rg{sub 1} induces angiogenesis by

  4. Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides.

    PubMed

    Dai, Zhubo; Liu, Yi; Zhang, Xianan; Shi, Mingyu; Wang, Beibei; Wang, Dong; Huang, Luqi; Zhang, Xueli

    2013-11-01

    Ginsenosides are the primary bioactive components of ginseng, which is a popular medicinal herb and exhibits diverse pharmacological activities. Protopanaxadiol is the aglycon of several dammarane-type ginsenosides, which also has anticancer activity. For microbial production of protopanaxadiol, dammarenediol-II synthase and protopanaxadiol synthase genes of Panax ginseng, together with a NADPH-cytochrome P450 reductase gene of Arabidopsis thaliana, were introduced into Saccharomyces cerevisiae, resulting in production of 0.05 mg/g DCW protopanaxadiol. Increasing squalene and 2,3-oxidosqualene supplies through overexpressing truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, farnesyl diphosphate synthase, squalene synthase and 2,3-oxidosqualene synthase genes, together with increasing protopanaxadiol synthase activity through codon optimization, led to 262-fold increase of protopanaxadiol production. Finally, using two-phase extractive fermentation resulted in production of 8.40 mg/g DCW protopanaxadiol (1189 mg/L), together with 10.94 mg/g DCW dammarenediol-II (1548 mg/L). The yeast strains engineered in this work can serve as the basis for creating an alternative way for production of ginsenosides in place of extraction from plant sources.

  5. Ginsenoside Rb1 is transformed into Rd and Rh2 by Microbacterium trichothecenolyticum.

    PubMed

    Kim, Hansoo; Kim, Jeong-Hoon; Lee, Phil Young; Bae, Kwang-Hee; Cho, Sayeon; Park, Byoung Chul; Shin, Heungsop; Park, Sung Goo

    2013-12-01

    Ginsenosides are the most important ingredient of ginseng and are known to possess many pharmacological and biological effects. Rb1, a major protopanaxadiol ginsenoside, is the most abundant ginsenoside in Panax ginseng C.A Meyer and can be hydrolyzed into more pharmaceutically potent minor ginsenosides. To identify a microorganism that is capable of converting Rb1 into other ginsenosides, we screened 12 Microbacterium spp., and M. trichothecenolyticum was identified as a likely candidate. M. trichothecenolyticum converted Rb1 into Rd and then into Rh2 based on TLC and HPLC analyses of reaction products. This biotransformation method can be easily applied for mass production of Rd and Rh2 by using Rb1.

  6. Red ginseng extract promotes the hair growth in cultured human hair follicles.

    PubMed

    Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

    2015-03-01

    Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

  7. Red Ginseng Extract Promotes the Hair Growth in Cultured Human Hair Follicles

    PubMed Central

    Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

    2015-01-01

    Abstract Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans. PMID:25396716

  8. Safety studies on an adenovirus recombinant vaccine for rabies (AdRG1.3-ONRAB) in target and non-target species.

    PubMed

    Knowles, M Kimberly; Nadin-Davis, Susan A; Sheen, Mary; Rosatte, Rick; Mueller, Rudi; Beresford, Andrew

    2009-11-05

    A replication-competent human adenovirus vector in which the rabies virus glycoprotein gene was inserted (AdRG1.3-ONRAB) was given by direct instillation into the oral cavity to representatives of three wildlife vector species of concern in Ontario (red fox, raccoon and striped skunk) and to a variety of non-target wildlife species, domestic and laboratory species. Despite use of a relatively high dose of vaccine, no untoward clinical signs were observed. Subsequent to vaccine exposure, detection of vaccine virus in lung, spleen, intestine, liver, kidney and brain of each animal was attempted using an ONRAB-specific assay combining PCR with Southern blotting (PCR-SB). Of the 1280 tissue samples obtained from vaccinates or contact animals, 18 (1.4%) were found to be PCR-SB positive. Virus isolation attempts were performed utilizing cell culture for all PCR-SB positive tissues and a selection of PCR-SB negative tissues. Histological examination performed on all PCR-SB positive tissues failed to identify lesions attributed to the vaccine. A quantitative real-time PCR was used to determine the excretion of the vaccine in feces and in the oral cavity with 0.8% of oral swabs and 6.8% of fecal specimens found to be positive. The low rates of recovery of vaccine virus from tissues, feces and the oral cavity suggest that the likelihood of ONRAB causing a negative impact on wildlife species is unlikely.

  9. Microbial transformation of ginsenoside Rb1 to compound K by Lactobacillus paralimentarius.

    PubMed

    Quan, Lin-Hu; Kim, Yeon-Ju; Li, Guan Hao; Choi, Kwang-Tea; Yang, Deok-Chun

    2013-06-01

    In this study, the major ginsenoside Rb1 was transformed into the more pharmacologically active minor compound K by food grade Lactobacillus paralimentarius LH4, which was isolated from kimchi, a traditional Korean fermented food. The enzymatic reaction was analyzed by TLC, HPLC, and NMR. Using the cell-free enzyme of Lactobacillus paralimentarius LH4 at optimal conditions for 30 °C at pH 6.0, 1.0 mg ml(-1) ginsenoside Rb1 was transformed into 0.52 mg ml(-1) compound K within 72 h, with a corresponding molar conversion yield of 88 %. The cell-free enzyme hydrolyzed the two glucose moieties attached to the C-3 position and the outer glucose moiety attached to the C-20 position of the ginsenoside Rb1. The cell-free enzyme hydrolyzed the ginsenoside Rb1 along the following pathway: ginsenoside Rb1 → gypenoside XVII and ginsenoside Rd → ginsenoside F2 → compound K. Our results indicate that Lactobacillus paralimentarius LH4 has the potential to be applied for the preparation of compound K in the food industry.

  10. Ginsenoside-Rg5 induces apoptosis and DNA damage in human cervical cancer cells

    PubMed Central

    LIANG, LI-DAN; HE, TAO; DU, TING-WEI; FAN, YONG-GANG; CHEN, DIAN-SEN; WANG, YAN

    2015-01-01

    Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside-Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside-Rg5 had any marked cytotoxic, apoptotic or DNA-damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT-3) were used to investigate the cytotoxicity of ginsenoside-Rg5 using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside-Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of γH2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside-Rg5 treatment compared with the C-33A, HT-3 and Me180 cells. As expected, ginsenoside-Rg5 induced significant concentration- and time-dependent increases in apoptosis. In addition, ginsenoside-Rg5 induced significant concentration-dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of γH2AX-positive HeLa and MS751 cells also revealed that ginsenoside-Rg5 caused DNA double-strands to break in a concentration-dependent manner. In conclusion, ginsenoside-Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer. PMID:25355274

  11. Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways.

    PubMed

    Li, Yue; Wang, Qi; Yao, Xiaomin; Li, Yan

    2010-08-25

    The herbal products baicalin, baicalein, chlorogenic acid, and ginsenoside Rf have multiple pharmacological effects and are extensively used in alternative and/or complementary therapies. The present study investigated whether baicalin, baicalein, chlorogenic acid, and ginsenoside Rf induced the expression of the cytochrome P450 3A4 (CYP3A4) and multi-drug resistance 1 (MDR1) genes through the pregnane X receptor and constitutive androstane receptor pathways. Real time PCR, western blotting, and a luminescent assay were used to assess the induction of gene expression and activity of CYP3A4 and MDR1 by the test compounds. The interactions of baicalein/chlorogenic acid/ginsenoside Rf with constitutive androstane receptor and pregnane X receptor were evaluated using luciferase reporter and gel shift assays. Baicalein induced the expression of CYP3A4 and MDR1 mRNA by activating pregnane X receptor and constitutive androstane receptor. Chlorogenic acid and ginsenoside Rf showed a relatively weak effect on CYP3A4 promoter activation only in HepG2 cells cotransfected with constitutive androstane receptor and demonstrated no effects on MDR1 via either the constitutive androstane receptor or pregnane X receptor pathway. Baicalin had no effect on either CYP3A4 or MDR1 gene expression. In conclusion, baicalein has the potential to up-regulate CYP3A4 and MDR1 through the direct activation of the constitutive androstane receptor and pregnane X receptor pathways. Chlorogenic acid and ginsenoside Rf only induced constitutive androstane receptor-mediated CYP3A4 expression.

  12. Effects and mechanisms of ginseng and ginsenosides on cognition.

    PubMed

    Smith, Imogen; Williamson, Elizabeth M; Putnam, Sophie; Farrimond, Jonathan; Whalley, Benjamin J

    2014-05-01

    Reviewed here is the existing evidence for the effects of ginseng extracts and isolated ginsenosides relevant to cognition in humans. Clinical studies in healthy volunteers and in patients with neurological disease or deficit, evidence from preclinical models of cognition, and pharmacokinetic data are considered. Conditions under which disease modification may indirectly benefit cognition but may not translate to cognitive benefits in healthy subjects are discussed. The number of chronic studies of ginseng effects in healthy individuals is limited, and the results from acute studies are inconsistent, making overall assessment of ginseng's efficacy as a cognitive enhancer premature. However, mechanistic results are encouraging; in particular, the ginsenosides Rg3 , Rh1 , Rh2 , Rb1 , Rd, Rg2 , and Rb3 , along with the aglycones protopanaxadiol and protopanaxatriol, warrant further attention. Compound K has a promising pharmacokinetic profile and can affect neurotransmission and neuroprotection. Properly conducted trials using standardized tests in healthy individuals reflecting the target population for ginseng supplementation are required to address inconsistencies in results from acute studies. The evidence summarized here suggests ginseng has potential, but unproven, benefits on cognition.

  13. Effect of gamma irradiation on the conversion of ginsenoside Rb1 to Rg3

    NASA Astrophysics Data System (ADS)

    Kim, Jae-Hun; Kwon, Sun-Kyu; Sung, Nak-Yun; Jung, Pil-Mun; Choi, Jong-il; Kim, Jae-Kyung; Sharma, Arun K.; Lee, Ju-Woon

    2012-08-01

    Ginsenosides, the most important secondary metabolites in ginseng, have various biological activities. Many studies have focused on the conversion of one of the major ginsenosides, Rb1, to the more active minor ginsenoside, Rg3. This study was carried out to investigate the effect of gamma irradiation on the conversion of Rb1 to Rg3. Rb1 solutions were gamma-irradiated at doses of 10 and 30 kGy and analyzed by high performance liquid chromatography (HPLC). HPLC chromatograms showed a decreased content of Rb1 with increasing irradiation dose, but the content of Rg3 was increased. The highest content of Rg3 was present in the 30 kGy-irradiated Rb1 sample. The cytotoxic effects tested in cancer cell lines were increased in the gamma-irradiated group. Therefore, these results suggest that gamma irradiation can be an effective method for the conversion of the ginsenoside Rb1 to Rg3.

  14. Fast determination of total ginsenosides content in ginseng powder by near infrared reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Hua-cai; Chen, Xing-dan; Lu, Yong-jun; Cao, Zhi-qiang

    2006-01-01

    Near infrared (NIR) reflectance spectroscopy was used to develop a fast determination method for total ginsenosides in Ginseng (Panax Ginseng) powder. The spectra were analyzed with multiplicative signal correction (MSC) correlation method. The best correlative spectra region with the total ginsenosides content was 1660 nm~1880 nm and 2230nm~2380 nm. The NIR calibration models of ginsenosides were built with multiple linear regression (MLR), principle component regression (PCR) and partial least squares (PLS) regression respectively. The results showed that the calibration model built with PLS combined with MSC and the optimal spectrum region was the best one. The correlation coefficient and the root mean square error of correction validation (RMSEC) of the best calibration model were 0.98 and 0.15% respectively. The optimal spectrum region for calibration was 1204nm~2014nm. The result suggested that using NIR to rapidly determinate the total ginsenosides content in ginseng powder were feasible.

  15. Structural Characterization of Ginsenosides from Flower Buds of Panax ginseng by RRLC-Q-TOF MS.

    PubMed

    Wu, Wei; Lu, Ziyan; Teng, Yaran; Guo, Yingying; Liu, Shuying

    2016-02-01

    Ginseng flower bud as a part of Panax ginseng has received much attention as a valuable functional food with medicinal potential. A few studies focused on systematic and comprehensive studies on its major ingredients. This study aims to rapidly characterize ginsenosides in ginseng flower buds and provide scientific basis for developing functional food, exploiting pharmaceutical effects and making full use of ginseng resources. A rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method was developed for rapid qualitative and quantitative analysis of ginsenosides in ginseng flower buds. The compounds were identified by comparing retention time of the reference standards, accurate mass measurement and the fragment ions obtained from RRLC-Q-TOF-MS/MS analyses. A total of 14 kinds of ginsenosides were identified and 5 kinds of malonyl-ginsenosides were first tentatively identified in ginseng flower buds. Ten kinds of main ginsenosides were quantitatively analyzed. The developed RRLC-Q-TOF-MS method was demonstrated as an effective analytical means for rapid characterization of the ginsenosides in flower buds of P. ginseng. The research result is valuable for quality control, assessment of authenticity and stability evaluation of ginseng flower buds.

  16. Ethosomes and Transfersomes for Topical Delivery of Ginsenoside Rhl from Red Ginseng: Characterization and In Vitro Evaluation.

    PubMed

    Choi, Jae-Hwan; Cho, Sun-Hang; Yun, Je-Jung; Yu, Young-Beob; Cho, Cheong-Weon

    2015-08-01

    Red ginseng (the steamed root of Panax ginseng C. A. Mayer), which contains ginsenosides as its main constituents, is frequently used to treat tumor, inflammation, diabetes, stress and acquired immunodeficiency syndrome in Asian countries. Ginsenoside Rhl, a bacterial metabolite of ginsenoside Rgl, is a protopanaxatriol type of ginsenosides. Liposomes do not deeply penetrate the skin and remain confined to the stratum corneum.Thus, new vesicular colloidal carriers such as ethosomes and transfersomes have been developed as an enhanced type of liposomes, recently. The aim of this study was to improve the topical delivery of ginsenoside Rhl isolated from red ginseng employing new vesicular system of ethosomes and transfersomes compared to conventional liposome. Characterization of ginsenoside Rhl-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (% EE), and transmission electron microscopy (TEM) studies. In addition, skin permeation profile was obtained using frantz diffusion cells and rat dorsal skin treated with ethosome and transfersome compared with conventional iposome. The size of vesicles range from 108.5 to 322.9 nm, and negatively charged from -20.95 to -31.37 mV. The % EE of ginsenoside Rh1 was obtained between 45.0 to 65.0%. Transfersomes provided a significantly higher skin permeation of ginsenoside Rhl compared to ethosome and conventional liposome. Therefore, based on the current study, ginsenoside Rhl-loaded transfersomes can act as a topical therapeutic effects potential.

  17. Therapeutic effect of ginsenoside Rd in rats with TNBS-induced recurrent ulcerative colitis.

    PubMed

    Yang, Xiao-Lai; Guo, Tian-Kang; Wang, Yan-Hong; Gao, Ming-Tang; Qin, Hong; Wu, Yong-Jie

    2012-07-01

    Ulcerative colitis (UC) is characterized by oxidative and nitrosative stress and neutrophil infiltration. In the present study, we aimed to investigate the therapeutic effect of ginsenoside Rd (GRd) in rats with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced recurrent UC. After UC was twice-induced by intracolonic injection of TNBS, rats were intragastrically administered different doses of GRd per day for 7 days. The colonic lesions and inflammation were evaluated both histologically and biochemically. Compared with the TNBS group, GRd treatment facilitated recovery of pathologic changes in the colon after induction of recurrent UC, as evidenced by a significant reduction of colonic weight/length ratio and macroscopic and microscopic damage scores (p < 0.01). The myeloperoxidase and inducible nitric oxide synthase activities with malonyldialdehyde and nitric oxide levels in colonic tissues were significantly decreased in the GRd group compared with those in the TNBS group (p < 0.01). GRd treatment was associated with remarkably increased superoxide dismutase and glutathione peroxidase activities. Results showed a valuable effect of GRd against TNBS-induced recurrent UC by inhibiting neutrophil infiltration and promoting the antioxidant capacity of the damaged colonic tissue.

  18. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  19. Structure–inhibition relationship of ginsenosides towards UDP-glucuronosyltransferases (UGTs)

    SciTech Connect

    Fang, Zhong-Ze; Cao, Yun-Feng; Hu, Cui-Min; Hong, Mo; Sun, Xiao-Yu; Ge, Guang-Bo; Liu, Yong; Zhang, Yan-Yan; Yang, Ling; Sun, Hong-Zhi

    2013-03-01

    The wide utilization of ginseng provides the high risk of herb–drug interaction (HDI) with many clinical drugs. The inhibition of ginsenosides towards drug-metabolizing enzymes (DMEs) has been regarded as an important reason for herb–drug interaction (HDI). Compared with the deep studies on the ginsenosides' inhibition towards cytochrome P450 (CYP), the inhibition of ginsenosides towards the important phase II enzymes UDP-glucuronosyltransferases (UGTs) remains to be unclear. The present study aims to evaluate the inhibition behavior of ginsenosides towards important UGT isoforms located in the liver and intestine using in vitro methods. The recombinant UGT isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed as in vitro probe reaction. The results showed that structure-dependent inhibition existed for the inhibition of ginsenosides towards UGT isoforms. To clarify the possibility of in vivo herb–drug interaction induced by this kind of inhibition, the ginsenoside Rg{sub 3} was selected as an example, and the inhibition kinetic type and parameters (K{sub i}) were determined. Rg{sub 3} competitively inhibited UGT1A7, 2B7 and 2B15-catalyzed 4-MU glucuronidation reaction, and exerted noncompetitive inhibition towards UGT1A8-catalyzed 4-MU glucuronidation. The inhibition parameters (K{sub i} values) were calculated to be 22.6, 7.9, 1.9, and 2.0 μM for UGT1A7, 1A8, 2B7 and 2B15. Using human maximum plasma concentration of Rg{sub 3} (400 ng/ml (0.5 μM)) after intramuscular injection of 60 mg Rg{sub 3}, the area under the plasma concentration-time curve (AUC) was extrapolated to increase by 2.2%, 6.3%, 26.3%, and 25% for the co-administered drugs completely undergoing the metabolism catalyzed by UGT1A7, 1A8, 2B7 and 2B15, respectively. All these results indicated that the ginsenosides' inhibition towards UGT isoforms might be an important reason for ginseng–drug interaction. - Highlights: ► Structure-dependent inhibition of

  20. Enzymatic formation of compound-K from ginsenoside Rb1 by enzyme preparation from cultured mycelia of Armillaria mellea

    PubMed Central

    Upadhyaya, Jitendra; Kim, Min-Ji; Kim, Young-Hoi; Ko, Sung-Ryong; Park, Hee-Won; Kim, Myung-Kon

    2015-01-01

    Background Minor saponins or human intestinal bacterial metabolites, such as ginsenosides Rg3, F2, Rh2, and compound K, are more pharmacologically active than major saponins, such as ginsenosides Rb1, Rb2, and Rc. In this work, enzymatic hydrolysis of ginsenoside Rb1 was studied using enzyme preparations from cultured mycelia of mushrooms. Methods Mycelia of Armillaria mellea, Ganoderma lucidum, Phellinus linteus, Elfvingia applanata, and Pleurotus ostreatus were cultivated in liquid media at 25°C for 2 wk. Enzyme preparations from cultured mycelia of five mushrooms were obtained by mycelia separation from cultured broth, enzyme extraction, ammonium sulfate (30–80%) precipitation, dialysis, and freeze drying, respectively. The enzyme preparations were used for enzymatic hydrolysis of ginsenoside Rb1. Results Among the mushrooms used in this study, the enzyme preparation from cultured mycelia of A. mellea (AMMEP) was found to convert ginsenoside Rb1 into compound K with a high yield, while those from G. lucidum, P. linteus, E. applanata, and P. ostreatus produced remarkable amounts of ginsenoside Rd from ginsenoside Rb1. The enzymatic hydrolysis pathway of ginsenoside Rb1 by AMMEP was Rb1 → Rd → F2 → compound K. The optimum reaction conditions for compound K formation from ginsenoside Rb1 were as follows: reaction time 72–96 h, pH 4.0–4.5, and temperature 45–55°C. Conclusion AMMEP can be used to produce the human intestinal bacterial metabolite, compound K, from ginsenoside Rb1 with a high yield and without food safety issues. PMID:27158230

  1. Morphological and Ginsenoside Differences among North American Ginseng Leaves

    PubMed Central

    Proctor, John T. A.; Sullivan, Alan J.; Rupasinghe, Vasantha P. V.; Jackson, Chung-Ja C.

    2011-01-01

    Leaf characteristics of mature 2, 3 and 4-year-old North American ginseng (Panax quinquefolius L.) leaves on fruiting and non-fruiting (NF) plants were studied. Leaflets of the 2-year-old plants had the lowest fresh and dry weight, area, volume and internal gas volume. Inflorescence removal in 3-year-old plants did not affect leaf characteristics or ginsenoside concentration but in 4-yearold plants it increased leaf fresh (38.6%) and dry (43.9%) weight, leaf area (29.1%), specific leaf mass (11.4%), leaf volume (43.1%), and leaf thickness (12.1%), and decreased leaf water content (6.2%). Cultivated ginseng, although an understorey plant, had the specific leaf mass, 35.6 g m-2 (range, 36 to 39 g m-2) and a chlorophyll a/b ratio of 2.40 to 2.61, both suggesting the ability to perform like a sunny habitat plant. Also, specific leaf mass of 35.6 g m-2 is similar to that reported for perennial plants, 36.8 g m-2, rather than that for annuals, 30.9 g m-2. PMID:23717057

  2. Induction of cyclooxygenase-2 by ginsenoside Rd via activation of CCAAT-enhancer binding proteins and cyclic AMP response binding protein

    SciTech Connect

    Jeong, Hye Gwang; Pokharel, Yuba Raj; Han, Eun Hee; Kang, Keon Wook . E-mail: kwkang@chosun.ac.kr

    2007-07-20

    Panax ginseng is a widely used herbal medicine in East Asia and is reported to have a variety of pharmacological effects against cardiovascular diseases and cancers. Here we show a unique effect of ginsenoside Rd (Rd) on cyclooxygenase-2 (COX-2) expression in RAW264.7 macrophages. Rd (100 {mu}g/ml), but not other ginsenosides induced COX-2 and increased prostaglandin E{sub 2} production. Gel shift and Western blot analyses using nuclear fractions revealed that Rd increased both the DNA binding of and the nuclear levels of CCAAT/enhancer binding protein (C/EBP){alpha}/{beta} and cyclic AMP response element binding protein (CREB), but not of p65, in RAW264.7 cells. Moreover, Rd increased the luciferase reporter gene activity in cells transfected with a 574-bp mouse COX-2 promoter construct. Site-specific mutation analyses confirmed that Rd-mediated transcriptional activation of COX-2 gene was regulated by C/EBP and CREB. These results provide evidence that Rd activated C/EBP and CREB, and that the activation of C/EBP and CREB appears to be essential for induction of COX-2 in RAW264.7 cells.

  3. Effects of Total Ginsenosides on the Feeding Behavior and Two Enzymes Activities of Mythimna separata (Walker) Larvae

    PubMed Central

    Zhang, Ai-Hua; Tan, Shi-Qiang; Zhao, Yan; Lei, Feng-Jie; Zhang, Lian-Xue

    2015-01-01

    Ginsenosides, the main effective components of Panax ginseng C.A. Meyer and Panax quinquefolius L., are important allelochemicals of ginseng. Although many studies have targeted the pharmacological, chemical, and clinical properties of ginsenosides, little is known about their ecological role in ginseng population adaptation and evolution. Pests rarely feed on ginseng, and it is not known why. This study investigated the effects of total ginsenosides on feeding behavior and activities of acetylcholinesterase (AChE) and glutathione s-transferase (GST) in Mythimna separata (Walker) larvae. The results showed that the total ginsenosides had significant antifeeding activity against M. separata larvae, determined by nonselective and selective antifeeding bioassays. In addition, the total ginsenosides had inhibitory effects on the activities of GST and AChE. The antifeeding ratio was the highest at 8 h, then decreased, and was the lowest at 16 h. Both GST and AChE activities decreased from 0 h to 48 h in all total ginsenosides treatments but increased at 72 h. Total ginsenosides had antifeeding activity against M. separata larvae and inhibitory effects on the activities of GST and AChE. PMID:26074991

  4. Daikenchuto (TU-100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K.

    PubMed

    Hasebe, Takumu; Ueno, Nobuhiro; Musch, Mark W; Nadimpalli, Anuradha; Kaneko, Atsushi; Kaifuchi, Noriko; Watanabe, Junko; Yamamoto, Masahiro; Kono, Toru; Inaba, Yuhei; Fujiya, Mikihiro; Kohgo, Yutaka; Chang, Eugene B

    2016-02-01

    Many pharmaceutical agents not only require microbial metabolism for increased bioavailability and bioactivity, but also have direct effects on gut microbial assemblage and function. We examined the possibility that these actions are not mutually exclusive and may be mutually reinforcing in ways that enhance long-term of these agents. Daikenchuto, TU-100, is a traditional Japanese medicine containing ginseng. Conversion of the ginsenoside Rb1 (Rb1) to bioactive compound K (CK) requires bacterial metabolism. Diet-incorporated TU-100 was administered to mice over a period of several weeks. T-RFLP and 454 pyrosequencing were performed to analyze the time-dependent effects on fecal microbial membership. Fecal microbial capacity to metabolize Rb1 to CK was measured by adding TU-100 or ginseng to stool samples to assess the generation of bioactive metabolites. Levels of metabolized TU-100 components in plasma and in stool samples were measured by LC-MS/MS. Cecal and stool short-chain fatty acids were measured by GC-MS. Dietary administration of TU-100 for 28 days altered the gut microbiota, increasing several bacteria genera including members of Clostridia and Lactococcus lactis. Progressive capacity of microbiota to convert Rb1 to CK was observed over the 28 days administration of dietary TU-100. Concomitantly with these changes, increases in all SCFA were observed in cecal contents and in acetate and butyrate content of the stool. Chronic consumption of dietary TU-100 promotes changes in gut microbiota enhancing metabolic capacity of TU-100 and increased bioavailability. We believe these findings have broad implications in optimizing the efficacy of natural compounds that depend on microbial bioconversion in general.

  5. Large Scale Culture of Ginseng Adventitious Roots for Production of Ginsenosides

    NASA Astrophysics Data System (ADS)

    Paek, Kee-Yoeup; Murthy, Hosakatte Niranjana; Hahn, Eun-Joo; Zhong, Jian-Jiang

    Ginseng (Panax ginseng C. A. Meyer) is one of the most famous oriental medicinal plants used as crude drugs in Asian countries, and now it is being used worldwide for preventive and therapeutic purposes. Among diverse constituents of ginseng, saponins (ginsenosides) have been found to be major components responsible for their biological and pharmacological actions. On the other hand, difficulties in the supply of pure ginsenosides in quantity prevent the development of ginseng for clinical medicines. Cultivation of ginseng in fields takes a long time, generally 5-7 years, and needs extensive effort regarding quality control since growth is susceptible to many environmental factors including soil, shade, climate, pathogens and pests. To solve the problems, cell and tissue cultures have been widely explored for more rapid and efficient production of ginseng biomass and ginsenosides. Recently, cell and adventitious root cultures of P. ginseng have been established in large scale bioreactors with a view to commercial application. Various physiological and engineering parameters affecting the biomass production and ginsenoside accumulation have been investigated. Advances in adventitious root cultures including factors for process scale-up are reviewed in this chapter. In addition, biosafety analyses of ginseng adventitious roots are also discussed for real application.

  6. The antitumor activity study of ginsenosides and metabolites in lung cancer cell

    PubMed Central

    Xu, Feng-Yuan; Shang, Wen-Qing; Yu, Jia-Jun; Sun, Qian; Li, Ming-Qing; Sun, Jian-Song

    2016-01-01

    Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and antitumor activity. Ginsenosides are the main biological components of ginseng. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides. However, the difference between these compounds in anti-lung cancer is unclear. The present study aimed to evaluate the antitumor activity of PPD, PPT, Ginsenosides-Rg3 (G-Rg3) and Ginsenosides-Rh2 (G-Rh2) in lung cancer cell. After treatment with cisplatin, PPD, PPT, G-Rg3 or G-Rh2, the viability, apoptosis level and invasiveness of lung cell lines (A549 cell, a lung adenocarcinoma cell line and SK-MES-1 cell, a lung squamous cell line) in vitro were analyzed by Cell Counting Kit-8 (CCK8), Annexin V/PI apoptosis and Matrigel invasion assays, respectively. Here we found that all these compounds led to significant decreases of viability and invasiveness and an obvious increase of apoptosis of A549 and SK-MES-1 cells. Among these, the viability of SK-MES-1 cell treated with PPT was decreased to 66.8%, and this effect was closest to Cisplatin. G-Rg3 had the highest stimulatory effect on apoptosis, and PTT had the highest inhibitory effect on cell invasiveness in A549 and SK-MES-1 cells. These results indicate that both ginsenosides and two metabolites have antitumor activity on lung cancer cell in vitro. However, PPT is more powerful for inhibiting the viability and invasiveness of lung cancer cell, especially lung squamous cell. G-Rg3 has the best pro-apoptosis effects. This study provides a scientific basis for potential therapeutic strategies targeted to lung cancer by further structure modification. PMID:27186294

  7. Localization of ginsenosides in the rhizome and root of Panax ginseng by laser microdissection and liquid chromatography-quadrupole/time of flight-mass spectrometry.

    PubMed

    Liang, Zhitao; Chen, Yujie; Xu, Liang; Qin, Minjian; Yi, Tao; Chen, Hubiao; Zhao, Zhongzhen

    2015-02-01

    The root and rhizome of Panax ginseng C.A. Mey, known as ginseng, is a commonly used medicinal plant. Ginsenosides are the major active components responsible for the tonic effects of this herb. Here, the combination of laser microdissection and ultra-high performance liquid chromatography quadrupole/time of flight-mass spectrometry (UHPLC-QTOF-MS) was applied to investigate the localization of ginsenosides in root and rhizome of P. ginseng. Five kinds of tissue cells were separated from the rhizome, main root and branch root of ginseng. Fifty-nine ginsenosides were identified and the results showed that the cork contained more kinds of ginsenosides than did the cortex, phloem, xylem and resin canals. It is interesting that the phloem, xylem and resin canals from branch root contained a greater number of ginsenosides than did from main root. This study provides solid evidence on the accumulation of ginsenosides in cork, cortex, phloem and xylem.

  8. Ginsenoside Rh2 inhibits proliferation and induces apoptosis in human leukemia cells via TNF-α signaling pathway.

    PubMed

    Huang, Jingjia; Peng, Kunjian; Wang, Linghao; Wen, Bin; Zhou, Lin; Luo, Tiao; Su, Min; Li, Jijia; Luo, Zhiyong

    2016-08-01

    Ginsenoside Rh2, a triterpene saponin extracted from Panax ginseng, exhibits pharmacological activity against multiple cancers. However, the anticancer mechanism of ginsenoside Rh2 is unclear. In this study, we found that ginsenoside Rh2 effectively inhibits growth and induces apoptosis of HL-60 cells. Using microarray technology, we found that tumor necrosis factor-α (TNF-α) is clearly up-regulated. Furthermore, anti-TNF-α antibody relieved the Rh2-induced HL-60 cell apoptosis via suppression of caspase-8, caspase-9, and caspase-3 activation. In addition, TNF-α up-regulation was also observed in other Rh2-treated cancer cell lines. These results demonstrate that TNF-α plays a key role in ginsenoside Rh2-induced cell apoptosis.

  9. Enhanced oral bioavailability and anti-tumour effect of paclitaxel by 20(s)-ginsenoside Rg3 in vivo.

    PubMed

    Yang, Lei-Qiong; Wang, Bin; Gan, Hui; Fu, Shou-Ting; Zhu, Xiao-Xia; Wu, Zhuo-Na; Zhan, Da-Wei; Gu, Ruo-Lan; Dou, Gui-Fang; Meng, Zhi-Yun

    2012-11-01

    The purpose of this study was to investigate the effect of paclitaxel in combination with 20(s)-ginsenoside Rg3 on its anti-tumour effect in nude mice. In the Caco-2 transport assay, the apparent permeability from the apical side to the basal side (P(app)) (A-B) and P(app) (B-A) of paclitaxel were measured when co-incubated with different concentrations of 20(s)-ginsenoside Rg3. The results indicated that the penetration of paclitaxel through the Caco-2 monolayer from the apical side to the basal side was facilitated by 20(s)-ginsenoside Rg3 in a concentration-dependent manner. Meanwhile, 20(s)-ginsenoside Rg3 inhibited P-glycoprotein (P-gp), and the maximum inhibition was achieved at 80 µM (p < 0.05). The pharmacokinetic parameters of paclitaxel after oral co-administration of paclitaxel (40 mg/kg) with various doses of 20(s)-ginsenoside Rg3 in rats were investigated by an in vivo pharmacokinetic experiment. The results showed that the AUC of paclitaxel co-administered with 20(s)-ginsenoside Rg3 was significantly higher (p < 0.001 at 10 mg/kg) compared with the control. The relative bioavailability (RB) % of paclitaxel with 20(s)-ginsenoside Rg3 was 3.4-fold (10 mg/kg) higher than that of the control. The effect of paclitaxel orally co-administered with 20(s)-ginsenoside Rg3 against human tumour MCF-7 xenografts in nude mice was also evaluated. Paclitaxel (20 mg/kg) co-administered with 20(s)-ginsenoside Rg3 (10 mg/kg) exhibited an effective anti-tumour activity with the relative tumor growth rate (T/C) values of 39.36% (p <0.05). The results showed that 20(s)-ginsenoside Rg3 enhanced the oral bioavailability of paclitaxel in rats and improved the anti-tumour activity in nude mice, indicating that oral co-administration of paclitaxel with 20(s)-ginsenoside Rg3 could provide an effective strategy in addition to the established i.v. route.

  10. Induction of G2/M phase cell cycle arrest and apoptosis by ginsenoside Rf in human osteosarcoma MG‑63 cells through the mitochondrial pathway.

    PubMed

    Shangguan, Wen-Ji; Li, He; Zhang, Yue-Hui

    2014-01-01

    Ginsenosides, extracted from the traditional Chinese herb ginseng, are a series of novel natural anticancer products known for their favorable safety and efficacy profiles. The present study aimed to investigate the cytotoxicity of ginsenoside Rf to human osteosarcoma cells and to explore the anticancer molecular mechanisms of ginsenoside Rf. Five human osteosarcoma cell lines (MG-63, OS732, U-2OS, HOS and SAOS-2) were employed to investigate the cytotoxicity of ginsenoside Rf by MTT and colony forming assays. After treatment with ginsenoside Rf, MG-63 cells which were the most sensitive to ginsenoside Rf, were subjected to flow cytometry to detect cell cycle distribution and apoptosis, and nuclear morphological changes were visualized by Hoechst 33258 staining. Caspase-3, -8 and -9 activities were also evaluated. The expression of cell cycle markers including cyclin B1 and Cdk1 was detected by RT-PCR and western blotting. The expression of apoptotic genes Bcl-2 and Bax and the release of cytochrome c were also examined by western blotting. Change in the mitochondrial membrane potential was observed by JC-1 staining in situ. Our results demonstrated that the cytotoxicity of ginsenoside Rf to these human osteosarcoma cell lines was dose-dependent, and the MG-63 cells were the most sensitive to exposure to ginsenoside Rf. Additionally, ginsenoside Rf induced G2/M phase cell cycle arrest and apoptosis in MG-63 cells. Furthermore, we observed upregulation of Bax and downregulation of Bcl-2, Cdk1 and cyclin B1, the activation of caspase-3 and -9 and the release of cytochrome c in MG-63 cells following treatment with ginsenoside Rf. Our findings demonstrated that ginsenoside Rf induces G2/M phase cell cycle arrest and apoptosis in human osteosarcoma MG-63 cells through the mitochondrial pathway, suggesting that ginsenoside Rf, as an effective natural product, may have a therapeutic effect on human osteosarcoma.

  11. Ginsenosides protect apical transporters of cultured proximal tubule cells from dysfunctions induced by h(2)o(2).

    PubMed

    Han, Ho Jae; Yoon, Byung Cheol; Park, Soo Hyun; Park, Ji Yeong; Oh, Young Joon; Lee, Yun Jung; Park, Kwon Moo

    2002-01-01

    Oxidative stress has been implicated as a primary cause of renal failure in certain renal diseases. Indeed, renal proximal tubule is a very sensitive site to oxidative stress and retains functionally fully characterized transporters. It has been reported that ginsenosides have a beneficial effect on diverse diseases including oxidative stress. However, the protective effect of ginsenosides on oxidative stress has not been elucidated in renal proximal tubule cells. Thus, we examined the effect of ginsenosides on oxidative stress-induced alteration of apical transporters and its related mechanism in renal proximal tubule cells. In the present study, hydrogen peroxide (H(2)O(2)) (>10(-5) M) inhibited alpha-methyl-D-glucopyranoside uptake in a dose-dependent manner (p < 0.05). It also inhibited Pi and Na(+) uptake. At a concentration of 20 microg/ml, total ginsenosides significantly reduced H(2)O(2)-induced inhibition of apical transporters. In contrast, protopanaxadiol (PD) and protopanaxatriol (PT) saponins exhibited a less preventive effect than total ginsenosides (p < 0.05). Furthermore, we examined its action mechanism. H(2)O(2) increased lipid peroxide formation, arachidonic acid (AA) release, and Ca(2+) uptake. These effects on H(2)O(2) were significantly prevented by total ginsenosides and PD or PT sanponins. However, total ginsenosides appear to be more protective than PD and PT saponins (p < 0.05). In conclusion, ginsenosides prevented H(2)O(2)-induced inhibition of apical transporters via a decrease in oxidative stress, AA release, and Ca(2+) uptake in primary cultured renal proximal tubule cells.

  12. Enzymatic transformation of ginsenosides in Korean Red Ginseng (Panax ginseng Meyer) extract prepared by Spezyme and Optidex

    PubMed Central

    Choi, Hyeon-Son; Kim, Sun Young; Park, Yooheon; Jung, Eun Young; Suh, Hyung Joo

    2014-01-01

    Background In this study, we examined the effects of various enzymes on chemical conversions of ginsenosides in ginseng extract prepared by amylases. Methods Rapidase, Econase CE, Viscozyme, Ultraflo L, and Cytolase PCL5 were used for secondary enzymatic hydrolysis after amylase treatment of ginseng extract, and ginsenoside contents, skin permeability, and chemical compositions including total sugar, acidic polysaccharide, and polyphenols were determined on the hydrolyzed ginseng extract. Results Rapidase treatment significantly elevated total ginsenoside contents compared with the control (p < 0.05). In particular, deglycosylated ginsenosides including Rg3, which are known as bioactive compounds, were significantly increased after Rapidase treatment (p < 0.05). The Rapidase-treated group also increased the skin permeability of polyphenols compared with the control, showing the highest level of total sugar content among the enzyme treatment groups. Conclusion This result showed that Rapidase induced the conversion of ginsenoside glycosides to aglycones. Meanwhile, Cytolase PCL5 and Econase treatments led to a significant increase of uronic acid (acidic polysaccharide) level. Taken together, our data showed that the treatments of enzymes including Rapidase are useful for the conversion and increase of ginsenosides in ginseng extracts or products. PMID:25379006

  13. Pharmacokinetics of ginsenoside Rb1 and its metabolite compound K after oral administration of Korean Red Ginseng extract.

    PubMed

    Kim, Hyung-Ki

    2013-10-01

    Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was 8.35±3.19 ng/mL, which was significantly higher than that of ginsenoside Rb1 (3.94±1.97 ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K.

  14. Ginsenoside Rb1, a novel activator of the TMEM16A chloride channel, augments the contraction of guinea pig ileum.

    PubMed

    Guo, Shuai; Chen, Yafei; Pang, Chunli; Wang, Xuzhao; Qi, Jinlong; Mo, Li; Zhang, Hailin; An, Hailong; Zhan, Yong

    2017-01-25

    Calcium-activated chloride channels (CaCCs) play important roles in many physiological processes, and the molecular basis of CaCCs has been identified as TMEM16A in many cell types. It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. In this study, we identified the first natural activator of TMEM16A from traditional Chinese medicine and explored its mechanism. Our data showed that Ginsenoside Rb1 (GRb1) can activate TMEM16A directly from the intracellular side in a dose-dependent manner at an EC50 of 38.4 ± 2.14 μM. GRb1 specifically activated TMEM16A/B, but not the other previously proposed CaCC mediators such as CFTR and bestrophin. Moreover, GRb1 promoted proliferation of CHO cells stably expressing TMEM16A, in a concentration-dependent manner. Finally, we showed that GRb1 increased the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo. In summary, GRb1 can be considered a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction.

  15. Microbial ketonization of ginsenosides F1 and C-K by Lactobacillus brevis.

    PubMed

    Jin, Yan; Jung, Sun Young; Kim, Yeon-Ju; Lee, Dae-Young; Min, Jin-Woo; Wang, Chao; Yang, Deok-Chun

    2014-12-01

    Ginsenosides are the major pharmacological components in ginseng. We isolated lactic acid bacteria from Kimchi to identify microbial modifications of ginsenosides. Phylogenetic analysis of 16S rRNA gene sequences indicated that the strain DCY65-1 belongs to the genus Lactobacillus and is most closely related to Lactobacillus brevis. On the basis of TLC and HPLC analysis, we found two metabolic pathways: F1 → 6α,12β-dihydroxydammar-3-one-20(S)-O-β-D-glucopyranoside and C-K → 12β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside. These results suggest that strain DCY65-1 is capable of potent ketonic decarboxylation, ketonizing the hydroxyl group at C-3. The F1 metabolite had a more potent inhibitory effect on mushroom tyrosinase than did the substrate. Therefore, the F1 and C-K derivatives may be more pharmacologically active compounds, which should be further characterized.

  16. Simultaneous enrichment of deglycosylated ginsenosides and monacolin K in red ginseng by fermentation with Monascus pilosus.

    PubMed

    Hong, Sung-Yun; Oh, Jee-Hwan; Lee, Inhyung

    2011-01-01

    To improve its bioavailability and pharmacological effects in humans, red ginseng was fermented with a newly isolated fungus, Monascus pilosus KMU103. Most of the ginsenosides were converted to deglycosylated ginsenocides, such as Rh(1), Rh(2), and Rg(3). The total amount of ginsenosides Rh(1), Rh(2), and Rg(3) was 838.7 mg/kg in the red ginseng, and increased to 4,117 mg/kg after 50 L fermentation in 13% red ginseng and 2% glucose. In addition, the Monascus-fermented red ginseng contained 3,089 mg/kg of monacolin K, one of the metabolites produced by Monascus known to reduce cholesterol in the blood. This newly developed Monascus-fermented red ginseng should result in improved health effects, not only by biotransforming gisenosides to deglycosylated ones but also by creating additional bioactive compounds.

  17. Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS

    SciTech Connect

    Yoon, Sung-Jin; Park, Jun-Young; Choi, Song; Lee, Jin-Bong; Jung, Haiyoung; Kim, Tae-Don; Yoon, Suk Ran; Choi, Inpyo; Shim, Sungbo; Park, Young-Jun

    2015-08-07

    Ginsenoside Rg3, a specific biological effector, is well-known as a major bioactive ingredient of Panax ginseng. However, its role in the inflammasome activation process remains unclear. In this report, we demonstrate that ginsenosides 20(R)-Rg3 and 20(S)-Rg3 are capable of suppressing both lethal endotoxic shock and the S-nitrosylation of the NLRP3 inflammasome by inhibiting nitric oxide (NO) production through the regulation of inducible nitric oxide synthase (iNOS) expression. In response to lipopolysaccharide (LPS), the reducing effect of 20(S)-Rg3 and 20(R)-Rg3 on nitric oxide led to an increase in the survival time of mice after lethal endotoxin-induced shock, and excess levels of NO inhibited IL-1β production via the S-nitrosylation of the NLRP3 inflammasome. In addition, ginsenosides 20(R)-Rg3 and 20(S)-Rg3 had suppressive effects on the LPS- or UV-irradiation-induced reactive oxygen species (ROS) levels in macrophage and HaCaT cells and thereby prevented apoptosis of spleen cells in mice. Altogether, these results demonstrate that ginsenoside 20(R)-Rg3 and 20(S)-Rg3, a naturally occurring compound, might act as a dual therapeutic regulator for the treatment of inflammatory and oxidative stress-related diseases. - Highlights: • Ginsenosides Rg3 inhibits NO production through the regulation of iNOS expression. • Ginsenosides Rg3 inhibits the S-nitrosylation of the NLRP3 inflammasome. • Ginsenosides Rg3 suppress on the LPS- or UV-irradiation-induced ROS levels in cells.

  18. Ginsenosides attenuate methylglyoxal-induced impairment of insulin signaling and subsequent apoptosis in primary astrocytes.

    PubMed

    Chu, John M T; Lee, Dicky K M; Wong, Daniella P K; Wong, Ricky N S; Yung, Ken K L; Cheng, Christopher H K; Yue, Kevin K M

    2014-10-01

    Diabetes mellitus (DM), which is characterized by chronic hyperglycemia, is known to increase the risk of neurodegeneration. In type 2 diabetes, hyperglycemia could cause insulin resistance and neurodegeneration in various cells including neurons and astrocytes. Hyperglycemia is also known to result in the formation of advanced glycation end-products (AGE) Methylglyoxal (MG) is one of the most reactive AGE precursors in which its abnormal accumulation is usually found in diabetic patients and induces neuronal cell death in central nervous system. Ginseng is a herb that has been widely used to treat various diseases in traditional Chinese medicine. Ginsenosides, the pharmacologically active component isolated from ginseng, have been shown to have cryoprotective effects in different neural cells. In the present study we investigated the effects of MG in disturbing insulin signaling and leading to further cellular apoptosis in rat primary astrocytes. Furthermore, the protective effects of different subtypes of ginsenosides were studied. From the results, impairment of insulin signaling was found in astrocytes under MG treatment. Moreover, cleavage of caspase and Poly ADP ribose polymerase (PARP) was observed in line with insulin signaling disruption, showing the neurotoxic effects of MG towards astrocytes. The effects of ginsenosides in MG treated astrocytes were also investigated. After treatment, ginsenosides Rd and R-Rh2 were shown to ameliorate the cell viability of MG-treated astrocytes. In addition, Rd and R-Rh2 could improve insulin signaling and inhibit apoptosis, indicating that Rd, R-Rh2 and related compounds may have therapeutic potential in treating diabetes-induced neurodegeneration.

  19. Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor {alpha}

    SciTech Connect

    Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung . E-mail: yoon60@mokwon.ac.kr

    2006-01-06

    We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-mediated pathways, using a PPAR{alpha}-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPAR{alpha} ligand Wy14,643. In contrast, no effect was detected in the PPAR{alpha}-null mice. Testing of eight main ginsenosides on PPAR{alpha} reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPAR{alpha}-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPAR{alpha}.

  20. Localization of ginsenosides in Panax ginseng with different age by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry imaging.

    PubMed

    Bai, Hangrui; Wang, Shujuan; Liu, Jianjun; Gao, Dan; Jiang, Yuyang; Liu, Hongxia; Cai, Zongwei

    2016-07-15

    The root of Panax ginseng C.A. Mey. (P. ginseng) is one of the most popular traditional Chinese medicines, with ginsenosides as its main bioactive components. Because different ginsenosides have varied pharmacological effects, extraction and separation of ginsenosides are usually required for the investigation of pharmacological effects of different ginsenosides. However, the contents of ginsenosides vary with the ages and tissues of P. ginseng root. In this research, an efficient method to explore the distribution of ginsenosides and differentiate P. ginseng roots with different ages was developed based on matrix assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI). After a simple sample preparation, there were 18 peaks corresponding to 31 ginsenosides with distinct localization in the mass range of m/z 700-1400 identified by MALDI-TOF-MSI and MALDI-TOF-MS/MS. All the three types of ginsenosides were successfully detected and visualized in images, which could be correlated with anatomical features. The P. ginseng at the ages of 2, 4 and 6 could be differentiated finely through the principal component analysis of data collected from the cork based on the ion images but not data from the whole tissue. The experimental result implies that the established method for the direct analysis of metabolites in plant tissues has high potential for the rapid identification of metabolites and analysis of their localizations in medicinal herbs. Furthermore, this technique also provides valuable information for the component-specific extraction and pharmacological research of herbs.

  1. Effects of ginseng rhizome and ginsenoside Ro on testosterone 5α-reductase and hair re-growth in testosterone-treated mice.

    PubMed

    Murata, Kazuya; Takeshita, Fumiaki; Samukawa, Keiichi; Tani, Tadato; Matsuda, Hideaki

    2012-01-01

    This research program on the novel functions of Panax ginseng C. A. Meyer focused on the effects of ginseng rhizome on hair re-growth in androgenetic alopecia. Extracts of red ginseng rhizome showed greater dose-dependent inhibitory effects against testosterone 5α-reductase (5αR) when compared with extracts of the main root. Ginsenoside Ro, the predominant ginsenoside in the rhizome, and ginsenoside Rg(3), a unique ginsenoside in red ginseng, showed inhibitory activity against 5αR with IC(50) values of 259.4 and 86.1 µm, respectively. The rhizome of P. japonicus, which contains larger amounts of ginsenoside Ro, also inhibited 5αR. Topical administration of extracts of red ginseng rhizomes (2 mg/mouse) and ginsenoside Ro (0.2 mg/mouse) to shaved skin inhibited hair re-growth suppression after shaving in the testosterone-treated C57BL/6 mice. These results suggest that red ginseng rhizomes containing both oleanane- and dammarane-type ginsenosides are a promising raw material for cosmetic use. This is the first report that ginsenoside Ro enhances in vivo hair re-growth based on their inhibitory activity against 5αR in the androgenetic alopecia model.

  2. Transcriptome profiling shows gene regulation patterns in ginsenoside pathway in response to methyl jasmonate in Panax Quinquefolium adventitious root

    PubMed Central

    Wang, Juan; Li, Jinxin; Li, Jianli; Liu, Shujie; Wu, Xiaolei; Li, Jing; Gao, Wenyuan

    2016-01-01

    Here, we combine elicitors and transcriptomics to investigate the inducible biosynthesis of the ginsenoside from the Panax quinquefolium. Treatment of P. quinquefolium adventitious root with methyl jasmonate (MJ) results in an increase in ginsenoside content (43.66 mg/g compared to 8.32 mg/g in control group). Therefore, we sequenced the transcriptome of native and MJ treated adventitious root in order to elucidate the key differentially expressed genes (DEGs) in the ginsenoside biosynthetic pathway. Through DEG analysis, we found that 5,759 unigenes were up-regulated and 6,389 unigenes down-regulated in response to MJ treatment. Several defense-related genes (48) were identified, participating in salicylic acid (SA), jasmonic acid (JA), nitric oxide (NO) and abscisic acid (ABA) signal pathway. Additionally, we mapped 72 unigenes to the ginsenoside biosynthetic pathway. Four cytochrome P450s (CYP450) were likely to catalyze hydroxylation at C-16 (c15743_g1, c39772_g1, c55422_g1) and C-30 (c52011_g1) of the triterpene backbone. UDP-xylose synthases (c52571_g3) was selected as the candidate, which was likely to involve in ginsenoside Rb3 biosynthesis. PMID:27876840

  3. Suppression of Hepatic Cyp1a2 by Total Ginsenosides in Lipopolysaccharide-Treated Mice and Primary Mouse Hepatocytes.

    PubMed

    Sun, Haiyan; Yan, Yijing; Xu, Chenshu; Wan, Hongxia; Liu, Dong

    2016-03-23

    The roots of Panax ginseng (ginseng) have been extensively used in traditional Chinese medicine. However, herb-drug interactions between ginseng and other co-administered drugs are not fully understood concerning the effect of ginseng on drug metabolism and clearance. The current study aimed to elucidate the effect of total ginsenosides, a typical ginseng extract, on the regulation of Cyp1a2, a key enzyme to regulate drug metabolism under the normal and inflammatory conditions in mice. Female C57BL/6J mice treated with vehicle and lipopolysaccharide (LPS) were intragastrically administered ginseng extract for 7 days before hepatic P450 expression was analyzed. Primary mouse hepatocytes were also employed to further explore the effects of total ginsenosides on Cyp1a2 expression. The results showed that total ginsenosides in P. ginseng extract exhibited a concentration-dependent suppression on Cyp1a2 mRNA and protein level in both mice and primary mouse hepatocytes. Notably, the inhibitory effects of total ginsenosides on Cyp1a2 mRNA and protein expression were further enhanced following LPS treatment. Therefore, future research is warranted to investigate the role of ginsenosides in the regulation of hepatic CYP450s. Moreover, consumption of ginseng as food or supplement should be monitored for patients on combinational therapy, especially those with inflammatory diseases.

  4. Based on SERS conformational studies of ginsenoside Rb1 and its metabolites before and after combined with human serum albumin

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Wang, Yingping; Bai, Xueyuan; Zhao, Bing

    2015-02-01

    Surface-enhanced Raman scattering (SERS) and fluorescence spectroscopy were employed to probe the interaction of the pharmaceutical and natural product molecules, ginsenoside Rb1, Rd, Rg3 and compound K (CK), with human serum albumin (HSA). Normal Raman spectra of these four ginsenosides were obtained from solid powder on glass slide. Based on the unsplit peak at 1445 cm-1, the stacking modes of ginsenoside Rb1, Rd, Rg3 and CK were quite similar, when the deconvolution of alkyl chain was not occurred. SERS spectra of ginsenoside Rb1, Rd, Rg3 and CK were obtained from a colloidal silver surface on a self-assembled SERS substrate, the most enhanced modes were those with certain motions perpendicular to the metal surface, such as C24dbnd C25 stretch and Csbnd H out-of-plane bending from alkyl chain. The SERS spectra were used to predict similar perpendicular orientation of flexible alkyl chain and parallel orientation of carbocyclic rings on Ag colloid particles. Therefore, when combined with HSA, the transformations of four ginsenosides still exhibit similar, although in different binding cavities in subdomain IIA and IIIA by making the methyls at C26 and C27 perpendicular plugging into the hydrophobic site of HSA, while the aglycone and glucose nearby are perpendicularly exposed outside to fit other suitable active targeting sites.

  5. Ginsenoside Reduces Cognitive Impairment During Chronic Cerebral Hypoperfusion Through Brain-Derived Neurotrophic Factor Regulated by Epigenetic Modulation.

    PubMed

    Wan, Qun; Ma, Xue; Zhang, Zhi-Jun; Sun, Ting; Xia, Feng; Zhao, Gang; Wu, Yu-Mei

    2016-03-28

    Increased expression of brain-derived neurotrophic factor (BDNF) has been associated with memory-enhancing and neuroprotective properties of some drugs under chronic cerebral hypoperfusion (CCH) condition. Ginsenoside Rd (GSRd), one of the main active ingredients in Panax ginseng, is widely used for brain protection. However, it is poorly understood whether epigenetic mechanisms implied in the BDNF modulation after GSRd treatment for CCH remain elusive. Here, we investigated the neuroprotective effects of GSRd and the involved mechanisms. We demonstrated that GSRd administration ameliorated CCH-induced impairment of learning and memory behaviors, evidenced by decreased escape latency and increased number of crossing the platform in Morris water maze test. This improvement was associated with promoted neuron survival and increased BDNF expression in the hippocampus and prefrontal cortex of CCH mice. GSRd improved neuron survival and decreased neuron apoptosis and the level of caspase-3 under oxygen-glucose deprivation/reoxygenation (OGD/R) by upregulation of BDNF as well as in vitro. The levels of acetylated histone H3 (Ac-H3) and histone deacetylase (histone deacetylase 2 (HDAC2)) were altered under OGD/R in a time-dependent manner, and GSRd reestablished the balance between Ac-H3 and HDAC2 which resulted in upregulation of BDNF and increased neuron survival. MS-275, an inhibitor of class I HDACs, abolished the levels of Ac-H3 at the bdnf promoters and enhanced upregulation of BDNF after GSRd administration, suggesting a synergistic effect between GSRd and MS-275. All the data suggested that GSRd provided neuroprotection by epigenetic modulation which accounted for the regulation of BDNF in CCH mice.

  6. Studies on the interactions between ginsenosides and liposome by equilibrium dialysis combined with ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Hou, Guangyue; Niu, Jun; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2013-04-01

    To study the interactions between components of Panax Ginseng and liposome biomembrane, we applied the equilibrium dialysis system combined with ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach to analyze and identify the bioactive components of ginseng. Moreover, the effect of pH value has also been investigated on their interactions between the ginsenosides of ginseng extract and biomembrane. The result shows that seven kinds of ginsenosides have obvious interactions with biomembrane in comparison with the standards in terms of tandem mass spectrometry (MS/MS) data along with retention time, including four panaxadiol ginsenosides (Rb1, Rb2, Rc, Rd) and three panaxatriol ginsenosides (Re, Rf, Rg2). The value of binding degree decreased with the increase of molecular weight. The sugar moieties which are attached to C-20 were the main factor affecting the binding degree of panaxadiol ginsenosides. The interactions between panaxadiol ginsenosides and biomembrane correlate to the type and number of sugar moieties in ginsenosides. The sugar moieties which are at C-6 and C-20 have been shown to influence the value of binding degree for panaxatriol ginsenosides. In addition, the pH value has been shown to have an impact on the interactions. Overall, ginsenoside Rd has a better absorption character among the seven ginsenosides. In the study, we have screened the potential bioactive components of ginseng in vitro using the equilibrium dialysis-UPLC-MS/MS method, and then predicted the potential bioactivities of ginseng, which contribute to the investigation of the efficacy of ginseng.

  7. Non-antibiotic agent ginsenoside 20(S)-Rh2 enhanced the antibacterial effects of ciprofloxacin in vitro and in vivo as a potential NorA inhibitor.

    PubMed

    Zhang, Jingwei; Sun, Yuan; Wang, Yaoyao; Lu, Meng; He, Jichao; Liu, Jiali; Chen, Qianying; Zhang, Xiaoxuan; Zhou, Fang; Wang, Guangji; Sun, Xianqiang

    2014-10-05

    The aim of this study is to explore the potential enhancing effect of ginsenoside 20(S)-Rh2 (Rh2) towards ciprofloxacin (CIP) against Staphylococcus aureus (S. aureus) infection in vitro and in vivo, and analyze the possible mechanisms through NorA inhibition from a target cellular pharmacokinetic view. In combination with non-toxic dosage of Rh2, the susceptibilities of S. aureus strains to CIP were significantly augmented, and the antibacterial kinetics of CIP in the S. aureus strains were markedly promoted. This enhancing effect of Rh2 towards CIP was also observed in S. aureus infected peritonitis mice, with elevated survival rate and reduced bacteria counts in blood. However, Rh2 did not influence the plasma concentrations of CIP. Further analysis indicated that Rh2 significantly promoted the accumulations of CIP in S. aureus, and inhibited the NorA mediated efflux of pyronin Y. The expressions of NorA gene on S. aureus were positively correlated with the enhancing effect of Rh2 with CIP. This is the first report of the enhancing effect of Rh2 with CIP for S. aureus infection in vitro and in vivo, of which it is probably that Rh2 inhibited NorA-mediated efflux and promoted the accumulation of CIP in the bacteria.

  8. Suppression of MAPKs/NF-κB Activation Induces Intestinal Anti-Inflammatory Action of Ginsenoside Rf in HT-29 and RAW264.7 Cells.

    PubMed

    Ahn, Sungeun; Siddiqi, Muhammad Hanif; Aceituno, Veronica Castro; Simu, Shakina Yesmin; Yang, Deok Chun

    2016-07-01

    This study investigated the intestinal anti-inflammatory action of ginsenoside Rf in inflammatory bowel disease (IBD). IBD is a chronic inflammatory disease that affects the intestinal tract. It is associated with elevated levels of various inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and reactive oxygen species (ROS). Ginsenosides, the main active constituents of ginseng, have been reported to exert potent therapeutic effects against diverse diseases. However, ginsenoside Rf treatment for inflammation has not yet been examined. In this study, we evaluated the inhibitory effect of ginsenoside Rf on the inflammatory mediators downstream of p38/NF-kB activation on TNF-α-stimulated intestinal epithelial cells (HT-29) and mouse macrophage cells (RAW264.7). Our results showed that ginsenoside Rf significantly reduced the production of IL-1β, IL-6, TNF-α, NO, and ROS, which are most highly activated in IBD. In addition, ginsenoside Rf significantly suppressed TNF-α/LPS-induced NF-κB transcriptional activity. These results suggest that ginsenoside Rf contains a compound that has potent intestinal anti-inflammatory effects that could be used to treat diseases such as IBD.

  9. Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

    PubMed

    Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

    2016-02-01

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

  10. Influence of sulphur-fumigation on the quality of white ginseng: a quantitative evaluation of major ginsenosides by high performance liquid chromatography.

    PubMed

    Jin, Xin; Zhu, Ling-Ying; Shen, Hong; Xu, Jun; Li, Song-Lin; Jia, Xiao-Bin; Cai, Hao; Cai, Bao-Chang; Yan, Ru

    2012-12-01

    White ginseng was reported to be sulphur-fumigated during post-harvest handling. In the present study, the influence of sulphur-fumigation on the quality of white ginseng and its decoction were quantitatively evaluated through simultaneous quantification of 14 major ginsenosides by a validated high performance liquid chromatography. Poroshell 120 EC-C18 (100mm×3.0mm, 2.7μm) column was chosen for the separation of the major ginsenosides, which were eluted with gradient water and acetonitrile as mobile phase. The analytes were monitored by UV at 203nm. The method was validated in terms of linearity, sensitivity, precision, accuracy and stability. The sulphur-fumigated and non-fumigated white ginseng samples, as well as their respective decoctions, were comparatively analysed with the newly-validated method. It was found that the contents of nine ginsenosides detected in raw materials decreased by about 3-85%, respectively, and the total content of the nine ginsenosides detected in raw materials, decreased by almost 54% after sulphur-fumigation. On the other hand, the contents of 10 ginsenosides detected in decoctions of sulphur-fumigated white ginseng were decreased by about 33-83%, respectively, and the total content of ginsenosides was decreased by up to 64% when compared with that of non-fumigated white ginseng. In addition, ginsenoside Rh(2) and Rg(5) could be detected in the decoctions of sulphur-fumigated white ginseng but not in that of non-fumigated white ginseng. It is suggested that sulphur-fumigation can significantly influence not only the contents of original ginsenosides, but also the decocting-induced chemical transformation of ginsenosides in white ginseng.

  11. Extraction, isolation, and aromatase inhibitory evaluation of low-polar ginsenosides from Panax ginseng leaves.

    PubMed

    Zhang, Yuchi; Zhang, Jianxu; Liu, Chunming; Yu, Min; Li, Sainan

    2017-02-03

    A hyphenated accelerated solvent extraction (ASE) technique was elaborately coupled with centrifugal partition chromatography (CPC), ultra-high-performance liquid chromatography (UHPLC), and photo-diode array detector (PDA). This approach was applied to obtain low-polar ginsenoside fractions from the leaves of Panax ginseng. The CPC fractions were isolated and analyzed using the hyphenated technique, and followed by testing and evaluation of their aromatase inhibitory effects. Subsequently, the aromatase inhibition rates of the compositions in the CPC fractions were calculated using a multivariable linear regression model. A biphasic ethyl acetate/n-butanol/ethanol/water solvent system with respective volume ratios of 10:2:2:8 was used for the ASE and CPC separation of 200g of leaves of P. ginseng raw material. The (lower) aqueous phase of the abovementioned solvent system was used as the extraction solvent. The ginsenosides were subjected to ASE, and the extraction solution was pumped into the sample loop and then directly into the CPC column. The CPC fractions were collected and monitored by an online UHPLC/PDA system at 5-min intervals. The aromatase inhibitory activities of CPC fractions were analyzed by a fluorescence method, with mathematical calculations indicating that the inhibition rates of ginsenosides Rk1, Rg5, Rs5, 20R-Rg3, and Rs4 exceeded 50.00%; indicating that the aforementioned chemical compounds have potential for further development. The results were validated by comparison with authentic standards, indicating that the method used in this research was accurate and advantageous for matrix analysis.

  12. Ginsenoside compound K-bearing glycol chitosan conjugates: synthesis, physicochemical characterization, and in vitro biological studies.

    PubMed

    Mathiyalagan, Ramya; Subramaniyam, Sathiyamoorthy; Kim, Yeon Ju; Kim, Youn-Chul; Yang, Deok Chun

    2014-11-04

    Ginsenosides are triterpenoids found in Panax ginseng and have a numerous structural, functional, and pharmacological properties. The purpose of this study was to develop hydrophilic polymer functionalized ginsenoside conjugates to enhance water solubility and targeted delivery. To this end, hydrophobic ginsenoside compound K (CK) was covalently conjugated to the backbone of hydrophilic glycol chitosan (GC) through an acid-labile linkage. The resulting GC-CK conjugates formed self-assembled spherical nanoparticles in an aqueous solution, and their particles sizes were (296 nm and 255 nm) dependent on the degree of CK substitution. The nanoparticles were stable in the physiological buffer (pH 7.4) over a period of 8 days, whereas they were readily degraded under acidic conditions (pH 5.0) mimicking the intracellular pH-conditions. From in vitro release experiment, it was found that CK released slowly from the self-assembled nanoparticles in the physiological buffer (pH 7.4). On the other hand, the release rate of CK was rapidly increased under the acidic condition (pH 5.0). In vitro cytotoxicity assays revealed that GC-CK conjugates exhibited higher cytotoxicity than CK in HT29, and similar cytotoxicity in HepG2, and HT22 cell lines. Moreover, RAW264.7 cells treated with GC-CK maintained good cell viability and exhibited decreased lipopolysaccharide-induced NO production. Taken together, these results suggest that the GC-CK conjugate may be potentially useful as a tumor-specific delivery vehicle.

  13. Comparative study on intestinal metabolism and absorption in vivo of ginsenosides in sulphur-fumigated and non-fumigated ginseng by ultra performance liquid chromatography quadruple time-of-flight mass spectrometry based chemical profiling approach.

    PubMed

    Zhu, He; Shen, Hong; Xu, Jun; Xu, Jin-Di; Zhu, Ling-Ying; Wu, Jie; Chen, Hu-Biao; Li, Song-Lin

    2015-04-01

    Our previous study indicated that sulphur-fumigation of ginseng in post-harvest handling processes could induce chemical transformation of ginsenosides to generate multiple ginsenoside sulphur derivatives. In this study, the influence of sulphur-fumigation on intestinal metabolism and absorption in vivo of ginsenosides in ginseng was sequentially studied. The intestinal metabolic and absorbed profiles of ginsenosides in rats after intra-gastric (i.g.) administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG) were comparatively characterized by a newly established ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with electrospray ionization negative (ESI-) mode. A novel strategy based on the characteristic product ions and fragmentation pathways of different types of aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully applied to rapid structural identification of ginsenoside sulphur derivatives and relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26 ginsenoside sulphur derivative metabolites in the faeces together with six ginsenoside sulphur derivatives in the plasma were identified in the SFG-administrated group but not in the NFG-administrated group. The results clearly demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides in sulphur-fumigated and non-fumigated ginseng were quite different, which inspired that sulphur-fumigation of ginseng should not be recommended before the bioactivity and toxicity of the ginsenoside sulphur derivatives were systematically evaluated.

  14. Effects of ginsenosides, the active ingredients of Panax ginseng, on development, growth, and life span of Caenorhabditis elegans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ginsenosides, the active ingredients of Panax ginseng, are saponins derived from sterols. The free-living nematode Caenorhabditis elegans is a well-established model for biochemical and genetic studies in animals. Although cholesterol is an essential requirement for the growth and development of C. ...

  15. [Study on the Effects of Ginsenoside Rb1 on DPPC Bilayers by Using Thermo-Raman Spectrum and DSC].

    PubMed

    Hui, Ge; Liu, Wei; Zhang, Jing-zhou; Zhou, Tie-li; Wang, Si-ming; Zhao, Yu; Zhao, Bing

    2015-08-01

    The research on the interactions between Ginsenosides and biomembranes plays a crucial role in thorough understanding the pharmacological activity and biologyical effect of Chinese medicine Panax ginseng. With the bilayer structure, DPPC often serves as an simulation model of the cell membrane to study the role of drug molecules and cell membranes. Ginsenoside Rb1, one of the most important components of Panaxginseng, playing the significant roles of pharmacological effects and biological properties. Raman and differential scanning calorimetry (DSC) are respectively a powerful tool for discussing the molecular interaction, and a kind of general technology by which researching the bilayer monomer structures and its interactions with drug molecules. However, rarely research reports on the interactions between drug molecules and biomembranes by means of both technologies above. In this paper, the influence of ginsenoside monomer Rb1 on DPPC membrane bilayers was investigated by thermo-Raman and DSC. In Raman spectra, the changes of DPPC molecule have been observed before and after interacted with ginsenoside Rb1, the data analysis indicates three aspects: the O-C-C-N+ polar head group skeleton, C-C stretching vibration area, and the C-H bond stretching vibrarion in terminated methyl group of alkyl chains. The results showed that ginsenoside Rb1 molecule with certain concentration has not changed the gauche conformation of the polar head backbone group in DPPC bilayers, the order of the internal molecular chain and the lateral chain-chain packing have been decreased as the temperature increased, the lateral disposed disorder has been increased. The changes of some thermodynamic constants obtained by DSC experiment such as phase transition temperature (Tm), the temperature at which the transition is half completed (ΔT1/2), and the transition enthalpy normalized per mol of DPPC (AH) have been showed further results of the thermo Raman experiments, with increasing the

  16. Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites

    PubMed Central

    Chen, Xiao-Jia; Zhang, Xiao-Jing; Shui, Yan-Mei; Wan, Jian-Bo

    2016-01-01

    Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Accumulating reports have shown that ginsenosides, the major active component of ginseng, were helpful for tumor treatment. 20(S)-Protopanaxadiol (PDS) and 20(S)-protopanaxatriol saponins (PTS) are two characteristic types of triterpenoid saponins in ginsenosides. PTS holds capacity to interfere with crucial metabolism, while PDS could affect cell cycle distribution and prodeath signaling. This review aims at providing an overview of PTS and PDS, as well as their metabolites, regarding their different anticancer effects with the proposal that these compounds might be potent additions to the current chemotherapeutic strategy against cancer. PMID:27446225

  17. [Ginsenoside-Rb1 as a suppressor in central modulation of feeding in the rat].

    PubMed

    Etou, H; Sakata, T; Fujimoto, K; Terada, K; Yoshimatsu, H; Ookuma, K; Hayashi, T; Arichi, S

    1988-01-01

    Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. The present study aimed to clarify the effects of ginsenoside-Rb1 on feeding behavior and endogenous chemical substances. Rb1 infusion into the rat third cerebroventricle was started at 1930 hr, and ingestive behavior was recorded in a soundproof room illuminated daily from 0800 to 2000 hr. Rb1 at doses of 0.05, 0.10 and 0.20 mumol potently decreased food intake dose-dependently during the first dark period after infusion. Analysis of meal patterns revealed that the suppressive effect was due to decreasing meal size, but not to postprandial intermeal interval and eating speed. Drinking episodes decreased concomitantly with feeding suppression only at the highest dose of 0.20 mumol. Ambulatory activity was not affected in the doses tested. Infusion of Rb1 increased plasma glucose, leaving insulin unaffected. Microinjection of 0.01 mumol Rb1 into the hypothalamic ventromedial nucleus (VMH) decreased food intake, but injection into the lateral hypothalamic area did not. Taking these data together, Rb1 was found to have a suppressive effect on feeding partly through the VMH.

  18. The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation.

    PubMed

    Chen, Fang; Zhang, Bing; Sun, Yong; Xiong, Zeng-Xing; Peng, Han; Deng, Ze-Yuan; Hu, Jiang-Ning

    2016-04-25

    Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome.

  19. [Effects of lead stress on net photosynthetic rate, SPAD value and ginsenoside production in Ginseng (Panax ginseng)].

    PubMed

    Liang, Yao; Jiang, Xiao-Li; Yang, Fen-Tuan; Cao, Qing-Jun; Li, Gang

    2014-08-01

    The paper aimed to evaluate the effects of lead stress on photosynthetic performance and ginsenoside content in ginseng (Panax ginseng). To accomplish this, three years old ginseng were cultivated in pot and in phytotron with different concentrations of lead, ranging from 0 to 1000 mg x kg(-1) soil for a whole growth period (about 150 days). The photosynthetic parameters in leaves and ginsenoside content in roots of ginseng were determined in green fruit stage and before withering stage, respectively. In comparison with the control, net photosynthetic rate and SPAD value in ginseng leaves cultivated with 100 and 250 mg x kg(-1) of lead changed insignificantly, however, ginseng supplied with 500 and 1 000 mg x kg(-1) of lead showed a noticeably decline in the net rate of photosynthesis and SPAD value (P < 0.05), the lowest net photosynthetic rate and SPAD value showed in the treatment supplied with 1 000 mg x kg(-1) of lead, with decline of 57.8%,11.0%, respectively. Total content of ginsenoside in ginseng roots cultivated with 100 mg x kg(-1) of lead showed insignificantly change compared to the control, but the content increased remarkably in treatments supplied with 250, 500, 1 000 mg x kg(-1) of lead (P < 0.05), and highest content appeared in these ginsengs exposed to 1000 mg x kg(-1) of lead. The net photosynthetic rate and SPAD value in leaves of ginseng both showed significantly negative linear correlations with lead stress level (P < 0.01), and significant positive linear correlations between total content of ginsenoside and lead concentration was also observed (P < 0.05). These results strongly indicate that exposing to high level of lead negatively affects photosynthetic performance in ginseng leaves, but benefits for accumulation of secondary metabolism (total content of ginsenoside) in ginseng root.

  20. Identification of ginsenoside markers from dry purified extract of Panax ginseng by a dereplication approach and UPLC-QTOF/MS analysis.

    PubMed

    Yang, Heejung; Lee, Dong Young; Kang, Kyo Bin; Kim, Jeom Yong; Kim, Sun Ok; Yoo, Young Hyo; Sung, Sang Hyun

    2015-05-10

    A dry purified extract of Panax ginseng (PEG) was prepared using a manufacturing process that includes column chromatography, acid hydrolysis, and an enzyme reaction. During the manufacturing process, the more polar ginsenosides were altered into less polar forms via cleavage of their sugar chains and structural modifications of the aglycones, such as hydroxylation and dehydroxylation. The structural changes of ginsenosides during the intermediate steps from dried ginseng extract (DGE) to PEG were monitored by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectroscopy (UPLC-QTOF/MS). 22 ginsenosides isolated from PEG were used as the reference standards for determining of unknown ginsenosides and further suggesting of the metabolic markers. The elution order of 22 ginsenosides based on the type of aglycones, and the location and number of sugar chains can be used for the structural elucidation of unknown ginsenosides. This information could be used in a dereplication process for quick and efficient identification of ginsenoside derivatives in ginseng preparations. A dereplication approach helped the identification of the metabolic markers in the UPLC-QTOF/MS chromatograms during the conversion process with multivariate analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) plots. These metabolic markers were identified by comparing with the dereplication information of the reference standards of 22 ginsenosides, or they were assigned using the pattern of the MS/MS fragmented ions. Consequently, the developed metabolic profiling approach using UPLC-QTOF/MS and multivariate analysis represents a new method for providing quality control as well as useful criteria for a similarity evaluation of the manufacturing process of ginseng preparations.

  1. Production of the rare ginsenosides compound K, compound Y, and compound Mc by a thermostable beta-glycosidase from Sulfolobus acidocaldarius.

    PubMed

    Noh, Kyeong-Hwan; Oh, Deok-Kun

    2009-11-01

    The rare ginsenosides compound K, compound Y, and compound Mc were produced from the major ginsenosides Rb(1), Rb(2), Rc, and Rd by a thermostable beta-glycosidase from Sulfolobus acidocaldarius via three pathways: Rb(1)-->Rd-->compound K, Rb(2)-->compound Y-->compound K, and Rc-->compound Mc. Each of the ginsenosides was identified by high-performance liquid chromatography using standards and liquid chromatography-mass spectrometry based on their molecular weights. The catalytic efficiency of the enzyme for ginsenosides followed the order Rb(1) (4.8)>Rc (4.5)>Rd (1.0)>Rb(2) (0.77 mM(-1) min(-1)). The enzyme converted 1 mg/ml reagent-grade Rb(1), Rb(2), and Rc to 0.53 mg/ml compound K, 0.56 mg/ml compound Y, and 0.70 mg/ml compound Mc, respectively, at pH 5.5 and 85 degrees C after 180 min, corresponding to mole conversion yields of 94, 80, and 100% (mol/mol), respectively. The enzyme converted the major ginsenosides Rb(1), Rb(2), Rc, and Rd in 10% (w/v) ginseng root extract to the rare ginsenosides with a mole yield of 99% after 24 h. These results suggest that beta-glycosidase from S. acidocaldarius can be used to produce compound K, compound Y, and compound Mc.

  2. Bioactivity Enhancement of Herbal Supplements by Intestinal Microbiota Focusing on the Ginsenosides

    PubMed Central

    Wang, Huai-You; Qi, Lian-Wen; Wang, Chong-Zhi; Li, Ping

    2012-01-01

    Intestinal microbiota contributes to diverse mammalian processes including the metabolic function of drugs. It is a potential new territory for drug targeting, especially for dietary herbal products. Because most of herbal drugs are orally administered, the chemical profile and corresponding bioactivities of herbal medicines may be altered by intestinal microbiota. Ginseng is one of the most commonly used herb and it is always an attractive natural product to understand. In this review, after briefly introduce the interactions of herbal products and gut microbiota, we discussed the microbiota-mediated metabolism of ginsenosides in ginseng and red ginseng. In particular, the major metabolite Compound K and its pharmacological advances are commented including anticancer, antidiabetic and antiinflammatory effects. In summary, the intestinal microbiota may play an important role in mediating the metabolism and enhancement of bioactivity of herbal medicines. PMID:22083984

  3. Melanin Biosynthesis Inhibition Effects of Ginsenoside Rb2 Isolated from Panax ginseng Berry.

    PubMed

    Lee, Dae Young; Jeong, Yong Tae; Jeong, Sang Chul; Lee, Mi Kyoung; Min, Jin Woo; Lee, Jae Won; Kim, Geum Soog; Lee, Seung Eun; Ahn, Young Sup; Kang, Hee Cheol; Kim, Jin Hee

    2015-12-28

    Ginsenoside Rb2 (Gin-Rb2) was purified from the fruit extract of Panax ginseng. Its chemical structure was measured by spectroscopic analysis, including HR-FAB-MS, (1)H-NMR, and IR spectroscopy. Gin-Rb2 decreased potent melanogenesis in melan-a cells, with 23.4% at 80 μM without cytotoxicity. Gin-Rb2 also decreased tyrosinase and MITF protein expression in melan-a cells. Furthermore, Gin-Rb2 presented inhibition of the body pigmentation in the zebrafish in vivo system and reduced melanin contents and tyrosinase activity. These results show that Gin-Rb2 isolated from P. ginseng may be an effective skin-whitening agent via the in vitro and in vivo systems.

  4. Antidepressant-like effects of ginsenosides: A comparison of ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K, and 20(S)-protopanaxadiol in mice models of despair.

    PubMed

    Zhang, Hualin; Li, Zhong; Zhou, Zhongliu; Yang, Hongyan; Zhong, Zhiyong; Lou, Caixia

    2016-01-01

    Ginsenoside Rb3 has been proved to have antidepressant-like effects, which possesses 1 xylose and 3 glucose moieties with 20(S)-protopanaxadiol (PPD) as the aglycone. However, it is commonly accepted that orally ingested ginsenosides can be deglycosylated or partially deglycosylated into active derivatives by the intestinal bacteria. To identify potential antidepressant drug candidates, we compared the antidepressant-like activities between ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K (C-K), and PPD. Effects of acute (1-day), short chronic (7-days), and longer chronic treatments (14-days) with these ginsenosides (50 and 100mg/kg, p.o.) on the behavioral changes in the forced swim test (FST), tail suspension test (TST) and open field test were investigated. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels and mouse brain monoamine neurotransmitters 5-HT, NA and DA levels were measured using commercially available competitive enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, C-K showed antidepressant-like activities similar to that of Rb3, and Rg3 displayed antidepressant-like effects at lower dosage and faster time, indicating it has better effects than Rb3, whereas Rh2 and PPD failed to show any effect. Our results also showed, unlike the positive control fluoxetine, Rb3, Rg3 and C-K significantly increased the NA levels in the brain regions of mice exposed to FST but did not affect the 5-HT and DA levels. Moreover, treatment with Rg3 could reverse swim stress-induced increased levels of serum ACTH and corticosterone. These results suggest that C-K and Rg3 are the active deglycosylated derivatives, especially the latter compound, which is more potent than Rb3 and exerts antidepressant-like effects by regulating NA, ACTH and corticosterone levels.

  5. Metabolomic evaluation of ginsenosides distribution in Panax genus (Panax ginseng and Panax quinquefolius) using multivariate statistical analysis.

    PubMed

    Pace, Roberto; Martinelli, Ernesto Marco; Sardone, Nicola; D E Combarieu, Eric

    2015-03-01

    Ginseng is any one of the eleven species belonging to the genus Panax of the family Araliaceae and is found in North America and in eastern Asia. Ginseng is characterized by the presence of ginsenosides. Principally Panax ginseng and Panax quinquefolius are the adaptogenic herbs and are commonly distributed as health food markets. In the present study high performance liquid chromatography has been used to identify and quantify ginsenosides in the two subject species and the different parts of the plant (roots, neck, leaves, flowers, fruits). The power of this chromatographic technique to evaluate the identity of botanical material and to distinguishing different part of the plants has been investigated with metabolomic technique such as principal component analysis. Metabolomics provide a good opportunity for mining useful chemical information from the chromatographic data set resulting an important tool for quality evaluation of medicinal plants in the authenticity, consistency and efficacy.

  6. Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis

    PubMed Central

    Li, Wei; Yan, Meng-Han; Liu, Ying; Liu, Zhi; Wang, Zi; Chen, Chen; Zhang, Jing; Sun, Yin-Shi

    2016-01-01

    Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects. PMID:27649238

  7. Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue

    PubMed Central

    Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo

    2015-01-01

    Objective: This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Methods: Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral “Pishu” once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Results: Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes and correct CD4+/CD8+ ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Conclusions: Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively. PMID:26770528

  8. A UHPLC-TOF/MS method based metabonomic study of total ginsenosides effects on Alzheimer disease mouse model.

    PubMed

    Gong, Yingge; Liu, Ying; Zhou, Ling; Di, Xin; Li, Wei; Li, Qing; Bi, Kaishun

    2015-11-10

    A metabonomic method was established to find potential biomarkers and study the metabolism disturbance in Alzheimer disease animal model. Total ginsenosides, as potential agent in neuroprotection and anti-inflammation, was also studied to learn the regulation mechanism to plasma metabolites in model animals. In experiment, amyloid beta 1-42 was occupied to form Alzheimer disease animal model. After drug administration, animals were evaluated by Morris water maze behavior test and sacrificed. Plasma samples were then analyzed using UHPLC-TOF/MS method to determine the endogenous metabolites. Behavior test results revealed that the spatial learning and memory abilities were deficit in model mice, and total ginsenosides could improve cognition abilities in dose-dependent manners. Principal component analysis showed that model and sham were divided into two groups, which means the metabolic network of mice was disturbed after modeling. Accordingly, 19 biomarkers were found and identified. In model group, the levels of proline, valine, tryptophan, LPC (14:0), LPC (15:0), LPC (15:1), LPC (17:0), LPC (18:2), LPC (18:3) and LPC (20:4) were up-regulated, while the levels of acetylcarnitine, palmitoylcarnitine, vaccenylcarnitine, phytosphingosine, N-eicosanoylethanolamine, hexadecenoic acid, docosahexaenoic acid, docosapentaenoic acid and octadecadienoic acid were down-regulated. The levels of these metabolites were recovered in different degrees after total ginsenosides administration. Combining with behavior study results, total ginsenosides could ameliorate both cognition symptoms and metabolic changes in model animals. This metabonomic approach provided a feasible way to understand the endogenous alterations of AD and to study the pharmacodynamic activity of novel agents.

  9. Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis.

    PubMed

    Li, Wei; Yan, Meng-Han; Liu, Ying; Liu, Zhi; Wang, Zi; Chen, Chen; Zhang, Jing; Sun, Yin-Shi

    2016-09-13

    Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

  10. Evaluation of liquid chromatography-ion trap-time of flight hybrid mass spectrometry on the quantitative analysis for ginsenosides.

    PubMed

    Xing, Lu; Xie, Lin; Liang, Yan; Xing, Rong; Rao, Tai; Zhou, Lijun; Wang, Qian; Fu, Hanxu; Ye, Wei; Wang, Guangji

    2014-07-01

    It is ideal and desirable for a single instrument to meet the requirement of both qualitative and quantitative analysis of complicated components in pharmacokinetic research for herbal medicine. Liquid chromatography combined with hybrid ion trap and time-of-flight mass spectrometry (LCMS-IT-TOF) was recently confirmed as a very powerful tool for the qualitative analysis of both target and nontarget components in herbal medicines. The present study was designed to investigate the feasibility of LCMS-IT-TOF on quantitative analysis of ginsenosides in biological matrices. A simple liquid-liquid extraction procedure was followed by injection of the extracts onto a C₁₈ column with gradient elution and detection based on LCMS-IT-TOF system in negative scan mode. The developed method was validated with respect to the limit of quantification, linear dynamic range, precision, accuracy, matrix effects and stabilities. All the results suggested that the presently developed method was sufficiently sensitive and robust enough to simultaneously monitor 15 ginsenosides with diverse properties and a large range of concentration differences. Therefore, this method would be expected to be highly useful for comprehensive studies of ginsenosides in complicated matrix.

  11. Intracellular Trafficking Modulation by Ginsenoside Rg3 Inhibits Brucella abortus Uptake and Intracellular Survival within RAW 264.7 Cells.

    PubMed

    Huy, Tran Xuan Ngoc; Reyes, Alisha Wehdnesday Bernardo; Hop, Huynh Tan; Arayan, Lauren Togonon; Min, WonGi; Lee, Hu Jang; Rhee, Man Hee; Chang, Hong Hee; Kim, Suk

    2017-03-28

    Ginsenoside Rg3, a saponin extracted from ginseng, has various pharmacological and biological activities; however, its effects against Brucella infection are still unclear. Herein, the inhibitory effects of ginsenoside Rg3 against intracellular parasitic Brucella infection were evaluated through bacterial infection, adherence assays, and LAMP-1 colocalization, as well as immunoblotting and FACS for detecting MAPK signaling proteins and F-actin polymerization, respectively. The internalization, intracellular growth, and adherence of Brucella abortus in Rg3-treated RAW 264.7 cells were significantly decreased compared with the Rg3-untreated control. Furthermore, an apparent reduction of F-actin content and intensity of F-actin fluorescence in Rg3-treated cells was observed compared with B. abortus-infected cells without treatment by flow cytometry analysis and confocal microscopy, respectively. In addition, treating cells with Rg3 decreased the phosphorylation of MAPK signaling proteins such as ERK 1/2 and p38 compared with untreated cells. Moreover, the colocalization of B. abortus-containing phagosomes with LAMP-1 was markedly increased in Rg3-treated cells. These findings suggest that ginsenoside Rg3 inhibits B. abortus infection in mammalian cells and can be used as an alternative approach in the treatment of brucellosis.

  12. The ginsenoside derivative 20(S)-protopanaxadiol inhibits solar ultraviolet light-induced matrix metalloproteinase-1 expression.

    PubMed

    Han, Eungmin; Lim, Tae-Gyu; Kim, Jong-Eun; Yang, Hee; Oh, Deok-Kun; Yoon Park, Jung Han; Yoon Park, Dalius; Kim, Hee Jung; Rhee, Young Kyoung; Lee, Ki Won

    2017-04-05

    Ginsenosides are major pharmacologically active compounds present in ginseng (Panax ginseng). Among the ginsenosides, 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPPD) and ginsenoside Rb1 (Rb1) have previously been reported to exhibit anti-wrinkle effects. In this study, 20(S)-protopanaxadiol (20(S)-PPD), an aglycone derivative of the Rb1 metabolite was investigated for its anti-wrinkle benefit and compared to GPPD and Rb1. The anti-wrinkle effect of 20(S)-PPD during solar UV light was investigated using a human skin equivalent model and human keratinocytes. 20(S)-PPD attenuated solar UV-induced matrix metalloproteinase (MMP)-1 expression to a greater extent than GPPD and Rb1. 20(S)-PPD treatment modulated MMP-1 mRNA expression and the transcriptional activity of activator protein (AP)-1, a major transcription factor of MMP-1. Two upstream signaling pathways for AP-1, the MEK1/2-ERK1/2-p90(RSK) and MEK3/6-p38 pathways, were also suppressed. Taken together, these findings highlight the potential of 20(S)-PPD for further development as a preventative agent for sunlight-induced skin wrinkle. This article is protected by copyright. All rights reserved.

  13. Post-exposure treatment with ginsenoside compound K ameliorates auditory functional injury associated with noise-induced hearing loss in mice.

    PubMed

    Hong, Bin Na; Kim, Se Young; Yi, Tae Hoo; Kang, Tong Ho

    2011-01-07

    Noise-induced hearing loss (NIHL) is thought to primarily involve damage to the sensory hair cells of the cochlea via mechanical and metabolic mechanisms. Unfortunately, initial studies assessing the effectiveness of post-exposure treatment after hearing loss have yielded largely disappointing results. This study explored the effects of oral treatment with Korean red ginseng (RG) and with two bioavailable ginsenoside metabolites, ginsenoside Rh1 and ginsenoside compound K (GCK), in response to NIHL in a murine model. Pharmacological treatments began 24h after noise exposure and were continued once daily for 7 days. Central auditory function was evaluated using auditory middle latency responses, and cochlear function was determined based on transient evoked otoacoustic emissions. Additionally, cochlear hair cell morphology was investigated after noise exposure. Both Korean red ginseng and compound K reduced threshold shifts, central auditory function damage, and cochlear functional and morphological deficits. In contrast, treatment with ginsenoside Rh1 did not result in recovery of NIHL in mice. These results suggest that consumption of Korean red ginseng may facilitate recovery from noise-induced hearing loss. Furthermore, one of the active constituents in ginseng is likely ginsenoside compound K.

  14. Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alpha-induced activation of the NF-kappaB and JNK pathways in human astroglial cells.

    PubMed

    Choi, Kyungsun; Kim, Myungsun; Ryu, Jeonghee; Choi, Chulhee

    2007-06-21

    Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific manner.

  15. Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells

    PubMed Central

    Han, Myoung-Sik; Han, Im-Ho; Lee, Dahae; An, Jun Min; Kim, Su-Nam; Shin, Myoung-Sook; Yamabe, Noriko; Hwang, Gwi Seo; Yoo, Hye Hyun; Choi, Suk-Jung; Kang, Ki Sung; Jang, Hyuk-Jai

    2015-01-01

    Background Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNK–p53–caspase-3 signaling cascade. PMID:27158234

  16. Effects of ginsenoside on large-conductance K(Ca) channels in human corporal smooth muscle cells.

    PubMed

    Sung, H H; Chae, M R; So, I; Jeon, J-H; Park, J K; Lee, S W

    2011-01-01

    Ginseng was known to be an effective natural product that enhances penile erection. However, the precise biological function and mechanisms of action of ginseng with regard to erectile function remain unknown. The principal objective of this study was to identify ginsenoside (principal molecular ingredients of ginseng)-induced activation of large-conductance K(Ca) channel in human corporal smooth muscle cells, and to determine ginseng's mechanism of action on penile erection. Electrophysiological studies using cultured human corporal smooth muscle cells were conducted. We evaluated the effects of total ginsenosides (TGS) and ginsenoside Rg3 on large-conductance K(Ca) channel by determining whole-cell currents and single-channel activities. There was an increase in outward current dependent on TGS concentration (at +60 mV, 1 μg ml(-1); 168.3±59.3%, n=6, P<0.05, 10 μg ml(-1); 173.2±36.8%, n=4, P<0.05, 50 μg ml(-1); 295.3±62.3%, n=19, P<0.001, 100 μg ml(-1); and 462.3±97.1%, n=5, P<0.001) and Rg3 concentration (at +60 mV, 1 μM (0.78 μg ml(-1)); 222.8±64.8%, n=11, P<0.0001, 10 μM; 672.6±137.1%, n=10, P<0.0001, 50 μM; and 1713.3±234.7%, n=15, P<0.001) in the solution that was blocked completely by tetraethylammonium (TEA). Channel opening in cell-attached mode and channel activity in the inside-out membrane patches was also increased significantly by 50 μg of TGS or 10 μM of Rg3. The results of this study suggested that the activation of large-conductance K(Ca) channels by ginsenoside could be one mechanism of ginsenoside-induced relaxation in corporal smooth muscle.

  17. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds.

    PubMed Central

    Shibata, S

    2001-01-01

    More than 25 dammarane-type tetracyclic triterpenoid saponins have been isolated from ginseng, the root and rhizome of Panax ginseng C.A. Meyer (Araliaceae). The genuine sapogenins of those saponins, 20(S)-protopanaxa-diol and -triol, were identified as 20(S) 12beta-hydroxy-and 20(S) 6alpha,12beta-dihydroxy-dammarenediol-II, respectively. There are two types of preparations from ginseng: white ginseng prepared by drying after peelling off and red ginseng prepared by steaming and drying. Some partly deglycosylated saponins such as ginsenoside Rh-1, Rh-2, and Rg-3 are obtained from red ginseng as artifacts produced during steaming. Several workers studied the metabolic transformation by human intestinal bacteria after oral administration of ginsenoside Rb-1 and Rb-2 and found that the stepwise deglyco-sylation yielded compound K and finally 20(S)-protopanaxadiol. Ginsenoside Rg-1 was converted into 20(S)-protopanaxatriol via ginsenoside Rh-1. Yun et al. in Korea conducted the epidemiological case-control studies of ginseng and suggested its cancer preventing activities. Kitagawa et al. demonstrated in vitro that ginsenosides, especially 20(R)-ginsenoside Rg-3, specifically inhibited cancer cell invasion and metastasis. Azuma et al. found that ginsenoside Rb-2 inhibited tumor angiogenesis, and Kikuchi et al. reported that ginsenoside Rh-2 inhibited the human ovarian cancer growth in nude mice. Recently, ginsenoside Rg-3 was produced as an anti-angiogenic anti-cancer drug in China. The aforementioned reports suggest that less glycosylated protopanaxadiol derivatives are effective in cancer prevention. Apart from Ginseng tetracyclic triterpenoid saponins, some oleanane-type pentacyclic triterpenoid compounds showed the anti-carcinogenic activity in the two-stage anti-cancer-promotion experiments in vitro and in vivo. PMID:11748374

  18. Effect of Fermented Red Ginseng Extract Enriched in Ginsenoside Rg3 on the Differentiation and Mineralization of Preosteoblastic MC3T3-E1 Cells

    PubMed Central

    Siddiqi, Muhammad Zubair; Siddiqi, Muhammad Hanif; Jin, Yan; Huq, Md. Amdadul

    2015-01-01

    Abstract In this study, red ginseng extract (RGE) was converted into high-content minor ginsenosides by fermenting with Bgp1 enzymes at 37°C for 5 days. Compared to the RGE, the minor ginsenoside contents were increased in fermented red ginseng extract (FRGE). Moreover, the amount of minor ginsenosides such as Rh1 (11%) and Rg2 (16%) was slightly augmented, while the level of Rg3 (33%) was significantly increased after bioconversion. Furthermore, we also examined and compared the effect of RGE and FRGE on the differentiation and mineralization of preosteoblastic MC3T3-E1 cells. Similarly, the level of mRNA expression of intracellular alkaline phosphatase (ALP) activity, type-1 collagen (Col-I) was also increased. Based on the comparison, it is clear that the FRGE has improved effects on bone formation and differentiation of preosteoblastic MC3T3-E1 cells. PMID:25764149

  19. Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.

    PubMed

    Wang, Lei; Li, Xiankui; Song, Yi-Min; Wang, Bin; Zhang, Fu-Rui; Yang, Rui; Wang, Hua-Qi; Zhang, Guo-Jun

    2015-07-01

    At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression.

  20. Effect of mobile phase additives on qualitative and quantitative analysis of ginsenosides by liquid chromatography hybrid quadrupole-time of flight mass spectrometry.

    PubMed

    Liang, Yan; Guan, Tianye; Zhou, Yuanyuan; Liu, Yanna; Xing, Lu; Zheng, Xiao; Dai, Chen; Du, Ping; Rao, Tai; Zhou, Lijun; Yu, Xiaoyi; Hao, Kun; Xie, Lin; Wang, Guangji

    2013-07-05

    This study was to systematically investigate the effect of mobile phase additives, including ammonia water, formic acid, acetic acid, ammonium chloride and water (as a control), on qualitative and quantitative analysis of fifteen representative ginsenosides based on liquid chromatography hybrid quadrupole-time of flight mass spectrometry (LC-Q-TOF/MS). To evaluate the influence of mobile phase additives on qualitative performance, the quality of the negative mode MS/MS spectra of ginsenosides produced by online LC-Q-TOF/MS analyses, particularly the numbers and intensities of fragment ions, were compared under different adduct ion states, and found to be strongly affected by the mobile phase additives. When 0.02% acetic acid was added in the mobile phase, the deprotonated ginsenosides ions produced the most abundant product ions, while almost no product ion was observed for the chlorinated ginsenoside ions when 0.1mM ammonium chloride was used as the mobile phase additive. On the other hand, sensitivity, linear range and precision were adopted to investigate the quantitative performance affected by different mobile phase additives. Validation results of the LC-Q-TOF/MS-based quantitative performance for ginsenosides showed that ammonium chloride not only provided the highest sensitivity for all the target analytes, but also dramatically improved the linear ranges, the intra-day and inter-day precisions comparing to the results obtained using other mobile phase additives. Importantly, the validated method, using 0.1mM ammonium chloride as the mobile phase additive, was successfully applied to the quantitative analysis of ginsenosides in rat plasma after intragastric administration of Ginsenoside Extract at 200mg/kg. In conclusion, 0.02% acetic acid was deemed to be the most suitable mobile phase additive for qualitative analysis of ginsenosides, and 0.1mM ammonium chloride in mobile phase could lead to the best quantitative performance. Our results reveal that

  1. Ginsenoside Rh2 induces ligand-independent Fas activation via lipid raft disruption

    SciTech Connect

    Yi, Jae-Sung; Choo, Hyo-Jung; Cho, Bong-Rae; Kim, Hwan-Myung; Kim, Yong-Nyun; Ham, Young-Mi; Ko, Young-Gyu

    2009-07-24

    Lipid rafts are plasma membrane platforms mediating signal transduction pathways for cellular proliferation, differentiation and apoptosis. Here, we show that membrane fluidity was increased in HeLa cells following treatment with ginsenoside Rh2 (Rh2), as determined by cell staining with carboxy-laurdan (C-laurdan), a two-photon dye designed for measuring membrane hydrophobicity. In the presence of Rh2, caveolin-1 appeared in non-raft fractions after sucrose gradient ultracentrifugation. In addition, caveolin-1 and GM1, lipid raft landmarkers, were internalized within cells after exposure to Rh2, indicating that Rh2 might disrupt lipid rafts. Since cholesterol overloading, which fortifies lipid rafts, prevented an increase in Rh2-induced membrane fluidity, caveolin-1 internalization and apoptosis, lipid rafts appear to be essential for Rh2-induced apoptosis. Moreover, Rh2-induced Fas oligomerization was abolished following cholesterol overloading, and Rh2-induced apoptosis was inhibited following treatment with siRNA for Fas. This result suggests that Rh2 is a novel lipid raft disruptor leading to Fas oligomerization and apoptosis.

  2. Anti-inflammatory activity of AP-SF, a ginsenoside-enriched fraction, from Korean ginseng

    PubMed Central

    Baek, Kwang-Soo; Hong, Yong Deog; Kim, Yong; Sung, Nak Yoon; Yang, Sungjae; Lee, Kyoung Min; Park, Joo Yong; Park, Jun Seong; Rho, Ho Sik; Shin, Song Seok; Cho, Jae Youl

    2014-01-01

    Background Korean ginseng is an ethnopharmacologically valuable herbal plant with various biological properties including anticancer, antiatherosclerosis, antidiabetic, and anti-inflammatory activities. Since there is currently no drug or therapeutic remedy derived from Korean ginseng, we developed a ginsenoside-enriched fraction (AP-SF) for prevention of various inflammatory symptoms. Methods The anti-inflammatory efficacy of AP-SF was tested under in vitro inflammatory conditions including nitric oxide (NO) production and inflammatory gene expression. The molecular events of inflammatory responses were explored by immunoblot analysis. Results AP-SF led to a significant suppression of NO production compared with a conventional Korean ginseng saponin fraction, induced by both lipopolysaccharide and zymosan A. Interestingly, AP-SF strongly downregulated the mRNA levels of genes for inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase) without affecting cell viability. In agreement with these observations, AP-SF blocked the nuclear translocation of c-Jun at 2 h and also reduced phosphorylation of p38, c-Jun N-terminal kinase, and TAK-1, all of which are important for c-Jun translocation. Conclusion Our results suggest that AP-SF inhibits activation of c-Jun-dependent inflammatory events. Thus, AP-SF may be useful as a novel anti-inflammatory remedy. PMID:26045689

  3. Ginsenoside Rb1 increases insulin sensitivity through suppressing 11β-hydroxysteroid dehydrogenase type I

    PubMed Central

    Song, Bing; Ding, Li; Zhang, Haoqiang; Chu, Yafen; Chang, Zhaohui; Yu, Yali; Guo, Dandan; Zhang, Shuping; Liu, Xuezheng

    2017-01-01

    Ginsenoside Rb1 (GRb1) is a major component of ginseng, which has been shown to ameliorate hyperglycemia in rodents and in humans with undetermined mechanisms. Here, we analyzed the molecular mechanisms by which GRb1 reduces the insulin resistance in high-fat diet (HFD)-induced mouse model for type 2 diabetes (T2D). HFD was applied for 4 weeks to induce T2D in mice, after which GRb1 was administrated and the effects on the fasting blood glucose, glucose tolerance and insulin sensitivity were analyzed. We found that HFD increased fasting blood glucose, glucose tolerance and reduced insulin sensitivity, which were all ameliorated by GRb1. GRb1 seemed to reduce the levels of 11β-Hydroxysteroid dehydrogenase type I (11β-HSD1) in liver and adipose tissue, to exert its anti-diabetes effects. Overexpression of 11β-HSD1 completely abolished the effects of GRb1 on HFD-induced increases in fasting blood glucose and glucose tolerance, and decreases in insulin sensitivity. Together, our data suggest that GRb1 may increase insulin sensitivity through suppressing 11β-HSD1 in treatment of T2D. PMID:28386332

  4. Apoptosis-inducing effect of ginsenoside Rg6 on human lymphocytoma JK cells.

    PubMed

    Chen, Bin; Jia, Xiao-Bin

    2013-07-09

    In this communication our aim was to study the JK cell growth inhibitory and apoptosis-inducing effects of ginsenoside Rg6 (GRg6) from steamed notoginseng on human lymphocytoma. The CCK-8 method was used to observe the anti-proliferative effect of GRg6 on human lymphocytoma JK cells. Flow cytometry was performed to analyze the influence of GRg6 on cell cycle. The Annexin-V FITC/PI double-staining method was used to detect the ratio of apoptotic cells. JC-1 staining was undertaken to observe the influence of GRg6 on intracellular mitochondrial membrane potential. Finally, western blots were conducted to detect the expression level of apoptosis-related Bax and the Bcl-2 proteins. The results suggested that GRg6 can inhibit the proliferation of human lymphocytoma JK cells. GRg6 blocks an S arrest in the cell cycle. With the increase in GRg6 concentration, the potential in the cell decreased in a dose dependent manner, and Bax protein expression gradually increased, whereas Bcl-2 protein expression gradually decreased. In conclusion, GRg6 can inhibit JK cell proliferation in human lymphocytoma and induce its apoptosis. The mechanism of action may be related to mitochondrial dysfunction and an increase of Bax expression and decrease of Bcl-2 expression caused by GRg6.

  5. [Development of a lateral flow dipstick immunoassay for rapid detection of ginsenoside Re].

    PubMed

    Nan, Tie-Gui; Cao, Zhen; He, Li-Shan; Yuan, Yuan; Huang, Lu-Qi; Wang, Bao-Min

    2013-08-01

    A sensitive antibody-based lateral flow dipstick was developed for ginsenoside Re (GRe) detection. The stick consisted of a sample pad, a conjugate pad, membrane and an absorbent pad. The membrane was coated with two capture reagents, GRe-BSA conjugate and goat anti-mouse antibodies, forming a test line and a control line, respectively. The conjugate pad was saturated with colloidal gold particles coated with affinity purified monoclonal anti-GRe antibody. The visual detection limit was 200 microg x L(-1) of GRe and the reaction time was 10 min. The Panax ginseng roots were identified after these samples (10 mg) were extracted with 5 mL tap water for 30 min at room temperature, and the extracts were tested by the dipsticks and ELISA kit. The true and false P. ginseng could be distinguished with dipsticks. The dipstick could be used to detect the quality of the P. ginseng samples when the extract was diluted 100-folds. The results were compared with those obtained using an indirect competitive enzyme-linked immunosorbent assay (icELISA). The dipstick assay proved to be a sensitive and rapid tool for quality control of P. ginseng.

  6. Ginsenoside Rb1 protects rat retinal ganglion cells against hypoxia and oxidative stress.

    PubMed

    Liu, Zhaochun; Chen, Juying; Huang, Wendong; Zeng, Zhi; Yang, Yongfei; Zhu, Banghao

    2013-11-01

    The current study was designed to investigate the effect of ginsenoside Rb1 (Rb1) on apoptosis induced by hypoxia and oxidative stress in a retinal ganglion cell line (RGC-5). The underlying mechanism was also investigated. RGC-5 cells were pretreated with 10 µmol/l Rb1 for 24 h and exposed to 400 µmol/l cobalt chloride (CoCl2) for 48 h or 600 µmol/l H2O2 for 24 h. The percentage of cells actively undergoing apoptosis was determined by flow cytometry with Annexin V/propidium iodide (PI) double staining. The expression of caspases was determined using western blot analysis. CoCl2 and H2O2 treatments significantly increased the apoptotic percentages to 24.5 and 21.63%, respectively. Pretreatment of Rb1 reduced the total apoptotic percentages to 15.12 and 12.03%, respectively. The expression of cleaved caspase-3, -9 and -8 was increased in the CoCl2-treated group, however, caspase-3 was not increased in the H2O2-treated group. Pretreatment of Rb1 reduced the expression of cleaved caspase-3 and -9 in the CoCl2-treated group, but reduced only cleaved caspase-9 in the H2O2-treated group. These results suggest that Rb1 may prevent RGC-5 cells from apoptosis against hypoxia and oxidative stress via the mitochondrial pathway.

  7. Rescue of PINK1 Protein Null-specific Mitochondrial Complex IV Deficits by Ginsenoside Re Activation of Nitric Oxide Signaling*

    PubMed Central

    Kim, Kyung-Hee; Song, Karen; Yoon, Seung-Hee; Shehzad, Omer; Kim, Yeong-Shik; Son, Jin H.

    2012-01-01

    PINK1, linked to familial Parkinson's disease, is known to affect mitochondrial function. Here we identified a novel regulatory role of PINK1 in the maintenance of complex IV activity and characterized a novel mechanism by which NO signaling restored complex IV deficiency in PINK1 null dopaminergic neuronal cells. In PINK1 null cells, levels of specific chaperones, including Hsp60, leucine-rich pentatricopeptide repeat-containing (LRPPRC), and Hsp90, were severely decreased. LRPPRC and Hsp90 were found to act upstream of Hsp60 to regulate complex IV activity. Specifically, knockdown of Hsp60 resulted in a decrease in complex IV activity, whereas antagonistic inhibition of Hsp90 by 17-(allylamino) geldanamycin decreased both Hsp60 and complex IV activity. In contrast, overexpression of the PINK1-interacting factor LRPPRC augmented complex IV activity by up-regulating Hsp60. A similar recovery of complex IV activity was also induced by coexpression of Hsp90 and Hsp60. Drug screening identified ginsenoside Re as a compound capable of reversing the deficit in complex IV activity in PINK1 null cells through specific increases of LRPPRC, Hsp90, and Hsp60 levels. The pharmacological effects of ginsenoside Re could be reversed by treatment of the pan-NOS inhibitor l-NG-Nitroarginine Methyl Ester (l-NAME) and could also be reproduced by low-level NO treatment. These results suggest that PINK1 regulates complex IV activity via interactions with upstream regulators of Hsp60, such as LRPPRC and Hsp90. Furthermore, they demonstrate that treatment with ginsenoside Re enhances functioning of the defective PINK1-Hsp90/LRPPRC-Hsp60-complex IV signaling axis in PINK1 null neurons by restoring NO levels, providing potential for new therapeutics targeting mitochondrial dysfunction in Parkinson's disease. PMID:23144451

  8. Effects of Natural Bioactive Products on the Growth and Ginsenoside Contents of Panax ginseng Cultured in an Aeroponic System

    PubMed Central

    Kim, Geum-Soog; Lee, Seung-Eun; Noh, Hyung-Jun; Kwon, Hyuck; Lee, Sung-Woo; Kim, Seung-Yu; Kim, Yong-Bum

    2012-01-01

    This study was conducted to evaluate the effects of natural bioactive products such as Manda enzyme (T1), Yangmyeongwon (T2), effective microorganisms (T3), and Kelpak (T4) on the growth and ginsenoside contents of Panax ginseng cultured in an aeroponic system using a two-layer vertical type of nutrient bath under natural light conditions. The growth of ginseng plants showed specific characteristics according to the positions in which they were cultured due to the difference of light transmittance and temperature in the upper and lower layers during aeroponic culture in a two-layer vertical type of system. The growth of the aerial part of the leaves and stems of ginseng plants cultured in the lower layer (4,000 to 6,000 lx, 23℃ to 26℃) of the nutrient bath was observed to be superior to that of the ginseng plants cultured in the upper layer (12,000 to 15,000 lx, 25℃ to 28℃). The leaf area was significantly larger in the treatment of T2 and T4 (46.70 cm2) than with other treatments. Conversely, the values of the root weight and root diameter were higher in ginseng plants cultured in the upper layer of the nutrient bath. The root weight was significantly heavier in the treatment of T4 (6.46 g) and T3 (6.26 g) than with other treatments. The total ginsenoside content in the leaves and roots was highest in the ginseng plants cultured by the treatment of T1, at 16.20%, while the total ginsenoside content obtained by other treatments decreased in the order of T4, T5 (control), T2, and T3, at 13.21%, 12.30%, 14.84%, and 14.86%, respectively. The total ginsenoside content of the ginseng leaves was found to be significantly higher in the treatment of T1 in the lower layer of the nutrient bath, at 15.30%, while the content of the ginseng roots in the treatments of T3 and T4, at 1.27% and 1.23%, respectively, was significantly higher than in other treatments in the upper layer of the nutrient bath. PMID:23717147

  9. SERS study of different configurations of pharmaceutical and natural product molecules ginsenoside Rg3 under the interaction with human serum albumin on simple self-assembled substrate.

    PubMed

    Zhang, Wei; Bai, Xueyuan; Wang, Yingping; Zhao, Bing; Zhao, Yu; Hou, Wei; Jin, Yinping; Zhao, Daqing

    2014-01-03

    Surface-enhanced Raman scattering (SERS) and fluorescence spectroscopy were employed to probe the interaction of the pharmaceutical and natural product molecules, 20(R) and 20(S)-ginsenoside Rg3, with human serum albumin (HSA). Normal Raman spectra of 20(R) and 20(S)-ginsenoside Rg3 were obtained from solid powder on glass slide. Based on the splitting peaks near 1440 cm(-1), the stacking modes of 20(R) and 20(S)-ginsenoside Rg3 were quite different. SERS spectra of both R and S configurations were obtained from a colloidal silver surface on a self-assembled SERS substrate, the most enhanced modes of 20(R) and 20(S)-ginsenoside Rg3 were those with certain motions perpendicular to the metal surface. The SERS spectra were used to predict a common orientation geometry for the alkyl chain portion of the drugs on the colloidal surface with a minor difference in the carbocyclic rings. Nevertheless, once combined with HSA, the flexible portion of alkyl chains assumes a collectively similar conformation on the Ag surface with the glucose rings perpendicularly plugging into the hydrophobic site of HSA.

  10. Liposome-based delivery systems for ginsenoside Rh2: in vitro and in vivo comparisons

    NASA Astrophysics Data System (ADS)

    Xu, Linqiang; Yu, Hua; Yin, Shaoping; Zhang, Ruixia; Zhou, Yudan; Li, Juan

    2015-10-01

    The Ginsenoside Rh2 (Rh2) has been shown to possess anti-cancer properties both in vitro and in vivo. However, the poor bioavailability and fast plasma elimination limit the further clinical applications of Rh2 for cancer treatments. In the present study, three types of Rh2-loaded liposomes including Rh2-loaded normal liposome (Rh2-LP), Rh2-loaded cationic liposome (Rh2-CLP), and Rh2-loaded Methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) liposome (Rh2-PLP) have been optimized and prepared with mean particle size of 80-125 nm. Compared to Rh2-LP, surface modifications with mPEG or octadecylamine significantly improve the physicochemical and biological properties both in vitro and in vivo. Moreover, PLP presented better tumor accumulation of the fluorescent cyanine dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) in HepG2-xenografted nude mice than CLP (1.3-fold) or LP (1.6-fold) and prolong the resident time of DiR in tumor and organs (more than 24 h). The in vivo anti-cancer efficacy assessments indicate that Rh2-PLP presents the most activity on suppressing tumor growth in HepG2-xenografted mice than Rh2-LP and Rh2-CLP and without any significant toxicity. Our results indicate that mPEG-PLA modified liposome should be a potential and promising strategy to enhance the therapeutic index for anti-cancer agents.

  11. Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training

    SciTech Connect

    Sun, Mengwei; Huang, Chenglin; Wang, Cheng; Zheng, Jianheng; Zhang, Peng; Xu, Yangshu; Chen, Hong; Shen, Weili

    2013-11-08

    Highlights: •Rg3 is an ergogenic aid. •Rg3 improves mitochondrial antioxidant capacity. •Rg3 regulates mitochondria dynamic remodeling. •Rg3 alone matches some the benefits of aerobic exercise. -- Abstract: Emerging evidence indicates exercise training could mediate mitochondrial quality control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, is well known in herbal medicine as a tonic and restorative agent. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. In the present study, we compared the effects of Rg3 administration with aerobic exercise on mitochondrial adaptation in cardiac muscle tissue of Sprague–Dawley (SD) rats. Three groups of SD rats were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise trained. Both aerobic exercise training and Rg3 supplementation enhanced peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The activation of PGC-1α led to increased mRNA levels of mitochondrial transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes were accompanied by increases in mitochondrial DNA copy number and complex protein levels, while activation of Nrf2 increased levels of phase II detoxifying enzymes, including nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein 7 (ATG7), these effects of aerobic exercise are comparable to that of Rg3. These results demonstrate that Rg3 mimics improved cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and enhancing the quantity and quality of mitochondria.

  12. Effect of ginsenoside Rh-2 via activation of caspase-3 and Bcl-2-insensitive pathway in ovarian cancer cells.

    PubMed

    Kim, Jin Hee; Choi, Jae-Sun

    2016-12-13

    Ginsenoside has been reported to have therapeutic effects for some types of cancer, but its effect on ovarian cancer cells has not been evaluated. In this study, we monitored the effects of ginsenoside-Rh2 (Rh2) on the inhibition of cell proliferation and the apoptotic process in the ovarian cancer cell line SKOV3 using an MTT assay and TUNEL assay. We found that Rh2 inhibited cell proliferation and significantly induced apoptosis. We confirmed the apoptotic effects of Rh2 using western blot analysis of apoptosis-related proteins. Specifically, the levels of cleaved poly ADP ribose polymerase (PARP) and cleaved caspase-3 significantly increased in SKOV3 cells treated with Rh2. Therefore, Rh2 clearly suppressed the growth of SKOV3 cells in vitro, which was associated with induction of the apoptosis pathway. Moreover, the migration assay showed that Rh2 inhibited the invasive ability of SKOV3 cells. Taken together, our results suggest that Rh2 has anticancer effects in SKOV3 cells through inhibition of cell proliferation and induction of apoptosis. Considering the therapeutic potential of Rh2, more studies should be carried out to facilitate the future application of this natural product as a potential anti-cancer agent.

  13. An in vitro metabolic system of gut flora and the metabolism of ginsenoside Rg3 and cholic acid.

    PubMed

    Zhao, Chunyan; Sun, Runbin; Cao, Bei; Gu, Shenghua; Zhao, Jieyu; Liu, Linsheng; Wang, Xinwen; Zha, Weibin; Yu, Xiaoyi; Xiao, Wenjing; Mao, Yong; Ge, Chun; Ju, Jiaqi; Aa, Lixiang; Fei, Fei; Ding, Yi; Aa, Jiye; Wang, Guangji

    2014-06-01

    For orally administered drugs, the metabolism of a drug by the gut flora plays an important role in the bioavailability, activation and disposition of the drug in vivo. However, no in vitro system is currently available to evaluate the metabolism of a drug by the gut flora before the drug is absorbed into the body. This paper presents an in vitro metabolic system in an anaerobic environment that could be used to evaluate the metabolism of an endogenous compound, cholic acid, and a xenobiotic compound, ginsenoside Rg3. We showed that the proliferation of the anaerobic bacteria of the gut content of hamsters produced a similar composition of gut flora in a culture medium for yeast to that in vivo. Incubation of ginsenoside Rg3 and cholic acid in the anaerobic in vitro system efficiently produced the metabolites Rh2 and deoxycholic acid, respectively, similar to those seen in the gut content in vivo. In comparison with in vivo analysis, this anaerobic in vitro metabolic system is convenient, reproducible, economic and animal saving, and can easily be applied to assess the transformation and disposition of a drug before it enters into the circulatory system.

  14. Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation-Induced Mouse Memory Impairment Model.

    PubMed

    Lu, Cong; Shi, Zhe; Dong, Liming; Lv, Jingwei; Xu, Pan; Li, Yinghui; Qu, Lina; Liu, Xinmin

    2017-02-28

    Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory-improving effects in normal mice and scopolamine-induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 μmol/kg; 40 μmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14-day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homogenized, and levels and activities of antioxidant defense biomarkers were evaluated to determine the level of oxidative stress. The results revealed that Rh1 prevented cognitive impairment induced by SD, and its ability to reduce oxidative stress in cortex and hippocampus may contribute to the mechanism of action. Copyright © 2017 John Wiley & Sons, Ltd.

  15. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

    PubMed Central

    Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

    2013-01-01

    Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng’s therapeutic effects. These include Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng. PMID:23717153

  16. Highly Selective Bioconversion of Ginsenoside Rb1 to Compound K by the Mycelium of Cordyceps sinensis under Optimized Conditions.

    PubMed

    Wang, Wei-Nan; Yan, Bing-Xiong; Xu, Wen-Di; Qiu, Ye; Guo, Yun-Long; Qiu, Zhi-Dong

    2015-10-23

    Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO₄ without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C-50 °C. Then, a biotransformation pathway of Rb1→Rd→F2→CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes.

  17. A chimera of green fluorescent protein with single chain variable fragment antibody against ginsenosides for fluorescence-linked immunosorbent assay.

    PubMed

    Sakamoto, Seiichi; Tanizaki, Yusuke; Pongkitwitoon, Benyakan; Tanaka, Hiroyuki; Morimoto, Satoshi

    2011-05-01

    A chimera of green fluorescent protein extracted from Aequorea coerulescens (AcGFP), a mutant that has been codon optimized for mammalian expression, with single-chain variable fragment (scFv) antibody against ginsenoside Re (GRe-scFv), named fluobody, has been successfully expressed in Escherichia coli (E. coli) to develop simple, speedy, and sensitive fluorescence-linked immunosorbent assay (FLISA). Two chimera proteins were constructed to contain GRe-scFv at the C-terminus of AcGFP (C-fluobody) and at the N-terminus of AcGFP (N-fluobody). These fluobodies were then purified by ion metal affinity chromatography and refolded by stepwise dialysis. The characterization of both fluobodies revealed that C-fluobody was found to be appropriate probe for FLISA as compare with N-fluobody. Furthermore, improvement of limit of detection (LOD) was observed in FLISA using C-fluobody (10 ng/mL) due to its strong fluorescence intensity of AcGFP compared with conventional enzyme-linked immunosorbent assay (ELISA) using parental monoclonal antibody against ginsenoside Re (G-Re), MAb-4G10 (100 ng/mL). Since some steps required in ELISA can be avoided in this present FLISA, speedy and sensitive immunoassay also could be performed using fluobody instead of monoclonal antibody and scFv.

  18. Structural investigation of ginsenoside Rf with PPARγ major transcriptional factor of adipogenesis and its impact on adipocyte

    PubMed Central

    Siraj, Fayeza Md; Natarajan, Sathishkumar; Huq, Md Amdadul; Kim, Yeon Ju; Yang, Deok Chun

    2014-01-01

    Background Adipocytes, which are the main cellular component of adipose tissue, are the building blocks of obesity. The nuclear hormone receptor PPARγ is a major regulator of adipocyte differentiation and development. Obesity, which is one of the most dangerous yet silent diseases of all time, is fast becoming a critical area of research focus. Methods In this study, we initially aimed to investigate whether the ginsenoside Rf, a compound that is only present in Panax ginseng Meyer, interacts with PPARγ by molecular docking simulations. After we performed the docking simulation the result has been analyzed with several different software programs, including Discovery Studio, Pymol, Chimera, Ligplus, and Pose View. All of the programs identified the same mechanism of interaction between PPARγ and Rf, at the same active site. To determine the drug-like and biological activities of Rf, we calculate its absorption, distribution, metabolism, excretion, and toxic (ADMET) and prediction of activity spectra for substances (PASS) properties. Considering the results obtained from the computational investigations, the focus was on the in vitro experiments. Results Because the docking simulations predicted the formation of structural bonds between Rf and PPARγ, we also investigated whether any evidence for these bonds could be observed at the cellular level. These experiments revealed that Rf treatment of 3T3-L1 adipocytes downregulated the expression levels of PPARγ and perilipin, and also decreased the amount of lipid accumulated at different doses. Conclusion The ginsenoside Rf appears to be promising compound that could prove useful in antiobesity treatments. PMID:26045687

  19. Ginsenosides Have a Suppressive Effect on c-Fos Expression in Brain and Reduce Cardiovascular Responses Increased by Noxious Stimulation to the Rat Tooth

    PubMed Central

    Jung, Ji-Yeon; Seong, Kyung-Joo; Moon, In-Ohk; Cho, Jin-Hyoung; Kim, Sun-Hun

    2013-01-01

    The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth. PMID:23626473

  20. The involvement of β-amyrin 28-oxidase (CYP716A52v2) in oleanane-type ginsenoside biosynthesis in Panax ginseng.

    PubMed

    Han, Jung-Yeon; Kim, Min-Jun; Ban, Yong-Wook; Hwang, Hwan-Su; Choi, Yong-Eui

    2013-12-01

    Panax species are the most popular medicinal herbs. The root of these plants contains pharmacologically active triterpene saponins, also known as ginsenosides, compounds that are divided into dammarane- and oleanane-type triterpenes. Two CYP716A subfamily genes (CYP716A47 and CYP716A53v2) were recently characterized, encoding an enzyme catalyzing the hydroxylation of dammarane-type triterpenes in Panax ginseng. Herein, we report that one CYP716A subfamily gene (CYP716A52v2) isolated from P. ginseng encodes a β-amyrin 28-oxidase, which is suggested to modify β-amyrin into oleanolic acid, a precursor of an oleanane-type saponin (mainly ginsenoside Ro) in P. ginseng. The ectopic expression of both PNY1 and CYP716A52v2 in recombinant yeast resulted in erythrodiol and oleanolic acid production, respectively. In vitro enzymatic activity assays biochemically confirmed that CYP716A52v2 catalyzed the oxidation of β-amyrin to produce oleanolic acid, and the chemical structure of the oleanolic acid product was confirmed using gas chromatography-mass spectrometry (GC/MS). Transgenic P. ginseng plants were generated via Agrobacterium tumefaciens-mediated transformation: the overexpression of CYP716A52v2 greatly increased the content of oleanane-type ginsenoside (ginsenoside Ro), whereas RNA interference against CYP716A52v2 markedly reduced it. Furthermore, the levels of other dammarene-type ginsenosides were not affected in these transgenic lines. These results indicate that CYP716A52v2 is a β-amyrin 28-oxidase that plays a key role in the biosynthesis of oleanane-type triterpenes in P. ginseng.

  1. Complete conversion of major protopanaxadiol ginsenosides to compound K by the combined use of α-L-arabinofuranosidase and β-galactosidase from Caldicellulosiruptor saccharolyticus and β-glucosidase from Sulfolobus acidocaldarius.

    PubMed

    Shin, Kyung-Chul; Oh, Hye-Jin; Kim, Baek-Joong; Oh, Deok-Kun

    2013-08-10

    The ginsenoside compound K has pharmaceutical activities, including anti-tumor, anti-inflammatory, anti-allergic, and hepatoprotective effects. To increase the production of compound K, the α-L-arabinofuranoside-hydrolyzing α-L-arabinofuranosidase (CS-abf) and/or the α-L-arabinopyranoside-hydrolyzing β-galactosidase from Caldicellulosiruptor saccharolyticus (CS-bgal) were mixed with the β-D-glucopyranoside-hydrolyzing β-glucosidase from Sulfolobus acidocaldarius (SA-bglu). The optimum conditions for the production of ginsenoside compound K from ginsenoside Rc or Rb₂, or from major protopanaxadiol ginsenosides in ginseng root extract were determined to be pH 6.0 and 75°C with 8 mg ml⁻¹ ginsenoside Rc, 8 mg ml⁻¹ Rb₂, or 10% (w/v) ginseng root extract; and 10.5 U ml⁻¹ CS-abf or CS-bgal supplemented with 4.5 U ml⁻¹ SA-bglu, or 10.5 U ml⁻¹ CS-abf and 10.5 U ml⁻¹ CS-bgal supplemented with 4.5 U ml⁻¹ SA-bglu, respectively. Under optimum conditions, ginsenosides Rc and Rb2, and major protopanaxadiol ginsenosides in ginseng root extract were completely converted to compound K after 12, 14, and 20 h, respectively, with the respective productivities of 388, 328, and 144 mg l⁻¹ h⁻¹. This is the first report of the complete conversion of major protopanaxadiol ginsenosides to compound K.

  2. Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

    PubMed

    Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

    2014-01-01

    This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

  3. Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines.

    PubMed

    Nam, Yunsung; Wie, Myung Bok; Shin, Eun-Joo; Nguyen, Thuy-Ty Lan; Nah, Seung-Yeol; Ko, Sung Kwon; Jeong, Ji Hoon; Jang, Choon-Gon; Kim, Hyoung-Chun

    2015-08-01

    Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)-induced dopaminergic toxicity in mice via genetic inhibition of PKCδ and attenuation of mitochondrial stress. In addition, we have reported that induction of mitochondrial glutathione peroxidase (GPx) is also important for neuroprotection mediated by ginsenoside Re. To extend our knowledge, we examined the effects of ginsenoside Re against MA toxicity in vitro condition using SH-SY5Y neuroblastoma cells. Treatment with ginsenoside Re resulted in significant attenuations against a decrease in the activity of GPx and an increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in glutathione (GSH) paralleled those in GPx in the same experimental condition. Consistently, ginsenoside Re treatment exhibited significant protections against cytosolic and mitochondrial oxidative damage (i.e. lipid peroxidation and protein oxidation), mitochondrial translocation of PKCδ, mitochondrial dysfunction (mitochondrial transmembrane potential and intra-mitochondrial Ca(2+)), apoptotic events [i.e., cytochrome c release from mitochondria, cleavage of caspase-3 and poly(ADP-ribose)polymerase-1, nuclear condensation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells], and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA in SH-SY5Y neuroblastoma cells. These protective effects of ginsenoside Re were comparable to those of PKCδ antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ. Our results suggest that PKCδ is a specific target for ginsenoside Re-mediated protective activity against MA toxicity in SH-SY5Y neuroblastoma cells.

  4. Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis.

    PubMed

    Yu, Tao; Rhee, Man Hee; Lee, Jongsung; Kim, Seung Hyung; Yang, Yanyan; Kim, Han Gyung; Kim, Yong; Kim, Chaekyun; Kwak, Yi-Seong; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng's various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that

  5. A strategy for efficient discovery of new natural compounds by integrating orthogonal column chromatography and liquid chromatography/mass spectrometry analysis: Its application in Panax ginseng, Panax quinquefolium and Panax notoginseng to characterize 437 potential new ginsenosides.

    PubMed

    Yang, Wen-zhi; Ye, Min; Qiao, Xue; Liu, Chun-fang; Miao, Wen-juan; Bo, Tao; Tao, Hai-yan; Guo, De-an

    2012-08-20

    To discover new natural compounds from herbal medicines tends to be more and more difficult. In this paper, a strategy integrating orthogonal column chromatography and liquid chromatography/mass spectrometry (LC/MS) analysis was proposed, and was applied for rapid discovery of new ginsenosides from Panax ginseng (PG), Panax quinquefolium (PQ), and Panax notoginseng (PN). The ginsenosides extracts were fractionated by MCI gel×silica gel orthogonal column chromatography. The fractions were then separated on a C(18) HPLC column, eluted with a three-component mobile phase (CH(3)CN/CH(3)OH/3mM CH(3)COONH(4)H(2)O), and detected by electrospray ionization tandem mass spectrometry. The structures of unknown ginsenosides were elucidated by analyzing negative and positive ion mass spectra, which provided complementary information on the sapogenins and oligosaccharide chains, respectively. A total of 623 comprising 437 potential new ginsenosides were characterized from the ethanol extracts of PG, PQ and PN. New acylations, diversified saccharide chains and C-17 side chains constituted novelty of the newly identified ginsenosides. An interpretation guideline was proposed for structural characterization of unknown ginsenosides by LC/MS. To confirm reliability of this strategy, two targeted unknown trace ginsenosides were obtained in pure form by LC/MS-guided isolation. Based on extensive NMR spectroscopic analysis and other techniques, they were identified as 3-O-[6-O-(E)-butenoyl-β-D-glucopyranosyl(1,2)-β-D-glucopyranosyl]-20(S)-protopanaxadiol-20-O-β-D-glucopyranosyl(1,6)-β-D-glucopyranoside (named ginsenoside IV) and 3-O-β-D-glucopyranosyl(1,2)-β-D-glucopyranosyl-3β,12β,20(S),24(R)-tetra hydroxy-dammar-25-ene-20-O-β-D-glucopyranosyl(1,6)-β-D-glucopyranoside (ginsenoside V), respectively. The fully established structures were consistent with the MS-oriented structural elucidation. This study expanded our understanding on ginsenosides of Panax species, and the

  6. The apoptosis-inducing effect of ginsenoside F4 from steamed notoginseng on human lymphocytoma JK cells.

    PubMed

    Chen, Bin; Shen, Yu-Ping; Zhang, Dong-Feng; Cheng, Jie; Jia, Xiao-Bin

    2013-01-01

    In this study, the inhibitory and apoptosis-inducing effect of ginsenoside F4 (GF4) from steamed notoginseng was investigated by using human lymphocytoma Jurkat (JK) cell. Cell Counting Kit-8 method was then used to assess the anti-proliferative effect of GF4, and Western blotting was run to detect the expression level of two apoptosis-related proteins including Bax and the Bcl-2. The results suggested that GF4 can effectively inhibit the proliferation of the cells, and Bax expression increased gradually, but Bcl-2 expression reduced with the increase of GF4 concentration. In conclusion, GF4 has inhibitory effect on human lymphocytoma JK cell by inducing its apoptosis. The mechanism of action could be related to the mitochondrial dysfunction and the increase of Bax expression and decrease of Bcl-2 expression by GF4.

  7. Anti-adipogenic Effects and Mechanisms of Ginsenoside Rg3 in Pre-adipocytes and Obese Mice.

    PubMed

    Zhang, Longyun; Zhang, Lijuan; Wang, Xiaoyong; Si, Hongwei

    2017-01-01

    Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in pre-adipocytes and obese mice to investigate the anti-adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells (30, 50, and 100 μM) and human primary pre-adipocytes (10, 20, and 30 μM). This inhibitory effect is accompanied by the attenuation of the expressions of adipogenic markers including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), fatty acid binding protein 4 (FABP4) and perilipin. Although dietary intake of Rg3 (0.1 mg Rg3/kg diet, 8 weeks) did not significantly affect body weight gain, fat pads and food intake as well as of PPAR-γ expression in fat tissues, we found that hepatic PPAR-γ and C/EBP-α protein expressions and hepatic glutathione reductase and glutathione S-transferase, two major antioxidants molecules were significantly reduced by Rg3. These results suggest that ginsenoside Rg3 may be a potential agent in reducing/preventing obesity.

  8. Anti-adipogenic Effects and Mechanisms of Ginsenoside Rg3 in Pre-adipocytes and Obese Mice

    PubMed Central

    Zhang, Longyun; Zhang, Lijuan; Wang, Xiaoyong; Si, Hongwei

    2017-01-01

    Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in pre-adipocytes and obese mice to investigate the anti-adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells (30, 50, and 100 μM) and human primary pre-adipocytes (10, 20, and 30 μM). This inhibitory effect is accompanied by the attenuation of the expressions of adipogenic markers including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), fatty acid binding protein 4 (FABP4) and perilipin. Although dietary intake of Rg3 (0.1 mg Rg3/kg diet, 8 weeks) did not significantly affect body weight gain, fat pads and food intake as well as of PPAR-γ expression in fat tissues, we found that hepatic PPAR-γ and C/EBP-α protein expressions and hepatic glutathione reductase and glutathione S-transferase, two major antioxidants molecules were significantly reduced by Rg3. These results suggest that ginsenoside Rg3 may be a potential agent in reducing/preventing obesity. PMID:28337143

  9. Korean Red Ginseng Saponin Fraction Rich in Ginsenoside-Rb1, Rc and Rb2 Attenuates the Severity of Mouse Collagen-Induced Arthritis

    PubMed Central

    Endale, Mehari; Im, Eun Ju; Lee, Joo Young; Kim, Sung Dae; Song, Yong-Bum; Kwak, Yi-Seong; Kim, Chaekyun; Kim, Seung-Hyung; Roh, Seong-Soo; Rhee, Man Hee

    2014-01-01

    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. PMID:24833816

  10. A green protocol for efficient discovery of novel natural compounds: characterization of new ginsenosides from the stems and leaves of Panax ginseng as a case study.

    PubMed

    Qiu, Shi; Yang, Wen-Zhi; Shi, Xiao-Jian; Yao, Chang-Liang; Yang, Min; Liu, Xuan; Jiang, Bao-Hong; Wu, Wan-Ying; Guo, De-An

    2015-09-17

    Exploration of new natural compounds is of vital significance for drug discovery and development. The conventional approaches by systematic phytochemical isolation are low-efficiency and consume masses of organic solvent. This study presents an integrated strategy that combines offline comprehensive two-dimensional liquid chromatography, hybrid linear ion-trap/Orbitrap mass spectrometry, and NMR analysis (2D LC/LTQ-Orbitrap-MS/NMR), aimed to establish a green protocol for the efficient discovery of new natural molecules. A comprehensive chemical analysis of the total ginsenosides of stems and leaves of Panax ginseng (SLP), a cardiovascular disease medicine, was performed following this strategy. An offline 2D LC system was constructed with an orthogonality of 0.79 and a practical peak capacity of 11,000. The much greener UHPLC separation and LTQ-Orbitrap-MS detection by data-dependent high-energy C-trap dissociation (HCD)/dynamic exclusion were employed for separation and characterization of ginsenosides from thirteen fractionated SLP samples. Consequently, a total of 646 ginsenosides were characterized, and 427 have not been isolated from the genus of Panax L. The ginsenosides identified from SLP exhibited distinct sapogenin diversity and molecular isomerism. NMR analysis was finally employed to verify and offer complementary structural information to MS-oriented characterization. The established 2D LC/LTQ-Orbitrap-MS/NMR approach outperforms the conventional approaches in respect of significantly improved efficiency, much less use of drug materials and organic solvent. The integrated strategy enables a deep investigation on the therapeutic basis of an herbal medicine, and facilitates new compounds discovery in an efficient and environmentally friendly manner as well.

  11. A Distinctive Pattern of Beauveria bassiana-biotransformed Ginsenoside Products Triggers Mitochondria/FasL-mediated Apoptosis in Colon Cancer Cells.

    PubMed

    Gum, Sang Il; Rahman, Md Khalilur; Won, Jong Soon; Cho, Min Kyung

    2016-01-01

    Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar-utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high-performance liquid chromatography coupled with evaporative light-scattering detection. The β-glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20-C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α-L-arabinopyranosidase and α-L-arabinofuranosidase, respectively. The fermentation product exerted dose-dependent cytotoxicity in HCT-15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana-fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use.

  12. Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE‑cadherin/EphA2/MMP9/MMP2 expression.

    PubMed

    Guo, Jing-Qiang; Zheng, Qing-Hui; Chen, Hui; Chen, Liang; Xu, Jin-Bo; Chen, Min-Yuan; Lu, Dian; Wang, Zhao-Hong; Tong, Hong-Fei; Lin, Shengzhang

    2014-09-01

    Ginsenoside Rg3 (Rg3), a trace tetracyclic triterpenoid saponin, is extracted from ginseng and shown to have anticancer activity against several types of cancers. This study explored the effect of Rg3 on pancreatic cancer vasculogenic mimicry. Altered vasculogenic mimicry formation was assessed using immunohistochemistry and PAS staining and associated with the expression of vascular endothelial-cadherin (VE-cadherin), epithelial cell kinase (EphA2), matrix metalloproteinase (MMP)-2 and MMP-9. The effect of Rg3 on the regulation of pancreatic cancer vasculogenic mimicry was evaluated in vitro and in vivo. The data showed vasculogenic mimicry in pancreatic cancer tissues. In addition, the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 proteins associated with formation of pancreatic cancer vasculogenic mimicry. Rg3 treatment reduced the levels of vasculogenic mimicry in nude mouse xenografts in vitro and in vivo, while the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 mRNA and proteins was downregulated by Rg3 treatment in vitro and in tumor xenografts. In conclusion, ginsenoside Rg3 effectively inhibited the formation of pancreatic cancer vasculogenic mimicry by downregulating the expression of VE-cadherin, EphA2, MMP9 and MMP2. Further studies are required to evaluate ginsenoside Rg3 as an agent to control pancreatic cancer.

  13. Ionic liquid and aqueous two-phase extraction based on salting-out coupled with high-performance liquid chromatography for the determination of seven rare ginsenosides in Xue-Sai-Tong injection.

    PubMed

    Li, Lan-Jie; Jin, Yong-Ri; Wang, Xiao-Zhong; Liu, Ying; Wu, Qian; Shi, Xiao-Lei; Li, Xu-Wen

    2015-09-01

    A method of ionic liquid salt aqueous two-phase extraction coupled with high-performance liquid chromatography has been developed for the analysis of seven rare ginsenosides including Rg6 , F4 , 20(S)-Rg3 , 20(R)-Rg3 , Rk3 , Rk1 , and Rg5 in Xue-Sai-Tong injection. The injection was mixed with ionic liquid 1-butyl-3-methylimidazolium bromide aqueous solution, and a mixture was obtained. With the addition of sodium dodecyl sulfate and dipotassium phosphate into the mixture, the aqueous two-phase mixture was formed after ultrasonic treatment and centrifuged. Rare ginsenosides were extracted into the upper phase. To obtain a high extraction factors, various influences were considered systematically, such as the volume of ionic liquid, the category and amount of salts, the amount of sodium dodecyl sulfate, the pH value of system, and the time of ultrasonic treatment. Under the optimal condition, rare ginsenosides in Xue-Sai-Tong injection were enriched and detected, the recoveries of seven rare ginsenosides ranged from 90.05 to 112.55%, while relative standard deviations were lower than 2.50%. The developed method was reliable, rapid and sensitive for the determination of seven rare ginsenosides in the injections.

  14. Transcriptome analysis reveals ginsenosides biosynthetic genes, microRNAs and simple sequence repeats in Panax ginseng C. A. Meyer

    PubMed Central

    2013-01-01

    Background Panax ginseng C. A. Meyer is one of the most widely used medicinal plants. Complete genome information for this species remains unavailable due to its large genome size. At present, analysis of expressed sequence tags is still the most powerful tool for large-scale gene discovery. The global expressed sequence tags from P. ginseng tissues, especially those isolated from stems, leaves and flowers, are still limited, hindering in-depth study of P. ginseng. Results Two 454 pyrosequencing runs generated a total of 2,423,076 reads from P. ginseng roots, stems, leaves and flowers. The high-quality reads from each of the tissues were independently assembled into separate and shared contigs. In the separately assembled database, 45,849, 6,172, 4,041 and 3,273 unigenes were only found in the roots, stems, leaves and flowers database, respectively. In the jointly assembled database, 178,145 unigenes were observed, including 86,609 contigs and 91,536 singletons. Among the 178,145 unigenes, 105,522 were identified for the first time, of which 65.6% were identified in the stem, leaf or flower cDNA libraries of P. ginseng. After annotation, we discovered 223 unigenes involved in ginsenoside backbone biosynthesis. Additionally, a total of 326 potential cytochrome P450 and 129 potential UDP-glycosyltransferase sequences were predicted based on the annotation results, some of which may encode enzymes responsible for ginsenoside backbone modification. A BLAST search of the obtained high-quality reads identified 14 potential microRNAs in P. ginseng, which were estimated to target 100 protein-coding genes, including transcription factors, transporters and DNA binding proteins, among others. In addition, a total of 13,044 simple sequence repeats were identified from the 178,145 unigenes. Conclusions This study provides global expressed sequence tags for P. ginseng, which will contribute significantly to further genome-wide research and analyses in this species. The novel

  15. Ginsenoside Rg3 Alleviates Lipopolysaccharide-Induced Learning and Memory Impairments by Anti-Inflammatory Activity in Rats

    PubMed Central

    Lee, Bombi; Sur, Bongjun; Park, Jinhee; Kim, Sung-Hun; Kwon, Sunoh; Yeom, Mijung; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

    2013-01-01

    The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer’s disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain. PMID:24244826

  16. Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4

    PubMed Central

    Li, Xiaodong; Shan, Xiu; Wang, Xiaoqi; Yan, Qiu; Liu, Jiwei

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer. PMID:26636541

  17. Ginsenoside Rb1 rescues anxiety-like responses in a rat model of post-traumatic stress disorder.

    PubMed

    Lee, Bombi; Sur, Bongjun; Cho, Seong-Guk; Yeom, Mijung; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

    2016-04-01

    Single prolonged stress (SPS), a rat model of post-traumatic stress disorder (PTSD), induces alterations in the hypothalamic-pituitary-adrenal axis. Korean red ginseng, whose major active component is ginsenoside Rb1 (GRb1), is one of the widely used traditional anxiolytics. However, the efficacy of GRb1 in alleviating PTSD-associated anxiety-like abnormalities has not been investigated. The present study used several behavioral tests to examine the effects of GRb1 on symptoms of anxiety in rats after SPS exposure and on the central noradrenergic system. Male Sprague-Dawley rats received GRb1 (10 or 30 mg/kg, i.p., once daily) during 14 days of SPS. Daily GRb1 (30 mg/kg) administration significantly increased the number and duration of open-arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, reduced grooming behaviors in the EPM test, and increased the total number of line crossings of an open field after SPS. The higher dose of GRb1 also blocked SPS-induced decreases in hypothalamic neuropeptide Y expression, increases in locus coeruleus tyrosine hydroxylase expression, and decreases in hippocampal mRNA expression of brain-derived neurotrophic factor. These findings suggest that GRb1 has anxiolytic-like effects on both behavioral and biochemical symptoms similar to those observed in patients with PTSD.

  18. Metabonomics approach to assessing the modulatory effects of St John's wort, ginsenosides, and clomipramine in experimental depression.

    PubMed

    Wang, Xiaoyan; Zeng, Chuiyu; Lin, Jingchao; Chen, Tianlu; Zhao, Tie; Jia, Zhiying; Xie, Xie; Qiu, Yunping; Su, Mingming; Jiang, Tao; Zhou, Mingmei; Zhao, Aihua; Jia, Wei

    2012-12-07

    The protective effects of St John's Wort extract (SJ), ginsenosides (GS), and clomipramine (CPM) on chronic unpredictable mild stress (CUMS)-induced depression in rats were investigated by using a combination of behavioral assessments and metabonomics. Metabonomic analyses were performed using gas chromatography/mass spectrometry in conjunction with multivariate and univariate statistical analyses. During and at the end point of the chronic stress experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Changes in these parameters reflected characteristic phenotypes of depression in rats. Metabonomic analysis of serum, urine, and brain tissue revealed that CPM and SJ mainly attenuated the alteration of monoamine neurotransmitter metabolites, while GS affected both excitatory/inhibitory amino acids and monoamine neurotransmitter metabolites. GS also attenuated the stress-induced alterations in cerebrum and peripheral metabolites to a greater extent than CPM and SJ. These results provide important mechanistic insights into the protective effects of GS against CUMS-induced depression and metabolic dysfunction.

  19. Direct and comprehensive analysis of ginsenosides and diterpene alkaloids in Shenfu injection by combinatory liquid chromatography-mass spectrometric techniques.

    PubMed

    Yang, Hua; Liu, Lei; Gao, Wen; Liu, Ke; Qi, Lian-Wen; Li, Ping

    2014-04-01

    Shenfu injection (SFI) is a widely used Chinese herbal formulation for cardiac diseases prepared from red ginseng and processed aconite root. Clinical observations and pharmacological effects on SFI have been well investigated. Chemical analysis and quality control studies of this formulation, however, are relatively limited, especially regarding toxic aconite alkaloids. In this work, a high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) method was applied to comprehensive analysis of constituents in SFI. Highly sensitive MS allows direct analysis of injections without additional sample pretreatment required. Using diagnostic ions and fragmentation rules, we identified 23 trace diterpene alkaloids, nineteen ginseng saponins, one panaxytriol, and one 5-hydroxymethylfurfural in SFI. A LC-MS method with selected ion monitoring was then used to quantify 24 major alkaloids and ginsenosides. The method was validated in terms of linearity, accuracy and precision. Especially, the limits of quantification were low to 0.4-18ng/mL for diterpene alkaloids. The total concentrations of saponins and alkaloids were about 676-742μg/mL and 3-7μg/mL in five batches of SFI samples, respectively. Finally, cosine ratio and euclidean distance were introduced to evaluate the batch-to-batch reproducibility of SFI samples, and the results demonstrated high quality consistency. Global identification and quantification of complex constituents based on LC-MS promises wide applications in quality control and batch monitoring for herbal products.

  20. Autophagy flux induced by ginsenoside-Rg3 attenuates human prion protein-mediated neurotoxicity and mitochondrial dysfunction

    PubMed Central

    Moon, Ji-Hong; Lee, Ju-Hee; Lee, You-Jin; Park, Sang-Youel

    2016-01-01

    Mitochondrial quality control is a process by which mitochondria undergo successive rounds of fusion and fission with dynamic exchange of components to segregate functional and damaged elements. Removal of mitochondrion that contains damaged components is accomplished via autophagy. In this study, we investigated whether ginsenoside Rg3, an active ingredient of the herbal medicine ginseng that is used as a tonic and restorative agent, could attenuate prion peptide, PrP (106-126)-induced neurotoxicity and mitochondrial damage. To this end, western blot and GFP-LC3B puncta assay were performed to monitor autophagy flux in neuronal cells; LC3B-II protein level was found to increase after Rg3 treatment. In addition, electron microscopy analysis showed that Rg3 enhanced autophagic vacuoles in neuronal cells. By using autophagy inhibitors wortmannin and 3-methyladenine (3MA) or autophagy protein 5 (Atg5) small interfering RNA (siRNA), we demonstrated that Rg3 could protect neurons against PrP (106-126)-induced cytotoxicity via autophagy flux. We found that Rg3 could also attenuate PrP (106-126)-induced mitochondrial damage via autophagy flux. Taken together, our results suggest that Rg3 is a possible therapeutic agent in neurodegenerative disorders, including prion diseases. PMID:27911875

  1. Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.

    PubMed

    Tian, Lili; Shen, Dachuan; Li, Xiaodong; Shan, Xiu; Wang, Xiaoqi; Yan, Qiu; Liu, Jiwei

    2016-01-12

    The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.

  2. Ameliorative effects of Compound K and ginsenoside Rh1 on non-alcoholic fatty liver disease in rats

    PubMed Central

    Chen, Xu-Jia; Liu, Wen-Jing; Wen, Meng-Liang; Liang, Hong; Wu, Shao-Mei; Zhu, Yun-Zhen; Zhao, Jiang-Yuan; Dong, Xiang-Qian; Li, Ming-Gang; Bian, Li; Zou, Cheng-Gang; Ma, Lan-Qing

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, which has no standard treatment available. Panax notoginseng saponines (PNS) have recently been reported to protect liver against hepatocyte injury induced by ethanol or high fat diet (HFD) in rats. Compound K and ginsenoside Rh1 are the main metabolites of PNS. In this study, we evaluated the effects of CK and Rh1 on NAFLD. Rats fed HFD showed significant elevations in liver function markers, lipids, glucose tolerance, and insulin resistance. Treatment with CK or Rh1 either alone or in combination dramatically ameliorated the liver function impairment induced by HFD. Histologically, CK and Rh1 significantly reversed HFD-induced hepatocyte injury and liver fibrosis. In vitro experiments demonstrated that treatment with CK or Rh1 alone or in combination markedly induced cell apoptosis, and inhibited cell proliferation and activation in HSC-T6 cells. Additionally, CK and Rh1, either alone or in combination, also repressed the expression of fibrotic factors TIMP-1, PC-I, and PC-III. Taken together, our results demonstrate that CK and Rh1 have positive effects on NAFLD via the anti-fibrotic and hepatoprotective activity. PMID:28106137

  3. Anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection in rat.

    PubMed

    Tan, Shanjun; Zhou, Feng; Li, Ning; Dong, Qiantong; Zhang, Xiaodong; Ye, Xingzhao; Guo, Jian; Chen, Bicheng; Yu, Zhen

    2013-01-01

    Ginsenoside Rb1 (GRb1), one of the principle active ingredients of Panax ginseng, exerts multiple pharmacological activities to fight fatigue. In the present study, we investigate the anti-fatigue effect of GRb1 on postoperative fatigue syndrome (POFS) in a rat model induced by major small intestinal resection. GRb1 (10 mg/kg) was administrated intraperitoneally once daily for 1, 3, 7, and 10 d from the operation day. Anti-fatigue effect was assessed by grasping test and biochemical parameters in blood or skeletal muscle were determined by autoanalyzer or commercially available kits. Transmission electron microscope was applied to observe the ultra microstructure of skeletal muscles. The results revealed that GRb1 significantly enhanced rat maximum grip strength with POFS. Similarly, negative alterations in biochemical parameters (lactic acid, hepatic glycogen, muscle glycogen and malondialdehyde) of POFS rats were improved by GRb1. In addition, GRb1 also increased the activity of lactate dehydrogenase and superoxide dismutase in POFS. No significant differences of levels of blood urea nitrogen and ultra microstructure of skeletal muscles were found between the POFS and GRb1 treatment rats. The potent anti-fatigue effect of GRb1 on POFS might be achieved through improvement of energy metabolism and suppression of skeletal muscle oxidative stress.

  4. Esterification of Ginsenoside Rh2 Enhanced Its Cellular Uptake and Antitumor Activity in Human HepG2 Cells.

    PubMed

    Chen, Fang; Deng, Ze-Yuan; Zhang, Bing; Xiong, Zeng-Xing; Zheng, Shi-Lian; Tan, Chao-Li; Hu, Jiang-Ning

    2016-01-13

    Our previous research had indicated that the octyl ester derivative of ginsenoside Rh2 (Rh2-O) might have a higher bioavailability than Rh2 in the Caco-2 cell line. The aim of this study was to investigate the cellular uptake and antitumor effects of Rh2-O in human HepG2 cells as well as its underlying mechanism compared with Rh2. Results showed that Rh2-O exhibited a higher cellular uptake (63.24%) than Rh2 (36.76%) when incubated with HepG2 cells for 24 h. Rh2-O possessed a dose- and time-dependent inhibitory effect against the proliferation of HepG2 cells. The IC50 value of Rh2-O for inhibition of HepG2 cell proliferation was 20.15 μM, which was roughly half the value of Rh2. Rh2-O induced apoptosis of HepG2 cells through a mitochondrial-mediated intrinsic pathway. In addition, the accumulation of ROS was detected in Rh2-O-treated HepG2 cells, which participated in the apoptosis of HepG2 cells. Conclusively, the findings above all suggested that Rh2-O as well as Rh2 inducing HepG2 cells apoptosis might involve similar mechanisms; however, Rh2-O had better antitumor activities than Rh2, probably due to its higher cellular uptake.

  5. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2.

    PubMed

    Wang, Wei; Zhang, Xu; Qin, Jiang-Jiang; Voruganti, Sukesh; Nag, Subhasree Ashok; Wang, Ming-Hai; Wang, Hui; Zhang, Ruiwen

    2012-01-01

    Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH(3)-PPD), a newly identified ginsenoside from Panax notoginseng, exerts activities against a variety of cancer cells in vitro and in vivo. This study was designed to investigate its anti-breast cancer activity and the underlying mechanisms of action. We observed that 25-OCH(3)-PPD decreased the survival of breast cancer cells by induction of apoptosis and G1 phase arrest and inhibited the growth of breast cancer xenografts in vivo. We further demonstrated that, in a dose- and time-dependent manner, 25-OCH(3)-PPD inhibited MDM2 expression at both transcriptional and post-translational levels in human breast cancer cells with various p53 statuses (wild type and mutant). Moreover, 25-OCH(3)-PPD inhibited in vitro cell migration, reduced the expression of epithelial-to-mesenchymal transition (EMT) markers, and prevented in vivo metastasis of breast cancer. In summary, 25-OCH(3)-PPD is a potential therapeutic and anti-metastatic agent for human breast cancer through down-regulating MDM2. Further preclinical and clinical development of this agent is warranted.

  6. Ginsenoside metabolite compound K exerts joint-protective effect by interfering with synoviocyte function mediated by TNF-α and Tumor necrosis factor receptor type 2.

    PubMed

    Wang, Ying; Chen, Jingyu; Luo, Xuexia; Zhang, Ying; Si, Ming; Wu, Huaxun; Yan, Chang; Wei, Wei

    2016-01-15

    Ginsenoside metabolite compound K (CK), metabolite of the ginsenoside, is considered to exert numerous pharmacological efficacies of ginsenoside, including anti-inflammation and immunoregulatory effects. Rheumatoid arthritis (RA) is a multi-systemic autoimmune disease characterized by hyperplastic synovial membrane and systemic inflammation, which ultimately lead to progressive destructive inflammatory arthropathy. To evaluate the potential joint-protective effects of CK and the underlying mechanism, adjuvant arthritis (AA) was induced by complete Freund's adjuvant in rats. After the onset of arthritis, The effect of CK on AA rats was evaluated by histopathology of the joint. The proliferation of fibroblast-like synoviocyte(FLS) was assayed by the Cell Counting Kit-8.The migration of FLS was assayed by transwell migration assay. Cytokines in the supernatant from FLS were measured by ELISA kit. Expression of Tumor Necrosis Factor Receptor Type 1(TNFR1) and Tumor Necrosis Factor Receptor Type 2(TNFR2) were detected by immunostaining analysis and western blot analysis. CK (80mg/kg) significantly ameliorated the histopathological change of joint in AA rats, balanced the RANKL/OPG ratio and attenuated the proliferation and migration of AA-FLS. CK suppressed the secretion of proinflammatory cytokines TNF-α and downregulated the expression of TNFR2 on AA-FLS. In vitro CK also significantly suppressed proliferation, migration and secretion of AA-FLS mediated by TNF-α. Further studies showed that the effects of CK on AA-FLS were reversed by using glucocorticoid receptor (GR) antagonist (mifepristone). Our data suggest that CK exerts joint-protective effect by interfering with synoviocyte function mediated by TNF-α and TNFR2, and this effect may be mediated by GR.

  7. Core bioactive components promoting blood circulation in the traditional Chinese medicine compound xueshuantong capsule (CXC) based on the relevance analysis between chemical HPLC fingerprint and in vivo biological effects.

    PubMed

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  8. Core Bioactive Components Promoting Blood Circulation in the Traditional Chinese Medicine Compound Xueshuantong Capsule (CXC) Based on the Relevance Analysis between Chemical HPLC Fingerprint and In Vivo Biological Effects

    PubMed Central

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  9. iTRAQ-Based Proteomic Analysis of Ginsenoside F2 on Human Gastric Carcinoma Cells SGC7901

    PubMed Central

    Mao, Qian; Zhang, Pin-Hu; Yang, Jie; Xu, Jin-Di; Kong, Ming; Shen, Hong; Zhu, He; Bai, Min; Zhou, Li; Li, Guang-Fu

    2016-01-01

    Ginsenoside F2 (F2), a protopanaxdiol type of saponin, was reported to inhibit human gastric cancer cells SGC7901. To better understand the molecular mechanisms of F2, an iTRAQ-based proteomics approach was applied to define protein expression profiles in SGC7901 cells in response to lower dose (20 μM) and shorter duration (12 hour) of F2 treatment, compared with previous study. 205 proteins were screened in terms of the change in their expression level which met our predefined criteria. Further bioinformatics and experiments demonstrated that F2 treatment downregulated PRR5 and RPS15 and upregulated RPL26, which are implicated in ribosomal protein-p53 signaling pathway. F2 also inhibited CISD2, Bcl-xl, and NLRX1, which are associated with autophagic pathway. Furthermore, it was demonstrated that F2 treatment increased Atg5, Atg7, Atg10, and PUMA, the critical downstream effectors of ribosomal protein-p53 signaling pathway, and Beclin-1, UVRAG, and AMBRA-1, the important molecules in Bcl-xl/Beclin-1 pathway. The 6 differentially abundant proteins, PRR5, CISD2, Bcl-xl, NLRX1, RPS15, and RPL26, were confirmed by western blot. Taken together, ribosomal protein-p53 signaling pathway and Bcl-xl/Beclin-1 pathway might be the most significantly regulated biological process by F2 treatment in SGC7901 cells, which provided valuable insights into the deep understanding of the molecular mechanisms of F2 for gastric cancer treatment. PMID:27829861

  10. The ginsenoside metabolite compound K, a novel agonist of glucocorticoid receptor, induces tolerance to endotoxin-induced lethal shock.

    PubMed

    Yang, Chul-Su; Ko, Sung-Ryong; Cho, Byung-Goo; Shin, Dong-Min; Yuk, Jae-Min; Li, Shengjin; Kim, Jin-Man; Evans, Ronald M; Jung, Jun-Sub; Song, Dong-Keun; Jo, Eun-Kyeong

    2008-01-01

    Compound K (C-K), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. Here, we describe a novel therapeutic role for C-K in the treatment of lethal sepsis through the modulation of Toll-like receptor (TLR) 4-associated signalling via glucocorticoid receptor (GR) binding. In mononuclear phagocytes, C-K significantly repressed the activation of TLR4/lipopolysaccharide (LPS)-induced NF-kappaB and mitogen-activated protein kinases (MAPKs), as well as the secretion of pro-inflammatory cytokines. However C-K did not affect the TLR3-mediated expression of interferon-beta or the nuclear translocation of IRF-3. C-K competed with the synthetic glucocorticoid dexamethasone for binding to GR and activated glucocorticoid responsive element (GRE)-containing reporter plasmids in a dose-dependent manner. In addition, the blockade of GR with either the GR antagonist RU486 or a siRNA against GR substantially reversed the anti-inflammatory effects of C-K. Furthermore, TLR4-dependent repression of inflammatory response genes by C-K was mediated through the disruption of p65/interferon regulatory factor complexes. Importantly, pre- or post-treatment with C-K significantly rescued mice from Gram-negative bacterial LPS-induced lethal shock by lowering their systemic inflammatory cytokine levels and by reversing the lethal sequelae of sepsis. Collectively, these results demonstrate that C-K, as a functional ligand of GR, regulates distinct TLR4-mediated inflammatory responses, and suggest a novel therapy for Gram-negative septic shock.

  11. Ginsenoside Rb1 Inhibits Doxorubicin-Triggered H9C2 Cell Apoptosis via Aryl Hydrocarbon Receptor

    PubMed Central

    Zhang, Yaxin; Wang, Yuguang; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Tan, Hongling; Xiao, Chengrong; Gao, Yue

    2017-01-01

    Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (− μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells. PMID:27829271

  12. Transcript pattern of cytochrome P450, antioxidant and ginsenoside biosynthetic pathway genes under heavy metal stress in Panax ginseng Meyer.

    PubMed

    Balusamy, Sri Renuka Devi; Kim, Yu-Jin; Rahimi, Shadi; Senthil, Kalai Selvi; Lee, Ok Ran; Lee, Sungyoung; Yang, Deok-Chun

    2013-02-01

    The differential transcript patterns of five antioxidant genes, four genes related to the ginsenoside pathway and five P450 genes related to defense mechanism were investigated in in vitro adventitious roots of Panax ginseng after exposure to two different concentrations of heavy metals for 7 days. PgSOD-1 and PgCAT transcription increased in a dose-dependent manner during the exposure to CuCl(2), NiCl(2), and CdCl(2), while all other tested scavenging enzymes didn't show significant increase during heavy metal exposure. Conversely, the mRNA transcripts of PgSQE, PgDDS were highly responsive to CuCl(2) compared to NiCl(2) exposure. However, the transcript profile of Pgβ-AS was highly induced upon NiCl(2) treatment compared to CuCl(2) and CdCl(2) exposure. The expressions of PgCYP716A42, PgCYP71A50U, and PgCYP82C22 were regulated in similar manners, and all showed the highest transcript profile at 100 μM of CuCl(2), CdCl(2), and NiCl(2) except PgCYP71D184, which showed the highest transcript level when subjected to 10 μM CuCl(2) and NiCl(2). Thus it may suggest that in P. ginseng heavy metal interaction on cell membrane induced expression of various defense related genes via jasmonic acid pathway and also possesses cross talk networks with other defense related pathways.

  13. Determination of ginsenoside compound K in human plasma by liquid chromatography–tandem mass spectrometry of lithium adducts

    PubMed Central

    Chen, Yunhui; Lu, Youming; Yang, Yong; Chen, Xiaoyan; Zhu, Liang; Zhong, Dafang

    2015-01-01

    Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography–tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile–water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 mL/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629→449 for the GCK-lithium adduct and m/z 860→292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00–1000 ng/mL (r2>0.9988) with intra- and inter-day precision of ±8.4% and accuracy in the range of −4.8% to 6.5%. Recovery, stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers. PMID:26579476

  14. Ginsenoside Rb1 ameliorates liver fat accumulation by upregulating perilipin expression in adipose tissue of db/db obese mice

    PubMed Central

    Yu, Xizhong; Ye, Lifang; Zhang, Hao; Zhao, Juan; Wang, Guoqiang; Guo, Chao; Shang, Wenbin

    2014-01-01

    Background Ginsenoside Rb1 (G-Rb1), the major active constituent of ginseng, improves insulin sensitivity and exerts antidiabetic effects. We tested whether the insulin-sensitizing and antidiabetic effects of G-Rb1 results from a reduction in ectopic fat accumulation, mediated by inhibition of lipolysis in adipocytes. Methods Obese and diabetic db/db mice were treated with daily doses of 20 mg/kg G-Rb1 for 14 days. Hepatic fat accumulation was evaluated by measuring liver weight and triglyceride content. Levels of blood glucose and serum insulin were used to evaluate insulin sensitivity in db/db mice. Lipolysis in adipocytes was evaluated by measuring plasma-free fatty acids and glycerol release from 3T3-L1 adipocytes treated with G-Rb1. The expression of relevant genes was analyzed by western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay kit. Results G-Rb1 increased insulin sensitivity and alleviated hepatic fat accumulation in obese diabetic db/db mice, and these effects were accompanied by reduced liver weight and hepatic triglyceride content. Furthermore, G-Rb1 lowered the levels of free fatty acids in obese mice, which may contribute to a decline in hepatic lipid accumulation. Corresponding to these results, G-Rb1 significantly suppressed lipolysis in 3T3-L1 adipocytes and upregulated the perilipin expression in both 3T3-L1 adipocytes and mouse epididymal fat pads. Moreover, G-Rb1 increased the level of adiponectin and reduced that of tumor necrosis factor-α in obese mice, and these effects were confirmed in 3T3-L1 adipocytes. Conclusion G-Rb1 may improve insulin sensitivity in obese and diabetic db/db mice by reducing hepatic fat accumulation and suppressing adipocyte lipolysis; these effects may be mediated via the upregulation of perilipin expression in adipocytes. PMID:26199550

  15. Metabolism of 20(S)-Ginsenoside Rg₂ by Rat Liver Microsomes: Bioactivation to SIRT1-Activating Metabolites.

    PubMed

    Ma, Li-Yuan; Zhou, Qi-Le; Yang, Xin-Bao; Wang, Hong-Ping; Yang, Xiu-Wei

    2016-06-10

    20(S)-Ginsenoside Rg₂ (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies on systematic metabolic profiles, the prospects for new drug development of 1 are still difficult to predict, which has become a huge obstacle for its safe clinical use. To solve this problem, investigation of the metabolic profiles of 1 in rat liver microsomes was first carried out. To identify metabolites, a strategy of combined analyses based on prepared metabolites by column chromatography and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. As a result, four metabolites M1-M4, including a rare new compound named ginsenotransmetin A (M1), were isolated and the structures were confirmed by spectroscopic analyses. A series of metabolites of 1, MA-MG, were also tentatively identified by UPLC-Q-TOF/MS in rat liver microsomal incubate of 1. Partial metabolic pathways were proposed. Among them, 1 and its metabolites M1, M3 and M4 were discovered for the first time to be activators of SIRT1. The SIRT1 activating effects of the metabolite M1 was comparable to those of 1, while the most interesting SIRT1 activatory effects of M3 and M4 were higher than that of 1 and comparable with that of resveratrol, a positive SIRT1 activator. These results indicate that microsome-dependent metabolism may represent a bioactivation pathway for 1. This study is the first to report the metabolic profiles of 1 in vitro, and the results provide an experimental foundation to better understand the in vivo metabolic fate of 1.

  16. Inhibiting PI3K-AKt signaling pathway is involved in antitumor effects of ginsenoside Rg3 in lung cancer cell.

    PubMed

    Xie, Qipeng; Wen, Huaikai; Zhang, Qiong; Zhou, Weihe; Lin, Xiaoming; Xie, Deyao; Liu, Yu

    2017-01-01

    Lung cancer is recognized as the most prevalent type of cancer with high death rate. Ginsenoside Rg3 isolated from Traditional Chinese Medicine Panax Ginseng has significant anticancer effects on many tumors. In this study, the effects of ginsenoside Rg3 on cells viability, apoptosis and PI3K/Akt signaling pathway in lung cancer cells were investigated in vitro and in vivo. In vitro, the viability of lung cancer cell lines A549,H23 was examined by CCK-8 kits; The proportion of cell apoptosis was measured by flow cytometry. The expression of p-PI3K/PI3K and p-Akt/Akt was evaluated with Western blot. In vivo, A549,H23 cells were subcutaneously injected into the nude mice. Histopathological analysis was stained with HE, and TUNEL assay was used to detect cell apoptosis. The results showed that Rg3 obviously inhibited cell viability, induced apoptosis and inhibited PI3K/Akt signalling pathway on A549, H23 cells in vitro and in vivo. Rg3 effectively inhibited the volume and weight of tumor in xenografts model, which may be related with inhibiting PI3K/Akt signaling pathways.

  17. Antimelanogenic effect of ginsenoside Rg3 through extracellular signal-regulated kinase-mediated inhibition of microphthalmia-associated transcription factor

    PubMed Central

    Lee, Seung Jae; Lee, Woo Jin; Chang, Sung Eun; Lee, Ga-Young

    2015-01-01

    Background Panax ginseng has been used to prolong longevity and is believed to be useful for improving skin complexion. Ginsenosides are the most active components isolated from ginseng, and ginsenoside Rg3 (G-Rg3) in particular has been demonstrated to possess antioxidative, antitumorigenic, and anti-inflammatory properties. The aim of this study was to examine the ability of G-Rg3 to inhibit melanogenesis. Methods The effects of G-Rg3 on melanin contents and the protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein 1 (TRP1) were evaluated. Melanogenesis-regulating signaling molecules such as Akt and extracellular signal-regulated kinase (ERK) were also examined to explore G-Rg3-induced antimelanogenic mechanisms. Results G-Rg3 was found to significantly inhibit the synthesis of melanin in normal human epidermal melanocytes and B16F10 cells in a dose-dependent manner. The activity of cellular tyrosinase and the expression of MITF, tyrosinase, and TRP1 were all reduced, whereas ERK was strongly activated. PD98059 (a specific inhibitor of ERK) attenuated the G-Rg3-induced inhibition of melanin synthesis and tyrosinase activity. Conclusion Taken together, these results showed that G-Rg3 induces the activation of ERK, which accounts for its antimelanogenic effects. G-Rg3 may be a promising safe skin-whitening agent, adding to the long list of uses of P. ginseng for the enhancement of skin beauty. PMID:26199555

  18. Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet.

    PubMed

    Wu, Yizhen; Yu, Yinghua; Szabo, Alexander; Han, Mei; Huang, Xu-Feng

    2014-01-01

    A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily) for 21 days significantly reduced body weight gain, fat mass accumulation, and improved glucose tolerance in obese mice on a HF diet compared to vehicle treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB pathway molecules (p-IKK and p-IκBα) in adipose tissue and liver. In the hypothalamus, Rb1 treatment decreased the expression of inflammatory markers (IL-6, IL-1β and p-IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore, Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has potential for use as an anti-obesity therapeutic agent that modulates obesity-induced inflammation and improves central leptin sensitivity in HF diet-induced obesity.

  19. An in-source multiple collision-neutral loss filtering based nontargeted metabolomics approach for the comprehensive analysis of malonyl-ginsenosides from Panax ginseng, P. quinquefolius, and P. notoginseng.

    PubMed

    Shi, Xiao-Jian; Yang, Wen-Zhi; Qiu, Shi; Yao, Chang-Liang; Shen, Yao; Pan, Hui-Qin; Bi, Qi-Rui; Yang, Min; Wu, Wan-Ying; Guo, De-An

    2017-02-01

    The simultaneous identification and quantification of target metabolites from herbal medicines are difficult to implement by the full-scan MS based nontargeted metabolomics approaches. Here an in-source multiple collision-neutral loss filtering (IMC-NLF) based nontargeted metabolomics approach is developed and applied to identify and quantify the variations of malonyl-ginsenosides, a common group of acyl saponins with potential anti-diabetic activity, among Panax ginseng, P. quinquefolius, and P. notoginseng. The key steps of the IMC-NLF strategy are the acquisition of specific high-resolution neutral loss data and the efficient filtering of target precursor ions from the full-scan spectra. Using a hybrid LTQ-Orbitrap mass spectrometer after UHPLC separation, abundant in-source product ions, [M-H-CO2](-) (due to the vulnerability of the carboxyl group) and [M-H-Mal.](-), were generated at the energies of 70 V and 90 V, respectively. After spectral deconvolution, the generated peak list was screened by dual NLF using a Neutral Loss MS Finder software (NL of 43.9898 Da for CO2 and 86.0004 Da for the malonyl substituent). By combining the precursor ions list-triggered HCD-MS/MS and basic hydrolysis, a total of 101 malonyl-ginsenosides (including 69 from P. ginseng, 52 from P. quinquefolius, and 44 from P. notoginseng) were identified or tentatively characterized. The variations of 81 characterized malonyl-ginsenosides among 45 batches of Ginseng samples were statistically analyzed disclosing ten potential markers. It is the first systematic analysis of malonyl-ginsenosides. The IMC-NLF approach by a single analytical platform is promising in targeted analyses of modification-specific metabolites in metabolomics and drug metabolism.

  20. Effects of the Combination of the Main Active Components of Astragalus and Panax notoginseng on Inflammation and Apoptosis of Nerve Cell after Cerebral Ischemia-Reperfusion.

    PubMed

    Huang, Xiao-Ping; Ding, Huang; Lu, Jin-Dong; Tang, Ying-Hong; Deng, Bing-Xiang; Deng, Chang-Qing

    2015-01-01

    Astragalus and Panax notoginseng are commonly used to treat cardio-cerebrovascular diseases in China and are often combined together to promote curative effect. We speculate that the enhancement of the combination on anticerebral ischemia injury may come from the main active components. The purpose of this work was to probe the effects and mechanisms of Astragaloside IV (the active component of Astragalus) combined with Ginsenoside Rg1, Ginsenoside Rb1, and Notoginsenoside R1 (the active components of P. notoginseng) to antagonize ischemia/reperfusion (I/R) injury via inflammation and apoptosis. C57BL/6 mice were randomly divided into sham, model, Astragaloside IV, Ginsenoside Rg1, Ginsenoside Rb1, Notoginsenoside R1, four active components combination, and Edaravone groups. After administration for 3 days, bilateral common carotid arteries (CCA) were occluded with artery clip for 20[Formula: see text]min followed by reperfusion for 24[Formula: see text]h. Our results showed that the survival rate of nerve cell in hippocampal CA1 decreased while the apoptotic rate increased, and the level of caspase-3 protein in brain tissues was elevated, the expressions of TNF-a, IL-1, and ICAM-1 mRNA as well as phosphorylated nuclear factor kappa B (NF-κB) inhibitor protein α (p-IκBa) in brain tissues were up-regulated, and the nuclear translocation rate of NF-κB was raised. Additionally, the protein expressions of phosphorylated tyrosine kinase 1 (p-JAK1), phosphorylated signal transducer and activator of transcription-1 (p-STAT1), glucose regulated protein 78 (GRP78), caspase-12, and phosphorylated c-Jun N-terminal kinases 1/2 (p-JNK1/2) in brain tissues were also significantly strengthened after I/R for 24 h. All drugs could increase neurocyte survival rate in hippocampal CA1, decrease the apoptotic rate, and inhibit caspase-3 protein expression, in contrast, the effects of four active components combination were better than those of active components alone. In addition

  1. Health Promotion

    DTIC Science & Technology

    1986-03-11

    Department of Defense DIRECTIVEAD-A269 638 , , AD-A29 638March 11, 1986 IIIIii!IN 111111111,11 Ii1111,111111[NUMBER 1010.10 SUBJECT: Health Promotion ...34 March 13, 1985 INC A. URPOSE SThis Directive establishes a health promotion policy within the Department of Defense to improve and maintain military...civilian employees. C. DEFINITIONS 1. Health Promotion . Any combination of health education and related organizational, social, economic or health care

  2. Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration.

    PubMed

    Zhang, Yuqiao; Tian, Dali; Huang, Yuyou; Li, Ling; Mao, Juan; Tian, Juan; Ding, Jinsong

    2016-11-01

    Shenfu Injection (SFI) is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc) and aconitum alkaloids (benzoylmesaconine and fuziline) were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC-MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2-8 mL/kg.

  3. Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors

    PubMed Central

    Chen, Ronald JY; Jinn, Tzyy-rong; Chen, Yi-ching; Chung, Tse-yu; Yang, Wei-hung; Tzen, Jason TC

    2011-01-01

    The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na+/K+-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na+/K+-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na+/K+-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na+/K+-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na+/K+-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na+/K+-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na+/K+-ATPase in the brain could be potential drugs for the treatment of ischemic stroke. PMID:21293466

  4. Inhibition of autophagy via activation of PI3K/Akt pathway contributes to the protection of ginsenoside Rb1 against neuronal death caused by ischemic insults.

    PubMed

    Luo, Tianfei; Liu, Guiying; Ma, Hongxi; Lu, Bin; Xu, Haiyang; Wang, Yujing; Wu, Jiang; Ge, Pengfei; Liang, Jianmin

    2014-09-01

    Lethal autophagy is a pathway leading to neuronal death caused by transient global ischemia. In this study, we examined the effect of Ginsenoside Rb1 (GRb1) on ischemia/reperfusion-induced autophagic neuronal death and investigated the role of PI3K/Akt. Ischemic neuronal death in vitro was induced by using oxygen glucose deprivation (OGD) in SH-SY5Y cells, and transient global ischemia was produced by using two vessels occlusion in rats. Cellular viability of SH-SY5Y cells was assessed by MTT assay, and CA1 neuronal death was evaluated by Hematoxylin-eosin staining. Autophagic vacuoles were detected by using both fluorescent microscopy in combination with acridine orange (AO) and Monodansylcadaverine (MDC) staining and transmission electronic microscopy. Protein levels of LC3II, Beclin1, total Akt and phosphor-Akt at Ser473 were examined by western blotting analysis. GRb1 inhibited both OGD and transient ischemia-induced neuronal death and mitigated OGD-induced autophagic vacuoles in SH-SY5Y cells. By contrast, PI3K inhibitor LY294002 counteracted the protection of GRb1 against neuronal death caused by either OGD or transient ischemia. LY294002 not only mitigated the up-regulated protein level of phosphor Akt at Ser473 caused by GRb1, but also reversed the inhibitory effect of GRb1 on OGD and transient ischemia-induced elevation in protein levels of LC3II and Beclin1.

  5. Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.

    PubMed

    Shin, Dae Hyun; Cha, Youn Jeong; Yang, Kyeong Eun; Jang, Ik-Soon; Son, Chang-Gue; Kim, Bo Hyeon; Kim, Jung Min

    2014-07-01

    Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products.

  6. Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.

    PubMed

    Cui, Yuan-Chen; Pan, Chun-Shui; Yan, Li; Li, Lin; Hu, Bai-He; Chang, Xin; Liu, Yu-Ying; Fan, Jing-Yu; Sun, Kai; -Li, Quan; Han, Jing-Yan

    2017-03-22

    Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome.

  7. Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway

    PubMed Central

    Cui, Yuan-Chen; Pan, Chun-Shui; Yan, Li; Li, Lin; Hu, Bai-He; Chang, Xin; Liu, Yu-Ying; Fan, Jing-Yu; Sun, Kai; -Li, Quan; Han, Jing-Yan

    2017-01-01

    Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome. PMID:28327605

  8. Red ginseng protects against gentamicin-induced balance dysfunction and hearing loss in rats through antiapoptotic functions of ginsenoside Rb1.

    PubMed

    Tian, Chun Jie; Kim, Seung Won; Kim, Yeon Ju; Lim, Hye Jin; Park, Raekil; So, Hong-Seob; Choung, Yun-Hoon

    2013-10-01

    The authors evaluated the protective effects of Korean red ginseng (KRG) against gentamicin (GM)-induced unilateral vestibular and hearing dysfunction and investigated its effective mechanism using in vitro cell cultures. Vestibular function was comprehensively evaluated by a scoring system that ranged from 0 (normal) to 3 (worst) points, using head tilt, tail hanging, and swimming tests. The GM group showed significantly more deteriorated vestibular function (0 point--5 rats, 1 point--1 rat, 2 points--3 rats, and 3 points--3 rats) than the KRG+GM group (0 point--9 rats and 1 point--1 rat) (p<0.01). The hearing thresholds were better in the KRG+GM group than in the GM group (p<0.05). Quantitative analysis of hair cell damage in the scanning electron microscopy was closely related with vestibular and hearing functional results. In vitro study showed that ginsenoside Rb1 (gRb1) attenuated reactive oxygen species production, suppressed JNK activation, up-regulated Bcl-xL and down-regulated Bax, cytochrome c, caspase 3, and cleaved poly (ADP-ribose) polymerase in GM-treated VOT-E36 cells. These findings suggest that KRG including gRb1 component protects against vestibular/hearing dysfunction by inhibiting apoptotic pathways when ototoxicity is induced by unilateral intratympanic injection with GM in rats.

  9. Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis.

    PubMed

    Yang, Xiao-Lai; Guo, Tian-Kang; Wang, Yan-Hong; Huang, Yan-Hui; Liu, Xia; Wang, Xiao-Xia; Li, Wan; Zhao, Xin; Wang, Li-Ping; Yan, Shuai; Wu, Di; Wu, Yong-Jie

    2012-02-01

    In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.

  10. Pseudoginsenoside F11, a Novel Partial PPARγ Agonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes

    PubMed Central

    Wu, Guoyu; Yi, Junyang; Liu, Ling; Wang, Pengcheng; Zhang, Zhijie

    2013-01-01

    PPARγ is a nuclear hormone receptor that functions as a master regulator of adipocyte differentiation and development. Full PPARγ agonists, such as the thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes. However, they are characterized by undesirable side effects due to their strong agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type ginsenoside isolated from Panax quinquefolium L. (American ginseng). In this study, we found that p-F11 activates PPARγ with modest adipogenic activity. In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1 adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of PPARγ at Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPARγ agonist, which might have the potential to be developed as a new PPARγ-targeted therapeutics for type 2 diabetes. PMID:24454336

  11. Health Promotion

    PubMed Central

    Wilson, Ron

    1992-01-01

    How physicians address issues of disease prevention and health promotion is discussed and current standards of screening for disease and counseling practices are reviewed. Collaboration among all health professionals is necessary if preventive medicine is to be effective. PMID:21221259

  12. Health Promotion

    PubMed Central

    Karmali-Rawji, Shameela; Kassim-Lakha, Shaheen; Taylor, Karmel

    1992-01-01

    Perceived lack or loss of control, stress, a rapidly again population and rising costs of health care necessitate effective health promotion and disease prevention in the elderly. In a collaborative health promotion effort, the private sector, public sector, and community partners have joined to increase the South Asian elders' sense of control over the decisions and circumstances that affect their everyday lives. The project was designed to help elders come to terms with the fragmentation of their extended families, cultural alienation, decreased autonomy, need for information, and greater risk of cardiovascular disease. Imagesp622-a

  13. Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets

    PubMed Central

    Kwon, Hyuk-Woo; Shin, Jung-Hae; Lee, Dong-Ha; Park, Hwa-Jin

    2015-01-01

    Intracellular Ca2+ ([Ca2+]i) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca2+-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated [Ca2+]i, which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser1756) to inhibit [Ca2+]i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser1756) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca2+ influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser1756) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca2+]i, which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca2+-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID:26355658

  14. Ginsenoside Rb₁ inhibits the carotid neointimal hyperplasia induced by balloon injury in rats via suppressing the phenotype modulation of vascular smooth muscle cells.

    PubMed

    Zhang, Shu; Deng, Jiang; Gao, Yang; Yang, Dan-li; Gong, Qi-hai; Huang, Xie-nan

    2012-06-15

    This study aims to investigate the effects of ginsenoside Rb(1) on vascular intimal hyperplasia in rats and explore the mechanisms. The rat vascular neointimal hyperplasia model was made by rubbing the endothelia of carotid artery with a balloon and Rb(1) (10 and 30 mg/kg/day) was given the day after surgery for 14 consecutive days. The neointimal hyperplasia level and the degree of vascular smooth muscle cells (VSMCs) proliferation were evaluated by histopathology and by calculating the proliferating cell nuclear antigen (PCNA) positive expression percentage; protein expressions of PCNA, phosphorylation extracellular signal-regulated kinase 1/2 (pERK1/2), smooth muscle α-actin (SM α-actin), and the mRNA expressions of proto-oncogene c-myc, SM α-actin, SM-emb (embryonic smooth muscle myosin heavy chain) and p38 MAPK were detected by immunohistochemistry and Real Time RT-PCR, respectively. Compared with the endothelia rubbing model group, Rb(1) 10 and 30 mg/kg/day medication significantly ameliorated the neointimal hyperplasia (P<0.05), and decreased the positive expression percentage of PCNA(P<0.05). Rb(1) medication also significantly decreased the elevated protein expression of pERK1/2 and the mRNA expression of c-myc(P<0.05), and tended to reduce the expression of p38 MAPK mRNA. Endothelial rubbing increased the SM-emb mRNA expression, but decreased the expression of SM α-actin mRNA which was reversed by Rb(1) (P<0.05). The results indicate that Rb(1) inhibits the vascular neointimal hyperplasia induced by balloon-injury in rats via suppressing the VSMC proliferation, which may be involved in part the inhibition of pERK1/2 protein and related to its inhibition on VSMC phenotype modulation.

  15. Ginsenoside Rd attenuates mitochondrial permeability transition and cytochrome C release in isolated spinal cord mitochondria: involvement of kinase-mediated pathways.

    PubMed

    Zhou, Jin-Song; Wang, Jiang-Feng; He, Bao-Rong; Cui, Yong-Sheng; Fang, Xiang-Yi; Ni, Jian-Long; Chen, Jie; Wang, Kun-Zheng

    2014-06-03

    Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has multifunctional activity via different mechanisms and neuroprotective effects that are exerted probably via its antioxidant or free radical scavenger action. However, the effects of Rd on spinal cord mitochondrial dysfunction and underlying mechanisms are still obscure. In this study, we sought to investigate the in vitro effects of Rd on mitochondrial integrity and redox balance in isolated spinal cord mitochondria. We verified that Ca2+ dissipated the membrane potential, provoked mitochondrial swelling and decreased NAD(P)H matrix content, which were all attenuated by Rd pretreatment in a dose-dependent manner. In contrast, Rd was not able to inhibit Ca2+ induced mitochondrial hydrogen peroxide generation. The results of Western blot showed that Rd significantly increased the expression of p-Akt and p-ERK, but had no effects on phosphorylation of PKC and p38. In addition, Rd treatment significantly attenuated Ca2+ induced cytochrome c release, which was partly reversed by antagonists of Akt and ERK, but not p-38 inhibitor. The effects of bisindolylmaleimide, a PKC inhibitor, on Rd-induced inhibition of cytochrome c release seem to be at the level of its own detrimental activity on mitochondrial function. Furthermore, we also found that pretreatment with Rd in vivo (10 and 50 mg/kg) protected spinal cord mitochondria against Ca2+ induced mitochondrial membrane potential dissipation and cytochrome c release. It is concluded that Rd regulate mitochondrial permeability transition pore formation and cytochrome c release through protein kinases dependent mechanism involving activation of intramitochondrial Akt and ERK pathways.

  16. Ginsenoside Rd Attenuates Mitochondrial Permeability Transition and Cytochrome c Release in Isolated Spinal Cord Mitochondria: Involvement of Kinase-Mediated Pathways

    PubMed Central

    Zhou, Jin-Song; Wang, Jiang-Feng; He, Bao-Rong; Cui, Yong-Sheng; Fang, Xiang-Yi; Ni, Jian-Long; Chen, Jie; Wang, Kun-Zheng

    2014-01-01

    Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has multifunctional activity via different mechanisms and neuroprotective effects that are exerted probably via its antioxidant or free radical scavenger action. However, the effects of Rd on spinal cord mitochondrial dysfunction and underlying mechanisms are still obscure. In this study, we sought to investigate the in vitro effects of Rd on mitochondrial integrity and redox balance in isolated spinal cord mitochondria. We verified that Ca2+ dissipated the membrane potential, provoked mitochondrial swelling and decreased NAD(P)H matrix content, which were all attenuated by Rd pretreatment in a dose-dependent manner. In contrast, Rd was not able to inhibit Ca2+ induced mitochondrial hydrogen peroxide generation. The results of Western blot showed that Rd significantly increased the expression of p-Akt and p-ERK, but had no effects on phosphorylation of PKC and p38. In addition, Rd treatment significantly attenuated Ca2+ induced cytochrome c release, which was partly reversed by antagonists of Akt and ERK, but not p-38 inhibitor. The effects of bisindolylmaleimide, a PKC inhibitor, on Rd-induced inhibition of cytochrome c release seem to be at the level of its own detrimental activity on mitochondrial function. Furthermore, we also found that pretreatment with Rd in vivo (10 and 50 mg/kg) protected spinal cord mitochondria against Ca2+ induced mitochondrial membrane potential dissipation and cytochrome c release. It is concluded that Rd regulate mitochondrial permeability transition pore formation and cytochrome c release through protein kinases dependent mechanism involving activation of intramitochondrial Akt and ERK pathways. PMID:24897022

  17. Flavobacterium panaciterrae sp. nov., a β-glucosidase producing bacterium with ginsenoside-converting activity isolated from the soil of a ginseng field.

    PubMed

    Jin, Yan; Kim, Yeon-Ju; Hoang, Van-An; Young Jung, Sun; Nguyen, Ngoc-Lan; Woo Min, Jin; Wang, Chao; Yang, Deok-Chun

    2014-01-01

    The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of strain DCY69(T) is JX233806. A Gram-reaction-negative, oxidase- and catalase-positive, non-gliding motile strain, designated strain DCY69(T), was isolated from the soil of a ginseng field in the Republic of Korea. Colonies of strain DCY69(T) were circular, 0.5-1.5 mm diameter, yellow, and convex on an R2A agar plate after 2 days. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DCY69(T) belonged to the genus Flavobacterium with 90.5-98.3% gene sequence similarity. The major predominant quinone was MK-6. The major cellular fatty acids were iso-C15:0, iso-C17:0 3-OH, iso-C15:0 3-OH and summed feature 3 (containing C16:1ω7c and/or C16:1ω6c). The major polar lipids were phosphatidylethanolamine, one unidentified aminolipid and unidentified polar lipids (L1, L2). The genomic DNA G+C content of strain DCY69(T) was 35.0mol%. The strain DCY69(T) transformed ginsenoside Rb1 into Rd and F2. Based on the polyphasic taxonomic data, strain DCY69(T) is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacterium panaciterrae sp. nov. is proposed. The type strain is DCY69(T)(= KCTC 32392(T) = JCM 19161(T)), isolated from the soil of a ginseng field in the Republic of Korea.

  18. Anti-Inflammatory Effects of Ginsenoside Rg3 via NF-κB Pathway in A549 Cells and Human Asthmatic Lung Tissue

    PubMed Central

    Lee, In-Seung; Uh, InJoon; Kim, Ki-Suk; Kim, Kang-Hoon; Park, Jiyoung; Kim, Yumi; Jung, Ji-Hoon; Jung, Hee-Jae

    2016-01-01

    Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549) and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB) activity. Methods. To induce the inflammation, IL-1β (10 ng/ml) was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured. Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues. Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines. PMID:28116321

  19. Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and -independent DR5 upregulation.

    PubMed

    Chen, Lei; Meng, Yue; Sun, Qi; Zhang, Zhongyu; Guo, Xiaoqing; Sheng, Xiaotong; Tai, Guihua; Cheng, Hairong; Zhou, Yifa

    2016-08-11

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. However, acquired resistance of cancer cells to TRAIL is a roadblock. Agents that can either potentiate the effect of TRAIL or overcome resistance to TRAIL are urgently needed. This article reports that ginsenoside compound K (CK) potentiates TRAIL-induced apoptosis in HCT116 colon cancer cells and sensitizes TRAIL-resistant colon cancer HT-29 cells to TRAIL. On a cellular mechanistic level, CK downregulated cell survival proteins including Mcl-1, Bcl-2, surviving, X-linked inhibitor of apoptosis protein and Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein, upregulated cell pro-apoptotic proteins including Bax, tBid and cytochrome c, and induced the cell surface expression of TRAIL death receptor DR5. Reduction of DR5 levels by siRNAs significantly decreases CK- and TRAIL-mediated apoptosis. Importantly, our results indicate, for the first time, that DR5 upregulation is mediated by autophagy, as blockade of CK-induced autophagy by 3-MA, LY294002 or Atg7 siRNAs substantially decreases DR5 upregulation and reduces the synergistic effect. Furthermore, CK-stimulated autophagy is mediated by the reactive oxygen species-c-Jun NH2-terminal kinase pathway. Moreover, we found that p53 and the C/EBP homologous (CHOP) protein is also required for DR5 upregulation but not related with autophagy. Our findings contribute significantly to the understanding of the mechanism accounted for the synergistic anticancer activity of CK and TRAIL, and showed a novel mechanism related with DR5 upregulation.

  20. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase

    SciTech Connect

    Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj; Oh, Seok Jeong; Lee, Moo Yeol; Kang, Keon Wook

    2010-08-01

    We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10 {mu}g/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase were enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.

  1. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase.

    PubMed

    Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj; Oh, Seok Jeong; Lee, Moo Yeol; Kang, Keon Wook

    2010-08-01

    We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10μg/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase were enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.

  2. Ginsenoside Rb2 enhances the anti-inflammatory effect of ω-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression

    PubMed Central

    Huang, Qi; Wang, Ting; Wang, He-yao

    2017-01-01

    Recent studies confirm that chronic low-grade inflammation is closely associated with metabolic syndromes, and anti-inflammatory therapy is a potential approach for treating cardiovascular diseases and type 2 diabetes. Accumulating evidence suggests that GPR120 activation is a feasible solution to ameliorating chronic inflammation and improving glucose metabolism. In this study we investigated whether ginsenoside Rb2 (Rb2), which exhibited regulatory activities in glucose and lipid metabolism, affected GPR120 expression in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells, and examined the contribution of GPR120 activation to reducing the LPS-induced inflammatory response. LPS (100 ng/mL) activated the macrophages, resulting in dramatic increases in TNF-α, IL-6, IL-1β and NO production. Treatment with a ω-3 fatty acid α-linolenic acid (ALA, 50 μmol/L) produced moderate reduction in LPS-stimulated inflammatory cytokines and NO production (TNF-α and IL-6 were decreased by 46% and 42%, respectively). Pre-incubation with Rb2 (1 or 10 μmol/L) for 12 h before ALA treatment dramatically amplified the inhibitory effects of ALA (TNF-α and IL-6 were decreased by 74% and 86%, respectively). Compared to the treatment with ALA alone, pre-incubation with Rb2 resulted in a more prominent reduction in LPS-stimulated expression of iNOS and COX-2 and LPS-stimulated IKK/NF-κB phosphorylation and MAPK pathway activation. Rb2 (0.1–100 μmol/L) dose- and time-dependently increased both mRNA and protein expression of GPR120 in RAW264.7 cells, but treatment with Rb2 alone did not exert anti-inflammatory effect in LPS-activated RAW264.7 cells. In RAW264.7 cells transfected with GPR120 shRNA, the ameliorating effects of Rb2 on LPS-induced inflammation were abolished. In conclusion, Rb2 exerts anti-inflammatory effect in LPS-stimulated mouse macrophage RAW264.7 cells in vitro by increasing GPR120 expression and subsequently enhancing ω-3 fatty acid-induced GPR120

  3. Stereoselective determination of ginsenosides Rg3 and Rh2 epimers in rat plasma by LC-MS/MS: application to a pharmacokinetic study.

    PubMed

    Bae, Soo Hyeon; Zheng, Yu Fen; Yoo, Young Hyo; Kim, Jeom Yong; Kim, Sun Ok; Jang, Min Jung; Seo, Jae Hong; Bae, Soo Kyung

    2013-06-01

    We developed and validated an accurate and sensitive LC-MS/MS method for the simultaneous quantitation of ginsenoside Rg3 and Rh2 epimers (R-Rg3, S-Rg3, R-Rh2, and S-Rh2) in rat plasma. Analytes were extracted from 0.1 mL aliquots of rat plasma by liquid-liquid extraction, using 2 mL of ethyl acetate. In this assay, dioscin (500 ng/mL) was used as an internal standard. Chromatographic separation was conducted using an Acclaim RSLC C18 column (150 × 2.1 mm, 2.2 μm) at 40°C, with a gradient mobile phase consisting of 0.1% formic acid in distilled water and in acetonitrile, a flow rate of 0.35 mL/min, and a total run time of 20 min. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with negative electrospray ionization at m/z 783.4 → 161.1 for R-Rg3 and S-Rg3, m/z 621.3 → 161.1 for R-Rh2 and S-Rh2, and m/z 867.2 → 761.5 for the internal standard. For R-Rg3 and S-Rg3, the lower limit of quantification was 5 ng/mL, with a linear range up to 500 ng/mL; for R-Rh2 and S-Rh2, the lower limit of quantification was 150 ng/mL, with a linear range up to 6000 ng/mL. The coefficient of variation for assay precision was less than 10.5%, with an accuracy of 86.4-112%. No relevant cross-talk or matrix effect was observed. The method was successfully applied to a pharmacokinetic study after oral administration of 400 mg/kg and 2000 mg/kg of BST204, a fermented ginseng extract, to rats. We found that the S epimers exhibited significantly higher plasma concentrations and area under curve values for both Rg3 and Rh2. This is the first report on the separation and simultaneous quantification of R-Rg3, S-Rg3, R-Rh2, and S-Rh2 in rat plasma by LC-MS/MS. The method should be useful in the clinical use of ginseng or its derivatives.

  4. Promoting Retention

    PubMed Central

    Hall, LaToya N.; Ficker, Lisa J.; Chadiha, Letha A.; Green, Carmen R.; Jackson, James S.; Lichtenberg, Peter A.

    2016-01-01

    Objectives: The objectives of this study were to evaluate the capability of a research volunteer registry to retain community-dwelling African American older adults, and to explore demographic and health factors associated with retention. Method: A logistic regression model was used to determine the influence of demographics, health factors, and registry logic model activities on retention in a sample of 1,730 older African American adults. Results: Almost 80% of participants active in the volunteer research registry between January 2012 and June 2015 were retained. Employment, being referred to research studies, a higher number of medical conditions, and more follow-up contacts were associated with an increased likelihood of retention. Older age, more months in the registry, and more mobility problems decreased the likelihood of retention. Discussion: These results suggest the Michigan Center for Urban African American Aging Research logic model promotes retention through involving older African American adults in research through study referrals and intensive follow-up. The loss of participants due to age- and mobility-related issues indicate the registry may be losing its most vulnerable participants. PMID:28138501

  5. Innovative method for the enrichment of high-polarity bioactive molecules present at low concentrations in complex matrices.

    PubMed

    Liu, Qing-Shan; He, Jie; Zhou, Wen-Bin; Gu, Yu-Long; Huang, Huoqiang; Li, Ke-Qin; Yin, Xiao-Ying

    2017-02-01

    Ginsenoside Rg1 is a valuable bioactive molecule but its high polarity and low concentration in complex mixtures makes it a challenge to separate Ginsenoside Rg1 from other saponins with similar structures, resulting in low extraction efficiency. The successful development of effective Rg1 molecularly imprinted polymers that exhibit high selectivity and adsorption may offer an improved method for the enrichment of active compounds. In this work, molecularly imprinted polymers were prepared with two different methods, precipitation polymerization or surface imprinted polymerization. Comparison of the adsorption abilities showed higher adsorption of the surface molecularly imprinted polymers prepared by surface imprinted polymerization, 46.80 mg/g, compared to the 27.74 mg/g observed for the molecularly imprinted polymers prepared by precipitation polymerization. Therefore, for higher adsorption of the highly polar Rg1, surface imprinted polymerization is a superior technique to make Rg1 molecularly imprinted polymers. The prepared surface molecularly imprinted polymers were tested as a solid-phase extraction column to directionally enrich Rg1 and its analogues from ginseng tea and total ginseng extracts. The column with surface molecularly imprinted polymers showed higher enrichment efficiency and better selectivity than a C18 solid-phase extraction column. Overall, a new, innovative method was developed to efficiently enrich high-polarity bioactive molecules present at low concentrations in complex matrices.

  6. Ginseng Compounds: An Update on Their Molecular Mechanisms and Medical Applications

    PubMed Central

    Lü, Jian-Ming; Yao, Qizhi; Chen, Changyi

    2010-01-01

    Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications. Ginsenosides, the major pharmacologically active ingredients of ginseng, appear to be responsible for most of the activities of ginseng including vasorelaxation, antioxidation, anti-inflammation and anti-cancer. Approximately 40 ginsenoside compounds have been identified. Researchers are now focused on using purified individual ginsenoside to reveal the specific mechanism of functions of ginseng instead of using whole ginseng root extracts. Each ginsenoside may have different effects in pharmacology and mechanisms due to their different chemical structures. Among them the most commonly studied ginsenosides are Rb1, Rg1, Rg3, Re, Rd and Rh1. The molecular mechanisms and medical applications of ginsenosides have attracted much attention and hundreds of papers have been published in the last few years. The general purpose of this update is to provide current information on recently described effects of ginsenosides on antioxidation, vascular system, signal transduction pathways and interaction with receptors. Their therapeutic applications in animal models and humans as well as the pharmacokinetics and toxicity of ginsenosides are also discussed in this review. This review concludes with some thoughts for future directions in the further development of ginseng compounds as effective therapeutic agents. PMID:19601854

  7. Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells

    SciTech Connect

    Hwang, Yong Pil; Jeong, Hye Gwang

    2010-01-01

    Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a popular traditional herbal medicine. Ginsenoside Rb1 (Rb1), an active component commonly found in ginseng root, is a phytoestrogen that exerts estrogen-like activity. In this study, we demonstrate that the phytoestrogen Rb1 inhibits 6-hydroxydopamine (6-OHDA)-induced oxidative injury via an ER-dependent Gbeta1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of SH-SY5Y cells with Rb1 significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. Rb1 also up-regulated HO-1 expression, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, Rb1 induced both Nrf2 nuclear translocation, which is upstream of HO-1 expression and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Also, Rb1-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that Rb1 augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the Gbeta1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress. Thus our study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell culture systems.

  8. Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

    PubMed

    Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

    2016-01-19

    The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

  9. Developing a Promotional Video

    ERIC Educational Resources Information Center

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  10. Health promotion in Brazil.

    PubMed

    Buss, Paulo Marchiori; de Carvalho, Antonio Ivo

    2007-01-01

    The evolution of health promotion within the Brazilian health system is examined, including an assessment of the intersectoral and development policies that have influenced the process. Particular attention is paid to the legal characteristics of the Unified Health System. Human resources formation and research initiatives in health promotion are outlined, with a summary of the obstacles that need to be overcome in order to ensure the effective implementation of health promotion in the future. Up to the end of the 20th Century health promotion was not used as a term in the Brazilian public heath context. Health promoting activities were concentrated in the area of health education, although targeting the social determinants of health and the principle of intersectoral action were part of the rhetoric. The situation has changed during the last decade, with the publication of a national policy of health promotion, issued by the Ministry of Health and jointly implemented with the States and Municipals Health Secretaries. More recently there has been a re-emergence of the discourse on the social determinants of health and the formation of intersectoral public policies as the basis of a comprehensive health promotion. Health promotion infrastructure, particularly around human resources and financing, requires strengthening in order to ensure capacity and sustainability in health promotion practice.

  11. Evaluation of embryotoxicity for major components of herbal extracts using the chick embryonic heart micromass and mouse D3 embryonic stem cell systems.

    PubMed

    Mohammed, Omar J; Latif, Muhammad Liaque; Pratten, Margaret K

    2016-01-01

    Herbal remedies are often used during the early stages of pregnancy, being considered 'harmless' and 'natural'. There are insufficient data regarding their potential embryotoxicity. The main components of selected herbs, including 6-gingerol from ginger, Ginkgolide A and Ginkgolide B from gingko biloba and Ginsenoside Rg1 from ginseng, have been investigated using chick embryonic heart micromass and Mouse D3 embryonic stem cells. The potential effects were evaluated via alteration in contractility, cell viability, and cell protein content. The myocytes in both systems were also demonstrated by immunocytochemistry using a specific cardiomyocyte marker (α-actinin). For 6-gingerol, Ginkgolide A, Ginkgolide B and Ginsenoside Rg1 in both methods, at moderate to high concentrations, there were alterations in the values for the endpoints. These data indicate that herbal remedies used in the first trimester of pregnancy might not be safe for fetal development.

  12. High expression Zymomonas promoters

    DOEpatents

    Viitanen, Paul V.; Tao, Luan; Zhang, Yuying; Caimi, Perry G.; McCole, Laura : Zhang, Min; Chou, Yat-Chen; McCutchen, Carol M.; Franden, Mary Ann

    2011-08-02

    Identified are mutants of the promoter of the Z. mobilis glyceraldehyde-3-phosphate dehydrogenase gene, which direct improved expression levels of operably linked heterologous nucleic acids. These are high expression promoters useful for expression of chimeric genes in Zymomonas, Zymobacter, and other related bacteria.

  13. Health Promotion Program.

    ERIC Educational Resources Information Center

    McClary, Cheryl

    The Health Promotion Program began with establishment of a one-credit course in health promotion and wellness and the training of family practice residents at the Mountain Area Health Education Center to serve as lab leaders in the course. The course later became part of the university's general education requirements. In addition, a health…

  14. Promoting Resilience in Children.

    ERIC Educational Resources Information Center

    Rolfe, Sharne A.

    2002-01-01

    This booklet invites reflection on ways in which childhood resilience can be promoted, thereby helping children to adapt effectively in the face of adversity. The attributes of resilient children are described, as is the importance of protective factors in building or promoting resilience. The booklet discusses the complex interplay between risk…

  15. Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro★

    PubMed Central

    Yan, Weihua; Liu, Junze

    2012-01-01

    Mitochondrial dysfunction is the key pathogenic mechanism of cerebral injury induced by high-altitude hypoxia. Some Chinese herbal monomers may exert anti-hypoxic effects through enhancing the efficiency of oxidative phosphorylation. In this study, effects of 10 kinds of Chinese herbal monomers on mitochondrial respiration and membrane potential of cerebral mitochondria isolated from hypoxia-exposed rats in vitro were investigated to screen anti-hypoxic drugs. Rats were exposed to a low-pressure environment of 405.35 mm Hg (54.04 kPa) for 3 days to establish high-altitude hypoxic models. Cerebral mitochondria were isolated and treated with different concentrations of Chinese herbal monomers (sinomenine, silymarin, glycyrrhizic acid, baicalin, quercetin, ginkgolide B, saffron, piperine, ginsenoside Rg1 and oxymatrine) for 5 minutes in vitro. Mitochondrial oxygen consumption and membrane potential were measured using a Clark oxygen electrode and the rhodamine 123 fluorescence analysis method, respectively. Hypoxic exposure significantly decreased the state 3 respiratory rate, respiratory control rate and mitochondrial membrane potential, and significantly increased the state 4 respiratory rate. Treatment with saffron, ginsenoside Rg1 and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rg1, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rg1, piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro. PMID:25558222

  16. Embryoid Formation by High Temperature Treatment from Multiple Shoots of Panax ginseng1.

    PubMed

    Asaka, I; Li, I; Yoshikawa, T; Hirotani, M; Furuya, T

    1993-08-01

    We developed a new technology to induce embryoids by a moderate high temperature treatment from multiple shoots of PANAX GINSENG (Araliaceae). The number of formed embryoids was 10 times higher than that of untreated tissue. Normal plantlets were regenerated from the embryoids by transplanting them on a hormone-free medium. They contained ginsenosides Rb (1), Rg (1) and the other saponins as well as those of natural ginseng.

  17. 77 FR 47820 - Invention Promoters/Promotion Firms Complaints

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... United States Patent and Trademark Office Invention Promoters/Promotion Firms Complaints ACTION: Proposed... participate in any legal proceedings against invention promoters or promotion firms. Complaints submitted to... promotion firm, explain the basis for the complaint, and include the signature of the complainant....

  18. Metabolite identification of seven active components of Huan-Nao-Yi-Cong-Fang in rat plasma using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry.

    PubMed

    Wang, Minchao; Lu, Yanzhen; Liu, Jiangang; Li, Hao; Wei, Yun

    2016-02-01

    Huan-Nao-Yi-Cong-Fang (HNYCF) is a potential prescription in treating Alzheimer's disease. Seven constituents [ferulic acid (FA), 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), berberine hydrochloride (BHCl), emodin, ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and ginsenoside Rb1 (Rb1)] have been used as quality chemical markers of HNYCF owing to their biological significance and high contents in crude plant materials. This study explored the metabolites of the seven bioactive components in rat plasma to give useful data for further study of the action mechanism of HNYCF. LC/MS-IT-TOF was used to simultaneously characterize the metabolites of the seven components. Using the combination of MetID Solution 1.0 software and accurate mass measurements, the metabolites of HNYCF were reliably characterized. Their structures were elucidated based on the accurate MS(2) spectra and comparisons of their changes in accurate molecular masses and fragment ions with those of parent compounds. A total of five parent active compounds (BHCl, emodin, Rg1, Rb1 and Re) and 10 metabolites were found from the rat plasma 2 h after oral administration of HNYCF dosage, of which two metabolites of emodin were observed for the first time. The proposed metabolic pathways of the bioactive components in the rat plasma are helpful for further studies on the pharmacokinetics and real active compound forms of this drug.

  19. Novelty and Promotional Items

    EPA Pesticide Factsheets

    Small novelty or promotional products, primarily used for outreach and educational purposes, must effectively convey a message, and their purchase will only be allowed if the item will contribute to the accomplishment of the Agency's mission.

  20. Promoting "Global" Attitudes.

    ERIC Educational Resources Information Center

    Case, Roland

    1996-01-01

    Discusses and illustrates three ways to promote prosocial attitudes towards global issues among students. Includes classroom environments that reinforce desired attitudes; facilitating direct "emotional" experiences that influence attitudes; and engaging students in thoughtful deliberation about global issues. Offers illustrative…

  1. The herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a neuroblastoma cells.

    PubMed

    Chen, JinYan; Sun, MengRu; Wang, XingHua; Lu, Jing; Wei, Yan; Tan, Yan; Liu, Ying; Götz, Jürgen; He, RongQiao; Hua, Qian

    2014-04-01

    The herbal medicine Tong Luo Jiu Nao (TLJN) contains geniposide (GP) and ginsenoside Rg1 at a molar ratio of 10:1. Rg1 is the major component of another herbal medicine, panax notoginseng saponin (PNS). TLJN has been shown to strengthen brain function in humans, and in animals it improves learning and memory. We have previously shown that TLJN reduces amyloidogenic processing in Alzheimer's disease (AD) mouse models. Together this suggests TLJN may be a potential treatment for patients with dementia. Because chronic damage of the central nervous system by formaldehyde (FA) has been presented as a risk factor for age-associated cognitive dysfunction, in the present study we investigated the protective effect of both TLJN and GP in neuron-like cells exposed to FA. FA-exposed murine N2a neuroblastoma cells were incubated with TLJN, its main ingredient GP, as well as PNS, to measure cell viability and morphology, the rate of apoptosis and expression of genes encoding Akt, FOXO3, Bcl2 and p53. The CCK-8 assay, cytoskeletal staining and flow cytometry were used to test cell viability, morphology and apoptosis, respectively. Fluorescent quantitative real-time PCR (qRT-PCR) was used to monitor changes in gene expression, and HPLC to determine the rate of FA clearance. Treatment of N2a cells with 0.09 mmol L(-1) FA for 24 h significantly reduced cell viability, changed cell morphology and promoted apoptosis. Both TLJN and GP conferred neuroprotection to FA-treated N2a cells, whereas PNS, which had to be used at lower concentrations because of its toxicity, did not. Our data demonstrate that TLJN can rescue neuronal damage caused by FA and that its main ingredient, GP, has a major role in this efficacy. This presents purified GP as a drug or lead compound for the treatment of AD.

  2. A novel strategy for rapid quantification of 20(S)-protopanaxatriol and 20(S)-protopanaxadiol saponins in Panax notoginseng P. ginseng and P. quinquefolium.

    PubMed

    Xu, Fa-Xiang; Yuan, Cen; Wan, Jian-Bo; Yan, Ru; Hu, Hao; Li, Shao-Ping; Zhang, Qing-Wen

    2015-01-01

    A novel strategy for the qualitative and quantitative determination of 20(S)-protopanaxatriol saponins (PTS) and 20(S)-protopanaxadiol saponins (PDS) in Panax notoginseng, Panax ginseng and Panax quinquefolium, based on the overlapping peaks of main components of PTS (calibrated by ginsenoside Rg1) and PDS (calibrated by ginsenoside Rb1), was proposed. The analysis was performed by using high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD). Under specific chromatographic conditions, all samples showed two overlapping peaks containing several main ginsenosides belonging to PTS and PDS, respectively. The overlapping peaks were also identified by using HPLC-MS. Based on the sum and ratio of PTS and PDS, 60 tested Panax samples were divided into three main clusters according to their species. The findings suggested that this strategy provides a simple and rapid approach to quantify PTS and PDS in Panax herbs.

  3. Promoting La Cultura Hispana

    ERIC Educational Resources Information Center

    Pluviose, David

    2007-01-01

    Launched in 1985 at Arizona State University, the Hispanic Research Center's (HRC) efforts to promote Latino and Chicano art and issues have flourished in recent years. In 2004, the HRC hosted the Arizona International Latina/o Arts Festival in collaboration with the Mesa Southwest Museum. The HRC has also founded a mentoring institute for…

  4. The Ideal Promotion Effort.

    ERIC Educational Resources Information Center

    Morris, Edward L.

    The ideal promotional effort for an educational television (ETV) station is dependent on a professional approach to the problem. This means that each ETV station should employ a public relations manager and should keep him informed about all major station decisions. The Public Broadcasting Service (PBS) has a campaign of its own to bring attention…

  5. Health Promotion Interventions.

    ERIC Educational Resources Information Center

    Jason, Leonard A.; Curie, Carrie J.; Townsend, Stephanie M.; Pokorny, Steven B.; Katz, Richard B.; Sherk, Joseph L.

    2002-01-01

    Reviews four areas from the prevention science field, including: promoting healthy behavior; preventing substance abuse; preventing high-risk sexual behaviors; and preventing child abuse and sexual abuse. Recommendations are made regarding strategies for implementing empirically validated programs, supplementing school programs with ecological…

  6. Does Paid Promotion Pay?

    ERIC Educational Resources Information Center

    Scherer, Chris

    1980-01-01

    A study to determine the cost effectiveness of newspaper display advertising for cooperative extension programs showed such publicity to be more effective in large metropolitan areas. Though not a technique for increasing enrollment, this method provided long-range benefits in the overall promotion of extension educational services. (SK)

  7. Promoting Healthy Dietary Behaviors.

    ERIC Educational Resources Information Center

    Perry, Cheryl L.; Story, Mary; Lytle, Leslie A.

    This chapter reviews the research on promoting healthy dietary behaviors in all youth, not just those who exhibit problems such as obesity or eating disorders. The first section of this chapter presents a rationale for addressing healthy dietary behavior with children and adolescents, on the basis of the impact of these behaviors on short- and…

  8. Partners: Promoting Accessible Recreation.

    ERIC Educational Resources Information Center

    Sable, Janet; Gravink, Jill

    1995-01-01

    The Promoting Accessible Recreation through Networking, Education, Resources and Services (PARTNERS) Project, a partnership between Northeast Passage, the University of New Hampshire, and Granite State Independent Living Foundation, helps create barrier-free recreation for individuals with physical disabilities. The paper describes PARTNERS and…

  9. Promoting Continuing Education Programs.

    ERIC Educational Resources Information Center

    Hendrickson, Gayle A.

    This handbook is intended for use by institutions in marketing their continuing education programs. A section on "Devising Your Strategy" looks at identifying a target audience, determining the marketing approach, and developing a marketing plan and promotional techniques. A discussion of media options looks at the advantages and…

  10. 50 Practical Promotion Ideas.

    ERIC Educational Resources Information Center

    Madeyski, Tom

    1997-01-01

    Includes 50 cost-effective ideas for promoting camp in the areas of recruiting new campers, encouraging returning campers, advertising strategies, printing brochures and other written materials, using photographs, targeting groups for camp facility rental, and effectively using the media. (LP)

  11. The promotion of breastfeeding.

    PubMed

    Tuluhungwa, R R; Yung, W

    1979-01-01

    To reverse the current trend of a significant decline worldwide in breast feeding means reeducation of medical and health personnel as well as the general public. Programs to promote breast feeding require the commitment of governments, with support from various ministries including health, education, labor, community development and judiciary. Examples of what 3 developing countries--Jamaica, Colombia and Thailand--are doing to promote breast feeding are reported. A large scale breast feeding campaign was launched in Jamaica in October 1977. The 3 phases of the campaign were: 1) preliminary surveys and research and motivation of professional, voluntary and extension groups through training seminars, panel discussions, and meetings; 2) promotion of breast feeding via mass media and motivation of target groups by trained personnel; and 3) evaluation of the campaign. A survey undertaken in 1978 showed that the breast feeding messages had achieved the desired effect--more mothers practiced breast feeding. In Colombia the breast feeding campaign emphasized non-formal education through the use of games and pictures. A game is used which is usually initiated by a health worker in the waiting room of a health center and involves the mothers, the general public, and sometimes the professional personnel. Through reading and interpreting rhymed breast feeding messages, the participants exchange opinions and experiences. Before starting a campaign to encourage low-income urban and semi-urban mothers to breast feed, the National Food and Nutrition Committee of Thailand pretested slogans and posters designed for the promotion of breast feeding. Posters develpoed in accordance with the suggestions made by the women were tested among 126 pregnant and lactating women. The Committee decided which picture to print for low-income and rural audiences and which to print for middle-class audiences.

  12. Democracy Promotion in Oman

    DTIC Science & Technology

    2013-01-01

    succession process . The “Ruling Family Council” will meet to designate a successor within 3 days of Qaboos’s death. If it fails to select someone, it will...the Gulf is to increase democracy promotion programs designed to encourage timely and peaceful transitions to more representative forms of govern...stronger efforts toward reform supported by the United States could foster a more peaceful political transformation. This process should begin with the

  13. Publishing and academic promotion.

    PubMed

    Dixon, A K

    2009-09-01

    Clearly, academic endeavour has to be the single most important criterion for appointment to an academic position and for subsequent promotion. It is rare for excellence either in teaching or clinical practice to offset a poor publication record. However, the pressure to publish and gain related grant income can lead to problems in the normal academic pursuits of a department or institution. These and other related issues will be explored in this editorial.

  14. Bicycle Promotion Plan

    SciTech Connect

    Simone, G. A.

    1981-03-09

    The objective of this Bicycle Promotion Plan is to outline a set of recommendations and supporting strategies for implementation by the US DOE toward increased use of the bicycle for energy conservation. The recommendations are designed in such a way as to function in concert with: (1) bicycle programs administered by other Federal government agencies; and (2) related programs and activities already sponsored by DOE. The approach to preparation of the Plan involved a review of all current and planned bicycle promotion programs at the Federal level as well as a review of the array of lierature on the subject. The UniWorld project staff also interacted with several DOE program offices, in order to determine the extent to which they might appropriately contribute to the implementation of bicycle promotional efforts. A synthesis of all the information gathered was published in January of 1981 as a part of the project (The Bicycle Program Review). Based upon this information and an examination of the barriers to bicycle use identified by bicycle transportation specialists in the field, UniWorld developed a series of the most potentially effective recommendations and program strategies for implementation by DOE. The recommendations address activities that could be undertaken in conjunction with existing DOE programs, new developments that might be considered to fulfill critical needs in the field, and interagency efforts that DOE could play a role in.

  15. The dynamics of mobile promoters: Enhanced stability in promoter regions.

    PubMed

    Rabbani, Mahnaz; Wahl, Lindi M

    2016-10-21

    Mobile promoters are emerging as a new class of mobile genetic elements, first identified by examining prokaryote genome sequences, and more recently confirmed by experimental observations in bacteria. Recent datasets have identified over 40,000 putative mobile promoters in sequenced prokaryote genomes, however only one-third of these are in regions of the genome directly upstream from coding sequences, that is, in promoter regions. The presence of many promoter sequences in non-promoter regions is unexplained. Here we develop a general mathematical model for the dynamics of mobile promoters, extending previous work to capture the dynamics both within and outside promoter regions. From this general model, we apply rigorous model selection techniques to identify which parameters are statistically justified in describing the available mobile promoter data, and find best-fit values of these parameters. Our results suggest that high rates of horizontal gene transfer maintain the population of mobile promoters in promoter regions, and that once established at these sites, mobile promoters are rarely lost, but are commonly copied to other genomic regions. In contrast, mobile promoter copies in non-promoter regions are more numerous and more volatile, experiencing substantially higher rates of duplication, loss and diversification.

  16. Human Promoters Are Intrinsically Directional

    PubMed Central

    Duttke, Sascha H.C.; Lacadie, Scott A.; Ibrahim, Mahmoud M.; Glass, Christopher K.; Corcoran, David L.; Benner, Christopher; Heinz, Sven; Kadonaga, James T.; Ohler, Uwe

    2015-01-01

    Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that up to half of promoters are unidirectional and that unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters. PMID:25639469

  17. PROMOTIONS: PROper MOTION Software

    NASA Astrophysics Data System (ADS)

    Caleb Wherry, John; Sahai, R.

    2009-05-01

    We report on the development of a software tool (PROMOTIONS) to streamline the process of measuring proper motions of material in expanding nebulae. Our tool makes use of IDL's widget programming capabilities to design a unique GUI that is used to compare images of the objects from two epochs. The software allows us to first orient and register the images to a common frame of reference and pixel scale, using field stars in each of the images. We then cross-correlate specific morphological features in order to determine their proper motions, which consist of the proper motion of the nebula as a whole (PM-neb), and expansion motions of the features relative to the center. If the central star is not visible (quite common in bipolar nebulae with dense dusty waists), point-symmetric expansion is assumed and we use the average motion of high-quality symmetric pairs of features on opposite sides of the nebular center to compute PM-neb. This is then subtracted out to determine the individual movements of these and additional features relative to the nebular center. PROMOTIONS should find wide applicability in measuring proper motions in astrophysical objects such as the expanding outflows/jets commonly seen around young and dying stars. We present first results from using PROMOTIONS to successfully measure proper motions in several pre-planetary nebulae (transition objects between the red giant and planetary nebula phases), using images taken 7-10 years apart with the WFPC2 and ACS instruments on board HST. The authors are grateful to NASA's Undergradute Scholars Research Program (USRP) for supporting this research.

  18. Promoting healthy sleep.

    PubMed

    Price, Bob

    2016-03-09

    Nurses are accustomed to helping others with their sleep problems and dealing with issues such as pain that may delay or interrupt sleep. However, they may be less familiar with what constitutes a healthy night's sleep. This article examines what is known about the process and purpose of sleep, and examines the ways in which factors that promote wakefulness and sleep combine to help establish a normal circadian rhythm. Theories relating to the function of sleep are discussed and research is considered that suggests that sleep deficit may lead to metabolic risks, including heart disease, obesity, type 2 diabetes mellitus and several types of cancer.

  19. Students Promoted Despite Test Failure

    ERIC Educational Resources Information Center

    Wakefield, Dara V.

    2012-01-01

    "No Child Left Behind" (NCLB) dictates students in Grades 3, 5, and 8 pass state tests to be promoted. Accordingly, most state education codes require students to pass reading and math exams for promotion. The majority of those who fail, however, appear to be promoted anyway. This article addresses core questions concerning the paradigm…

  20. TWEAK Promotes Peritoneal Inflammation

    PubMed Central

    Sanz, Ana Belen; Aroeira, Luiz Stark; Bellon, Teresa; del Peso, Gloria; Jimenez-Heffernan, Jose; Santamaria, Beatriz; Sanchez-Niño, Maria Dolores; Blanco-Colio, Luis Miguel; Lopez-Cabrera, Manuel; Ruiz-Ortega, Marta; Egido, Jesus; Selgas, Rafael; Ortiz, Alberto

    2014-01-01

    Peritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses while minimizing peritoneal injury. There is no information on the expression and function of the cytokine TWEAK and its receptor Fn14 during peritoneal injury. Fn14 expression and soluble TWEAK levels were measured in human PD peritoneal effluent cells or fluids with or without peritonitis. Fn14 expression was also analyzed in peritoneal biopsies from PD patients. Actions of intraperitoneal TWEAK were studied in mice in vivo. sTWEAK levels were increased in peritoneal effluent in PD peritonitis. Effluent sTWEAK levels correlated with the number of peritoneal macrophages (r = 0.491, p = 0.002). Potential TWEAK targets that express the receptor Fn14 include mesothelial cells and macrophages, as demonstrated by flow cytometry of peritoneal effluents and by analysis of peritoneal biopsies. Peritoneal biopsy Fn14 correlated with mesothelial injury, fibrosis and inflammation, suggesting a potential deleterious effect of TWEAK/Fn14. In this regard, intraperitoneal TWEAK administration to mice promoted peritoneal inflammation characterized by increased peritoneal effluent MCP-1, Fn14 and Gr1+ macrophages, increased mesothelial Fn14, MCP-1 and CCL21 expression and submesothelial tissue macrophage recruitment. Taken together these data suggest that the TWEAK/Fn14 system may promote inflammation and tissue injury during peritonitis and PD. PMID:24599047

  1. Dendritic Cells Promoted by Ginseng Saponins Drive a Potent Th1 Polarization

    PubMed Central

    Takei, Masao; Tachikawa, Eiichi; Umeyama, Akemi

    2008-01-01

    Dendritic cells (DC) play a pivotal role in the initiation of T-cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. The interaction of T cells with DC is crucial for directing T cell differentiation towards the Th1, Th2 or Th17 type, and several factors determining the direction of the T cell polarization. IL-12 plays a central role in the immune system, not only by augmenting the cytotoxic activity of T cells and NK cells and regulating IFN-γ production, but also by the capacity of IL-12 to promote the development of Th1 cells. Therefore, it is important to identify factors that might affect the differentiation, maturation and function of DC. Ginseng is a medicinal herb widely used in Asian countries, and many of its pharmacological actions are attributed to the ginsenosides. Moreover, T-cadinol and calamenene are sesquterpenes isolated from the heartwood of Cryptomeria japonica being pharmacologically active substances. We investigated whether M1 and M4, end products of steroidal ginseng saponins metabolized in digestive tracts, as well as T-cadinol and calamenene can drive DC maturation from human monocytes in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days under standard conditions, followed by another 2 days in the presence of M1, M4, T-cadinol or calamenene. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR on M1-primed DC, M4-primed DC, T-cadinol-primed DC and calamenene-primed DC were enhanced with a concomitant decrease in endocytic activity. M1-primed DC, M4-primed DC, T-cadinol-primed DC or calamenene-primed DC enhanced the T cell stimulatory capacity in an allo MLR (allogeneic mixed lymphocyte reaction). Naïve T cells co-cultured with allogeneic M1-primed DC, M4-primed DC, T-cadinol-primed DC or calamenene-primed DC turned into typical Th1 cells, which produced large quantities of IFN-γ and released small amounts of IL-4 depending on IL-12 secretion. In the CTL assay

  2. Leptin Promotes Glioblastoma

    PubMed Central

    Lawrence, Johnathan E.; Cook, Nicholas J.; Rovin, Richard A.; Winn, Robert J.

    2012-01-01

    The hormone leptin has a variety of functions. Originally known for its role in satiety and weight loss, leptin more recently has been shown to augment tumor growth in a variety of cancers. Within gliomas, there is a correlation between tumor grade and tumor expression of leptin and its receptor. This suggests that autocrine signaling within the tumor microenvironment may promote the growth of high-grade gliomas. Leptin does this through stimulation of cellular pathways that are also advantageous for tumor growth and recurrence: antiapoptosis, proliferation, angiogenesis, and migration. Conversely, a loss of leptin expression attenuates tumor growth. In animal models of colon cancer and melanoma, a decline in the expression and secretion of leptin resulted in a reduction of tumor growth. In these models, positive mental stimulation through environmental enrichment decreased leptin secretion and improved tumor outcome. This review explores the link between leptin and glioblastoma. PMID:22263109

  3. Love promotes health.

    PubMed

    Esch, Tobias; Stefano, George B

    2005-06-01

    Love has consequences for health and well-being. Engaging in joyful activities such as love may activate areas in the brain responsible for emotion, attention, motivation and memory (i.e., limbic structures), and it may further serve to control the autonomic nervous system, i.e., stress reduction. This specific CNS activity pattern appears to exert protective effects, even on the brain itself. Moreover, anxiolytic effects of pleasurable experiences may occur by promotion of an inhibitory tone in specific areas of the brain. Thus, love and pleasure clearly are capable of stimulating health, well-being and (re)productivity: This wonderful biological instrument makes procreation and maintenance of organisms and their species a deeply rewarding and pleasurable experience, thus ensuring survival, health, and perpetuation.

  4. Surface Protonics Promotes Catalysis

    NASA Astrophysics Data System (ADS)

    Manabe, R.; Okada, S.; Inagaki, R.; Oshima, K.; Ogo, S.; Sekine, Y.

    2016-12-01

    Catalytic steam reforming of methane for hydrogen production proceeds even at 473 K over 1 wt% Pd/CeO2 catalyst in an electric field, thanks to the surface protonics. Kinetic analyses demonstrated the synergetic effect between catalytic reaction and electric field, revealing strengthened water pressure dependence of the reaction rate when applying an electric field, with one-third the apparent activation energy at the lower reaction temperature range. Operando–IR measurements revealed that proton conduction via adsorbed water on the catalyst surface occurred during electric field application. Methane was activated by proton collision at the Pd–CeO2 interface, based on the inverse kinetic isotope effect. Proton conduction on the catalyst surface plays an important role in methane activation at low temperature. This report is the first describing promotion of the catalytic reaction by surface protonics.

  5. Surface Protonics Promotes Catalysis

    PubMed Central

    Manabe, R.; Okada, S.; Inagaki, R.; Oshima, K.; Ogo, S.; Sekine, Y.

    2016-01-01

    Catalytic steam reforming of methane for hydrogen production proceeds even at 473 K over 1 wt% Pd/CeO2 catalyst in an electric field, thanks to the surface protonics. Kinetic analyses demonstrated the synergetic effect between catalytic reaction and electric field, revealing strengthened water pressure dependence of the reaction rate when applying an electric field, with one-third the apparent activation energy at the lower reaction temperature range. Operando–IR measurements revealed that proton conduction via adsorbed water on the catalyst surface occurred during electric field application. Methane was activated by proton collision at the Pd–CeO2 interface, based on the inverse kinetic isotope effect. Proton conduction on the catalyst surface plays an important role in methane activation at low temperature. This report is the first describing promotion of the catalytic reaction by surface protonics. PMID:27905505

  6. Quality Assessment of Panax notoginseng from Different Regions through the Analysis of Marker Chemicals, Biological Potency and Ecological Factors

    PubMed Central

    Zhang, Ding-kun; Wang, Yan-hui; Li, Gang; Yan, Gui-lin; Cao, Li-juan; Xiao, Xiao-he; Huang, Lu-qi; Wang, Jia-bo

    2016-01-01

    Panax notoginseng (Burk.) F.H. Chen, called Sanqi in China, is a perennial herb that has been used as a medicinal herb in traditional Chinese medicine for more than 400 years. Because notoginseng is included in many proprietary Chinese medicines, the quality of notoginseng directly affects its efficacy and safety. However, considering the complex and special growth environment requirements of notoginseng, it is insufficient to evaluate its quality based solely on the analysis of marker chemicals. Thus, in this study, we tried to evaluate the quality of notoginseng with integrated indicators: (1) the concentration of five marker chemicals, notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd; (2) the anticoagulant activity (ACA); and (3) twenty-one ecological factors (e.g., longitude, latitude, elevation and soil data). Using these 27 parameters, notoginseng from different regions could be distinguished effectively, indicating a remarkable divergence of quality. A correlation analysis showed that variations of the ecological factors were closely associated with the saponins content and biopotency. For instance, the total nitrogen (TN), alkali hydrolysis nitrogen (AHN) and rapidly available potassium (RAPT) were significantly correlated with ACA, and RAPT was significantly correlated with the content of ginsenoside Rd and notoginsenoside R1. The results demonstrated that the high-quality notoginseng was produced from the emerging regions such as Kunming, Qujing and Honghe, which had higher ACA and saponin content than the notoginseng produced in traditional regions such as Wenshan and Baise. PMID:27723805

  7. Influence of aging process on the bioactive components and antioxidant activity of ginseng (Panax ginseng L.).

    PubMed

    Bae, Hyun Jung; Chung, Soo Im; Lee, Sang Chul; Kang, Mi Young

    2014-10-01

    The effects of aging process on the ginsenosides and antioxidant activity of ginseng was investigated. Fresh ginseng roots were aged in oven at 70 or 80 °C for 7, 14, 21, or 28 d. Their ginsenosides, phenolics, and antioxidant activity were analyzed. Ginseng aged at 80 °C for 14 d exhibited the highest amounts of total saponins and phenolics. It also showed markedly higher free radical scavenging activity, reducing power, and ferrous ion chelating ability than the other aged ginsengs. The ginsenosides Rb1 , Rb3 , Rg3 , Re, Rg1 , and Rg2 were generated during aging. The Rg2 was the most abundant ginsenoside in aged ginseng, with samples treated at 80 °C for 14 d having the highest amount. These findings provide the first evidence that aging, particularly at 80 °C for 14 d, could increase the bioactive compounds, indicating that this heating process may be useful in enhancing the biological activity of ginseng. PRACTICALAPPLICATION: Ginseng has long been recognized for its various health beneficial effects. The present study showed that aging of ginseng roots at 80 °C for 14 d substantially increased the amount of bioactive compounds ginsenosides and phenolics and enhanced the antioxidant activity. The food industry could use the aging process to improve the functional quality of ginseng.

  8. Sales promotions and food consumption.

    PubMed

    Hawkes, Corinna

    2009-06-01

    Sales promotions are widely used to market food to adults, children, and youth. Yet, in contrast to advertising, practically no attention has been paid to their impacts on dietary behaviors, or to how they may be used more effectively to promote healthy eating. This review explores the available literature on the subject. The objective is to identify if and what literature exists, examine the nature of this literature, and analyze what can be learned from it about the effects of sales promotions on food consumption. The review finds that while sales promotions lead to significant sales increases over the short-term, this does not necessarily lead to changes in food-consumption patterns. Nevertheless, there is evidence from econometric modeling studies indicating that sales promotions can influence consumption patterns by influencing the purchasing choices of consumers and encouraging them to eat more. These effects depend on the characteristics of the food product, sales promotion, and consumer. The complexity of the effects means that sales promotions aiming to encourage consumption of nutritious foods need to be carefully designed. These conclusions are based on studies that use mainly sales data as a proxy for dietary intake. The nutrition (and economics) research communities should add to this existing body of research to provide evidence on the impact of sales promotions on dietary intake and related behaviors. This would help support the development of a sales promotion environment conducive to healthy eating.

  9. Environmental Health Promotion: Bridging Traditional Environmental Health and Health Promotion

    ERIC Educational Resources Information Center

    Howze, Elizabeth H.; Baldwin, Grant T.; Kegler, Michelle Crozier

    2004-01-01

    This article highlights the juncture between environmental health and health promotion and underscores the need for health promotion involvement in environmental health practice. It begins with a synopsis of current issues in environmental public health and deficiencies in environmental public health practice that could be partly ameliorated by an…

  10. 7 CFR 1219.22 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...

  11. 7 CFR 1219.22 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...

  12. 7 CFR 1219.22 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...

  13. 7 CFR 1219.22 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.22 Promotion. Promotion means any action to advance the image, desirability, or marketability of Hass...

  14. 7 CFR 1217.22 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOFTWOOD LUMBER RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Softwood Lumber Research, Promotion, Consumer Education, and Industry Information Order Definitions § 1217.22 Promotion. Promotion means any action...

  15. 7 CFR 1217.22 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOFTWOOD LUMBER RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Softwood Lumber Research, Promotion, Consumer Education, and Industry Information Order Definitions § 1217.22 Promotion. Promotion means any action...

  16. 7 CFR 1217.22 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOFTWOOD LUMBER RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Softwood Lumber Research, Promotion, Consumer Education, and Industry Information Order Definitions § 1217.22 Promotion. Promotion means any action...

  17. The pharmacokinetic screening of multiple components of the Nao Mai Tong formula in rat plasma by liquid chromatography tandem mass spectrometry combined with pattern recognition method and its application to comparative pharmacokinetics.

    PubMed

    Wu, Chunwei; Zhao, Lu; Rong, Yueying; Zhu, Guoxue; Liang, Shengwang; Wang, Shumei

    2016-11-30

    The Nao Mai Tong formula (NMT) is composed of Rhubarb, Ginseng, Ligusticum wallichii and Pueraria in a ratio of 3:3:2:2 (w/w) and is a well-known traditional Chinese prescription that has been clinically employed for treating ischemia cerebrovascular disease. The goal of this study was to investigate the pharmacokinetics of multiple components (chryohol-8-O-β-D-glucoyroide, physcion-8-O-β-D-glucopyranoside, aloe-emodin, rhein, emodin, chrysophanol, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rc, senkyunolide I, ligustilide puerarin, daidzein, 3'-methoxy puerarin) after the oral administration of the NMT formula in rats. A rapid and sensitive UHPLC-Quadrupole-Orbitrap-MS with a sequential positive and negative ionization mode was developed to determine the 15 absorbed ingredients. After extraction from blood, the analytes and internal standards were subjected to ultra-high performance liquid chromatography with Agela Venusil MPC18 (2.1mm×100mm, 3μm, Agela, USA). The mobile phase consisted of methanol and ammonium acetate (3mmolL(-1)) under gradient elution conditions. This validated method was successfully applied to a comparative pharmacokinetic study of fifteen components in rat plasma after oral administration of the NMT formula or single herb extracts to normal and stroke-afflicted rats. A principal component analysis (PCA) was utilized to evaluate the differences in the pharmacokinetic behavior (time-course) of the absorbed components of NMT, and the absorbed components were assigned to 3 separate clusters. A comparison of the body dynamics of each group indicated that cluster B (ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rc) might be the most important constituents controlling the pharmacological effects of NMT. The comparative pharmacokinetic study showed that the different groups had different pharmacokinetic characteristics. The pharmacokinetics-based UHPLC Quadrupole-Orbitrap-MS using a full-scan mode combined

  18. Health-promoting schools: an opportunity for oral health promotion.

    PubMed Central

    Kwan, Stella Y. L.; Petersen, Poul Erik; Pine, Cynthia M.; Borutta, Annerose

    2005-01-01

    Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated framework and appropriate methodologies for the evaluation of school oral health projects is emphasized. PMID:16211159

  19. Promoting Leadership in Australian Universities

    ERIC Educational Resources Information Center

    Bradley, Andrew P.; Grice, Tim; Paulsen, Neil

    2017-01-01

    In this paper we review current practices for developing and promoting academic leadership in universities. We consider the forms of leadership that are appropriate for academic organisations, while exploring the types of leadership favoured by recruitment and promotion committees. Using the Australian higher education context as a case study, we…

  20. ACTFL's Accent! on Promoting FL's.

    ERIC Educational Resources Information Center

    Accent on ACTFL, 1975

    1975-01-01

    This insert in "Accent on ACTFL" is devoted to ways of promoting the study of foreign languages. The first section is a comic book, "The Continuing Story of Captain Fore Lang," created as an assignment by education students. The comic points out several benefits of language study. The second section is a language-specific promotion focusing on…

  1. Promoting Reading in Developing Countries.

    ERIC Educational Resources Information Center

    Greaney, Vincent, Ed.

    With the intention of illuminating the many obstacles involved with literacy promotion in the developing nations of Africa, Asia, and South America, the authors of the 10 articles in this collection share their knowledge and experience of literacy promotion in the developing world--including the unique challenges faced by those who publish, print,…

  2. Promoting Creativity in Young Children.

    ERIC Educational Resources Information Center

    Honig, Alice Sterling

    This paper discusses creativity in young children and what teachers can do to support and promote it. Topics addressed in the paper include: (1) teacher interest in promoting creativity; (2) defining creativity; (3) creativity in the socioemotional domain; (4) the relationship between creativity and empathy for others; (4) bibliotherapy; (5)…

  3. Information technology in health promotion.

    PubMed

    Lintonen, T P; Konu, A I; Seedhouse, D

    2008-06-01

    eHealth, the use of information technology to improve or enable health and health care, has recently been high on the health care development agenda. Given the vivid interest in eHealth, little reference has been made to the use of these technologies in the promotion of health. The aim of this present study was to conduct a review on recent uses of information technology in health promotion through looking at research articles published in peer-reviewed journals. Fifteen relevant journals with issues published between 2003 and June 2005 yielded altogether 1352 articles, 56 of which contained content related to the use of information technology in the context of health promotion. As reflected by this rather small proportion, research on the role of information technology is only starting to emerge. Four broad thematic application areas within health promotion were identified: use of information technology as an intervention medium, use of information technology as a research focus, use of information technology as a research instrument and use of information technology for professional development. In line with this rather instrumental focus, the concepts 'ePromotion of Health' or 'Health ePromotion' would come close to describing the role of information technology in health promotion.

  4. Health promotion: an ethical analysis.

    PubMed

    Carter, Stacy M

    2014-04-01

    Thinking and practising ethically requires reasoning systematically about the right thing to do. Health promotion ethics - a form of applied ethics - includes analysis of health promotion practice and how this can be ethically justified. Existing frameworks can assist in such evaluation. These acknowledge the moral value of delivering benefits. But benefits need to be weighed against burdens, harms or wrongs, and these should be minimised: they include invading privacy, breaking confidentiality, restraining liberty, undermining self-determination or people's own values, or perpetuating injustice. Thinking about the ethics of health promotion also means recognising health promotion as a normative ideal: a vision of the good society. This ideal society values health, sees citizens as active and includes them in decisions that affect them, and makes the state responsible for providing all of its citizens, no matter how advantaged or disadvantaged, with the conditions and resources they need to be healthy. Ethicists writing about health promotion have focused on this relationship between the citizen and the state. Comparing existing frameworks, theories and the expressed values of practitioners themselves, we can see common patterns. All oppose pursuing an instrumental, individualistic, health-at-all-costs vision of health promotion. And all defend the moral significance of just processes: those that engage with citizens in a transparent, inclusive and open way. In recent years, some Australian governments have sought to delegitimise health promotion, defining it as extraneous to the role of the state. Good evidence is not enough to counter this trend, because it is founded in competing visions of a good society. For this reason, the most pressing agenda for health promotion ethics is to engage with communities, in a procedurally just way, about the role and responsibilities of the citizen and the state in promoting and maintaining good health.

  5. Photovoltaic module with adhesion promoter

    SciTech Connect

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  6. Zoning should promote public health.

    PubMed

    Hirschhorn, Joel S

    2004-01-01

    Legally, governments use their police powers to protect public health, safety, and welfare through zoning. This paper presents a case for revisiting zoning on the basis of increasing evidence that certain types of community design promote public health, as opposed to the dominant pattern of sprawl development, which does not. Zoning, and the land use planning linked to it, that prohibits or disfavors health-promoting community designs contradicts the inherent public policy goal on which it is based. If there is a paradigm shift underway, from traditional sprawl to health-promoting community designs, then health professionals and others should understand why zoning must be reassessed.

  7. Nutritional Recommendation Should Promote Sustainability.

    ERIC Educational Resources Information Center

    Reber, Robert J.

    1991-01-01

    Any process or event that disrupts the flow of nutrients and energy becomes a nutrition problem. Nutritionists should promote practices that protect the integrity, stability, and beauty of the land community (soil, water, air, all biological species). (Author)

  8. The Business of Radio Promotion.

    ERIC Educational Resources Information Center

    Hall, Jonathan

    This speech suggests that public radio stations should examine and use the techniques employed by commercial stations to increase their listening audience--creative promotion based on community involvement and participation. Some examples are included. (SC)

  9. [Five paradoxes in health promotion].

    PubMed

    López-Dicastillo, Olga; Canga-Armayor, Navidad; Mujika, Agurtzane; Pardavila-Belio, Miren Idoia; Belintxon, Maider; Serrano-Monzó, Inmaculada; Pumar-Méndez, María J

    2017-02-17

    The World Health Organization states that health promotion is a key strategy to improve health, and it is conceived as a global process of enabling people to increase control over, and to improve, their health. Health promotion does not focus solely on empowering individuals dealing with their knowledge, attitudes and skills, but it also takes political, social, economic and environmental aspects influencing health and wellbeing into account. The complexity of applying these concepts is reflected in the five paradoxes in health promotion; these arise in between the rhetoric in health promotion and implementation. The detected paradoxes which are described herein involve the patient versus the person, the individual versus the group, disease professionals versus health professionals, disease indicators versus health indicators, and health as an expense versus health as an investment. Making these contradictions explicit can help determine why it is so complex to put the concepts related to health promotion into practice. It can also help to put forward aspects that need further work if health promotion is to put into practice.

  10. 7 CFR 1260.122 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1260.122 Section 1260.122 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions § 1260.122 Promotion. Promotion means any action, including...

  11. 7 CFR 1160.111 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1160.111 Section 1160.111 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order Definitions § 1160.111 Promotion. Promotion means the following activities: (a) Consumer Education,...

  12. 7 CFR 1250.310 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1250.310 Section 1250.310 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.310 Promotion. Promotion means any action, including...

  13. 7 CFR 1206.17 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1206.17 Section 1206.17 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion...

  14. 7 CFR 1150.114 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1150.114 Section 1150.114 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.114 Promotion. Promotion means actions such as paid advertising,...

  15. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1210.312 Section 1210.312 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means...

  16. Creating and Promoting a Natural History Collection.

    ERIC Educational Resources Information Center

    Belben, Cathy

    2003-01-01

    Discusses the value of developing and promoting a natural history library by school library media specialists. Topics include benefits to students; promoting outdoor education; recommended reading for high school students; using technology; and other aids to promote outdoor education. (LRW)

  17. DNA signals at isoform promoters

    PubMed Central

    Dai, Zhiming; Xiong, Yuanyan; Dai, Xianhua

    2016-01-01

    Transcriptional heterogeneity is extensive in the genome, and most genes express variable transcript isoforms. However, whether variable transcript isoforms of one gene are regulated by common promoter elements remain to be elucidated. Here, we investigated whether isoform promoters of one gene have separated DNA signals for transcription and translation initiation. We found that TATA box and nucleosome-disfavored DNA sequences are prevalent in distinct transcript isoform promoters of one gene. These DNA signals are conserved among species. Transcript isoform has a RNA-determined unstructured region around its start site. We found that these DNA/RNA features facilitate isoform transcription and translation. These results suggest a DNA-encoded mechanism by which transcript isoform is generated. PMID:27353836

  18. Introduction to Global Health Promotion.

    PubMed

    Torres, Jennifer

    2017-03-01

    Global health education is becoming increasingly prominent in universities throughout the country especially in programs focused on health and behavioral sciences, law, economics, and political science. Introduction to Global Health Promotion is a book that can be used by both instructors and students in the field of global health. The book provides theories and models, human rights, and technology relevant to the field. In addition the book is designed to share best evidence for promoting health and reducing morbidity and mortality in a variety of areas. The book can be used by health educators, public health practitioners, professors, and students as a resource for research and practice in the field of health promotion and disease prevention.

  19. Promoter Hypermethylation in Prostate Cancer

    PubMed Central

    Park, Jong Y.

    2011-01-01

    Background The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. Methods This review discusses current information on methylated genes associated with prostate cancer development and progression. Results Over 30 genes have been investigated for promoter methylation in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is reviewed. Conclusions These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use. PMID:20861812

  20. AAHD's Health Promotion and Wellness, Part 2: Health Promotion Programs

    ERIC Educational Resources Information Center

    Exceptional Parent, 2011

    2011-01-01

    This article is part 2 of a 4-part series on "Health Promotion and Wellness" from the American Association on Health and Disability (AAHD). According to the U.S. Census Bureau, more than 54 million people--one in five Americans--have a disability, and these Americans are more likely to report: (1) Being in poorer overall health; (2) Having less…

  1. Promoting recovery from ischemic stroke.

    PubMed

    Schmidt, Antje; Minnerup, Jens

    2016-01-01

    Over recent decades, experimental and clinical stroke studies have identified a number of neurorestorative treatments that stimulate neural plasticity and promote functional recovery. In contrast to the acute stroke treatments thrombolysis and endovascular thrombectomy, neurorestorative treatments are still effective when initiated days after stroke onset, which makes them applicable to virtually all stroke patients. In this article, selected physical, pharmacological and cell-based neurorestorative therapies are discussed, with special emphasis on interventions that have already been transferred from the laboratory to the clinical setting. We explain molecular and structural processes that promote neural plasticity, discuss potential limitations of neurorestorative treatments, and offer a speculative viewpoint on how neurorestorative treatments will evolve.

  2. Synthetic Core Promoters for Pichia pastoris

    PubMed Central

    2013-01-01

    Synthetic promoters are commonly used tools for circuit design or high level protein production. Promoter engineering efforts in yeasts, such as Saccharomyces cerevisiae and Pichia pastoris have mostly been focused on altering upstream regulatory sequences such as transcription factor binding sites. In higher eukaryotes synthetic core promoters, directly needed for transcription initiation by RNA Polymerase II, have been successfully designed. Here we report the first synthetic yeast core promoter for P. pastoris, based on natural yeast core promoters. Furthermore we used this synthetic core promoter sequence to engineer the core promoter of the natural AOX1 promoter, thereby creating a set of core promoters providing a range of different expression levels. As opposed to engineering strategies of the significantly longer entire promoter, such short core promoters can directly be added on a PCR primer facilitating library generation and are sufficient to obtain variable expression yields. PMID:24187969

  3. Health Promotion at the Ballpark.

    PubMed

    Hodges, Bonni C

    2017-03-01

    The arrival of a new summer collegiate baseball league franchise to a small central New York city was seen as an opportunity for health promotion. The initiative was set up to explore two overarching questions: (1) Are summer collegiate baseball events acceptable to local public health organizations as viable places for health promotion activities addressing local health issues? (2) Are summer collegiate baseball organizations amenable to health promotion activities built in to their fan and/or player experiences? Planning and implementation were guided by precede-proceed, social cognitive theory, social marketing, and diffusion of innovations constructs. Environmental changes were implemented to support healthy eating and nontobacco use by players and fans; four health awareness nights were implemented at home games corresponding to local public health priorities and included public service announcements, between inning quizzes, information dissemination at concession and team market locations, and special guests. Sales and fan feedback support mostly healthy concession offerings and a tobacco-free ballpark; postseason evaluations from team staff and public health partners support continuing the trials of this sports event as a venue for health promotion.

  4. Teachers Promoting Student Mathematical Reasoning

    ERIC Educational Resources Information Center

    Mueller, Mary; Yankelewitz, Dina; Maher, Carolyn

    2014-01-01

    During an informal, after-school, math program, a group of middle school students worked collaboratively on open-ended problems. The students co-constructed arguments, provided justifications for their solutions, and engaged in mathematical reasoning. This paper describes the specific teacher moves that promoted this phenomenon. The findings of…

  5. Women's Studies Online: Promoting Visibility.

    ERIC Educational Resources Information Center

    Hildenbrand, Suzanne

    1986-01-01

    Three problems in online searching in women's studies are type of indexing, database quality, and adequacy of coverage. Results of a recent study show there is significant end-user satisfaction and the searches done are described in order to promote greater and more effective use of online retrieval in women's studies. (Author/EM)

  6. Using Data to Promote Equity

    ERIC Educational Resources Information Center

    Shum, Brenda

    2016-01-01

    Data plays a starring role in promoting educational equity, and data-driven decision making begins with good state policies. With the recent passage of the Every Student Succeeds Act (ESSA) and a proposed federal rule to address racial disproportionality in special education, states will shoulder increased responsibility for eliminating…

  7. The Rhetoric of "Promoting Health."

    ERIC Educational Resources Information Center

    Hamilton, Margaret

    2002-01-01

    Uses Chaim Perelman's theories of argumentation to examine a recent Institute of Medicine report, "Promoting Health: Intervention Strategies from Social and Behavioral Research" (2000). Notes that it focuses on social, economic, behavioral, and political health as a means of assuring population health--and thereby expands the…

  8. Promoting Inclusive Education in Ghana

    ERIC Educational Resources Information Center

    Djietror, Beauty B. K.; Okai, Edward; Kwapong, Olivia A. T. Frimpong

    2011-01-01

    Inclusive education is critical for nation building. The government of Ghana has put in measures for promoting inclusion from basic through to tertiary level of education. Some of these measures include expansion of school facilities, implementation of the Free Compulsory Universal Basic Education (FCUBE); the change of policy on girls who drop…

  9. Promoting Discussions in ESL Students

    ERIC Educational Resources Information Center

    Navarro, Ann

    2010-01-01

    Background: Teachers who work with English as a Second Language (ESL) students, struggle with promoting discussion during guided reading. When ESL students are asked comprehension questions during group discussions and throughout the reading of a book, often teachers receive minimal feedback. Purpose: The purpose of this research is to identify…

  10. Promoting and Assessing Mathematical Generalising

    ERIC Educational Resources Information Center

    Hill, Tiffany; Lannin, John; van Garderen, Delinda

    2015-01-01

    Helping students generalise mathematical ideas is an essential component of teaching and learning of mathematics (Lannin, Ellis, Elliott & Zbiek, 2011). However, it can be challenging for primary teachers to assess and promote generalisation. Because generalisation is an essential part of mathematics instruction, the authors highlight the…

  11. Advertising and Sales Promotion Guide.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Vocational Education.

    This document contains teacher materials for a 4-unit, 1-year marketing education course in advertising and sales promotion offered in grades 11 and 12 in North Carolina. The preface contains a rationale for the development of the course, a course description, course objectives, a list of the instructional units of the course, and a list of the…

  12. Promoting SETI in the UK

    NASA Astrophysics Data System (ADS)

    Penny, Alan

    2013-10-01

    MEETING REPORT What does the UK presently do in the search for extraterrestrial intelligence and what are the plans for the future? Alan Penny reports on a meeting of UK academics active in SETI, held as sessions in the recent National Astronomy Meeting in Scotland - and the formation of the UK SETI Research Network to promote UK academic work.

  13. University Festival Promotes STEM Education

    ERIC Educational Resources Information Center

    Quagliata, Andrew B.

    2015-01-01

    STEM education is argued as an essential ingredient in preparing our children for careers of the future. This study describes a university festival that includes the promotion of STEM-related career interests in young people among its goals. A total of 203 participants between the age of 7 and 17 completed both pre-event and post-event surveys. In…

  14. Promoting Multiculturalism in Developmental Education.

    ERIC Educational Resources Information Center

    Higbee, Jeanne L.

    2001-01-01

    Asserts that the teaching profession needs to recognize the natural connections between multicultural and developmental education. Presents eight steps developmental educators can take to promote pluralism, including (1) establishing a clear link between cultural pluralism and institutional and programmatic mission and goals; (2) striving for…

  15. Promoting science together with art

    NASA Astrophysics Data System (ADS)

    Peacock, John

    2011-08-01

    The divide between science and art will forever be fuel for discussion, as two articles in the June issue of Physics World show. In the first, Leonardo Colletti (p16) calls for physicists to invite poets to conferences, while in the second (p19) Robert P Crease urges us to take insights from the study of culture when we try to promote science.

  16. Promoting Community Cohesion in England

    ERIC Educational Resources Information Center

    Morris, Andrew B.; McDaid, Maggie; Potter, Hugh

    2011-01-01

    Following serious disturbances in some northern cities in England in 2001, concerns about possible rising inter-communal tension have led to a statutory duty to promote community cohesion being placed on schools. Inspectors from the Office for Standards in Education (Ofsted) are required to make judgements in the leadership and management section…

  17. Ecological Foundations of Health Promotion.

    ERIC Educational Resources Information Center

    Green, Lawrence W.; And Others

    1996-01-01

    In this article, human ecology is defined; its historical and intellectual roots are traced through various disciplines to its applications in public health and health promotion today; its strengths and limitations are described; some potential contributions to systems theory are suggested; and some emerging ecological models of health promotion…

  18. Promoting Metacognition in Music Classes

    ERIC Educational Resources Information Center

    Benton, Carol W.

    2013-01-01

    Metacognition is a type of thinking in which learners think about their own cognitive processes. Because it transcends disciplines and grade levels, metacognition is useful in many educational settings and can be transferred from the music classroom to other subject areas. Music educators can promote metacognition by designing and implementing…

  19. Plant-growth-promoting rhizobacteria.

    PubMed

    Lugtenberg, Ben; Kamilova, Faina

    2009-01-01

    Several microbes promote plant growth, and many microbial products that stimulate plant growth have been marketed. In this review we restrict ourselves to bacteria that are derived from and exert this effect on the root. Such bacteria are generally designated as PGPR (plant-growth-promoting rhizobacteria). The beneficial effects of these rhizobacteria on plant growth can be direct or indirect. This review begins with describing the conditions under which bacteria live in the rhizosphere. To exert their beneficial effects, bacteria usually must colonize the root surface efficiently. Therefore, bacterial traits required for root colonization are subsequently described. Finally, several mechanisms by which microbes can act beneficially on plant growth are described. Examples of direct plant growth promotion that are discussed include (a) biofertilization, (b) stimulation of root growth, (c) rhizoremediation, and (d) plant stress control. Mechanisms of biological control by which rhizobacteria can promote plant growth indirectly, i.e., by reducing the level of disease, include antibiosis, induction of systemic resistance, and competition for nutrients and niches.

  20. When Promoting Democracy Is Counterproductive

    ERIC Educational Resources Information Center

    Esfandiari, Haleh; Litwak, Robert S.

    2007-01-01

    The United States has begun a $75-million program to promote democracy by supporting Iranian nongovernmental organizations (NGOs). That program, coupled with loose talk about regime change from members of Congress, commentators close to the administration, and individuals within the administration, has fed a sense of vulnerability and paranoia…

  1. [Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

    PubMed

    Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

    2015-08-01

    This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract.

  2. 7 CFR 1221.23 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...

  3. 7 CFR 1221.23 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...

  4. 7 CFR 1221.23 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...

  5. 7 CFR 1221.23 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23 Promotion. Promotion means any action taken to present a favorable image of sorghum to the public and the...

  6. 7 CFR 1218.17 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...

  7. 7 CFR 1218.17 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...

  8. 7 CFR 1218.17 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...

  9. 7 CFR 1218.17 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion. Promotion means any action taken to present a favorable image of blueberries to the general public and...

  10. 7 CFR 1216.23 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...

  11. 7 CFR 1216.23 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...

  12. 7 CFR 1216.23 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...

  13. 7 CFR 1216.23 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion... image of peanuts to the public to improve the competitive position of peanuts in the...

  14. 7 CFR 1216.23 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1216.23 Section 1216.23 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion....

  15. 78 FR 24239 - Temporary Mailing Promotion

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... Temporary Mailing Promotion AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is... with offering a Technology Credit Promotion. This notice informs the public of the Postal Service's... changes associated with offering a Technology Credit Promotion.\\1\\ The promotion is planned to begin...

  16. 29 CFR 541.503 - Promotion work.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Promotion work. 541.503 Section 541.503 Labor Regulations... Outside Sales Employees § 541.503 Promotion work. (a) Promotion work is one type of activity often.... Promotion activities directed toward consummation of the employee's own sales are exempt....

  17. 76 FR 34871 - Mobile Barcode Promotion

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... 111 Mobile Barcode Promotion AGENCY: Postal Service TM . ACTION: Final rule. SUMMARY: The Postal... ) 709.4 to add a temporary promotion for First-Class Mail cards, letters and flats, and Standard Mail... barcode promotion, and the new mailing standards to implement the promotion. To be eligible,...

  18. 7 CFR 1280.118 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1280.118 Section 1280.118 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Lamb Promotion, Research, and Information Order Definitions § 1280.118 Promotion....

  19. 5 CFR 532.407 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Promotion. 532.407 Section 532.407... Administration § 532.407 Promotion. (a) An employee who is promoted is entitled to be paid at the lowest.... (c) If the promotion is to a position in a different wage area, the agency shall determine...

  20. 7 CFR 1212.20 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1212.20 Section 1212.20 Agriculture..., PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion, Consumer Education, and Industry Information Order Definitions § 1212.20 Promotion. “Promotion” means...

  1. 7 CFR 1206.17 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...

  2. 7 CFR 1206.17 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...

  3. 7 CFR 1206.17 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...

  4. 7 CFR 1206.17 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.17 Promotion. Promotion means any action taken to present a favorable image of mangos to the general public and the food...

  5. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  6. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  7. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  8. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  9. 21 CFR 601.45 - Promotional materials.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  10. 21 CFR 601.45 - Promotional materials.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  11. 21 CFR 601.45 - Promotional materials.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  12. 21 CFR 601.94 - Promotional materials.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Promotional materials. 601.94 Section 601.94 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  13. 21 CFR 601.94 - Promotional materials.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Promotional materials. 601.94 Section 601.94 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  14. 21 CFR 601.45 - Promotional materials.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Promotional materials. 601.45 Section 601.45 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  15. 21 CFR 601.94 - Promotional materials.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Promotional materials. 601.94 Section 601.94 Food... Promotional materials. For biological products being considered for approval under this subpart, unless... preapproval review period copies of all promotional materials, including promotional labeling as well...

  16. Electrochemical promotion of catalytic reactions

    NASA Astrophysics Data System (ADS)

    Imbihl, R.

    2010-05-01

    The electrochemical promotion of heterogeneously catalyzed reactions (EPOC) became feasible through the use of porous metal electrodes interfaced to a solid electrolyte. With the O 2- conducting yttrium stabilized zirconia (YSZ), the Na + conducting β″-Al 2O 3 (β-alumina), and several other types of solid electrolytes the EPOC effect has been demonstrated for about 100 reaction systems in studies conducted mainly in the mbar range. Surface science investigations showed that the physical basis for the EPOC effect lies in the electrochemically induced spillover of oxygen and alkali metal, respectively, onto the surface of the metal electrodes. For the catalytic promotion effect general concepts and mechanistic schemes were proposed but these concepts and schemes are largely speculative. Applying surface analytical tools to EPOC systems the proposed mechanistic schemes can be verified or invalidated. This report summarizes the progress which has been achieved in the mechanistic understanding of the EPOC effect.

  17. [Empowerment and health promotion programming].

    PubMed

    Laverack, G

    2008-12-01

    Health promotion often presents a tension between "bottom up" and "top down" programming. "Bottom-up" is associated with community empowerment and begins on issues of concern to particular groups or individuals and regards an increase in overall control as an important element of the health outcome. "Top-down" is associated with disease prevention efforts and begins by seeking to involve beneficiaries on issues defined by health agencies. It regards improvements in health behaviours or bio-medical indicators as the important outcome and community empowerment is viewed simply as a means to the end of health behaviour change. The tension between these two approaches is not unresolvable, and this article presents a framework, the "parallel-track", intended to assist health promotion practitioners to systematically accommodate community empowerment goals within "top-down" health programming.

  18. Promoting the exotic pet practice.

    PubMed

    Harris, Don J

    2005-09-01

    The marketing and promotion of an exotic pet veterinary practice allows the use of strategies that are not necessarily available in other veterinary disciplines. The advantage that an exotics practice enjoys is that it is able to capitalize not only on the unique nature of the species being attended but also on the specialized features of the hospital itself that make it specifically appropriate in caring for exotic pets. Before marketing, however, comes the responsibility that the practice live up to the claims made in promotional materials. A practice cannot ethically be presented as an "exotics" practice if it is nothing more than a dog and cat facility that is willing to attend to exotic pets. It is the competence of the veterinary staff and the appropriateness of the facility that determines the suitability of the practice for exotics management.

  19. Drugs that promote dental caries.

    PubMed

    2015-02-01

    Dental caries result from erosion of tooth enamel or cementum by acidic substances produced by bacteria found in dental plaque. Caries can lead to pulp necrosis and tooth loss. Risk factors include certain dietary habits, poor oral hygiene, and dry mouth. Diabetes and Sjogren's syndrome can also promote dental caries. Psychotropic substances such as cocaine, methamphetamine, heroin and cannabis can promote dental caries. Many medicinal drugs facilitate the formation of dental caries, through various mechanisms; they include formulations with a high sugar content; drugs that cause dry mouth (especially antimuscarinics); drugs that lower the buccal pH (inhaled powders, etc.); and drugs that cause demineralisation (tetracyclines, etc.). In practice, patients (and parents) should be informed that some drugs can increase the risk of dental caries. They should be encouraged to adapt and reinforce dental hygiene, and advised to visit a dentist regularly.

  20. South Asia's health promotion kaleidoscope.

    PubMed

    Mukhopadhyay, Alok

    2007-01-01

    South Asia has 22 percent of the world's population but only 1.3 percent of the global income. Consequently 40 percent of the population is living in absolute poverty. However the health transition in some of its countries including India and Sri Lanka is a testimony to the fact that there are proven solutions to the problems of health and development within the region. The countries of the region have much in common, including a democratic political system, four major religions, a vibrant and living tradition of voluntarism and an extensive health infrastructure which is operating well below par. Despite the underlying unity, South Asia enjoys enormous cultural, linguistic and ethnic diversity. In this large, complex and vibrant region, health promotion is a challenging task, but it also holds the key to a dramatic change in the global health situation. Many of these solutions lie in wider areas of socio-political action. There are much needed shifts in the health promotion and development efforts, particularly in the area of poverty and social justice; gender inequity; population stabilisation; health and environment; control of communicable and non-communicable diseases; and urban health strategies. The principle of cooperation, partnership and intersectoral collaboration for health will be explored. Developing an appropriate, sustainable and people centred health and development strategy in the coming decades is an enormous challenge. There has been an attempt to focus on the emerging needs of the region, which call for health promotion, and involvement of civil society, private sector and the governments bestowed with the increased responsibility of ensuring health security for people. Strengthening the existing health systems, allocating adequate resources for health development and ensuring community participation are all prerequisites to the success of health promotion in the region.

  1. PARP promoter-mediated activation of a VSG expression site promoter in insect form Trypanosoma brucei.

    PubMed

    Urményi, T P; Van der Ploeg, L H

    1995-03-25

    In trypanosomes the rRNA, PARP and VSG gene promoters mediate alpha-amanitin-resistant transcription of protein coding genes, presumably by RNA polymerase (pol) I. We compared the activity of PARP and VSG promoters integrated at one of the alleles of the largest subunit of pol II genes in insect form trypanosomes. Even though both promoters are roughly equally active in transient transformation assays in insect form trypanosomes, only the PARP promoter functioned effectively when integrated at the pol II largest subunit or other loci. Promoter activity in transient transformation assays is therefore not necessarily predictive of transcriptional activity once integrated into the trypanosome genome. The integrated fully active PARP promoter could upregulate in cis an otherwise poorly active integrated VSG promoter. The PARP promoter nucleotide sequence elements responsible for VSG promoter activation coincided with most of the important PARP promoter elements mapped previously by linker scanning mutagenesis, indicating that it is not a single unique promoter element that was responsible for VSG promoter activation. The data suggest that PARP promoter-mediated activation of the VSG promoter does not result from complementation of the VSG promoter with a single insect form-specific transcription factor whose binding site is missing from the VSG promoter and present in the PARP promoter. We favor a model in which chromatin structure at the locus is altered by the PARP promoter, allowing VSG promoter activation in insect form trypanosomes. We discuss the significance of these observations for the control of VSG promoters in insect form trypanosomes.

  2. Physical characteristics in eucaryotic promoters.

    PubMed Central

    Bensimhon, M; Gabarro-Arpa, J; Ehrlich, R; Reiss, C

    1983-01-01

    For a series of wild type and mutated eucaryotic gene prelude sequences (mainly "promoters" of SV40 early gene (Benoist and Chambon, Nature 290, 304 (1981); Moreau et al., Nuc. Acids Res. 9, 6047 (1982)) and of Herpes Simplex Virus TK gene (McKnight and Kingsbury, Science 217, 316 (1982)), in vivo promoter activity and local stability (denaturability) have been correlated. In agreement with the conclusions drawn in these papers, the correlation points to three major eucaryotic promoter elements and loci: (i) enzyme enabling by an enhancer sequence; SV40 and Moloney Sarcoma Virus enhancers have a striking stability homology; (ii) enzyme activation, occurring 50-70 b.p. upstream the cap site in a high stability domain; the enzyme apparently deactivates exponentially upon moving away to trap site; (iii) enzyme positioning at trap site, 30 +/- 5 b.p. upstream the cap site. The trap site contains the TATA box, or, when absent, other low stability domains downstream the activator. The number and occupancy of cap sites may depend on the stability and size of the trap site-cap site couple and its distance from the activator. PMID:6306592

  3. Incentives to promote family planning

    PubMed Central

    Heil, Sarah H.; Gaalema, Diann E.; Herrmann, Evan S.

    2012-01-01

    Objective Over the past 60 years, population control has become an increasingly urgent issue worldwide as a growing population strains already limited resources. The use of financial incentives to promote family planning is an innovative approach that has potential to make a contribution to efforts to better manage population growth. This report reviews eight studies that examined the effect of incentives on family planning. Method Published studies that tested the impact of incentives to promote some aspect of family planning and included an appropriate control or comparison condition were reviewed. Results Incentives have been used to promote attendance at contraceptive education sessions, adoption and continuation of contraceptive methods, sterilization, and to limit family size. All but one of the eight studies reviewed reported positive outcomes, but weaknesses in study design and execution limit the strength of the conclusions that can be drawn. Conclusion Review of this literature suggests that family planning behaviors, like other behaviors, are sensitive to incentives. Given the tremendous need for efficacious interventions in global efforts to manage population growth, further research on this topic using more rigorous experimental methods is warranted. PMID:22743293

  4. Programming gene expression with combinatorial promoters

    PubMed Central

    Cox, Robert Sidney; Surette, Michael G; Elowitz, Michael B

    2007-01-01

    Promoters control the expression of genes in response to one or more transcription factors (TFs). The architecture of a promoter is the arrangement and type of binding sites within it. To understand natural genetic circuits and to design promoters for synthetic biology, it is essential to understand the relationship between promoter function and architecture. We constructed a combinatorial library of random promoter architectures. We characterized 288 promoters in Escherichia coli, each containing up to three inputs from four different TFs. The library design allowed for multiple −10 and −35 boxes, and we observed varied promoter strength over five decades. To further analyze the functional repertoire, we defined a representation of promoter function in terms of regulatory range, logic type, and symmetry. Using these results, we identified heuristic rules for programming gene expression with combinatorial promoters. PMID:18004278

  5. Promotion to professor: a career development resource.

    PubMed

    Sanfey, Hilary

    2010-10-01

    By the time a faculty member is being considered for promotion to full professor, he/she will be about 10 years out of residency training and will almost certainly have prior experience with the academic promotion process. The preparation for promotion to full professor should begin soon after the promotion to associate professor. This is a time to reassess opportunities, resources, skills, and career goals. The timing of the promotion to full professor is usually less rigid than the timeframe for promotion at lower ranks, but schools vary in this regard.

  6. Natural selection promotes antigenic evolvability.

    PubMed

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  7. Immune cell promotion of metastasis

    PubMed Central

    Kitamura, Takanori; Qian, Bin-Zhi; Pollard, Jeffrey W.

    2015-01-01

    Metastatic disease is the major cause of death from cancer, and immunotherapy and chemotherapy have had limited success in reversing its progression. Data from mouse models suggest that the recruitment of immunosuppressive cells to tumours protects metastatic cancer cells from surveillance by killer cells, which nullifies the effects of immunotherapy and thus establishes metastasis. Furthermore, in most cases, tumour-infiltrating immune cells differentiate into cells that promote each step of the metastatic cascade and thus are novel targets for therapy. In this Review, we describe how tumour-infiltrating immune cells contribute to the metastatic cascade and we discuss potential therapeutic strategies to target these cells. PMID:25614318

  8. 7 CFR 1209.17 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....

  9. 7 CFR 1209.17 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....

  10. 7 CFR 1209.17 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....

  11. 7 CFR 1209.17 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209... desirability of mushrooms, including paid advertising....

  12. 7 CFR 1212.20 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...

  13. 7 CFR 1208.20 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PROCESSED RASPBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Processed Raspberry Promotion, Research, and Information Order Definitions... raspberries to the general public and the food industry for the purpose of improving the competitive...

  14. 7 CFR 1208.20 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PROCESSED RASPBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Processed Raspberry Promotion, Research, and Information Order Definitions... raspberries to the general public and the food industry for the purpose of improving the competitive...

  15. 7 CFR 1212.20 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...

  16. 7 CFR 1212.20 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...

  17. 7 CFR 1212.20 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HONEY PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion... action, including paid advertising and public relations that presents a favorable image for honey...

  18. Promotion of social change: a conceptual framework.

    PubMed

    Tseng, Vivian; Chesir-Teran, Daniel; Becker-Klein, Rachel; Chan, May L; Duran, Valkiria; Roberts, Ann; Bardoliwalla, Nenshad

    2002-06-01

    This paper argues for the need to advance promotion efforts and proposes a conceptual framework for promotion of social change. A brief review is presented of traditional frameworks for the prevention of mental and social disorders and the promotion of wellness and social competencies, with attention to the ways in which promotion of social change extends and departs from these frameworks. In a framework for promoting social change, we advocate for promoting dynamic processes within systems, rather than outcomes within individuals. Systems are viewed as flexible and capable of facilitating multiple adaptive pathways for individuals and groups. Promoting social change also involves careful attention to critical analysis, values, language, and contextual processes. Examples are discussed throughout to illustrate how these principles have been used in the past and can be implemented in future efforts to promote social change.

  19. 48 CFR 13.104 - Promoting competition.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and...

  20. 48 CFR 13.104 - Promoting competition.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and...

  1. 7 CFR 1218.17 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1218.17 Section 1218.17 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17...

  2. 7 CFR 1215.16 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1215.16 Section 1215.16 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions §...

  3. 7 CFR 1221.23 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1221.23 Section 1221.23 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.23...

  4. 7 CFR 1209.17 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1209.17 Section 1209.17 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions §...

  5. 7 CFR 1230.22 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1230.22 Section 1230.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions §...

  6. 12 CFR 4.64 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Promotion. 4.64 Section 4.64 Banks and Banking...; Contracting for Goods and Services § 4.64 Promotion. (a) Scope. The OCC, under the direction of the Deputy Comptroller for Resource Management, engages in promotion and outreach activities designed to identify...

  7. 7 CFR 1219.22 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1219.22 Section 1219.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions §...

  8. 7 CFR 1220.121 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...

  9. 7 CFR 1220.121 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...

  10. 7 CFR 1220.121 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...

  11. 7 CFR 1220.121 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...

  12. 7 CFR 1220.121 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign...

  13. Health Promotion: An Overview. Unit Technical Paper.

    ERIC Educational Resources Information Center

    Anderson, Robert

    Because health promotion is a relatively new concept in Europe, a study was undertaken to gather information on informal and organized health promoting behavior and programs in Europe. The study attempts, through a review of literature, interviews, and surveys, to clarify the meaning of health promotion in both theory and practice and to identify…

  14. 12 CFR 4.64 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Comptroller for Resource Management, engages in promotion and outreach activities designed to identify MWOBs... promotion events sponsored by other government agencies and attended by minorities, women and individuals... promotion events comprised of or attended by MWOBs and IDOBs to explain OCC contracting opportunities and...

  15. 48 CFR 13.104 - Promoting competition.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and...

  16. 48 CFR 13.104 - Promoting competition.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and...

  17. 48 CFR 13.104 - Promoting competition.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Promoting competition. 13... METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Procedures 13.104 Promoting competition. The contracting officer must promote competition to the maximum extent practicable to obtain supplies and...

  18. 17 CFR 33.8 - Promotional material.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Promotional material. 33.8... DOMESTIC EXCHANGE-TRADED COMMODITY OPTION TRANSACTIONS § 33.8 Promotional material. Each futures commission... promotional material it provides, directly or indirectly, to option customers as well as the true source...

  19. 17 CFR 33.8 - Promotional material.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Promotional material. 33.8... DOMESTIC EXCHANGE-TRADED COMMODITY OPTION TRANSACTIONS § 33.8 Promotional material. Each futures commission... promotional material it provides, directly or indirectly, to option customers as well as the true source...

  20. 21 CFR 314.550 - Promotional materials.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Promotional materials. 314.550 Section 314.550... Serious or Life-Threatening Illnesses § 314.550 Promotional materials. For drug products being considered... the agency for consideration during the preapproval review period copies of all promotional...

  1. Disease Prevention and Health Promotion

    PubMed Central

    Ali, Ather; Katz, David L.

    2015-01-01

    As a discipline, preventive medicine has traditionally been described to encompass primary, secondary, and tertiary prevention. The fields of preventive medicine and public health share the objectives of promoting general health, preventing disease, and applying epidemiologic techniques to these goals. This paper discusses a conceptual approach between the overlap and potential synergies of integrative medicine principles and practices with preventive medicine in the context of these levels of prevention, acknowledging the relative deficiency of research on the effectiveness of practice-based integrative care. One goal of integrative medicine is to make the widest array of appropriate options available to patients, ultimately blurring the boundaries between conventional and complementary medicine. Both disciplines should be subject to rigorous scientific inquiry so that interventions that are efficacious and effective are systematically distinguished from those that are not. Furthermore, principles of preventive medicine can be infused into prevalent practices in complementary and integrative medicine, promoting public health in the context of more-responsible practices. The case is made that an integrative preventive approach involves the responsible use of science with responsiveness to the needs of patients that persist when conclusive data are exhausted, providing a framework to make clinical decisions among integrative therapies. PMID:26477898

  2. Condom ads promote illicit sex.

    PubMed

    Kippley, J F

    1994-01-01

    Written in 1987, this opinion was republished in the wake of US President Bill Clinton's AIDS prevention media campaign promoting condom use which began January 1994, targeted at young adults aged 18-25. The author staunchly opposes condom use even though he admits that people do not consider abstinence from sex to be a serious option for the prevention of HIV/STD infection. He believes that there is no moral use of sex with a condom and that condoms have always been a sign of immorality, be it prostitution, adultery, fornication, or marital contraception. Likewise, the author laments the success enjoyed by Planned Parenthood in achieving the social acceptance of marital contraception and sex outside of marriage. The complete social acceptance of homosexual activity, however, remains to be achieved. Magazines, newspapers, and television receive income in exchange for publishing or airing advertisements. Finding offensive advertisements which promote the use of condoms against HIV infection, the author recommends writing letters of complaint to the responsible media sources. If the television stations or publications in question continue to advertise condoms to the public, stop watching them or end one's subscriptions to the particular printed media. Such action taken collectively among many individuals will reduce product sales and income, and potentially sway corporate policy against condom ads.

  3. Synthetic promoter design for new microbial chassis

    PubMed Central

    Gilman, James; Love, John

    2016-01-01

    The judicious choice of promoter to drive gene expression remains one of the most important considerations for synthetic biology applications. Constitutive promoter sequences isolated from nature are often used in laboratory settings or small-scale commercial production streams, but unconventional microbial chassis for new synthetic biology applications require well-characterized, robust and orthogonal promoters. This review provides an overview of the opportunities and challenges for synthetic promoter discovery and design, including molecular methodologies, such as saturation mutagenesis of flanking regions and mutagenesis by error-prone PCR, as well as the less familiar use of computational and statistical analyses for de novo promoter design. PMID:27284035

  4. Endothelium-dependent vasodilation effects of Panax notoginseng and its main components are mediated by nitric oxide and cyclooxygenase pathways

    PubMed Central

    Wang, Yanyan; Ren, Yu; Xing, Leilei; Dai, Xiangdong; Liu, Sheng; Yu, Bin; Wang, Yi

    2016-01-01

    Panax notoginseng, a traditional Chinese herbal medicine, has been used for the treatment of cardiovascular diseases. The main bioactive components of this species are Panax notoginseng saponins (PNS). The present study aimed to investigate the effects of PNS and five of its main components (ginsenosides Rg1, Re, Rb1 and Rd, and notoginsenoside R1) on rat aorta rings pre-contracted with norepinephrine (NE) and to determine the underlying mechanism of action. Isolated aorta rings (with or without intact endothelium) from adult male Wistar rats were stimulated with NE to induce vasoconstriction, and subsequently treated with different concentrations of PNS and its five main components (Rg1, Re, Rb1, R1 and Rd) separately. This procedure was repeated after pre-incubation with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cyclooxygenase (COX) inhibitor indomethacin (INDO), in order to elucidate the mechanism of action of PNS and its components. The results demonstrated that PNS and the components Rg1, Re, Rb1 and R1, but not Rd, induced vessel relaxation in a concentration-dependent manner when the endothelium lining was intact. NO synthase inhibitor L-NAME and guanylate cyclase inhibitor ODQ attenuated the diastolic effects of PNS, Rg1, Re, Rb1 and R1 in aortic rings with intact endothelium. By contrast, INDO, a known COX inhibitor weakened the vasodilation effects of PNS, Re and Rb1 but demonstrated no effect on Rg1 and R1. In conclusion, PNS and two of its main components (Re and Rb1) exert vasodilating effects through the NO and COX pathways. PMID:28101178

  5. Towards a relational health promotion.

    PubMed

    Veenstra, Gerry; Burnett, Patrick John

    2016-03-01

    The Ottawa Charter for Health Promotion exhibits a substantialist approach to the agency-structure dichotomy. From a substantialist point of view, both individual agency and social structure come preformed and subsequently relate to and influence one another, starkly positioning the choices made by individuals against the structured sets of opportunities and constraints in reference to which choices are made. From a relational perspective, however, relations between elements, not the elements themselves, are the primary ontological focus. We advocate for a relational approach to the structure-agency dichotomy, one that locates both agency and structure in social relations and thereby dissolves the stark distinction between them, suggesting that relational theories can provide useful insights into how and why people 'choose' to engage in health-related behaviours. Pierre Bourdieu's theory of practice, predicated upon the notions of field, capital and habitus, is exemplary in this regard.

  6. Promoting Teen Mothers' Mental Health.

    PubMed

    Freed, Patricia; SmithBattle, Lee

    2016-01-01

    In this second article in a two-part series, we call for the integration of strengths-based and trauma-informed care into services for teen mothers. Nurses working with teen mothers in health clinics, schools and home visiting programs can play a pivotal role in promoting their mental health. Many teen mothers have high levels of psychological distress and histories of adverse experiences that cannot be ignored, and cannot solely be addressed by referral to mental health services. Nurses must be prepared to assess for trauma and be open to listening to teen mothers' experiences. Principles of strengths-based and trauma-informed care are complementary and can be integrated in clinical services so that teen mothers' distress is addressed and their strengths and aspirations are supported. Potential screening tools, interviewing skills and basic strategies to alleviate teen mothers' distress are discussed.

  7. Promoter usage and alternative splicing.

    PubMed

    Kornblihtt, Alberto R

    2005-06-01

    Recent findings justify a renewed interest in alternative splicing (AS): the process is more a rule than an exception as it affects the expression of 60% of human genes; it explains how a vast mammalian proteomic complexity is achieved with a limited number of genes; and mutations in AS regulatory sequences are a widespread source of human disease. AS regulation not only depends on the interaction of splicing factors with their target sequences in the pre-mRNA but is coupled to transcription. A clearer picture is emerging of the mechanisms by which transcription affects AS through promoter identity and occupation. These mechanisms involve the recruitment of factors with dual functions in transcription and splicing (i.e. that contain both functional domains and hence link the two processes) and the control of RNA polymerase II elongation.

  8. Junking Science to Promote Tobacco

    PubMed Central

    Yach, Derek; Bialous, Stella Aguinaga

    2001-01-01

    Despite the tobacco industry's claims that it has changed its practices, the toll of tobacco-related disease and death continues to grow worldwide, and the industry continues to use a vast array of strategies to promote its products and increase profits. This commentary discusses the ways the tobacco industry has created controversy about risk assessment and about the scientific evidence of the health hazards of secondhand smoke. The authors recommend that policymakers be more vigilant and that they demand transparency about affiliations and linkages between allegedly independent scientists and tobacco companies. They also urge policymakers to be prepared for new and continuing challenges posed by the tobacco industry, because, despite the industry's claims, there is little evidence of fundamental change in its objectives. PMID:11684592

  9. Vessel Noise Promotes Hull Fouling.

    PubMed

    Stanley, Jenni A; Wilkens, Serena; McDonald, Justin I; Jeffs, Andrew G

    2016-01-01

    Fouling of submerged vessel hulls due to the rapid settlement of algae and invertebrates is a longstanding and costly problem. It is widely thought that the presence of extensive vacant surfaces on vessel hulls is responsible for the rapid attachment and growth of biofouling. We investigated whether noise from vessels in port could also be involved in promoting the settlement and growth of common biofouling organisms on vessel hulls. Three important biofouling species exhibited significantly faster development and settlement and better survival when exposed to vessel noise compared with control species. The extent of these responses appeared to vary in relation to the intensity of the vessel noise and may help to explain differences in biofouling observed on vessel hulls.

  10. NEDDylation promotes stress granule assembly

    PubMed Central

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-01-01

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly. PMID:27381497

  11. Preconception care: promoting reproductive planning

    PubMed Central

    2014-01-01

    Introduction Preconception care recognizes that many adolescent girls and young women will be thrust into motherhood without the knowledge, skills or support they need. Sixty million adolescents give birth each year worldwide, even though pregnancy in adolescence has mortality rates at least twice as high as pregnancy in women aged 20-29 years. Reproductive planning and contraceptive use can prevent unintended pregnancies, unsafe abortions and sexually-transmitted infections in adolescent girls and women. Smaller families also mean better nutrition and development opportunities, yet 222 million couples continue to lack access to modern contraception. Method A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Results Comprehensive interventions can prevent first pregnancy in adolescence by 15% and repeat adolescent pregnancy by 37%. Such interventions should address underlying social and community factors, include sexual and reproductive health services, contraceptive provision; personal development programs and emphasizes completion of education. Appropriate birth spacing (18-24 months from birth to next pregnancy compared to short intervals <6 months) can significantly lower maternal mortality, preterm births, stillbirths, low birth weight and early neonatal deaths. Conclusion Improving adolescent health and preventing adolescent pregnancy; and promotion of birth spacing through increasing correct and consistent use of effective contraception are fundamental to preconception care. Promoting reproductive planning on a wider scale is closely interlinked with the

  12. Does sleep promote false memories?

    PubMed

    Darsaud, Annabelle; Dehon, Hedwige; Lahl, Olaf; Sterpenich, Virginie; Boly, Mélanie; Dang-Vu, Thanh; Desseilles, Martin; Gais, Stephen; Matarazzo, Luca; Peters, Frédéric; Schabus, Manuel; Schmidt, Christina; Tinguely, Gilberte; Vandewalle, Gilles; Luxen, André; Maquet, Pierre; Collette, Fabienne

    2011-01-01

    Memory is constructive in nature so that it may sometimes lead to the retrieval of distorted or illusory information. Sleep facilitates accurate declarative memory consolidation but might also promote such memory distortions. We examined the influence of sleep and lack of sleep on the cerebral correlates of accurate and false recollections using fMRI. After encoding lists of semantically related word associates, half of the participants were allowed to sleep, whereas the others were totally sleep deprived on the first postencoding night. During a subsequent retest fMRI session taking place 3 days later, participants made recognition memory judgments about the previously studied associates, critical theme words (which had not been previously presented during encoding), and new words unrelated to the studied items. Sleep, relative to sleep deprivation, enhanced accurate and false recollections. No significant difference was observed in brain responses to false or illusory recollection between sleep and sleep deprivation conditions. However, after sleep but not after sleep deprivation (exclusive masking), accurate and illusory recollections were both associated with responses in the hippocampus and retrosplenial cortex. The data suggest that sleep does not selectively enhance illusory memories but rather tends to promote systems-level consolidation in hippocampo-neocortical circuits of memories subsequently associated with both accurate and illusory recollections. We further observed that during encoding, hippocampal responses were selectively larger for items subsequently accurately retrieved than for material leading to illusory memories. The data indicate that the early organization of memory during encoding is a major factor influencing subsequent production of accurate or false memories.

  13. Pmp27 promotes peroxisomal proliferation

    PubMed Central

    1995-01-01

    Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth substrate is metabolized by peroxisomal enzymes. We have identified a protein, Pmp27, that promotes peroxisomal proliferation. This protein, previously termed Pmp24, was purified from peroxisomal membranes, and the corresponding gene, PMP27, was isolated and sequenced. Pmp27 shares sequence similarity with the Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane protein but it can be extracted by high pH, suggesting that it does not fully span the bilayer. Its expression is regulated by oleate. The function of Pmp27 was probed by observing the phenotype of strains in which the protein was eliminated by gene disruption or overproduced by expression from a multicopy plasmid. The strain containing the disruption (3B) was able to grow on all carbon sources tested, including oleate, although growth on oleate, glycerol, and acetate was slower than wild type. Strain 3B contained peroxisomes with all of the enzymes of beta-oxidation. However, in addition to the presence of a few modestly sized peroxisomes seen in a typical thin section of a cell growing on oleate-containing medium, cells of strain 3B also contained one or two very large peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed contained an increased number of normal-sized peroxisomes. We suggest that Pmp27 promotes peroxisomal proliferation by participating in peroxisomal elongation or fission. PMID:7721939

  14. Single promoters as regulatory network motifs

    NASA Astrophysics Data System (ADS)

    Zopf, Christopher; Maheshri, Narendra

    2012-02-01

    At eukaryotic promoters, chromatin can influence the relationship between a gene's expression and transcription factor (TF) activity. This additional complexity might allow single promoters to exhibit dynamical behavior commonly attributed to regulatory motifs involving multiple genes. We investigate the role of promoter chromatin architecture in the kinetics of gene activation using a previously described set of promoter variants based on the phosphate-regulated PHO5 promoter in S. cerevisiae. Accurate quantitative measurement of transcription activation kinetics is facilitated by a controllable and observable TF input to a promoter of interest leading to an observable expression output in single cells. We find the particular architecture of these promoters can result in a significant delay in activation, filtering of noisy TF signals, and a memory of previous activation -- dynamical behaviors reminiscent of a feed-forward loop but only requiring a single promoter. We suggest this is a consequence of chromatin transactions at the promoter, likely passing through a long-lived ``primed'' state between its inactive and competent states. Finally, we show our experimental setup can be generalized as a ``gene oscilloscope'' to probe the kinetics of heterologous promoter architectures.

  15. Insights into the control of geminiviral promoters.

    PubMed

    Borah, B K; Zarreen, F; Baruah, G; Dasgupta, I

    2016-08-01

    Geminiviruses constitute one of the largest groups of plant viruses, having characteristic twinned geminate particles encapsidating small circular single-stranded DNA molecules. Geminiviral promoters are generally located within the intergenic region, although promoters have also been detected within the genes. Similarly, the geminivirus-associated betasatellite also harbours a promoter element for driving the expression of its only ORF. These regulatory elements of geminiviral and satellite origins have been subject of great interest to develop heterologous gene expression modules. Geminiviral promoter and regulatory elements show a complex regulation that is mediated by several host as well as viral proteins. Here, the structural and functional features of geminiviral and satellite promoters are discussed along with their regulation by plant and viral proteins. Although generalization in many cases is difficult and demands further studies, a pattern is seen to emerge on the regulation of the promoters.

  16. Hypercholesterolemia promotes an osteoporotic phenotype.

    PubMed

    Pelton, Kristine; Krieder, Jaclynn; Joiner, Danese; Freeman, Michael R; Goldstein, Steven A; Solomon, Keith R

    2012-09-01

    A role for hypercholesterolemia in the development of osteoporosis has been suggested in published reports. However, few studies contain direct evidence of a role for maintenance of cholesterol homeostasis in bone health. Using isocaloric high-fat/high-cholesterol and low-fat/no-cholesterol diets in a 4-month feeding study combined with micro computed tomography analysis, we demonstrated in two different mouse strains that mice with hypercholesterolemia lose cortical and trabecular bone in the femurs and vertebrae (bone mineral density was decreased on average by ≈90 mg/mL in the cortical vertebrae in one strain) and cortical bone in the calvariae (bone mineral density was decreased on average by ≈60 mg/mL in one strain). Mechanical testing of the femurs demonstrated that loss of bone in the mice with hypercholesterolemia caused changes in the mechanical properties of the bone including loss of failure load (failure load was decreased by ≈10 N in one strain) and energy to failure. Serologic and histomorphologic analyses suggested that hypercholesterolemia promotes osteoclastogenesis. These studies support a role for hypercholesterolemia in the development of osteoporosis and provide a model with which to test intervention strategies to reduce the effects of hypercholesterolemia on bone health.

  17. Promotional Guide for Navy Family Service Centers

    DTIC Science & Technology

    1985-10-01

    managers of FSCs with a guide to using effective marketing and to increase awareness of FSC products and services. Successful promotional strategies of...they are delivered. kiIl 14. SUBJECT TERMS 15. NUMBER OF PAGES Family Service Center, marketing , promotional approach, delivery system, evaluation 28...customers, the authors have prepared a guide that explains how to use various marketing and promotional strategies to achieve that end. A Marketing Approach

  18. Profit Negotiations and Promotion of Contractor Efficiency.

    DTIC Science & Technology

    1981-03-01

    AOA097 06 ARMY POCUREMNT RESARCH OFFICE FORT LEE VA F/B 5/I PROFIT NEGOTIATIONS AND PROMOTION OF CONTRACTOR EFFICIENCY.(U) MAR 81 R W NICK, 6 A...08 0.5 FINAL PROFIT NEGOTIATIONS MD PROMOTION OF CONTRACTOR EFFICIENCY MARCH 1981 Approved for Public Release; Distribution Unlimited APRO iU. ANIr...DRXMC-PRO 2 April 1981 SUBJECT: Army Procurement Research Office Report APRO 80-08, Profit Negotiations and Promotion of Contractor Efficiency SEE

  19. Promoter-Based Theranostics for Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0430 TITLE: Promoter -Based Theranostics for Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Pomper CONTRACTING...ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES COVERED 15 Sep 2014 – 14 Sep 2015 4. TITLE AND SUBTITLE Promoter -Based...n/a 1. INTRODUCTION: This project leverages cancer-specific promoters for molecular- genetic endoradiotherapy and in the development of a universal

  20. An engineered strong promoter for streptomycetes.

    PubMed

    Wang, Weishan; Li, Xiao; Wang, Juan; Xiang, Sihai; Feng, Xiaozhou; Yang, Keqian

    2013-07-01

    Well-characterized promoters are essential tools for metabolic engineering and synthetic biology. In Streptomyces coelicolor, the native kasOp is a temporally expressed promoter strictly controlled by two regulators, ScbR and ScbR2. In this work, first, kasOp was engineered to remove a common binding site of ScbR and ScbR2 upstream of its core region, thus generating a stronger promoter, kasOp3. Second, another ScbR binding site internal to the kasOp3 core promoter region was abolished by random mutation and screening of the mutant library to obtain the strongest promoter, kasOp* (where the asterisk is used to distinguish the engineered promoter from the native promoter). The activities of kasOp* were compared with those of two known strong promoters, ermEp* and SF14p, in three Streptomyces species. kasOp* showed the highest activity at the transcription and protein levels in all three hosts. Furthermore, relative to ermEp* and SF14p, kasOp* was shown to confer the highest actinorhodin production level when used to drive the expression of actII-ORF4 in S. coelicolor. Therefore, kasOp* is a simple and well-defined strong promoter useful for gene overexpression in streptomycetes.

  1. An Engineered Strong Promoter for Streptomycetes

    PubMed Central

    Wang, Weishan; Li, Xiao; Wang, Juan; Xiang, Sihai; Feng, Xiaozhou

    2013-01-01

    Well-characterized promoters are essential tools for metabolic engineering and synthetic biology. In Streptomyces coelicolor, the native kasOp is a temporally expressed promoter strictly controlled by two regulators, ScbR and ScbR2. In this work, first, kasOp was engineered to remove a common binding site of ScbR and ScbR2 upstream of its core region, thus generating a stronger promoter, kasOp3. Second, another ScbR binding site internal to the kasOp3 core promoter region was abolished by random mutation and screening of the mutant library to obtain the strongest promoter, kasOp* (where the asterisk is used to distinguish the engineered promoter from the native promoter). The activities of kasOp* were compared with those of two known strong promoters, ermEp* and SF14p, in three Streptomyces species. kasOp* showed the highest activity at the transcription and protein levels in all three hosts. Furthermore, relative to ermEp* and SF14p, kasOp* was shown to confer the highest actinorhodin production level when used to drive the expression of actII-ORF4 in S. coelicolor. Therefore, kasOp* is a simple and well-defined strong promoter useful for gene overexpression in streptomycetes. PMID:23686264

  2. Career development resource: promotion to associate professor.

    PubMed

    Sanfey, Hilary; Hollands, Celeste

    2012-07-01

    This will most likely be the first time through the promotion and tenure process for the faculty member. The faculty member is responsible for meeting with the department chair and/or division chief on a regular basis to determine if she is on the right time line to successfully achieve promotion to associate professor. A physician will begin seriously preparing her portfolio for promotion to associate professor about 5 to 6 years out of training, at which time she will have some considerable experience running a practice and managing her time. However, the planning process for promotion should begin immediately upon starting the first academic position.

  3. WHO Health Promotion Glossary: new terms.

    PubMed

    Smith, Ben J; Tang, Kwok Cho; Nutbeam, Don

    2006-12-01

    The WHO Health Promotion Glossary was written to facilitate understanding, communication and cooperation among those engaged in health promotion at the local, regional, national and global levels. Two editions of the Glossary have been released, the first in 1986 and the second in 1998, and continued revision of the document is necessary to promote consensus regarding meanings and to take account of developments in thinking and practice. In this update 10 new terms that are to be included in the Glossary are presented. Criteria for the inclusion of terms in the Glossary are that they differentiate health promotion from other health concepts, or have a specific application or meaning when used in relation to health promotion. The terms defined here are: burden of disease; capacity building; evidence-based health promotion; global health; health impact assessment; needs assessment; self-efficacy; social marketing; sustainable health promotion strategies, and; wellness. WHO will continue to periodically update the Health Promotion Glossary to ensure its relevance to the international health promotion community.

  4. 76 FR 314 - Sorghum Promotion, Research, and Information Program: Referendum

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... Agricultural Marketing Service Sorghum Promotion, Research, and Information Program: Referendum AGENCY: Agricultural Marketing Service, USDA. ACTION: Notice of Opportunity to Participate in the Sorghum Promotion... Promotion, Research, and Information Order (Order), as authorized under the Commodity Promotion,...

  5. Promoting Strong Written Communication Skills

    NASA Astrophysics Data System (ADS)

    Narayanan, M.

    2015-12-01

    The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

  6. Marketing and Promotion of Library Services

    NASA Astrophysics Data System (ADS)

    Nicholas, Julie

    As librarians we should be actively marketing and promoting our library services. This paper aims to demystify marketing for librarians. Practical solutions are provided on how to implement a marketing strategy, with particular emphasis on the value of using electronic information resources. It also shows the link between promoting library services and raising the profile of the library.

  7. Promoting Relationships and Eliminating Violence in Canada

    ERIC Educational Resources Information Center

    Pepler, Debra; Craig, Wendy

    2011-01-01

    The Promoting Relationships and Eliminating Violence Network (PREVNet) involves Canadian researchers and national organizations working to promote healthy relationships and prevent bullying. In this paper, we provide the rationale for establishing PREVNet, a description of the work of the network, and an assessment of the success of PREVNet.…

  8. Linking Core Promoter Classes to Circadian Transcription

    PubMed Central

    Westermark, Pål O.

    2016-01-01

    Circadian rhythms in transcription are generated by rhythmic abundances and DNA binding activities of transcription factors. Propagation of rhythms to transcriptional initiation involves the core promoter, its chromatin state, and the basal transcription machinery. Here, I characterize core promoters and chromatin states of genes transcribed in a circadian manner in mouse liver and in Drosophila. It is shown that the core promoter is a critical determinant of circadian mRNA expression in both species. A distinct core promoter class, strong circadian promoters (SCPs), is identified in mouse liver but not Drosophila. SCPs are defined by specific core promoter features, and are shown to drive circadian transcriptional activities with both high averages and high amplitudes. Data analysis and mathematical modeling further provided evidence for rhythmic regulation of both polymerase II recruitment and pause release at SCPs. The analysis provides a comprehensive and systematic view of core promoters and their link to circadian mRNA expression in mouse and Drosophila, and thus reveals a crucial role for the core promoter in regulated, dynamic transcription. PMID:27504829

  9. Cloning the human SUMO1 promoter.

    PubMed

    Nanos-Webb, Angela; Deyrieux, Adeline; Bian, Xue-lin; Rosas-Acosta, Germán; Wilson, Van G

    2010-03-01

    Regulation of the sumoylation system at the level of gene expression has not yet been explored. To begin to define transcriptional regulatory features, the promoter region for the SUMO1 gene was cloned from human genomic DNA and characterized. Initially, a 532 base pair fragment upstream of and including the predicted SUMO1 transcription start site (TSS) was cloned and shown to possess promoter activity. Subsequent deletion analysis showed that a smaller fragment containing 158 bp upstream of the TSS region exhibited basal promoter activity in both human and rodent cell lines. Within this basal promoter fragment, there were predicted binding sites for numerous transcription factors, including the nude mouse gene product, Whn (FoxN1). Electrophoretic mobility shift assays showed that Whn could bind to an ACGC motif adjacent to the TSR, and in transfection studies Whn stimulated a 3-fold increase in transcription from this cloned promoter in keratinocytes (HaCaT cells). Mutation of the ACGC motif abrogated both Whn binding and transcriptional activation, indicating that the Whn effect is likely due to direct interaction with this promoter element. Consistent with these observations on the cloned promoter region, Whn also modestly stimulated transcription from the endogenous, genomic SUMO1 promoter in HaCaT cells, consistent with Whn potentially playing a regulatory role for SUMO1 transcription in keratinocytes.

  10. Promoting Transformative Learning through Reading Fiction

    ERIC Educational Resources Information Center

    Hoggan, Chad; Cranton, Patricia

    2015-01-01

    This article is a report on research into the role of fiction in promoting transformative learning in higher education settings. Participants were 131 undergraduate and graduate students from two universities in the United States. To determine the type of learning promoted by reading fiction, we performed qualitative analyses on participants'…

  11. Media Characteristics in Promoting Management Education Courses

    ERIC Educational Resources Information Center

    Berry, Dick

    1978-01-01

    The effectiveness of direct media employed for promoting marketing, service and sales management conferences and institutes was analyzed. Direct mail was the preferred media for program promotion for business clientele. Three enrollment tables illustrate the effectiveness of different media by program area and course type. (EM)

  12. Promoting people's health: challenges and opportunities.

    PubMed

    Heitkamp, P

    1998-01-01

    Promoting health underlines the right of each individual to the highest attainable standard of health. It stresses the importance of the participation of people and recognizes different sociocultural values and beliefs that are prevalent throughout the world. Working on health development has a sustainable effect only when done comprehensively: personal development, community development, organizational development, and political development. The international conferences that have marked the way of health promotion have been goal posts of an energetic movement to strengthen health worldwide. The Ottawa Charter on Health Promotion has been a worldwide source of guidance for health promotion through its five strategies: building health policy, creating supportive elements, strengthening community action, developing personal skills, and reorienting health services. Moreover, the Jakarta Declaration on "Leading Health Promotion into the 21st Century" identifies five priorities in the next millennium: 1) promote social responsibility for health; 2) increase investments for health development; 3) consolidate and expand partnerships for health; 4) increase community capacity and empower the individual in matters of health; and 5) secure an infrastructure for health promotion. Increasing the investment in health development calls for the need to find new mechanisms for funding as well as reorienting existing resources towards health promotion and health education.

  13. How should vasectomy be promoted in Guatemala?

    PubMed

    Piotrow, P T; Kincaid, D L

    1988-01-01

    In the article "Evaluation of a Communications Program to Increase Adoption of Vasectomy in Guatemala" by J.T. Bertrand et al (Stud Fam Plann 1987 Nov/Dec), the authors conclude that the use of a male promoter alone was 4 times more cost-effective in increasing the number of vasectomies than the use of radio alone because the costs of the radio program were 4 times higher. This conclusion is questionable for several reasons. 1) The district where the promoter was used alone was twice as large as the radio-only district. 2) In one of the promoter-only districts the same promoter worked throughout the program, but in the other, 3 different promoters had to be recruited and trained, due to high personnel turnover. 3) The initial costs of a radio program may be higher, but 1 program can be broadcast in all districts with little or no extra cost, whereas the costs of a promoter would have to be multiplied by the number of districts. 4) Although the promoter and the radio program produced approximately equal numbers of vasectomies, the radio messages reached over 70% of the people surveyed. Thus, on a national basis, radio broadcasts would be far more cost-effective than the use of salaried promoters in each district.

  14. The Literature on Social Promotion versus Retention.

    ERIC Educational Resources Information Center

    Southwest Educational Development Lab., Austin, TX.

    This general review of the relative merits of social promotion and retention examines research on the benefits of each, describes current strategies for resolving the policy dilemma involved, and considers issues raised by abolishing social promotion and establishing remedial programs. A summary of the history of the widespread adoption of the…

  15. The Grade Retention/Social Promotion Debate.

    ERIC Educational Resources Information Center

    Lindelow, John

    1985-01-01

    This publication focuses on the retention/promotion debate regarding failing and low-achieving students. An introductory essay describes the inherent limitation in the research done on this issue--the impossibility of obtaining an appropriate control group--and suggests that the retention/promotion quandary can best be resolved by accommodating…

  16. Health-Promoting Behaviours in Conservatoire Students

    ERIC Educational Resources Information Center

    Kreutz, Gunter; Ginsborg, Jane; Williamon, Aaron

    2009-01-01

    This study focuses on health-promoting behaviours in students from two conservatoires, the Royal Northern College of Music (RNCM, Manchester, UK; n =199) and the Royal College of Music (RCM, London, UK; n = 74). The research questions concern (a) the levels and types of health-promoting behaviours among performance students and (b) the association…

  17. Effective Promotion in a Greater Metropolitan Area.

    ERIC Educational Resources Information Center

    Kelly, J. Terence

    Community colleges offering or contemplating offering television-based courses will be successful in promotional efforts if the fundamental, philosophical purpose is built upon a need for expanding current educational services to a population thus far unaffected by on-campus programs. Efforts in promoting television courses should be made so that…

  18. Identifying Opinion Leaders to Promote Behavior Change

    ERIC Educational Resources Information Center

    Valente, Thomas W.; Pumpuang, Patchareeya

    2007-01-01

    This article reviews 10 techniques used to identify opinion leaders to promote behavior change. Opinion leaders can act as gatekeepers for interventions, help change social norms, and accelerate behavior change. Few studies document the manner in which opinion leaders are identified, recruited, and trained to promote health. The authors categorize…

  19. [Concept of tumor promoters in hepatocarcinogenesis].

    PubMed

    Frayssinet, C; Lafarge-Frayssinet, C

    1990-01-01

    Tumor promotion is defined as 1 step of carcinogenesis. Its intervention occurred when cell DNA was already damaged by a carcinogen and is the support of quiescent mutations. This leads to a complete malignant transformation of the cells by a non genotoxic mechanism. The presence of tumor promoters in our environment, although difficult to estimate, must be taken into account. This requires further research.

  20. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Consumer promotions. 6.96... OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act by an industry member of furnishing to consumers coupons which are redeemable at a retail...

  1. 17 CFR 200.70 - Business promotions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Business promotions. 200.70 Section 200.70 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION ORGANIZATION; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.70 Business promotions. A member...

  2. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Consumer promotions. 6.96 Section 6.96 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act...

  3. Promotion in Call Centres: Opportunities and Determinants

    ERIC Educational Resources Information Center

    Gorjup, Maria Tatiana; Valverde, Mireia; Ryan, Gerard

    2008-01-01

    Purpose: The purpose of this paper is to examine the quality of jobs in call centres by focusing on the opportunities for promotion in this sector. More specifically, the research questions focus on discovering whether promotion is common practise in the call centre sector and on identifying the factors that affect this.…

  4. Activities for Engaging Schools in Health Promotion

    ERIC Educational Resources Information Center

    Bardi, Mohammad; Burbank, Andrea; Choi, Wayne; Chow, Lawrence; Jang, Wesley; Roccamatisi, Dawn; Timberley-Berg, Tonia; Sanghera, Mandeep; Zhang, Margaret; Macnab, Andrew J.

    2014-01-01

    Purpose: The purpose of this paper is to describe activities used to initiate health promotion in the school setting. Design/Methodology/Approach: Description of successful pilot Health Promoting School (HPS) initiatives in Canada and Uganda and the validated measures central to each program. Evaluation methodologies: quantitative data from the…

  5. 17 CFR 200.70 - Business promotions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Business promotions. 200.70... AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.70 Business promotions. A member must not engage in any other business, employment or vocation while in office, nor may he ever use...

  6. 17 CFR 200.70 - Business promotions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Business promotions. 200.70... AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.70 Business promotions. A member must not engage in any other business, employment or vocation while in office, nor may he ever use...

  7. 17 CFR 200.70 - Business promotions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Business promotions. 200.70... AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.70 Business promotions. A member must not engage in any other business, employment or vocation while in office, nor may he ever use...

  8. 17 CFR 200.70 - Business promotions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Business promotions. 200.70... AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.70 Business promotions. A member must not engage in any other business, employment or vocation while in office, nor may he ever use...

  9. Composing a Tumor Specific Bacterial Promoter

    PubMed Central

    Deyneko, Igor V.; Kasnitz, Nadine; Leschner, Sara; Weiss, Siegfried

    2016-01-01

    Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy. PMID:27171245

  10. [Promoting "well-treatment" in medical imaging].

    PubMed

    Renouf, Nicole; Llop, Marc

    2012-12-01

    A project to promote "well-treatment" has been initiated in the medical imaging department of a Parisian hospital. With the aim of promoting the well-being of the patient and developing shared values of empathy and respect, the members of this medico-technical team have undertaken to build a culture of "well-treatment" which respects the patient's dignity and rights.

  11. The double jeopardy of sales promotions.

    PubMed

    Jones, J P

    1990-01-01

    The maturing of most consumer markets in the United States has put great pressure on manufacturers in their search for growth. They have concentrated on building sales and expanding share proportions in the stagnant markets with devices like niche products, product extensions, mergers, and international ventures. They have shifted emphasis to sales promotions at the expense of advertising. But promotions, when you come right down to it, mean price reductions. Trade promotions are almost always rebates, and consumer promotions are usually temporary price reductions or coupons. The cost in reduced profit, demonstrated mathematically through calculations of price elasticity, is severe. Besides, when the promotion is over, the manufacturer has not moved forward an inch in shoring up the brand franchise. Promotions bring volatile demand, whereas the producer seeks stable demand. By sustaining a brand image and building customer loyalty, on the other hand, theme advertising can stabilize demand. Moreover, this type of advertising is less likely than promotion is to invite destructive competitive retaliation. Calculation of the advertising elasticity of a brand indicates that sometimes even modest sales increases can produce healthy profit improvement. In a well-planned marketing campaign, there is often good reason to include trade or consumer promotion--to counter a leading competitor's moves, for example. But there is no point in carrying out wild swings at rivals in a struggle for market share. Mathematical techniques can aid the efficiency of marketing planning and put on a more rational basis the decision on where to put the dollars.

  12. Promoting Tech Schools within Your Community

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2010-01-01

    This article describes a number of promotional events and practices that the author's school engages in. The author hopes that his school's experiences will serve as an inspiration and useful model for other "Tech Directions" readers. There are many methods for successfully promoting one's tech program. Two key strategies are: (1) Connect in…

  13. Promoting School Connectedness through Whole School Approaches

    ERIC Educational Resources Information Center

    Rowe, Fiona; Stewart, Donald; Patterson, Carla

    2007-01-01

    Purpose: The purpose of this paper is to develop a framework to demonstrate the contribution of whole school approaches embodied by the health-promoting school approach, to the promotion of school connectedness, defined as the cohesiveness between diverse groups in the school community, including students, families, school staff and the wider…

  14. 7 CFR 1214.18 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.18... favorable image of Christmas trees to the general public with the intent of improving the perception...

  15. 7 CFR 1214.18 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.18... favorable image of Christmas trees to the general public with the intent of improving the perception...

  16. 7 CFR 1214.18 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.18... favorable image of Christmas trees to the general public with the intent of improving the perception...

  17. 77 FR 56552 - Holiday Mobile Shopping Promotion

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ...] [Pages 56552-56554] [FR Doc No: 2012-22507] POSTAL SERVICE 39 CFR Part 111 Holiday Mobile Shopping... Holiday Mobile Shopping Promotion (``Promotion''), which will take place between November 7, 2012 and.../ Cyber Monday holiday shopping timeframe. In this final rule, the Postal Service provides a...

  18. Transcription Factor Binding Site Positioning in Yeast: Proximal Promoter Motifs Characterize TATA-Less Promoters

    PubMed Central

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

    The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of ‘proximal promoter motifs’ (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters. PMID:21931670

  19. Transcription factor binding site positioning in yeast: proximal promoter motifs characterize TATA-less promoters.

    PubMed

    Erb, Ionas; van Nimwegen, Erik

    2011-01-01

    The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of 6 'proximal promoter motifs' (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.

  20. The Dual Lives of Bidirectional Promoters

    PubMed Central

    Wakano, Clay; Byun, Jung S.; Di, Li-Jun; Gardner, Kevin

    2012-01-01

    The sequencing of the human genome led to many insights into gene organization and structure. One interesting observation was the high frequency of bidirectional promoters characterized by two protein encoding genes whose promoters are arranged in a divergent or “head-to-head” configuration with less than 2000 base pairs of intervening sequence. Computational estimates published by various groups indicate that nearly 10% of the coding gene promoters are arranged in such a manner and the extent of this bias is a unique feature of mammalian genomes. Moreover, as a class, head-to-head promoters appear to be enriched in specific categories of gene function. Here we review the structure, composition, genomic properties and functional classifications of genes controlled by bidirectional promoters and explore the biological implication of these features. PMID:22366276