Sample records for ginsenoside rg3 combined

  1. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    XU Tian-min; CUI Man-hua; XIN Ying; GU Li-ping; JIANG Xin; SU Man-man; WANG Ding-ding; WANG Wen-jia


    Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

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

    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


    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 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 tumor growth rate (T/C) values of 39.36% (p 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.

  3. Influence of As2O3 combined with ginsenosides Rg3 on inhibition of lung cancer NCI-H1299 cells and on subsistence of nude mice bearing hepatoma

    Jian-Bo Che; Zhong-Hua Liu; Hong-Bing Ma; Yong Li; Hui Zhao; Xiao-Hui Li; Wei-Chao Liu; Gong-Ning Shi


    Objective:To study the effect of arsenic trioxide(As2O3) combined with ginsenosidesRg3 on inhibiting theNCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma. Methods:MTT method was used to measure the inhibition effect ofAs2O3 combinedRg3 onNCI-H1299 cells, and the proliferation inhibiting effect was observed via establishing the transplanted tumor modelin vitro.A total of40 tumor-bearing nude mice were randomly divided into normal saline group,As2O3,Rg3 andAs2O3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed, followed by injection of certain concentrations of normal saline, As2O3, ginseng saponinRg3 andAs2O3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and theKaplan-Meier curve was made; microscopic observation of apoptosis of tumor cellsin vivo was done usingTUNEL staining.Results:After72 h of injection, inhibition rate of tumor cell in normal saline group,As2O3 group,Rg3 group andAs2O3+Rg3 group was(5.66±0.31)%,(65.58±4.75)%,(44.69±3.32)% and(82.67±5.43)%, respectively.Inhibition rate of tumor cell inAs2O3 group,Rg3 group andAs2O3+Rg3 group was significantly higher than that of normal saline group(P<0.01); inhibition rate of tumor cells ofAs2O3+Rg3 group was significantly higher than that of the two groups givenAs2O3 orRg3 alone(P<0.01).The tumor volume of As2O3 group,Rg3 group andAs2O3+Rg3 group shrank to(65.38±3.25)%,(77.68±3.43)% and(42.65±3.55)% of the original, tumor volume of saline group was1.21 times of the original size(P<0.01);Median survival of saline group,Rg3 group,As2O3 group were significantly shorter than that of As2O3+Rg3 group(P<0.01); co-ordinated intervention ability ofAs2O3+Rg3 onNCI-H1299 cell was significantly higher than that ofAs2O3 orRg3, separately.Conclusions:As2O3 combined with Rg3 can significantly inhibit proliferation ofNCI-H1299 cells in lung cancer, prolong survival of tumor-bearing nude mice, and promote tumor cell apoptosis, and

  4. Preparation and Characterization of Biodegradable Polylactide(PLA) Microspheres Encapsulating Ginsenoside Rg3

    LIU Cheng-bai; ZHANG Di; LI De-guan; JIANG Dan; CHEN Xia


    In this study,the process of a biodegradable polylactide(PLA) microsphere encapsulating ginsenoside Rg3 was first studied by the emulsion solvent evaporation method,for enhancing solubility and stability of ginsenoside Rg3.Alabum was also first used as a modifier in this method.The mean diameter of the prepared PLA microspheres containing Rg3 was 40 μm.Ginsenoside Rg3 released from the microspheres was studied by HPLC and detected by UV.It was found that the drug release curve fitted the Model Heller-Baker best.

  5. Biotransformation of ginsenosides Rb1, Rg3 and Rh2 in rat gastrointestinal tracts

    Qian Tianxiu


    Full Text Available Abstract Background Ginsenosides such as Rb1, Rg3 and Rh2 are major bioactive components of Panax ginseng. This in vivo study investigates the metabolic pathways of ginsenosides Rb1, Rg3 and Rh2 orally administered to rats. Methods High performance liquid chromatography-mass spectrometry (LC-MS and tandem mass spectrometry (MS-MS techniques, particularly liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS, were used to identify the metabolites. Results Six metabolites of Rb1, six metabolites of Rg3 and three metabolites of Rh2 were detected in the feces samples of the rats. Rh2 was a metabolite of Rb1 and Rg3, whereas Rg3 was a metabolite of Rb1. Some metabolites such as protopanaxadiol and monooxygenated protopanaxadiol are metabolites of all three ginsenosides. Conclusion Oxygenation and deglycosylation are two major metabolic pathways of the ginsenosides in rat gastrointestinal tracts.

  6. 人参皂苷Rg3联合化学治疗对老年非小细胞肺癌术后辅助治疗的临床观察%Observation of ginsenoside Rg3 combined with chemotherapy as adjuvant treatment for elder nonsmall-cell lung cancer patients

    靳彩玲; 寇小格; 苗战会


    目的 观察人参皂苷Rg3联合吉西他滨+顺铂(GP方案)治疗老年非小细胞肺癌的细胞免疫功能变化及毒副反应.方法 老年非小细胞肺癌40例随机分为2组,观察组20例采用人参皂苷Rg3联合GP方案,对照组20例单用GP方案.治疗2个周期后检测血清细胞免疫指标、血管内皮细胞生长因子(VEGF)水平,并评价毒副反应.结果 观察组治疗后CD4/CD8值及自然杀伤(NK)细胞阳性率显著提高(P<0.05),且明显高于对照组(P<0.05).2组治疗后血清VEGF水平均低于治疗前(P<0.05),观察组治疗后VEGF水平低于对照组(P<0.05).观察组白细胞减少发生率低于对照组(P<0.05).观察组Karnofsky评分较对照组改善明显(P<0.05).结论 人参皂苷Rg3联合GP方案治疗老年非小细胞肺癌,可使白细胞减少发生率降低,提高患者细胞免疫功能和生活质量.%Objective To observe cellular immune function and side effect of ginsenoside Rg3 combined with gemcit-abine plus cisplatin ( GP) regimen for non-small-cell lung cancer ( NSCLC ). Methods Forty patients with stage Ⅱ - Ⅲa NSCLC of aged person were randomly divided into CP adding ginsenoside Rg3 group(observation group) and CP group(control group) .twenty in each group. After two cycles, the cellular immune function, the level of vascular endothelial growth factor (VEGF) and the side reaction were evaluated. Results The improvement of CD4/CD8 ratio and natural killer cell positive ratio in observation group was higher than that before treatment and it was higher than that in control group (P < 0.05 ). The levels of VEGF in two groups were decreased as compared with that before treatment(P <0.05). After treatment, the VEGF levels and incidence of toxicity leucopenia in observation group were lower than those in control group( P < 0.05 ). Kamofslcy scale was improved in observation group (P<0.05). Conclusion Ginsenoside Rg3 combined GP regimen was safe in treatment of elderly NSCLC

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

    Sun, Mengwei [Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200031 (China); Huang, Chenglin [Shanghai Key Laboratory of Vascular Biology, Department of Hypertension and Pharmacology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Cheng; Zheng, Jianheng; Zhang, Peng; Xu, Yangshu [Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200031 (China); Chen, Hong, E-mail: [Shanghai Key Laboratory of Vascular Biology, Department of Hypertension and Pharmacology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Shen, Weili, E-mail: [Shanghai Key Laboratory of Vascular Biology, Department of Hypertension and Pharmacology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)


    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.

  8. 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin

    Kim, Dong-Gun; Jung, Kyung Hee; Lee, Da-Gyum; Yoon, Jung-Ho; Choi, Kyeong Sook; Kwon, Sung Won; Shen, Han-Ming; Morgan, Michael J.; Hong, Soon-Sun; Kim, You-Sun


    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. High mortality from HCC is mainly due to widespread prevalence and the lack of effective treatment, since systemic chemotherapy is ineffective, while the targeted agent Sorafenib extends median survival only briefly. The steroidal saponin 20(S)-ginsenoside Rg3 from Panax ginseng C.A. Meyer is proposed to chemosensitize to various therapeutic drugs through an unknown mechanism. Since autophagy often serves as cell survival mechanism in cancer cells exposed to chemotherapeutic agents, we examined the ability of Rg3 to inhibit autophagy and chemosensitize HCC cell lines to doxorubicin in vitro. We show that Rg3 inhibits late stage autophagy, possibly through changes in gene expression. Doxorubicin-induced autophagy plays a protective role in HCC cells, and therefore Rg3 treatment synergizes with doxorubicin to kill HCC cell lines, but the combination is relatively nontoxic in normal liver cells. In addition, Rg3 was well-tolerated in mice and synergized with doxorubicin to inhibit tumor growth in HCC xenografts in vivo. Since novel in vivo inhibitors of autophagy are desirable for clinical use, we propose that Rg3 is such a compound, and that combination therapy with classical chemotherapeutic drugs may represent an effective therapeutic strategy for HCC treatment. PMID:24970805

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

    Yoon, Sung-Jin; Park, Jun-Young [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon (Korea, Republic of); Choi, Song [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Jin-Bong; Jung, Haiyoung; Kim, Tae-Don; Yoon, Suk Ran; Choi, Inpyo [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon (Korea, Republic of); Shim, Sungbo, E-mail: [Department of Biomedical Sciences & Neuromarker Resource Bank (NRB), University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Young-Jun, E-mail: [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon (Korea, Republic of)


    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.

  10. Apoptosis Induced by Ginsenoside Rg3 in a Human Bladder Carcinoma Cell Line

    Junxia Chen; Huimin Peng; Shuping Pu; Yuping Guo


    OBJECTIVE This study was conducted to explore the effect of Rg3 on inhibition of proliferation and induction of apoptosis in bladder cancer cells.METHODS The EJ bladder cancer cell line was treated with Rg3 at various concentrations. Cell proliferation was measured by the MTT assay. Morphological changes in the cells were observed by fluorescent staining using Hoechst 33258. The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3 in cells was detected by immunocytochemistry. DNA ladder analysis was conducted by agarose gel electrophoresis.RESULTS Rg3 inhibited proliferation of EJ cells in a concentration-dependent manner, resulting in an IC50 for Rg3 at 48 h of 125.5 μg/ml. When treated with 150 μg/ml of Rg3 for 24 h and 48 h, the cells showed apoptotic morphological characteristics including condensed chromatin, nuclear fragmentation, apoptotic bodies and bright fluorescent granules as well as a higher caspase-3 expression. The FCM assay indicated that Rg3 altered the cell cycle and induced apoptosis of the EJ cells, when treated for 24 h and 48 h with 75 μg/ml of Rg3 as well as for 48 h with 150 μg/ml. The percentages of cells in the S phase and the G2/M transition were increased, whereas the percentages of cells in the G0-G1 transition were decreased. The apoptotic rates were increased from (1.05±0.17)% in the control group cells to (8.41 ±0.98)%, (18.57±2.20)% and (33.98±1.64)% respectively. Significant changes in the DNA ladders, showed that the effects of Rg3 were displayed in a dose and time dependent manner.CONCLUSION The results suggest that Ginsenoside Rg3 exerts an inhibitory effect on proliferation of EJ cells by inducing apoptosis.

  11. Evaluation of glucosidases of Aspergillus niger strain comparing with other glucosidases in transformation of ginsenoside Rb1 to ginsenosides Rg3

    Kyung Hoon Chang


    Full Text Available The transformation of ginsenoside Rb1 into a specific minor ginsenoside using Aspergillus niger KCCM 11239, as well as the identification of the transformed products and the pathway via thin layer chromatography and high performance liquid chromatography were evaluated to develop a new biologically active material. The conversion of ginsenoside Rb1 generated Rd, Rg3, Rh2, and compound K although the reaction rates were low due to the low concentration. In enzymatic conversion, all of the ginsenoside Rb1 was converted to ginsenoside Rd and ginsenoside Rg3 after 24 h of incubation. The crude enzyme (β-glucosidase from A. niger KCCM 11239 hydrolyzed the β-(1→6-glucosidic linkage at the C-20 of ginsenoside Rb1 to generate ginsenoside Rd and ginsenoside Rg3. Our experimental demonstration showing that A. niger KCCM 11239 produces the ginsenoside-hydrolyzing β-glucosidase reflects the feasibility of developing a specific bioconversion process to obtain active minor ginsenosides.

  12. 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.

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


    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.

  13. Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell

    Eun-Hwa Park


    Results and Conclusion: HAG significantly reduced the cancer cell proliferation, and the contents of ginsenosides Rb1 and Re were markedly decreased, whereas the peaks of less-polar ginsenosides [20(S,R-Rg3, Rk1, and Rg5] were newly detected. Based on the activity-guided fractionation of HAG, ginsenoside 20(S-Rg3 played a key role in inducing apoptosis in human gastric cancer AGS cells, and it was generated mainly from ginsenoside Rb1. Ginsenoside 20(S-Rg3 induced apoptosis through activation of caspase-3, caspase-8, and caspase-9, as well as regulation of Bcl-2 and Bax expression. Taken together, these findings suggest that heat-processing serves as an increase in the antitumor activity of American ginseng in AGS cells, and ginsenoside 20(S-Rg3, the active component produced by heat-processing, induces the activation of caspase-3, caspase-8, and caspase-9, which contributes to the apoptotic cell death.

  14. Preparation of Ginsenoside Rg3 and Protection against H2O2-Induced Oxidative Stress in Human Neuroblastoma SK-N-SH Cells

    Gang Li


    Full Text Available The aim of this study is to evaluate the protection of ginsenoside Rg3 against oxidative stress in human neuroblastoma SK-N-SH cells. 20(R-ginsenoside Rg3 (20(R-Rg3 and 20(S-ginsenoside Rg3 (20(S-Rg3 were prepared by the method of chemical degradation and column chromatography, and the structure of the two compounds was characterized by 1H-NMR and 13C-NMR spectroscopy. MTT assay and LDH leakage assay were used to determine the cell viability and the oxidative stress cellular model was established by means of H2O2 (600 μM for 4 h. We also investigated the changes of intracellular MDA content, SOD activity, and ROS formation after the treatment of ginsenoside Rg3 for 20 h. The results indicated that both 20 (R-Rg3 and 20 (S-Rg3 had obvious protection against H2O2-induced oxidative stress in SK-N-SH cells. Moreover, 20(R-Rg3 exhibited better antioxidant activity than 20(S-Rg3 in vitro. These findings are expected to provide some implication for further research and application of ginsenoside Rg3 in neuroprotection.

  15. Enhanced antitumor activity in A431 cells via encapsulation of 20(R)-ginsenoside Rg3 in PLGA nanoparticles.

    Zhang, Shaozhi; Liu, Jiwei; Ge, Baojian; Du, Meiling; Fu, Li; Fu, Yushan; Yan, Qiu


    The objective of this study is to investigate the encapsulation of 20(R)-ginsenoside Rg3 (20(R)-Rg3) using polylactic-co-glycolic acid (PLGA) and promotion for its antitumor activity. Preparation and evaluation of the antitumor efficacy of 20(R)-Rg3-loaded PLGA nanoparticles were the first reported. The data will be helpful to apply 20(R)-Rg3 efficiently and broadly in new drug form development and clinical cancer treatment. The nanoparticles were prepared using emulsion and solvent evaporation methods. The uniform particle size and good dispersion were further confirmed by scanning electron microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to detect cell proliferation after 20(R)-Rg3-loaded PLGA nanoparticles treatment. Western blotting and immunofluorescent staining were used for observation of key proteins related with proliferation and apoptosis. Cell cycle and apoptosis were analyzed by flow cytometer technology. The results showed that the size of 20(R)-Rg3-loaded PLGA was 97.5 nm in diameter, and zeta potential was -28 mV detected by Malvern particle size analyzer. The encapsulation efficiency was 97.5%, and drug loading was 70.2% measured by high-performance liquid chromatography. The in vitro study showed that the encapsulated 20(R)-Rg3 was consecutively released and the release ratio reached to the highest value (19.36%) at the time point of 96 h. The encapsulated 20(R)-Rg3 significantly inhibited the proliferation and induced apoptosis in A431 cancer cells compared with the unencapsulated 20(R)-Rg3, control and PLGA alone. 20(R)-Rg3-loaded PLGA nanoparticles was well prepared and characterized. The antitumor activity was increased after PLGA encapsulation. The data will be beneficial to the development of new dosage forms of 20(R)-Rg3 and extensive application.

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

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


    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.

  17. Preliminary study for the roles and mechanisms of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles in the Lewis lung cancer mice%人参皂苷 Rg3和 PEG-PLGA-Rg3纳米微粒对Lewis 肺癌小鼠的作用及其机制

    耿良; 范敬; 高启龙; 俞静; 花宝金


    目的:观察并比较20(R)-人参皂苷 Rg3[20(R)-ginsenoside Rg3Rg3]和聚乙二醇(polyethylene glycol, PEG)-聚乳酸羟基乙酸(poly lactic-co-glycolic acid,PLGA)-Rg3纳米微粒(Rg3-N)对 Lewis 肺癌荷瘤小鼠的影响,探讨它们体内抗肿瘤作用的机制。方法:建立小鼠 Lewis 肺癌动物模型,60只小鼠随机分为人参皂苷 Rg3纳米微粒组(Rg3-N)、PEG-PLGA 纳米载体组(PEG)、20(R)-人参皂苷 Rg3单体组(Rg3)、生理盐水组(NS)和空白对照组(C),每组12只,灌胃给药共14 d。每隔2 d 测量小鼠的体重并绘制小鼠体重变化曲线,观察各组小鼠毛色、活动和精神状态等一般情况。实验结束当天处死小鼠,计算抑瘤率和肿瘤质量与体重比值;免疫组织化学法 CD31抗体标记来计算微血管密度(microvessel density,MVD),以评价 Rg3Rg3纳米缓释微粒的体内抗血管生成作用,并通过实时定量 PCR、免疫组织化学和 Western blot 法检测基质金属蛋白酶(matrix metalloproteinase-9,MMP-9)、缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、Ki-67等血管新生和细胞增殖相关因子水平,以探讨其体内抗肿瘤作用的分子机制。结果:NS 组和 PEG 组小鼠的体重呈现先升后降的趋势,而其余3组小鼠的体重则呈现逐渐上升并保持稳定的趋势。相对于 NS 组,Rg3组和 Rg3-N组小鼠的毛色更亮,精神状态更好,更加活跃,一般状况较好。PEG 组、Rg3组和 Rg3-N 组的肿瘤质量与 NS 组相比差异无统计学意义,但 Rg3组和 Rg3-N 组的肿瘤质量与体重比值和微血管密度明显下降,与 NS 组之间差异有统计学意义(P <0.01),Rg3组和 Rg3-N 组之间差异无统计学意义。与 NS 组相比,Rg3组和 Rg3-N 组的 VEGF mRNA、MMP-9、HIF-1α、VEGF 的

  18. Curative effect of ginsenoside Rg3 combined with Lewis Y monoclonal antibody for endometrial cancer%人参皂甙Rg3联合Lewis Y单克隆抗体对子宫内膜癌的治疗作用

    刘佳; 邓燕杰; 李秀娟; 燕秋


    目的:研究人参皂甙Rg3(GS-Rg3)联合Lewis Y(LeY)单克隆抗体对人子宫内膜移行上皮癌细胞株A431的增殖抑制作用及诱导其凋亡的作用.方法:体外培养A431细胞,分为对照组和实验组.采用MTT法观察GS-Rg3联合LeY单克隆抗体对A431细胞的增殖抑制作用;Hoechst33342荧光染色观察各组细胞凋亡的形态学情况;流式细胞术分析各组细胞周期变化及凋亡情况;western-blot方法检测各组Bcl-2和Bax蛋白的表达.结果:GS-Rg3和LeY单克隆抗体对A431细胞的增殖有明显的抑制作用,且以二者联合处理组作用最显著,呈协同作用,差异有统计学意义(P< 0.05);经GS-Rg3和LeY单克隆抗体处理后,细胞周期停滞于G1期,S期无明显变化,A431细胞的凋亡率与对照组相比明显增加,以联合处理组最显著,差异有统计学意义(P<0.05);western-blot显示,GS-Rg3和LeY单克隆抗体作用A431细胞后,与对照组相比,Bcl-2表达减少,Bax表达增多,以联合作用组最为显著,差异有统计学意义(P<0.05).结论:人参皂甙Rg3和Lewis Y单克隆抗体均能够抑制A431细胞的增殖,并通过下调Bcl-2和上调Bax诱导其凋亡,且二者具有协同增效作用.

  19. Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells

    Jun Yeon Park


    Full Text Available Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S-Rg3.

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

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


    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.

  1. Antiangiogenesis of ginsenoside Rg3 in severe combined immunodeficient mice with human ovarian carcinoma%人参皂甙Rg3对荷卵巢癌的严重联合免疫缺陷鼠的抗肿瘤血管生成作用的研究

    潘子民; 叶大风; 谢幸; 陈怀增; 吕卫国


    目的研究人参皂甙Rg3体内抗卵巢癌血管生成的作用. 方法建立荷卵巢癌的严重联合免疫缺陷(SCID)鼠腹腔移植瘤模型,分为3组.空白组:SCID鼠荷瘤后不干预;对照组:荷瘤SCID鼠予磷酸盐缓冲液(PBS)灌胃;实验组:荷瘤SCID鼠予人参皂甙Rg3和PBS混悬液灌胃.分别采用逆转录聚合酶链反应技术、酶联免疫吸附法、免疫组织化学法检测3组荷瘤SCID鼠的血管内皮生长因子(VEGF)mRNA、蛋白及微血管密度(MVD).结果 (1)人参皂甙Rg3处理后,荷瘤SCID鼠体内无腹水形成,腹腔中肿块播散减少.(2)实验组肿瘤组织VEGF mRNA表达的相对量为119±16,显著低于空白组、对照组(分别为254±4和273±44, P 均<0.05).(3)实验组血中VEGF蛋白的表达量为(14.6±0.7)pg/ml,显著低于空白组和对照组[分别为(18.5±2.1)和(20.5±1.7) pg/ml, P 均<0.05].(4)实验组肿瘤组织中MVD为(43±7)个/mm3,显著低于空白组和对照组[分别为(65±12)个/mm3和(73±10)个/mm3, P 均<0.05].结论人参皂甙Rg3通过下调肿瘤VEGF mRNA及蛋白的表达量,阻滞肿瘤血管生成从而抑制肿瘤生长和转移.

  2. The Amelioration of N-Acetyl-p-Benzoquinone Imine Toxicity by Ginsenoside Rg3: The Role of Nrf2-Mediated Detoxification and Mrp1/Mrp3 Transports

    Sang Il Gum


    Full Text Available Previously, we found that Korean red ginseng suppressed acetaminophen (APAP-induced hepatotoxicity via alteration of its metabolic profile involving GSTA2 induction and that ginsenoside Rg3 was a major component of this gene induction. In the present study, therefore, we assessed the protective effect of Rg3 against N-acetyl-p-benzoquinone imine (NAPQI, a toxic metabolic intermediate of APAP. Excess NAPQI resulted in GSH depletion with increases in the ALT and AST activities in H4IIE cells. Rg3 pretreatment reversed GSH depletion by NAPQI. Rg3 resulted in increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase (GCL, the rate-limiting steps in GSH synthesis and subsequently increased GSH content. Rg3 increased levels of nuclear Nrf2, an essential transcriptional factor of these genes. The knockdown or knockout of the Nrf2 gene abrogated the inductions of mRNA and protein by Rg3. Abolishment of the reversal of GSH depletion by Rg3 against NAPQI was observed in Nrf2-deficient cells. Rg3 induced multidrug resistance-associated protein (Mrp 1 and Mrp3 mRNA levels, but not in Nrf2-deficient cells. Taken together, these results demonstrate that Rg3 is efficacious in protecting hepatocytes against NAPQI insult, due to GSH repletion and coordinated gene regulations of GSH synthesis and Mrp family genes by Nrf2.

  3. Ginsenoside Rg3 Serves as an Adjuvant Chemotherapeutic Agent and VEGF Inhibitor in the Treatment of Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review

    He, Shulin; Hou, Wei


    Objective. To evaluate ginsenoside Rg3 combined with chemotherapy for non-small-cell lung cancer (NSCLC) treatment, in a meta-analysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure, and the VIP and Wanfang databases for eligible studies. We manually searched for printed journals and relevant textbooks. Statistical analyses were performed with Revman 5.3 and STATA 14.0 software packages. Results. Twenty studies were included. Ginsenoside Rg3 combined with chemotherapy could enhance response, improve disease control, prolong overall survival, improve patient quality of life, reduce leucocyte count decrease due to chemotherapy, reduce vascular endothelial growth factor expression in peripheral blood, and increase CD4/CD8 T cell ratio. Conclusion. Ginsenoside Rg3 combined with chemotherapy may enhance short-term efficacy and overall survival, alleviate treatment-induced side effects, reduce vascular endothelial growth factor expression, increase CD4/CD8 T cell ratio, and serve as a potential therapeutic regimen for NSCLC. However, considering the limitations, the conclusion should be interpreted carefully, and these results need to be confirmed by more high-quality trials.

  4. Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression.

    Shan, Xiu; Aziz, Faisal; Tian, Li Li; Wang, Xiao Qi; Yan, Qiu; Liu, Ji Wei


    Malignant melanoma is a destructive and lethal form of skin cancer with poor prognosis. An effective treatment for melanoma is greatly needed. Ginsenoside Rg3 is a herbal medicine with high antitumor activity. It is reported that abnormal glycosylation is correlated with the tumor cell growth. However, the antitumor effect of Rg3 on melanoma and its mechanism on regulating glycosylation are unknown. We found that Rg3 did not only inhibit A375 melanoma cell proliferation in a dose-dependent manner, but also decreased the expression of fucosyltransferase IV (FUT4) and its synthetic product Lewis Y (LeY), a tumor-associated carbohydrate antigen (TACA). Knocking down FUT4 expression by siRNA dramatically reduced FUT4/LeY level and inhibited cell proliferation through preventing the activation of EGFR/MAPK pathway. Consistently, the inhibitory effect of the Rg3 and FUT4 knockdown on melanoma growth was also seen in a xenograft melanoma mouse model. In conclusion, Rg3 effectively inhibited melanoma cell growth by downregulating FUT4 both in vitro and in vivo. Targeting FUT4/LeY mediated fucosylation by Rg3 inhibited the activation of EGFR/MAPK pathway and prevented melanoma growth. Results from this study suggest Rg3 is a potential novel therapy agent for melanoma treatment.

  5. 20(R)-Ginsenoside Rg3 protects SH-SY5Y cells against apoptosis induced by oxygen and glucose deprivation/reperfusion.

    He, Bo; Chen, Peng; Xie, Yu; Li, Shude; Zhang, Xiaochao; Yang, Renhua; Wang, Guihua; Shen, Zhiqiang; Wang, Hui


    As shown in our previous studies, 20(R)-ginsenoside Rg3 [20(R)-Rg3] exerts a neuroprotective effect on a rat model of transient focal cerebral ischemia, and the mechanism through which it decreases the mRNA expression of calpain I and caspase-3 has been delineated. However, researchers do not know whether 20(R)-Rg3 exhibits a neuroprotective effect following oxygen-glucose deprivation and reperfusion (OGD/R) injury in vitro. In the present study, 20(R)-Rg3 increased cell viability, decreased the LDH leakage rate, and inhibited the apoptosis rate in a concentration-dependent manner. In addition, 20(R)-Rg3 markedly decreased cleaved caspase-3 protein expression. Furthermore, 20(R)-Rg3 significantly decreased the Bax mRNA and protein levels and increased the levels of Bcl-2 mRNA and protein, subsequently decreasing the Bax/Bcl-2 protein ratio. Based on these findings, 20(R)-Rg3 exerts a neuroprotective effect against OGD/R-induced apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Microbiological Transform Ginsenoside Rb1 into Rg3%微生物转化人参皂苷Rb1为Rg3的研究

    白龙律; 臧蕴霞; 尹成日


    利用18种菌株对人参皂苷Rb1进行生物转化研究,发现一种绿毛状GY-06菌使人参皂苷Rb1有效地转化为Rg3.经形态学和内转录间隔区(internal transcribed spacer, ITS)基因序列分析,确定其为一种扩展青霉(Penicillium expansum).

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

    In-Seung Lee


    Full Text Available 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.

  8. Effects of ginsenoside Rg3 on proliferation and induced differentiation of erythroleukemia cell line K562 in vitro%人参皂甙Rg3在体外对白血病K562细胞增殖和诱导分化的影响

    肖凤; 刘彬; 张建平; 王伴青; 方木水; 胡玮; 孙续禄; 朱清仙


    背景:文献报道人参皂甙Rg3具有抗肿瘤作用,但对白血病作用研究很少.目的:观察人参皂甙Rg3对白血病K562细胞的作用,并探讨其相关机制.方法:以白血病K562细胞为靶细胞,实验分为对照组和人参皂甙Rg3组,人参皂甙Rg3组分别添加10,20,40,80,100 mg/L Rg3.结果与结论:MTT检测结果显示,不同浓度人参皂甙Rg3组K562细胞生长抑制率均显著高于对照组(P < 0.05~0.01).NBT结果显示,人参皂甙Rg3组培养1,2,3 d K562细胞还原率均高于对照组(P < 0.01);人参皂甙Rg3组部分K562细胞体积变小,核仁消失,同时阳性细胞增多,细胞向成熟分化;流式细胞仪检测显示人参皂甙Rg3组培养2 d细胞周期G2期增高了3.84倍.提示人参皂甙Rg3在体外可抑制K562细胞增殖活性,其机制可能与人参皂甙Rg3将K562细胞周期阻滞在G2期,使细胞不能进行正常的有丝分裂,从而抑制细胞增殖有关.%BACKGROUND: Evidence exists that ginsenoside Rg3 can inhibit the growth of carcinoma cells. However, there are fewer studies describing ginsenoside Rg3 effects on leukemia.OBJECTIVE: To investigate the effects of ginsenoside Rg3 on proliferation of erythroleukemia cell line K562 and the underlying mechanism.METHODS: Erythroleukemia cell line K562 was used as target cell. The cells were divided into a control group and an Rg3 group. 10, 20, 40, 80, 100 mg/L Rg3 was added in the Rg3 group.RESULTS AND CONCLUSION: The MTT colorimetric assay indicated that K562 growth inhibition rate was significantly higher in the Rg3 groups than in the control group (P < 0.05-0.01). The nitroblue tetrazolium assay showed that after culture for 1,2, 3 days, the reducing power of K562 cells in the Rg3 group was significantly higher than in the control group (P < 0.01). In the Rg3 group, some K563 cell somas became small, nucleoli disappeared, nitroblue tetrazolium positive cells increased, and cells developed toward maturation. Flow cytometry detection showed

  9. Ginsenoside 20(S-Rg3 targets HIF-1α to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells.

    Ting Liu

    Full Text Available The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S-Rg3, which reduces the expression of hypoxia-inducible factor 1α (HIF-1α by activating the ubiquitin-proteasome pathway to promote HIF-1α degradation. A decrease in HIF-1α in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy.

  10. Ginsenoside Rg3 Improves Recovery from Spinal Cord Injury in Rats via Suppression of Neuronal Apoptosis, Pro-Inflammatory Mediators, and Microglial Activation

    Dong-Kyu Kim


    Full Text Available Spinal cord injury (SCI is one of the most devastating medical conditions; however, currently, there are no effective pharmacological interventions for SCI. Ginsenoside Rg3 (GRg3 is one of the protopanaxadiols that show anti-inflammatory, anti-oxidant, and neuroprotective effects. The present study investigated the neuroprotective effect of GRg3 following SCI in rats. SCI was induced using a static compression model at vertebral thoracic level 10 for 5 min. GRg3 was administrated orally at a dose of 10 or 30 mg/kg/day for 14 days after the SCI. GRg3 (30 mg/kg treatment markedly improved behavioral motor functions, restored lesion size, preserved motor neurons in the spinal tissue, reduced Bax expression and number of TUNEL-positive cells, and suppressed mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL-1β, and IL-6. GRg3 also attenuated the over-production of cyclooxygenase-2 and inducible nitric oxide synthase after SCI. Moreover, GRg3 markedly suppressed microglial activation in the spinal tissue. In conclusion, GRg3 treatment led to a remarkable recovery of motor function and a reduction in spinal tissue damage by suppressing neuronal apoptosis and inflammatory responses after SCI. These results suggest that GRg3 may be a potential therapeutic agent for the treatment of SCI.

  11. Study on the antiviral activaties of ginsenoside-Rg3 and Rb3%人参皂甙-Rg3、-Rb3抗病毒作用的研究

    李平亚; 郝秀华; 赵春芳; 常雅萍; 王博藯; 吴浩


    目的观察人参皂甙-Rg3、-Rb3抗病毒的活性。方法在FL细胞中扩增病毒,进行TCID50滴定,采用细胞病变抑制效应(CPE)的测定法观察药物的抗病毒作用。结果 0.125~4.0μg/ml浓度的人参皂甙-Rg3因浓度不同可以以不同方式抑制HSV-1和Polio V致CPE发生;156.2~250μg/ml浓度的人参皂甙-Rb3因浓度不同可以不同方式抑制HSV-1和VSV致CPE发生。结论人参皂甙-Rg3具有抗HSV-1和Poli Ⅴ活性,人参皂甙-Rb3具有抗HSV-1和VSV活性。

  12. Ultraviolet- and infrared-induced 11 beta-hydroxysteroid dehydrogenase type 1 activating skin photoaging is inhibited by red ginseng extract containing high concentration of ginsenoside Rg3(S).

    Nam, Jin-Ju; Min, Ji-Eun; Son, Min-Ho; Oh, Jin-Hwan; Kang, Seunghyun


    Sun irradiation is one of major extrinsic stressors responsible for premature skin aging through activation and expression of 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive cortisone to active cortisol. The aim of this study was to evaluate the inhibitory effects of red ginseng extract containing high concentrations of ginsenoside Rg3 (S) (GERg3) on 11β-HSD1-induced skin photoaging. To evaluate the inhibitory effects of GERg3 on ultraviolet- (UV) or infrared (IR)-induced skin photoaging, human dermal fibroblasts or a normal human 3D skin model was exposed to UV or an IR. RT-PCR, ELISA, Western blot, and H&E staining were used for evaluations. GERg3 was isolated from crude red ginseng. GERg3 inhibited the increased expressions of 11β-HSD1, interleukin (IL)-6, and matrix metalloproteinase-1 (MMP-1) in UVB- or IR-exposed Hs68 cells. Additionally, the increased cortisol, IL-6, and MMP-1 expressions were effectively reduced by GERg3 in UVA-exposed 3D skin models. The photoinduced decrease in type 1 procollagen also recovered as a result of GERg3 treatment in Hs68 cells and the 3D skin model. In addition, the UVA-exposed dermal thickness was decreased in comparison with the UVA-protected 3D skin model, recovered with GERg3 treatment. GERg3 had antiphotoaging effects in UV- or IR-exposed human dermal fibroblasts and normal human 3D skin model. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Antioxidant effect of parsley and panax ginseng extract standardized with ginsenosides Rg3 against alteration induced in reproductivefunctions in male mice

    Aziza M. Hassan1 and Mosaad A. Abdel-Wahhab2


    Full Text Available In the present study, the antigcidant effects of parsley oil and panax ginseng have been evaluated against the clastogenecity of ZEN. One hundred and eight mature male mice were distributed into nine treatment groups, including the control group and the groups treated with parsley oil (0.6 ml/kg b.w, panax ginseng extract (40 mg/kg b.w or parsley oil plus panax ginseng extract with or without ZEN (10 µg/kg b.w. Animals within different treatment groups were divided into two subgroups (A and B. Subgroup A were used for the determination of serum testosterone levels and chromosomal aberrations and received their respective doses for two weeks whereas, subgroup B were used for sperm abnormality and received their respective doses twice a day for one week and sacrificed after 30 days. The results indicated that ZEN treatment resulted in a significant decrease in testosterone concentration, sperm count and sperm motility. Whereas it caused a significant increase in abnormal sperms counts and total chromosomal aberrations in germ cells. Animals treated with parsley oil or panax ginseng extract alone or in combination were comparable to the controls regarding all the tested parameters. The combined treatment with ZEN and parsley oil, panax ginseng or parsley oil plus panax ginseng extract resulted in a significant improvement in all tested parameters. Moreover, parsley oil was found to be effective than panax ginseng extract and the combined treatment was more effective than the single treatment. It could be concluded that both parsley oil and panax ginseng extract induced a protective action against ZEN-induced alteration in the reproductive performance and the combined treatment may be useful than the single treatment.

  14. Stimulation of DDX3 expression by ginsenoside Rg3 through the Akt/p53 pathway activates the innate immune response via TBK1/IKKε/IRF3 signalling.

    Choi, Yeo-Jin; Kang, Li-Jung; Lee, Seong-Gene


    DEAD-box RNA helicase DDX3 is a well-known host factor that inhibits hepatitis B viral proliferation and boosts innate immune responses via TANK-binding kinase 1 (TBK1)/IKKε-mediated and/or interferon (IFN)-β promoter stimulator-1 (IPS-1)-mediated IFN-β induction. Previously, we demonstrated the anti-hepatitis B activity of Rg3 via stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signaling. To determine the effects of Rg3 on innate immunity, an IFN-β promoter assay was performed. Rg3 ameliorated IFN-β expression via upregulation of both the TBK1/IKKε pathway and DDX3 expression. In addition, Rg3 induced the phosphorylation of IRF3 and its translocation into nucleus, which is a key molecule to induction of IFN-β expression. To evaluate the molecular mechanism of Rg3 on DDX3 expression, the DDX3 promoter (-1406/+105) was subjected to luciferase assay and ChIP analysis. p53 phosphorylation resulted in upregulation of DDX3 expression, which enhanced DDX3 promoter transactivation activity. Transient transfection with wild-type p53 increased DDX3 promoter activity in Hep3B cells which have null mutant of p53, whereas knockdown p53 by si-p53 reduced DDX3 promoter activity in HepG2.2.15 and HepG2 cells, respectively. Rg3- mediated phosphorylation of p53 resulted in inhibition of Akt phosphorylation, which in turn reduced MDM2-mediated p53 degradation. An Akt inhibitor augmented DDX3 promoter activity and reduced the secretion of hepatitis B surface antigen. Our data indicate that Rg3 enhances innate immunity by inducing IFN-β expression through upregulation of DDX3 promoter activity via p53-mediated transactivation and activation of the TBK1/IKKε/IRF3 pathway.

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

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


    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. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Qun Zhao


    Full Text Available 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.

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

    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


    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.

  18. Analysis of Low-polar Ginsenosides in Steamed Panax Ginseng at High-temperature by HPLC-ESI-MS/MS

    ZHANG Yu-chi; PI Zi-feng; LIU Chun-ming; SONG Feng-rui; LIU Zhi-qiang; LIU Shu-ying


    A high performance liquid chromatography coupled with electrospray ionization-tandem mass spectrometry(HPLC-ESI-MS/MS) method was developed for the analysis and identification of ginsenosides in the extracts of raw Panax ginseng(RPG) and steamed Panax ginseng at high temperatures(SPGHT).A total of 25 ginsenosides were extracted include of which 10 low-polar ginsenosides,such as ginsenosides F4,Rk3,Rh4,20S-Rg3,20R-Rg3 and so on,were identified according to their HPLC retention time and MS/MS data.The results indicated that the low polar ginsenosides were seldom found in RPG.For the exploration of the transformation pattern of the ginsenosides in steam processing,the standards of ginsenosides Re,Rgl,Rbl,Rc,Rb2,Rb3 and Rd were selected and hydrolyzed at a temperature of 120 ℃.The results show that these polar ginsenosides can be converted to low-polar ginsenosides such as Rg2,Rg6,F4,Rk3 and Rg5 by hydrolyzing the sugar chains.

  19. Modification of ginsenoside composition in red ginseng (Panax ginseng by ultrasonication

    Sung-hyun Yoon


    Full Text Available The result of USRG-12 indicated that ultrasonication-processed (100°C, 12 h red ginseng extracts had the highest amount of ginsenosides Rg3 (0.803%, Rg5 (0.167%, and Rk1 (0.175%.

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

    Gao, Shengli; Kushida, Hirotaka; Makino, Toshiaki


    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.

  1. The in Vitro Structure-Related Anti-Cancer Activity of Ginsenosides and Their Derivatives

    Liang Liu


    Full Text Available Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE, protopanaxadiol (PPD-type, protopanaxatriol (PPT-type ginsenosides fractions, and their hydrolysates, which were prepared by stepwise hydrolysis of the sugar moieties of the ginsenosides. The results showed that the cytotoxic potency of the hydrolysates of RSE and total PPD-type or PPT-type ginsenoside fractions was much stronger than the original RSE and ginsenosides; especially the hydrolysate of PPD-type ginsenoside fractions. Subsequently, two derivatives of protopanaxadiol (1, compounds 2 and 3, were synthesized via hydrogenation and dehydration reactions of compound 1. Using those two derivatives and the original ginsenosides, a comparative study on various cancer cell lines was conducted; the results demonstrated that the cytotoxic potency was generally in the descending order of compound 3 > 20(S-dihydroprotopanaxadiol (2 > PPD (1 > 20(S-Rh2 > 20(R-Rh2 ≈ 20(R-Rg3 ≈ 20(S-Rg3. The results clearly indicate the structure-related activities in which the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells.

  2. Ginseng ginsenoside pharmacology in nervous systems: involvement of the regulations of ion channels and receptors

    Seung-Yeol eNah


    Full Text Available Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional medicines and is thought to be a tonic. It has been claimed that ginseng may improve vitality and health. Recent studies have advanced ginseng pharmacology and shown that ginseng has various pharmacological effects in the nervous system. Ginsenosides, steroid glycosides extracted from ginseng, were one of the first class of biologically active plant glycosides identified. The diverse pharmacological effects of ginsenosides have been investigated through the regulation of various types of ion channels and receptors in neuronal cells and heterologous expression systems. Ginsenoside Rg3 regulates voltage-gated ion channels such as Ca2+, K+, and Na+ channels, and ligand-gated ion channels such as GABAA, 5-HT3, nicotinic acetylcholine, and N-methyl-D-aspartate (NMDA receptors through interactions with various sites including channel blocker binding sites, toxin-binding sites, channel gating regions, and allosteric channel regulator binding sites when the respective ion channels or receptors are stimulated with depolarization or ligand treatment. Treatment with ginsenoside Rg3 has been found to stabilize excitable cells by blocking influxes of cations such as Ca2+ and Na+, or by enhancing Cl- influx. The aim of this review is to present recent findings on the pharmacological functions of the ginsenosides through the interactions with ion channels and receptors. This review will detail the pharmacological applications of ginsenosides as neuroprotective drugs that target ion channels and ligand-gated ion channels.

  3. Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography

    Park, Hee-Won; In, Gyo; Han, Sung-Tai; Lee, Myoung-Woo; Kim, So-Young; Kim, Kyung-Tack; Cho, Byung-Goo; Han, Gyeong-Ho; Chang, Il-Moo


    A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides. PMID:24235860

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

    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


    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.

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

    Yanping Deng

    Full Text Available 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.

  6. Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

    Li-Yuan Ma


    Full Text Available A high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg1 (1; 20(S-ginsenoside Rh1 (2; 20(S-ginsenoside Rg2 (3; 20(R-ginsenoside Rh1 (4; 20(R-ginsenoside Rg2 (5; ginsenoside Rd (6; 20(S-ginsenoside Rg3 (7; and 20(R-ginsenoside Rg3 (8 in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long tmax values, suggesting that they were slowly absorbed, while the ginsenosides 1–5, belonging to protopanaxatriol-type saponins, had different tmax values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t1/2 of 20(S-epimers were always longer than those of 20(R-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL.

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

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


    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.

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

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


    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

  9. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases

    Chang Ho Lee


    Full Text Available Ginseng is widely used for its promising healing and restorative properties as well as for its possible tonic effect in traditional medicine. Nowadays, many studies focus on purified individual ginsenoside, an important constituent in ginseng, and study its specific mechanism of action instead of whole-plant extracts on cardiovascular diseases (CVDs. Of the various ginsenosides, purified ginsenosides such as Rb1, Rg1, Rg3, Rh1, Re, and Rd are the most frequently studied. Although there are many reports on the molecular mechanisms and medical applications of ginsenosides in the treatment of CVDs, many concerns exist in their application. This review discusses current works on the countless pharmacological functions and the potential benefits of ginseng in the area of CVDs. Results: Both in vitro and in vivo results indicate that ginseng has potentially positive effects on heart disease through its various properties including antioxidation, reduced platelet adhesion, vasomotor regulation, improving lipid profiles, and influencing various ion channels. To date, approximately 40 ginsenosides have been identified, and each has a different mechanism of action owing to the differences in chemical structure. This review aims to present comprehensive information on the traditional uses, phytochemistry, and pharmacology of ginseng, especially in the control of hypertension and cardiovascular function. In addition, the review also provides an insight into the opportunities for future research and development on the biological activities of ginseng.

  10. Ginsenoside composition and antiproliferative activities of explosively puffed ginseng (Panax ginseng C.A. Meyer).

    Yoon, Sung-Ran; Lee, Gee-Dong; Park, Jung-Hyun; Lee, In-Seon; Kwon, Joong-Ho


    The puffing process was evaluated as an alternative to the steaming process for producing a biologically more active ginseng product, like red ginseng, from raw ginseng. A puffing treatment of dried raw ginseng roots induced an overall increase in crude saponin content. As puffing pressure increased, the content of ginsenoside Re, Rg1, Rb1, Rc, and Rb2 decreased, while ginsenoside Rg3 increased significantly as compared to raw ginseng. The content of ginsenoside Rg3 in puffed ginseng at a pressure of 490 kPa was similar to that of red ginseng. Cancer cell lines (HeLa, MCF-7, and HepG2) showed that antiproliferative effects of saponin extract of puffed ginseng increased with an increase in puffing pressure. Ginseng explosively puffed at 490 kPa had similar saponin constituents and antiproliferative effects as those of red ginseng. The puffing process could provide an alternative mean to produce functional ginseng products, along with a reduction in processing time as compared to traditional red ginseng processing by steam.

  11. Bioconversion of Ginsenosides in the American Ginseng (西洋參 Xī Yáng Shēn Extraction Residue by Fermentation with Lingzhi (靈芝 Líng Zhī, Ganoderma Lucidum

    Bo Yang Hsu


    Full Text Available Ginseng (人参 Rén Shēn has been widely employed in functional foods and traditional medicines in many Asian countries. Owing to the high consumer demand of ginseng products, a large amount of ginseng residue is generated after extraction of ginseng. However, the ginseng residue still contains many bioactive compounds such as ginsenosides. The objective of this research was to convert ginsenosides in American ginseng (西洋參 Xī Yáng Shēn extraction residue (AmR by fermentation with lingzhi (靈芝 Líng Zhī, Ganoderma lucidum and the fermentation products will be used for further hypoglycemic activity research. Thus, this study was primarily focused on the ginsenosides that have been reported to possess hypoglycemic activity. In this study, the changes in seven ginsenoside [Rg1, Re, Rb1, Rc, Rg3(S, compound K (CK, and Rh2(S] in the products as affected by fermentation were investigated. Our results showed that the levels of ginsenosides, namely, Rg1, Rg3(S, and CK increased, while the other ginsenosides (Re, Rb1, and Rc decreased during the fermentation process.

  12. Pharmacokinetic compatibility of ginsenosides and Schisandra Lignans in Shengmai-san: from the perspective of p-glycoprotein.

    Yan Liang

    Full Text Available 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.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.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 Rb1 significantly.

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

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


    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.

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

    Kang, Hee; Hwang, Yun-Gu; Lee, Taek-Guen; Jin, Cheng-Ri; Cho, Chi Heung; Jeong, Hee-Yeong; Kim, Dae-Ok


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

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

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


    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.

  16. The effect of extrusion conditions on the acidic polysaccharide, ginsenoside contents and antioxidant properties of extruded Korean red ginseng

    Gui, Ying; Ryu, Gi Hyung


    This study was conducted to investigate the effect of extrusion conditions (moisture content 20% and 30%, screw speed 200 and 250 rpm, barrel temperature 115℃ and 130℃) on the acidic polysaccharide, ginsenoside contents and antioxidant properties of extruded Korean red ginseng (KRG). Extruded KRGs showed relatively higher amounts of acidic polysaccharide (6.80% to 9.34%) than nonextruded KRG (4.34%). Increased barrel temperature and screw speed significantly increased the content of acidic polysaccharide. The major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg2s, Rg3s, Rh1, and Rg3r) of KRG increased through extrusion, while the ginsenoside (Rg1) decreased. The EX8 (moisture 30%, screw speed 250 rpm, and temperature 130℃) had more total phenolics and had a better scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals than those of extruded KRG samples. The extrusion cooking showed a significant increase (6.8% to 20.9%) in reducing power. Increased barrel temperature significantly increased the values of reducing power, the highest value was 1.152 obtained from EX4 (feed moisture 20%, screw speed 250 rpm, and temperature 130℃). These results suggest that extrusion conditions can be optimized to retain the health promoting compounds in KRG products. PMID:23717175

  17. 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.

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


    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.

  18. Biotransformation of major ginsenosides in ginsenoside model culture by lactic acid bacteria

    Seong-Eun Park


    Conclusion: Ginsenosides Rb1, Rb2, Rc, and Re continuously decreased, whereas ginsenosides Rd, Rg1, and Rg2 increased after 1–2 d of fermentation. This study may provide new insights into the metabolism of ginsenosides and can clarify the metabolic changes in ginsenosides biotransformed by LAB.

  19. Effects of ginsenoside of stem and leaf combined with choline on learning and memory ability of rat models with Alzheimer diseases

    Xiaomin Zhao; Xianglin Xie; Zuoli Xia; Yunsheng Gao; Yuyun Zhu; Hongxia Gu


    BACKGROUND: Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf (GSL) can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease (AD).OBJECTIVE: To observe the effects of GSL combining with choline on learning and memory of AD model rats.DESIGN: Randomized grouping design and controlled animal study.SETTING: Department of Pharmacology, Taishan Medical College.MATERIALS: The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications: GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [(55±1)%, CV= 2%, n= 5]. Choline was provided by the Third Shanghai Laboratory Factory.METHODS: 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled jumped up safe platform when they were shocked with 36 V

  20. Simultaneous quantification of 19 ginsenosides in black ginseng developed from Panax ginseng by HPLC-ELSD.

    Sun, Bai-Shen; Gu, Li-Juan; Fang, Zhe-Ming; Wang, Chun-yan; Wang, Zhen; Lee, Mi-Ra; Li, Zheng; Li, Jing-Jie; Sung, Chang-Keun


    A high-performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD) has been developed to identify and quantify 19 ginsenosides (Rg(1), Re, Rf, Rb(1), Rc, Rb(2), Rd, F(4), Rg(6), Rk(3), Rh(4), 20(S)-, 20(R)-Rg(3), 20(S)-, 20(R)-Rs(3), Rk(1), Rg(5), Rs(4), and Rs(5)) in black ginseng (BG, Korean white ginseng that was subjected to nine cycles of steam treatment). Ultrasonication is employed for sample preparation, and the analysis is achieved on a Discovery C(18) column using gradient elution of CH(3)CN-H(2)O-CH(3)COOH without buffer in 40min. The method was validated by linearity (r(2)> or =0.9994), precision (92.0-107.5%), intra- and inter-day accuracy (R.S.D.<3.21%), and limit of detection (LOD< or =93ng). The quantification method was applied to analyze the composition of ginsenosides in Korean white, red, and black ginsengs. During the preparatory process of BG, ginsenosides transform into constituents of low polarity by hydrolysis, isomerization, and dehydration at C-20, and hydrolysis also occurs at C-3 or C-6. The validated HPLC method is expected to provide the basis for the quality assessment of ginseng products.

  1. Purification and Characterization of a Ginsenoside Rb1-Hydrolyzing β-Glucosidase from Aspergillus niger KCCM 11239

    Kyung Hoon Chang


    Full Text Available Rb1-hydrolyzing β-glucosidase from Aspergillus niger KCCM 11239 was studied to develop a bioconversion process for minor ginsenosides. The specific activity of the purified enzyme was 46.5 times greater than that of the crude enzyme. The molecular weight of the native enzyme was estimated to be approximately 123 kDa. The optimal pH of the purified enzyme was pH 4.0, and the enzyme proved highly stable over a pH range of 5.0–10.0. The optimal temperature was 70 °C, and the enzyme became unstable at temperatures above 60 °C. The enzyme was inhibited by Cu2+, Mg2+, Co2+, and acetic acid (10 mM. In the specificity tests, the enzyme was found to be active against ginsenoside Rb1, but showed very low levels of activity against Rb2, Rc, Rd, Re, and Rg1. The enzyme hydrolyzed the 20-C,β-(1→6-glucoside of ginsenoside Rb1 to generate ginsenoside Rd and Rg3, and hydrolyzed 3-C,β-(1→2-glucoside to generate F2. The properties of the enzyme indicate that it could be a useful tool in biotransformation applications in the ginseng industry, as well as in the development of novel drug compounds.

  2. Screening of QHF formula for effective ingredients from Chinese herbs and its anti-hepatic cell cancer effect in combination with chemotherapy


    Background Recent studies have shown that effective ingredients of Chinese herbs are used more and more widely in the treatment or co-treatment of cancers,however,they are usually used separately and there has been limited research about joint application of Chinese herbs in multi-modal treatment.The aim of this study was to screen a QHF(Q:Qingrejiedu,H:Huoxuehuayu and F:Fuzhengguben)formula for effective ingredients from Chinese medicines and assess its anti-hepatic cell cancer(HCC)effect in combination with chemotherapy.Methods Six effective ingredients from Chinese medicine were selected based on the previous literature and used in the study.The QHF formula and the best ratio of ingredients were evaluated in H22 mouse(KM)models with solid tumors and ascites tumors by uniform design and monitoring inhibition of tumor growth and survival.We then observed the anti-hepatic cell cancer(HCC)effect of QHF when combined with cisplatin(DDP)in H22 mouse(Balb/c)models with solid tumors and ascites tumors.Evaluating of the therapeutic effect included the general condition of the mice,inhibition of tumor growth,survival,changes in body weight,thymus index,spleen index and WBC counts.Results The optimal QHF dose ratio for anti-hepatic cell cancer treatment was:800 mg/kg Cinobufotalin,14 mg/kg Ginsenosides Rg3,5.5 mg/kg PNS and 100 mg/kg Lentinan.Treatment was more efficient in inhibiting the growth of transplanted tumors in H22 mice when using the QHF formula(55.91%)than using Cinobufotalin(33.25%),Ginsenosides Rg3(35.11%),PNS(27.12%)or Lentinan(4.97%)separately.QHF also prolonged the life of H22 ascites hepatic cancer mice more efficiently(38.13%)than Cinobufotalin(25.00%),Ginsenosides Rg3(27.27%),PNS(23.30%) or Lentinan (24.43%).QHF combined with DDP could reduce DDP-induced leucopenia,spleen and thymus atrophy and other toxic reactions.Combining QHF with DDP the tumor growth inhibition reached 82.54% with a 66.83% increase in survival.Conclusions QHF is more efficient in

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

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


    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. Copyright © 2015 John Wiley & Sons, Ltd.

  4. A Strategy for Simultaneous Isolation of Less Polar Ginsenosides, Including a Pair of New 20-Methoxyl Isomers, from Flower Buds of Panax ginseng

    Sha-Sha Li


    Full Text Available The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG. Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic extraction, Diaion Hp-20 macroporous resin column enrichment, solid phase extraction (SPE, reversed-phase high-performance liquid chromatography (RP-HPLC analysis and preparation, and nuclear magnetic resonance (NMR analysis. The quantification of the five ginsenosides was also discussed by a developed method with validations within acceptable limits. Ginsenoside Rg5 showed content of about 1% in FBPG. The results indicated that FBPG might have many different ginsenosides with diverse chemical structures, and the less polar ginsenosides were also important to the quality control and standardization of FBPG.

  5. A Strategy for Simultaneous Isolation of Less Polar Ginsenosides, Including a Pair of New 20-Methoxyl Isomers, from Flower Buds of Panax ginseng.

    Li, Sha-Sha; Li, Ke-Ke; Xu, Fei; Tao, Li; Yang, Li; Chen, Shu-Xiao; Gong, Xiao-Jie


    The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG). Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic extraction, Diaion Hp-20 macroporous resin column enrichment, solid phase extraction (SPE), reversed-phase high-performance liquid chromatography (RP-HPLC) analysis and preparation, and nuclear magnetic resonance (NMR) analysis. The quantification of the five ginsenosides was also discussed by a developed method with validations within acceptable limits. Ginsenoside Rg5 showed content of about 1% in FBPG. The results indicated that FBPG might have many different ginsenosides with diverse chemical structures, and the less polar ginsenosides were also important to the quality control and standardization of FBPG.

  6. 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.

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


    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.

  7. Endophytic Bacteria Isolated from Panax ginseng Improves Ginsenoside Accumulation in Adventitious Ginseng Root Culture

    Xiaolin Song


    Full Text Available Ginsenoside is the most important secondary metabolite of ginseng. Natural sources of wild ginseng have been overexploited. Although root culture could reduce the length of the growth cycle of ginseng, the number of ginsenosides is fewer and their contents are lower in adventitious roots of ginseng than that in ginseng cultivated in the field. In this study, we investigated the effects of endophytic bacterial elicitors on biomass and ginsenoside production in adventitious roots cultures of Panax ginseng. Endophyte LB 5-3 as an elicitor could increase biomass and ginsenoside accumulation in ginseng adventitious root culture. After 6 days elicitation with a 10.0 mL of strain LB 5-3, the content of total ginsenoside was 2.026 mg g−1 which was four times more than that in unchallenged roots. The combination of methyl jasmonate and strain LB 5-3 had a negative effect on ginseng adventitious root growth and ginsenoside production. The genomic DNA of strain LB 5-3 was sequenced, and was found to be most closely related to Bacillus altitudinis (KX230132.1. The challenged ginseng adventitious root extracts exerted inhibitory effect against the HepG2 cells, which IC50 value was 0.94 mg mL−1.

  8. Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property

    Chang-Hao Cui


    Full Text Available Minor ginsenosides, such as compound K, Rg3(S, which can be produced by deglycosylation of ginsenosides Rb1, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb1, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231 in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb1. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries.

  9. Extraction of ginsenosides from fresh ginseng roots (Panax ginseng C.A. Meyer) using commercial enzymes and high hydrostatic pressure.

    Sunwoo, Hoon H; Kim, Chong-Tai; Kim, Do-Yeon; Maeng, Jin-Soo; Cho, Chang-Won; Lee, Soo-Jeong


    A combination of high hydrostatic pressure (HHP) and enzymatic hydrolysis (HHP-EH) was applied for the extraction of ginsenosides from fresh ginseng roots (Panax ginseng C.A. Myer). The highest yield of ginsenosides was obtained by using a mixture of three enzymes (Celluclast + Termamyl + Viscozyme) along with HHP (100 MPa, at 50 °C for 12 h) in comparison to control samples (no enzymes, atmosphere pressure, P enzyme activity. Thus HHP-EH significantly improves the extraction of ginsenosides from fresh ginseng roots.

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

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


    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Remarkable Impact of Acidic Ginsenosides and Organic Acids on Ginsenoside Transformation from Fresh Ginseng to Red Ginseng.

    Liu, Zhi; Xia, Juan; Wang, Chong-Zhi; Zhang, Jin-Qiu; Ruan, Chang-Chun; Sun, Guang-Zhi; Yuan, Chun-Su


    Panax ginseng contains many chemical components, including acidic ginsenosides and organic acids. However, whether these acidic substances play a role in ginsenoside transformation during steaming treatment has not yet been explored. In this paper, the content of neutral ginsenosides, acidic ginsenosides, and their degradation products in unsteamed and steamed P. ginseng were simultaneously quantified by high-performance liquid chromatography. We observed that neutral ginsenosides were converted to rare ginsenosides during the root steaming but not during the individual ginsenoside steaming. In contrast, acidic malonyl ginsenosides released malonic acid and acetic acid through demalonylation, decarboxylation, deacetylation reactions during the steaming at 120 °C. These malonyl ginsenosides not only were converted to rare ginsenosides but also promoted the degradation of neutral ginsenosides. Further studies indicated that a low concentration of organic acid was the determining factor for the ginsenoside conversion. The related mechanisms were deduced to be mainly acidic hydrolysis and dehydration. In summary, acidic ginsenosides and organic acids remarkably affected ginsenoside transformation during the steaming process. Our results provide useful information for precisely understanding the ginsenoside conversion pathways and mechanisms underlying the steaming process.

  12. 人参皂甙Rg3对乳腺癌细胞表达MMP-2和MMP-9的影响

    李博; 杨威; 郑永晨; 杨艳秋



  13. Complete 1H-NMR and 13C-NMR spectral analysis of the pairs of 20(S and 20(R ginsenosides

    Heejung Yang


    Methods: We isolated 21 compounds, including 10 pairs of 20(S and 20(R less polar ginsenosides (1–20, and an oleanane-type triterpene (21 from a processed ginseng preparation and obtained complete 1H-NMR and 13C-NMR spectroscopic data for the following compounds, referred to as compounds 1–21 for rapid identification: 20(S-ginsenosides Rh2 (1, 20(R-Rh2 (2, 20(S-Rg3 (3, 20(R-Rg3 (4, 6′-O-acetyl-20(S-Rh2 [20(S-AcetylRh2] (5, 20(R-AcetylRh2 (6, 25-hydroxy-20(S-Rh2 (7, 25-hydroxy-20(S-Rh2 (8, 20(S-Rh1 (9, 20(R-Rh1 (10, 20(S-Rg2 (11, 20(R-Rg2 (12, 25-hydroxy-20(S-Rh1 (13, 25-hydroxy-20(R-Rh1 (14, 20(S-AcetylRg2 (15, 20(R-AcetylRg2 (16, Rh4 (17, Rg5 (18, Rk1 (19, 25-hydroxy-Rh4 (20, and oleanolic acid 28-O-β-D-glucopyranoside (21.

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

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


    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

  15. Nootropic effects and mechanism of ginsenoside Rg



    Ginsenoside Rg 1 is a main active principle of ginseng which shares many activities of ginseng. In present paper we will take overview of the proven memory-enhancing effect of Rgl and discuss all its possible mechanics in detail.

  16. Ginsenosides stimulated the proliferation of mouse spermatogonia involving activation of protein kinase C

    Da-lei ZHANG; Kai-ming WANG; Cai-qiao ZHANG


    The effect of ginsenosides on proliferation of type A spermatogonia was investigated in 7-day-old mice.Spermatogonia were characterized by c-kit expression and cell proliferation was assessed by immunocytochemical demonstration of proliferating cell nuclear antigen (PCNA).After 72-h culture,Sertoli cells formed a confluent monolayer to which numerous spermatogonial colonies attached.Spermatogonia were positive for c-kit staining and showed high proliferating activity by PCNA expression.Ginsenosides (1.0~10 μg/ml) significantly stimulated proliferation of spermatogonia.Activation of protein kinase C (PKC) elicited proliferation of spermatogonia at 10-8 to 107 mol/L and the PKC inhibitor H7 inhibited this effect.Likewise,ginsenosides-stimulated spermatogonial proliferation was suppressed by combined treatment of H7.These results indicate that the proliferating effect ofginsenosides on mouse type A spermatogonia might be mediated by a mechanism involving the PKC signal transduction pathway.

  17. Effect of Ginsenoside Re on shock

    L(U) Shuang; XU Feng; MA Wen-hui; YAO Yao


    Objective To evaluate the effect of Ginsenoside Re on Shock through different animal models in order to provide preclinical pharmacological experimental data. Methods In superior mesenteric artery occlusion(SMAO) of rats model was established by clamping superior mesenteric artery (SMA) for 2 hours and then reperfusing for another 2 hours. During the whole process mean artery pressure (MAP) and heart rate (HR) were recorded. The blood samples were collected before and 2 hours after damping respectively, to determine serum GOT, GPT, LDH, GLU, CK, BUN, Cr and NO. Intestine, lung, heart, kidney and liver tissue samples were also collected after reperfusion 2 hours, and (1) protein concentration of bronehia alveolus lung fluid [BALF], (2) HSP70 expression in heart and kidney (3) histology pathology and (4) oxidation injury (MDA and GSH-Px) in above tissues were determined. Hemorrhagic shock (HS) of eats, scald shock model and insulin shock model were also introduced here. Results Ginsenoside Re decreased the morality of SMAO rats and the GOT, GPT, LDH, CK, BUN, NO and Cr level, the GSH-Px activity was increased and MDA content was decreased. The expression of HSP70 in heart and kidney were up-regulated and the protein content in BALF was inhibited after Ginsenoside Re treatment. Ginsenoside Re corrected acidosis induced by HS, and elevated Hb content, reduced serum MDA, LD level. Ginsenoside Re eould attenuate liver and lung tissue injury. In scald shock, Ginsenoside Re decreased LDH, CK-MB, a-HBD and Het of serum and in insulin shock survival time was prolonged. Conclusions Ginsenoside Re showed an anti-shock activity.

  18. Biotransformation of ginsenoside Rb1 to ginsenoside C-K by endophytic fungus Arthrinium sp. GE 17-18 isolated from Panax ginseng.

    Fu, Y; Yin, Z-H; Wu, L-P; Yin, C-R


    This research aimed to isolate β-glycosidase-producing endophytic fungus in Panax ginseng to achieve biotransformation of ginsenoside Rb1 to ginsenoside C-K. Of these 15 β-glucosidase-producing endophytic fungus isolated from ginseng roots, a β-glucosidase-producing endophytic fungi GE 17-18 could hydrolyse major ginsenosides Rb1 to minor ginsenoside C-K with metabolic pathways: ginsenoside Rb1→ginsenoside Rd→ginsenoside F2→ginsenoside C-K. Phylogenetic analysis of ITS gene sequences indicated that the strain GE 17-18 belongs to the genus Arthrinium and is most closely related to Arthrinium sp. HQ832803.1. This is the first study to provide information of cultivable β-glycosidase-producing Endophytic fungus in Panax ginseng. The strain GE 17-18 has potential to be applied on the preparation for minor ginsenoside C-K in pharmaceutical industry. © 2016 The Society for Applied Microbiology.

  19. Facile reduction and stabilization of ginsenoside-functionalized gold nanoparticles: optimization, characterization, and in vitro cytotoxicity studies

    Hurh, Joon; Markus, Josua; Kim, Yeon-Ju; Ahn, Sungeun; Castro-Aceituno, Veronica; Mathiyalagan, Ramya; Kim, Yu Jin; Yang, Deok Chun


    Gold nanoparticles (GNPs) are forecasted to provide an attractive platform in biomedicine and catalysis with their potentials of combining a variety of biophysicochemical properties into an integrated nanodevice with great therapeutic and optical functions. There are several reports of crude plant extracts mediating the conversion of metal ions into nanoparticles. However, we aimed to investigate the capability of single bioactive compounds, namely ginsenosides compound K (C-K) and Rh2, to accommodate a synergistic chemical reduction of gold salts by one-pot green chemistry. Ginsenosides C-K and Rh2 are unique triterpenoid saponins present in Panax ginseng Meyer, a perennial plant traditionally used as an oriental medicinal herbal with long history. C-K and Rh2 have demonstrated diverse pharmacological properties such as anticancer, anti-inflammation, anti-aging, and neuroprotective properties. The reduction of gold ions by these ginsenosides led to the production of nontoxic GNPs as tested in mouse macrophage (J774A.1) and human kidney epithelial (HEK-293) in vitro. The kinetics of the bioreduction and the influence of pH were examined by an ultraviolet-visible (UV-Vis) spectrophotometer. GNPs were characterized by field emission transmission electron microscopy (FE-TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy. Ginsenoside loading efficiency of C-K-GNPs and Rh2-GNPs was determined to be approximately 62.83% and 54.91%, respectively, by thermogravimetric analysis (TGA). These results suggest that one-pot synthesis by ginsenosides C-K and Rh2 may be useful for producing ginsenoside-loaded gold nanocarriers. [Figure not available: see fulltext.

  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

    Jun Wang


    Full Text Available 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.

  1. Co-transformation of Panax major ginsenosides Rb₁ and Rg₁ to minor ginsenosides C-K and F₁ by Cladosporium cladosporioides.

    Wu, Lunpeng; Jin, Yan; Yin, Chengri; Bai, Longlv


    Rb₁ and Rg₁ are the major ginsenosides in protopanaxadiol and protopanaxatriol. Their content in ginsenosides was 23.8 and 17.6%, respectively. A total of 22 isolates of β-glucosidase producing microorganisms were isolated from the soil of a ginseng field using Esculin-R2A agar. Among these isolates, the strain GH21 showed the strongest activities to convert ginsenoside Rb₁ and Rg₁ to minor ginsenosides compound-K and F₁, respectively. Ginsenosides Rb₁ and Rg₁ bioconversion rates were 74.2 and 89.3%, respectively. Meanwhile, the results demonstrated that the ginsenoside Rg₁ could change the biotransformation pathway of ginsenoside Rb₁ by inhibiting the formation of the intermediate metabolite gypenoside-XVII. GH21 was identified as a Cladosporium cladosporioides species based on the internal transcribed spacers (ITS) ITS1-5.8S-ITS2 rRNA gene sequences constructed phylogenetic trees.

  2. Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation

    Ai-wu SHI; Xiao-bin WANG; Feng-xiang LU; Min-min ZHU; Xiang-qing KONG; Ke-jiang CAO


    Aim: To investigate the effect of ginsenoside Rgl on the migration, adhesion, proliferation, and VEGF expression of endothe-lial progenitor cells (EPCs).Methods: EPCs were isolated from human peripheral blood and incubated with different concentrations of ginsenoside Rgl (0.1, 0.5, 1.0, and 5.0 μmol/L) and vehicle controls. EPC migration was detected with a modified Boyden chamber assay. EPC adhesion was determined by counting adherent cells on fibronectin-coated culture dishes. EPC proliferation was analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro vasculogenesis was assayed using an in vitro vasculogenesis detection kit. A VEGF-ELISA kit was used to measure the amount of VEGF protein in the cell culture medium.Results: Ginsenoside Rgl promoted EPC adhesionp proliferation, migration and in vitro vasculogenesis in a dose- and time-dependent manner. Cell cycle analysis showed that 5.0 μmol/L of ginsenoside Rgl significantly increased the EPC prolifera-tive phase (S phase) and decreased the resting phase (G0/G1 phase). Ginsenoside Rgl increased vascular endothelial growth factor production.Conclusion: The results indicate that ginsenoside Rgl promotes proliferation, migration, adhesion and in vitro vasculogen-esis.

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

    Seyed Fazel Nabavi


    Full Text Available 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.

  4. Biotransformation of ginsenoside Rd in the ginseng extraction residue by fermentation with lingzhi (Ganoderma lucidum).

    Hsu, Bo Yang; Lu, Ting Jang; Chen, Chia Hui; Wang, Shing Jung; Hwang, Lucy Sun


    Ginseng and lingzhi (Ganoderma lucidum) both are valuable traditional Chinese medicines and have been extensively utilised in functional foods and traditional medicines in many Asian countries. However, massive quantity of ginseng residue is produced after extraction of ginseng which still contains a lot of bioactive compounds such as ginsenosides. The goal of this study was to reuse the American ginseng extraction residue as the fermentation medium of G. lucidum to produce bioactive ginsenoside enriched biotransformation products. The changes of ginsenosides in the fermentation products were analysed during fermentation. Our results showed that after 30 days of fermentation, ginsenoside Rg1, Rd, and compound K (CK) significantly increased, especially Rd, while other ginsenosides (Re, Rb1 and Rc) decreased during fermentation. Ginsenoside Rd is the major ginsenoside in the final fermentation product. Furthermore, the biotransformation of ginsenosides was the major reaction in this fermentation process. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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


    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 (digestion and that ginsenosides are poorly absorbed in humans.

  6. Accumulation characteristics and correlation analysis of five ginsenosides with different cultivation ages from different regions

    Dan Xiao


    Conclusion: In our study, only the contents of ginsenosides Rg1 and Re were affected by the root age. Ginsenosides Rb1, Rc, and Rd varied widely with ages in samples from different cultivation regions.

  7. Microbial conversion of major ginsenosides in ginseng total saponins by Platycodon grandiflorum endophytes

    Lei Cui


    Conclusion: This is the first report about conversion of major ginsenosides into minor ginsenosides by fermentation with P. grandiflorum endophytes. The results of the study indicate endophyte JG09 would be a potential microbial source for obtaining minor ginsenosides.

  8. Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage

    Lining Ke; Wei Guo; Jianwen Xu; Guodong Zhang; Wei Wang; Wenhua Huang


    The microglia-mediated inlfammatory reaction promotes neuronal damage under cerebral isch-emia/hypoxia conditions. We therefore speculated that inhibition of hypoxia-induced microglial activation may alleviate neuronal damage. To test this hypothesis, we co-cultured ginsenoside Rb1, an active component of ginseng, and cortical neurons. Ginsenoside Rb1 protected neuronal morphology and structure in a single hypoxic culture system and in a hypoxic co-culture system with microglia, and reduced neuronal apoptosis and caspase-3 production. The protective effect was observable prior to placing in co-culture. Additionally, ginsenoside Rb1 inhibited levels of tumor necrosis factor-αin a co-culture system containing activated N9 microglial cells. Ginse-noside Rb1 also signiifcantly decreased nitric oxide and superoxide production induced by N9 microglia. Our ifndings indicate that ginsenoside Rb1 attenuates damage to cerebral cortex neu-rons by downregulation of nitric oxide, superoxide, and tumor necrosis factor-αexpression in hypoxia-activated microglia.

  9. Improvement of memory in mice and increase of hippocampal excitability in rats by ginsenoside Rg1's metabolites ginsenoside Rh1 and protopanaxatriol.

    Wang, Yu-Zhu; Chen, Ji; Chu, Shi-Feng; Wang, Yong-Sheng; Wang, Xiao-Ying; Chen, Nai-Hong; Zhang, Jun-Tian


    Ginsenoside Rg1 has been reported to improve cognitive function in many memory-impaired animal models. However, little is known about the bioactivity of its metabolites in the central nervous system in vivo. In the present study, we employed the step through test and electrophysiological approach to investigate the effects of ginsenoside Rg1's primary metabolite ginsenoside Rh1 and end metabolite protopanaxatriol (Ppt) on learning and memory as well as hippocampal excitability. The behavioral study showed that both ginsenoside Rh1 and Ppt significantly ameliorated memory-impaired models induced by scopolamine in mice. Consistently, the electrophysiological work revealed that ginsenoside Rh1 and Ppt as well as their precursor ginsenoside Rg1 all increased hippocampal excitability in the dentate gyrus of anesthetized rats. These results demonstrated that both ginsenoside Rh1 and Ppt had similar but more potent actions than ginsenoside Rg1 in improving memory and hippocampal excitability, suggesting the role of ginsenoside's sugar moieties in biological activities is not as necessary as traditionally considered.

  10. Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid.

    Lü, Jian-Ming; Weakley, Sarah M; Yang, Zhen; Hu, Ming; Yao, Qizhi; Chen, Changyi


    Reactive oxygen species (ROS) have been implicated in a variety of inflammatory diseases including cardiovascular disease (CVD), cancer, diabetes, Alzheimer's disease, autism, cataracts and aging. When endogenous mechanisms for the maintenance of redox homeostasis are overwhelmed, dietary intake of antioxidants contributes substantially to balancing the body's oxidant/antioxidant status. Ginsenosides are thought to be primarily responsible for the pharmacological effect of P. ginseng root extracts on oxidative stress and inflammation. However, little is known about the underlying antioxidant mechanisms of individual ginsenoside; specifically, the reactivity of ginsenoside Rb1 with ROS has not been well studied. We found that Rb1 can significantly and selectively reduce hydroxyl radical (●OH) and hypochlorous acid (HOCl), two of the strongest ROS, with unique molecular mechanisms in a cell-free system. Rb1 directly scavenges the ●OH and protects plasmid DNA from damage induced by ●OH. ●OH likely attacks the double bond on the side chain of Rb1 as well as hydrogen atoms adjacent to the -OH groups, including those of sugar moieties. Rb1 also shows a high reactivity to HOCl and effectively inhibits HOCl-induced tyrosine chlorination in a cell free system. HOCl is added to the double bond of Rb1; the -Cl group and -OH group of HOCl possibly bond at C-24 and C-25 of Rb1 based on the regioselectivity of Markovnikov's Rule. To our knowledge, this is the first demonstration that ginsenoside Rb1 scavenges HOCl and protects tyrosine from HOCl-induced chlorination. Thus, this study reveals unique antioxidant mechanisms of individual ginsenoside Rb1, which may contribute to the pharmacological effect of P. ginseng and to the development of effective strategies for clinical applications of ginsenosides.

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

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


    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.

  12. Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells

    Neo Soek-Ying


    Full Text Available Abstract Background Panax notoginseng is a potential source of anticancer compounds. This study aims to investigate the effects of steaming on the chemical profile of P. notoginseng and the anti-proliferative effects of P. notoginseng on liver cancer cells. Methods Samples of powdered raw P. notoginseng roots were steamed for various durations. Extracts of the raw and steamed samples were subjected to ultra-high pressure liquid chromatography/mass spectrometry (UHPLC-MS analysis for chemical profiling. The anti-proliferative effects on three human liver cancer cells, namely SNU449, SNU182 and HepG2, were evaluated using colorimetric WST-1 assay. Results Steaming changed chromatographic and pharmacological profiles of P. notoginseng, causing differences in activities such as inhibition of cancer growth. Steamed P. notoginseng exhibited greater anti-proliferative effects against liver cancer cells (SNU449, SNU182 and HepG2 than its raw form; steaming up to 24 hours increased bioactivities. Steaming increased the concentrations of ginsenoside Rh2, Rk1, Rk3 and 20S-Rg3 and enhanced growth inhibition of liver cancer cells. Conclusion Steaming changes the chemical profile as well as anti-cancer biological activities of P. notoginseng. Steamed P. notoginseng contains potential compounds for the treatment of liver cancer.

  13. A New Saponin Transformed from Ginsenoside Rhl by Bacillus subtilis

    Guo Hong LI; Yue Mao SHEN; Ke Qin ZHANG


    A novel saponin was isolated from the transformed products of ginsenoside Rh1 by Bacillus subtilis. It's structure was determined to be 3-O-β-D-glucopyranosyl-6-O-β-D-glucopyranosyl-20 (S)-protopanaxatriol on the basis of the spectral data.

  14. Antidepressant Effects of Ginsenosides from Panax notoginseng

    YAO Yang; SANG Wei; YANG Xiu-shi; ZHAI Mei-jing; WANG Li-li; QIN Pei-you; WU Li; ZHOU Xian-rong; WANG Li-jun; ZHU Zhi-hua; REN Gui-xing


    Ginsenosides Rg1,Rb1,R1,Rd,and Re are major constituents of Panax notoginseng,a famous traditional Chinese medicinal herb,which has both stimulative and inhibitory effects on the central nervous system (CNS).The monoamine hypothesis proposes that depression is a result of the depletion of 5-hydroxytryptamine (5-HT),norepinephrine (NE) and dopamine (DA) in addition to the activation of monoamine oxidase in the CNS.The purpose of this study was to determine whether P.notoginseng Saponin (PNS) has an antidepressant activity.We investigated the antidepressant-like activities of Rg1,Rb1,R1,Rd,and Re in mice,using two animal models of depression.In addition,we analyzed the neurochemicals by the chronic unpredictable mild stress test.Our results showed that Rb 1,Rd,and Re treatment at 10 mg kg-1 significantly reduced the duration of immobility in both the tail suspension and forced swimming tests.Rb1,Rd,and Re increases in 5HT and NE levels at 10 mg kg-1 in both the frontal cortex and hippocampus.Dopamine levels increased in the hippocampus and the striatum.Moreover,5-hydroxyindoleacetic acid (5-HIAA) levels were found increased in the hippocampus.These findings suggest that the antidepressant effects of Rb1,Rd,and Re may be related to the increase in 5-HT and NE in the CNS,and through the alterations in the synthesis or metabolism of dopamine.

  15. Integrated Transcriptomic and Metabolomic Analysis of Five Panax ginseng Cultivars Reveals the Dynamics of Ginsenoside Biosynthesis

    Yun Sun Lee


    Full Text Available Panax ginseng C.A. Meyer is a traditional medicinal herb that produces bioactive compounds such as ginsenosides. Here, we investigated the diversity of ginsenosides and related genes among five genetically fixed inbred ginseng cultivars (Chunpoong [CP], Cheongsun [CS], Gopoong [GO], Sunhyang [SH], and Sunun [SU]. To focus on the genetic diversity related to ginsenoside biosynthesis, we utilized in vitro cultured adventitious roots from the five cultivars grown under controlled environmental conditions. PCA loading plots based on secondary metabolite composition classified the five cultivars into three groups. We selected three cultivars (CS, SH, and SU to represent the three groups and conducted further transcriptome and gas chromatography-mass spectrometry analyses to identify genes and intermediates corresponding to the variation in ginsenosides among cultivars. We quantified ginsenoside contents from the three cultivars. SH had more than 12 times the total ginsenoside content of CS, with especially large differences in the levels of panaxadiol-type ginsenosides. The expression levels of genes encoding squalene epoxidase (SQE and dammarenediol synthase (DDS were also significantly lower in CS than SH and SU, which is consistent with the low levels of ginsenoside produced in this cultivar. Methyl jasmonate (MeJA treatment increased the levels of panaxadiol-type ginsenosides up to 4-, 13-, and 31-fold in SH, SU, and CS, respectively. MeJA treatment also greatly increased the quantity of major intermediates and the expression of the underlying genes in the ginsenoside biosynthesis pathway; these intermediates included squalene, 2,3-oxidosqualene, and dammarenediol II, especially in CS, which had the lowest ginsenoside content under normal culture conditions. We conclude that SQE and DDS are the most important genetic factors for ginsenoside biosynthesis with diversity among ginseng cultivars.

  16. Cellular and molecular mechanisms underlying the action of ginsenoside Rg1 against Alzheimer's disease

    Xi Li; Ming Li; Yuan Li; Qiankun Quan; Juan Wang


    Ginsenoside Rg1 inhibits oxidation, aging and cell apoptosis, and improves cognitive function. In this study, we pretreated rat brain tissue sections with ginsenoside Rg1, and established brain slice models of Alzheimer's disease induced by okadaic acid. The results revealed that ginsenoside Rg1 pretreatment suppressed the increase in phosphorylated Tau protein expression induced by incubation with okadaic acid, and reduced brain-derived neurotrophic factor expression. These results suggest that ginsenoside Rg1 upregulates brain-derived neurotrophic factor expression and inhibits Tau protein phosphorylation in brain slices from a rat model of Alzheimer's disease.

  17. An optimized microwave-assisted extraction method for increasing yields of rare ginsenosides from Panax quinquefolius L.

    Hua Yao


    Conclusion: The results indicate that rare ginsenosides can be extracted effectively by MAE from P. quinquefolius L. in a short time. Microwave radiation plays an important role in MAE. The probable generation process of rare ginsenosides is also discussed in the article. It will be meaningful for further investigation or application of rare ginsenosides.

  18. Effects of ginsenosides on opioid-induced hyperalgesia in mice.

    Li, Peng; Tang, Minke; Li, Hui; Huang, Xinjie; Chen, Lei; Zhai, Haifeng


    Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.

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

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


    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.

  20. Ginsenoside Rg1-induced alterations in gene expression in TNF-α stimulated endothelial cells

    吕俊萍; 马增春; 杨静; 黄坚; 王树人; 王升启


    Background In China the ginseng root began to be used in medicine over 2000 years ago. Ginsenosides are the most important component isolated from ginseng. The authors investigated the effect of ginsenoside Rg1 on the spectrum of gene expression in the endothelial cells stimulated by TNF-α and further explored the potential molecular mechanism of endothelial protection by ginsenoside Rg1.Methods Nitric oxide (NO) production in the cultured human umbilical vein endothelial cells(HUVECs) was measured by using an NO assay kit. A home-made oligonucleotide microarray containing approximately 400 cardiovascular disease-related genes was constructed. The alteration of the spectrum of gene expression induced by ginsenoside Rg1 in HUVECs which were activated by TNF-α were detected by oligonucleotide microarray analysis.Results NO production in HUVECs was decreased significantly after TNF-α treatment, while pretreatment with ginsenoside Rg1 enhanced NO production in TNF-αstimulated HUVECs. Ginsenoside Rg1 affected the expression levels of genes involved in vascular constriction, cell adherence, coagulation, cell growth and signal transduction in TNF-αstimulated HUVECs.Conclusions Ginsenoside Rg1 could enhance NO production and the expression of eNOS mRNA in TNF-α stimulated HUVECs. Ginsenoside Rg1 regulated sets of genes in endothelial cells and protected endothelial cells from TNF-αactivation. Microarray analysis provided us with valuable insights into the atheroprotective mechanism by gingsenoside Rg1.

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

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


    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.

  2. HPLC法测定人参毛状根及不同人参样品中9种人参皂苷的含量%Quantitation of nine ginsenosides in Panax ginseng hairy roots and other Panax ginseng plant components by HPLC

    陈泠; 李春艳; 王政; 贾敏; 韩婷


    Objective To establish an HPLC method for the quantitation of nine ginsenosides (Rc ,Rb1 ,Rb2 ,Re ,Rd , Rg1 ,Rg2 ,Rg3 and Rh2 ) in Panax ginseng samples .Methods An HPLC method was developed to determine the quantities of the nine ginsenosides .The determination was performed on a Zorbax SB C18 column (4 .6 mm × 250 mm ,5μm) with an Extend-C18 guard column (4 .6 mm × 12 .5 mm ,5 μm) at 35 ℃ .The mobile phase was a multi-step acetonitrile-water gradient run at a flow rate of 1 .0 ml/min .The detection wavelength was 203 nm .Results The nine ginsenosides were baseline separated with-in 120 min .The method had good linearity ,precision ,stability and reproducibility with RSDs all less than 2 .0% .The sample recoveries were between 98 .3% to 102% .The quantity of total saponins in leaves and fibrous roots of Panax ginseng ,which were measured as 48 .9 mg/g and 23 .6 mg/g ,respectively ,were higher than those in the other plant components .The amounts of total saponins in Panax ginseng hairy roots were similar to those in taproots and fruits of Panax ginseng ,which was 7 .47 mg/g .Conclusion The established HPLC method is accurate ,simple ,rapid ,precise and reproducible and could be used for the quantitation of these nine ginsenosides in Panax ginseng samples .%目的:采用HPLC法测定不同人参样品中9种人参皂苷(Rc、Rb1、Rb2、Re、Rd、Rg1、Rg2、Rg3和 Rh2)的含量。方法色谱条件:Zorbax SB C18柱(4.6 mm ×250 mm ,5μm),保护柱Extend-C18柱(4.6 mm ×12.5 mm ,5μm);以乙腈-水为流动相,梯度洗脱;流速:1.0 ml/min;检测波长:203 nm ;柱温:35℃。结果9种人参皂苷Rg1、Rb1、Re、Rc、Rg2、Rh2、Rg3、Rb2和Rd在120 min内基线分离。方法学表明其线性关系良好,精密度、稳定性和重复性 RSD均小于2.0%,加样回收率在98.3%~102%之间。测得人参叶和人参须根中的总皂苷含量最高,分别为48.9、23.6 mg/g ;人参

  3. Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

    Qi Huang


    Full Text Available Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK and silent information regulator 1 (sirt1. Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD and glucose tolerance.

  4. Effects of ginsenosides on vascular reactivity in rat cerebral and renal arteries

    WONG Wing-tak; LEUNG Fung-ping; YUNG Lai-hang; TIAN Xiao-yu; WONG Ricky Ngok Shun; HUANG Yu


    Objective To investigate possible mechanisms underlying the antioxidant property (1) and the in vitro vasodilator effects (2) of the two ginsenosides, Rb1 and Rg1, in isolated rat renal and cerebral arteries. Methods Arterial rings were mounted in a multi-channel myograph for recording of isometric tension. To examine the antioxidant activity, some rings were exposed to a free radical-generating reaction (hypoxan-thine and xanthine oxidase) with and without pre-treatment with ginsenosides. The calcium antagonistic effects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions, a condition that promoted Ca2+ influx in vascular smooth muscle cells. Results Ginsenosides protected endothelial function (endothelial nitric oxide-dependent relaxation) against oxidative stress; (2) ginsenoside Rb1 reduced the high K+ -induced contractions of both renal and cerebral arteries while ginsenoside Rgl relaxed the rat cerebral artery but not the renal artery. Conclusions Ginsenosides are vaso-protective via (1) the antioxidant activity which protects endothelial cell function and (2) the inhibition of Ca2+ influx through voltage-sensitive Ca2+ channels in vascular smooth muscle. The vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.

  5. Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injur y

    Baogang Wang; Qingsan Zhu; Xiaxia Man; Li Guo; Liming Hao


    Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de-pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper-fusion injury. These ifndings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

  6. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    Ying-bo Li


    Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  7. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    Ying-bo Li; Yan Wang; Ji-ping Tang; Di Chen; Sha-li Wang


    Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10–80 μM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent exper-iments. Whole-cell patch clamp showed that neural stem cells induced by 20 μM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypox-ic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplantedvia intracerebroventricular injection. These tests conifrmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a signiifcantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-speciifc enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  8. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

    Sena Lee


    Full Text Available The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80. Ginsenoside Re (20 mg/kg or 100 mg/kg was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration and xanthine oxidase (XO and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation and decreases in the contents of hexosamine (a marker of gastric mucus and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

  9. Neuroprotective effects of ginsenoside Rb1 on hippocampal neuronal injury and neurite outgrowth

    Juan Liu; Jing He; Liang Huang; Ling Dou; Shuang Wu; Qionglan Yuan


    Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta (25-35) in cultured hippocampal neu-rons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippo-campal neurons were exposed to amyloid beta (25-35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta (25-35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta (25-35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta (25-35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.

  10. Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen cells

    Jun-li YU; De-qiang DOU; Xiao-hong CHEN; Hong-zhen YANG; Na GUO; Gui-fang CHENG


    AIM: To investigate the immunoenhancing activity of ginsenoside-F3 in murine spleen cells and explore its mechanism.METHODS: The enhancing effect of ginsenoside-F3 on murine spleen cell proliferation was studied using [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of type 1 cytokines IL-2, IFN-γ, and type 2 cytokines IL-4 and IL-10 from murine spleen cells were detected by ELISA method. Effects of ginsenosideF3 on mRNA level of cytokines IL-4, IFN-γ, and transcription factors T-bet and GATA-3 were evaluated by RTPCR analysis. Effect of ginsenoside-F3 on NF-κB DNA binding activity in murine spleen cells was investigated by electrophoretic mobility shift assays (EMSA). RESULTS: Ginsenoside-F3 at 0.1-100μmol/L not only promoted the murine spleen cell proliferation, but also increased the production of IL-2 and IFN-γ, while decreased the production of IL-4 and IL-10 from murine spleen cells with the maximal effect at 10μmol/L. RT-PCR analysis displayed that ginsenoside-F3 enhanced the IFN-γ and T-bet gene expression and decreased IL-4 and GATA-3 gene expression. EMSA experiment showed that ginsenoside-F3 10μmol/L enhanced the NF-κB DNA binding activity induced by ConA in murine spleen cells. CONCLUSION: Ginsenoside-F3 has immunoenhancing activity by regulating production and gene expression of type 1 cytokines and type 2 cytokines in murine spleen cells.

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

    Mehari Endale


    Full Text Available 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.

  12. 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.

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


    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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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


    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.

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

    Wei-Nan Wang


    Full Text Available 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.

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

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


    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.

  16. Microbial deglycosylation and ketonization of ginsenoside by Cladosporium cladosporioide and their anticancer activity.

    Jin, Yan; Jung, Sun Young; Kim, Yeon-Ju; Lee, Dae-Young; Aceituno, Verónica Castro; Wang, Chao; Yang, Deok-Chun


    Ginseng has been used for thousands of years in Asian countries as a traditional medicinal herb and has gained great popularity in the past decade. Ginsenosides are the major pharmacological components in ginseng. We here show that Cladosporium cladosporioide is able to convert the major ginsenoside Rb1 into four known metabolites (ginsenosides Rd, F2, CK and PPD) and two new metabolites [12β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside (3-oxo-CK) and dammar-24-en-12β,20(S)-diol-3-one (3-oxo-PPD)]. CK, PPD and 3-oxo-PPD were shown to have a potent antiproliferative activity against A549 lung cancer cells. We found that Rb1 → Rd → F2 → CK → PPD or 3-oxo-CK → 3-oxo-PPD represents the ginsenoside metabolic pathway.

  17. Microbial transformation of ginsenosides extracted from Panax ginseng adventitious roots in an airlift bioreactor

    Xiaolin Song


    Conclusion: These findings may not only solve the problem of low productivity of metabolite in ginseng root culture but may also result in the development of a new valuable method of manufacturing ginsenoside CK.

  18. The Potential of Minor Ginsenosides Isolated from the Leaves of Panax ginseng as Inhibitors of Melanogenesis

    Dae-Young Lee


    Full Text Available Three minor ginsenosides, namely, ginsenoside Rh6 (1, vina-ginsenoside R4 (2 and vina-ginsenoside R13 (3, were isolated from the leaves of hydroponic Panax ginseng. The chemical structures were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy (FAB-MS, 1D-nuclear magnetic resonance (NMR, 2D-NMR, and, infrared (IR spectroscopy. The melanogenic inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%, respectively, at a concentration of 80 µM. Likewise, the three compounds showed inhibitory activity on body pigmentation on a zebrafish model, which is commonly used as a model for biomedical or cosmetic research. These results from in vitro and in vivo systems suggest that the three aforementioned compounds isolated from Panax ginseng may have potential as new skin whitening compounds.

  19. The ginsenosides and carbohydrate profiles of ginseng cultivated under mountainous forest

    Jian-kui Zhang; Rui Gao; De-qiang Dou; Ting-guo Kang


    Background: Ginseng cultivated under mountainous forest, called "Lin-Xia-Shan-Shen" (LXSS) in China′s Pharmacopoeia. In recent years, it has been quickly propelled to plant at a large scale. Objective: To study the profiles of ginsenosides and carbohydrate profiles of LXSS. Materials and Methods: The contents of ginsenosides and carbohydrates, such as soluble sugar, polysaccharide, pectin, and starch in LXSS, were determined. All the above components were profiled, and the correlations betwee...

  20. Neuroprotective effects of ginsenosides Rh1 and Rg2 on neuronal cells

    Jiang Zhi-Hong


    Full Text Available Abstract Background The present study investigates the effects of ginsenosides Rh1 and Rg2 against 6-hydroxydopamine (6-OHDA, a neurotoxin on SH-SY5Y cells and PC-12 cells. The effects of these two ginsenosides on neuronal differentiation are also examined. Methods LDH assay was used to measure cell viability after exposure to 6-OHDA and ginsenosides. Neuronal differentiation was evaluated by changes in cell morphology and density of neurite outgrowths. Western blotting was used to determine the ginsenosides' effects on activation of extracellular signal-regulated protein kinases (ERKs. Results Rh1 and Rg2 attenuated 6-OHDA toxicity in SH-SY5Y cells and induced neurite outgrowths in PC-12 cells. 6-OHDA-induced ERK phosphorylation was decreased by Rh1 and Rg2. 20(R-form and 20(S-form of the ginsenosides exerted similar effects in inducing neurite outgrowths in PC-12 cells. Conclusion The present study demonstrates neuroprotective effects of ginsenosides Rh1 and Rg2 on neuronal cell lines. These results suggest potential Chinese medicine treatment for neurodegenerative disorders (eg Parkinson's disease.

  1. Bioconversion of ginsenoside Rb1 into compound K by Leuconostoc citreum LH1 isolated from kimchi

    Lin-Hu Quan


    Full Text Available About 40 different types of ginsenoside (ginseng saponin, a major pharmacological component of ginseng, have been identified along with their physiological activities. Among these, compound K has been reported to prevent the development of and the metastasis of cancer by blocking the formation of tumors and suppressing the invasion of cancerous cells. In this study, ginsenoside Rb1 was converted into compound K via interaction with the enzyme secreted by β-glucosidase active bacteria, Leuconostoc citreum LH1, extracted from kimchi. The optimum time for the conversion of Rb1 to compound K was about 72 hrs at a constant pH of 6.0 and an optimum temperature of about 30ºC. Under optimal conditions, ginsenoside Rb1 was decomposed and converted into compound K by 72 hrs post-reaction (99%. Both TLC and HPLC were used to analyze the enzymatic reaction. Ginsenoside Rb1 was consecutively converted to ginsenoside Rd, F2, and compound K via the hydrolyses of 20-C β-(1 → 6-glucoside, 3-C β-(1 → 2glucoside, and 3-C β-glucose of ginsenoside Rb1.

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

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


    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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:

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

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


    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.

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

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


    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.

  5. The beneficial effect of ginsenosides extracted by pulsed electric field against hydrogen peroxide-induced oxidative stress in HEK-293 cells

    Di Liu


    Conclusion: The present study demonstrated the antioxidative effect of ginsenosides extracted by PEF in vitro. Furthermore, rather than SCSE, PEF may be more useful as an alternative extraction technique for the extraction of ginsenosides with enhanced antioxidant activity.

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

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


    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

  7. Integrated evaluation of malonyl ginsenosides, amino acids and polysaccharides in fresh and processed ginseng.

    Wan, Jin-Yi; Fan, Yong; Yu, Qing-Tao; Ge, Ya-Zhong; Yan, Chen-Pu; Alolga, Raphael N; Li, Ping; Ma, Zhong-Hua; Qi, Lian-Wen


    Many analytical methods have been developed to characterize ginsenosides in ginseng. Relatively less attention has been paid to the malonyl ginsenosides, amino acids and polysaccharides in various processing ginsengs. In this study, malonyl ginsenosides were characterized by LC-Q-TOF/MS. In positive mode, the most abundant ions at m/z 425.38 were observed corresponding to the protopanoxadiol-type ginsenosides. A rich diagnostic ion at 835.48 was shown representing the malonyl ginsenosides with at least two glucosides. Twelve malonyl ginsenosides were rapidly screened using 835.48-835.49 to restructure ion chromatograms. In negative mode, besides the high deprotonated ion, a neutral loss of 44 Da (CO2) was found. High-energy collision-induced dissociation at 50 V produced the most abundant product ion [M-H-malonyl](-) by a neutral loss of 86 Da. Determination of 17 common amino acids was performed on an automatic amino acid analyzer. Arginine, glutamic acid, and aspartic acid were abundant. The contents of amino acids were 9.1% in fresh ginseng and 3.1% in black ginseng. Phenol-sulfuric acid method was applied to analysis of polysaccharides. The contents of polysaccharides were 29.1% in fresh ginseng and 11.1% in black ginseng. The optimal growth age for the accumulation of constituents was supposed to be 5-6 years. In conclusion, the contents of malonyl ginsenosides, amino acids, and polysaccharides, based on decreasing order, ranked as follows: fresh ginseng>frozen ginseng>white ginseng>stoved ginseng>red ginseng>black ginseng. Processing should be paid more attention for the quality control of ginseng products. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Ginsenoside Rg1 Attenuates Isoflurane-induced Caspase-3 Activation via Inhibiting Mitochondrial Dysfunction

    MIAO Hui Hui; ZHEN Yu; DING Guan Nan; HONG Fang Xiao; XIE Zhong Cong; TIAN Ming


    Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rg1 is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rg1 can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. Methods We investigated the effects of ginsenoside Rg1 at concentrations of 12.5, 25, and 50 µmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naïve and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein (APP) (H4-APP cells). For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore (mPTP) and adenosine-5’-triphosphate (ATP) levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. Results Here we show that pretreatment with 50 µmol/L ginsenoside Rg1 for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 µmol/L ginsenoside Rg1 for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naïve and H4-APP cells. Conclusion These data suggest that ginsenoside Rg1 may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rg1 in preventing and treating isoflurane-induced neurotoxicity.

  9. Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity

    Ronald JY CHEN; Tse-yu CHUNG; Feng-yin LI; Nan-hei LIN; Jason TC TZEN


    Aim: To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Methods: The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginseno-sides and ouabain on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na+/K+-ATPase. Results: Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na+/K+-ATPase activity. However, their inhibi-tory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 posi-tion of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these posi-tions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na+/K+-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure. Conclusion: The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhi-bition of Na+/K+-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure.

  10. Determination of Seven Major Ginsenosides in Different Parts of Panax quinquefolius L.(American Ginseng) with Different Ages

    ZHANG Kun; WANG Xiao; DING Lan; LI Juan; QU Chen-ling; CHEN Li-gang; JIN Hai-yan; ZHANG Han-qi


    Ginsenosides Rg1,Re,Rb1,Rc,Rb2,Rb3,and Rd in different parts of the American ginseng plant were investigated.The extraction process was a pressurized microwave-assisted extraction(PMAE).The seven ginsenosides were separated and determined by high-performance liquid chromatography(HPLC) with a ultraviolet(UV) detector,at 203 nm.The experiment results showed significant variations in the individual ginsenoside contents of the American ginseng in different parts and ages of the plant.The results demonstrated that the leaves,root hairs,and rhizomes of Panax quinquefolius L.contained higher ginsenoside contents,followed by the main roots and stems.The leaves contained dramatically higher levels of ginsenoside Rg1,Rb3,and Rd than the other four parts.Higher contents of Rb1 and Re were present in the main roots,root hairs,and rhizomes.The amount of ginsenoside content in the stems was the lowest.The total content of the seven ginsenosides in main roots,root hairs and rhizomes increased with the age of the plant.In contrast,the ginsenoside contents in the leaves and stems decreased with a year of growth.

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

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


    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.

  12. Snailase Preparation of Ginsenoside M1 from Protopanaxadiol-Type Ginsenoside and Their Protective Effects Against CCl4-Induced Chronic Hepatotoxicity in Mice

    Li Chen


    Full Text Available To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG and its metabolite ginsenoside M1 (G-M1 on carbon tetrachloride (CCl4-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl4-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl4-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.

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

    Fang, Zhong-Ze [The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, No.457, Zhongshan Road, Dalian 116023 (China); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (United States); Cao, Yun-Feng [Key Laboratory of Contraceptives and Devices Research(NPFPC),Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032 (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, No.457, Zhongshan Road, Dalian 116023 (China); Hu, Cui-Min [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 (United States); Hong, Mo; Sun, Xiao-Yu [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, No.457, Zhongshan Road, Dalian 116023 (China); Ge, Guang-Bo; Liu, Yong; Zhang, Yan-Yan; Yang, Ling [Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian (China); Sun, Hong-Zhi, E-mail: [The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)


    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

  14. Profiling the ginsenosides of three ginseng products by LC-Q-TOF/MS.

    Chu, Chu; Xu, Shaojing; Li, Xingnuo; Yan, Jizhong; Liu, Li


    Ginseng is a well-known herbal medicine that has been gaining increasingly popularity as a potential chemopreventive agent. In traditional Chinese medicine practice, white ginseng (WG), red ginseng (RG), and dali ginseng (DG) are 3 different ginseng-processed products used for different purposes. Although the morphological appearance and some constituents contained in these ginseng products are similar, their pharmacological activities are significantly different due to the varied types and quantity of ginsenosides in each product. In the present study, a practical method based on rapid liquid chromatography coupled with quadrupole time of flight mass spectrometry (LC-Q-TOF/MS) was developed to identify the chemical profiles of ginsenosides in these 3 ginseng products. The results demonstrated that a total of 55, 53, and 43 compounds were unambiguously assigned or tentatively identified in DG, WG, and RG samples, respectively. The featured compounds are mainly malonyl ginsenosides in WG, and decarboxyl products of mal-ginsenosides and the dehydrated compounds from polar ginsenosides were characteristic in RG, while DG contain some characteristic components present both in WG and RG. We presume that heating processing is the major factor affecting the chemical profile of ginseng products. The difference of chemical information revealed by LC-Q-TOF/MS could be used to discriminate the WG, RG, and DG samples. © 2013 Institute of Food Technologists®

  15. The ginsenosides and carbohydrate profiles of ginseng cultivated under mountainous forest

    Jian-kui Zhang


    Full Text Available Background: Ginseng cultivated under mountainous forest, called "Lin-Xia-Shan-Shen" (LXSS in China′s Pharmacopoeia. In recent years, it has been quickly propelled to plant at a large scale. Objective: To study the profiles of ginsenosides and carbohydrate profiles of LXSS. Materials and Methods: The contents of ginsenosides and carbohydrates, such as soluble sugar, polysaccharide, pectin, and starch in LXSS, were determined. All the above components were profiled, and the correlations between them were analyzed. Results: The results indicated that the contents of total ginsenoside, protopanaxadiol, protopanaxatriol, Rg 1 , Re, Rb 1 , Rc, Rb 2 , Rd, starch, and pectin were negatively correlated with the growing years within 17 years. Among them, the content of starch was positively correlated with that of pectin. The total ginsenosides was positively correlated with starch and pectin, which cannot be found in garden ginseng, maybe resulting of fertilizer and other manual intervention in process of cultivation of garden ginseng. Discussion and Conclusions: The accumulation of ginsenosides and carbohydrate, especially starch and pectin, was different in garden ginseng and LXSS. This research may provide the scientific basis for germplasm evaluation, the cultivation and utilization of ginseng cultivated under mountainous forest.

  16. Ginsenoside Rb1 in asymmetric somatic hybrid calli of Daucus carota with Panax quinquefolius.

    Han, Lu; Zhou, Chuanen; Shi, Junying; Zhi, Daying; Xia, Guangmin


    American ginseng (Panax quinquefolius L.) is one of the most valuable herbs in the world. Its major active components are ginsenosides. In order to produce ginsenoside heterogeneously, somatic hybridization, a novel approach for genetic introgression, was employed in this study. Protoplasts derived from respective calli of carrot (Daucus carota var. sativus Hoffm.) and American ginseng (P. quinquefolius L.) were used as the fusion partners. Hybrid calli derived from single cell lines containing chromatin of American ginseng were confirmed by the analyses of isozyme, Random amplified polymorphic DNA (RAPD) and genomic in situ hybridization (GISH). High performance liquid chromatography (HPLC) results showed that the ginseng monomer Rb(1) was synthesized in seven of the hybrid calli identified as well as in the parent American ginseng calli but not in the parent carrot calli. Results indicated that hybrid introgression lines could produce ginsenoside Rb(1) and the ginsenoside Rb(1) biosynthesis pathway has been introgressed into carrot cells via somatic hybridization. From the point of biosafety view concerning the consumer acceptance, the potential predominance to produce ginsenosides with somatic hybridization other than with genetic transformation is discussed.

  17. Isolation and determination of ginsenosides in American ginseng leaves and root extracts by LC-MS.

    Ligor, T; Ludwiczuk, A; Wolski, T; Buszewski, B


    Ginseng saponins (ginsenosides) were extracted from the root and leaves of locally cultivated American ginseng (Panax quinquefolium L.). For the isolation of compounds from plant samples three different extraction methods were utilized: accelerated solvent extraction, the ultrasound-assisted solvent extraction and mechanical shaking assisted solvent extraction. The separation of compounds was achieved with a water-acetonitrile gradient system using a C18 reversed-phase column. Target compounds were identified in MS(2) and MS(3) experiments. The relative distribution of these ginsenosides in each root and leaf extract was established. The limit of detection of the method was less than 30 ng/ml. Recovery of ginseng saponins in spiked samples exceeded 80%, while the relative standard deviation ranged from 7.1 to 9.1%. The total concentrations of ginsenosides were 41 and 13 mg/g in root and leaves.

  18. Synchronous characterization of carbohydrates and ginsenosides yields deeper insights into the processing chemistry of ginseng.

    Zhou, Shan-Shan; Xu, Jun; Kong, Ming; Yip, Ka-Man; Xu, Jin-Di; Shen, Hong; Zhao, Zhong-Zhen; Li, Song-Lin; Chen, Hu-Biao


    Carbohydrates and ginsenosides in ginseng are biologically interrelated. Their synchronous analysis is therefore essential in chemical research on ginseng to characterize its "holistic" quality. Here we investigated the processing chemistry of red ginseng (RG), a ginseng product processed by water-steaming, for which both carbohydrates and ginsenosides were qualitatively and quantitatively determined through multiple analytical techniques. Results revealed that the steam-processing not only qualitatively and quantitatively altered the ginsenosides but also affected the polymeric carbohydrates via changing their physiochemical parameters, i.e. water-solubility, molecular size, types and ratios of constituent monosaccharides. Potential mechanisms involved in the transformation of ginseng chemicals are proposed and discussed, including hydrolysis (deglycosylation, demalonylation, deacetylation), dehydration, polymerization, volatilization, reduction and the Maillard reaction. The study strengthens the research on the processing chemistry of RG, and therefore should be helpful for elucidating the scientific basis of RG preparation and application. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Tissue-Specific Distribution of Ginsenosides in Different Aged Ginseng and Antioxidant Activity of Ginseng Leaf

    Ying-Chun Zhang


    Full Text Available The aim of this study was to systematically evaluate the effect of the cultivation year on the quality of different ginseng tissues. Qualitative and quantitative analyses of ginsenosides were conducted using a UPLC-UV-MS method. Eight main ginsenosides in three tissues (leaf, rhizome and main root and four parts (periderm, phloem, cambium and xylem of ginseng aged from 1 to 13 years were determined using a UPLC-PDA method. Additionally, the antioxidant capacities of ginseng leaves were analyzed by the DPPH, ABTS and HRSA methods. It was found that the contents of ginsenosides increased with cultivation years, causing a sequential content change of ginsenosides in an organ-specific manner: leaf > rhizome > main root. The ratio between protopanaxatriol (PPT, Rg1, Re and RF and protopanaxadiol (PPD, Rb1, Rb2, RC and Rd in the main root remained stable (about 1.0, while it increased in leaf from 1.37 to 3.14 and decreased in the rhizome from 0.99 to 0.72. The amount of ginsenosides accumulated in the periderm was 45.48 mg/g, which was more than twice as high compared with the other three parts. Furthermore, the antioxidant activities of ginseng leaves were measured as Trolox equivalents, showing that antioxidant activity increased along with time of cultivation. The results show that the best harvest time for shizhu ginseng is the fifth year of cultivation, and the root and rhizome could be used together within seven planting years for their similar PPT/PPD level. Besides, the quality of the ginseng products would be enhanced with the periderm. The ginseng leaf is rich in ginsenosides and has potential application for its antioxidant capacity.

  20. Effects of Ginsenoside Rb1 on Skin Changes

    Yoshiyuki Kimura


    Full Text Available Ginseng roots (Panax ginseng CA Meyer have been used traditionally for the treatment, especially prevention, of various diseases in China, Korea, and Japan. Both experimental and clinical studies suggest ginseng roots to have pharmacological effects in patients with life-style-related diseases such as non-insulin-dependent diabetic mellitus, atherosclerosis, hyperlipidemia, and hypertension. The topical use of ginseng roots to treat skin complaints including atopic suppurative dermatitis, wounds, and inflammation is also described in ancient Chinese texts; however, there have been relatively few studies in this area. In the present paper, we describe introduce the biological and pharmacological effects of ginsenoside Rb1 isolated from Red ginseng roots on skin damage caused by burn-wounds using male Balb/c mice (in vivo and by ultraviolet B irradiation using male C57BL/6J and albino hairless (HR-1 mice (in vivo. Furthermore, to clarify the mechanisms behind these pharmacological actions, human primary keratinocytes and the human keratinocyte cell line HaCaT were used in experiments in vitro.

  1. Ginsenoside Rb1 Preconditioning Enhances eNOS Expression and Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats

    Rui Xia


    Full Text Available Diabetes mellitus is associated with decreased NO bioavailability in the myocardium. Ginsenoside Rb1 has been shown to confer cardioprotection against ischemia reperfusion injury. The aim of this study was to investigate whether Ginsenoside Rb1 exerts cardioprotective effects during myocardial ischemia-reperfusion in diabetic rats and whether this effect is related to increase the production of NO via enhancing eNOS expression in the myocardium. The myocardial I/R injury were induced by occluding the left anterior descending artery for 30 min followed by 120 min reperfusion. An eNOS inhibitor L-NAME or Rb1 were respectively administered 25 min or 10 min before inducing ischemia. Ginsenoside Rb1 preconditioning reduced myocardial infarct size when compared with I/R group. Ginsenoside Rb1 induced myocardial protection was accompanied with increased eNOS expression and NO concentration and reduced plasma CK and LDH (P<0.05. Moreover, the myocardial oxidative stress and tissue histological damage was attenuated by Ginsenoside Rb1 (P<0.05. L-NAME abolished the protective effects of Ginsenoside Rb1. It is concluded that Ginsenoside Rb1 protects against myocardium ischemia/reperfusion injury in diabetic rat by enhancing the expression of eNOS and increasing the content of NO as well as inhibiting oxidative stress.

  2. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

    Zhu, G; Wang, Y; Li, J; Wang, J


    Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus.

    Hou, Jingang; Xue, Jianjie; Lee, Mira; Yu, Jiaojiao; Sung, Changkeun


    Ginsenosides, the secondary plant metabolites produced by Panax ginseng are responsible for the enhancing effects on learning observed following treatment with Panax ginseng. A number of studies have provided correlational evidence that cell proliferation and survival are closely associated with hippocampal-dependent learning tasks. In this study, to investigate the beneficial effects of ginsenoside Rh1 on hippocampal cells and learning, mice (6 months old) were administered ginsenoside Rh1 at a dose of 5 and 10 mg/kg/day for a period of 3 months. Saline-treated mice were used as controls. The enhancement of memory and learning in the mice was evaluated by hippocampal-dependent tasks (passive avoidance tests and Morris water maze tests) and the immunohistochemical marker of cell proliferation, bromodeoxyuridine (BrdU). In addition, the levels of brain-derived neurotrophic factor (BDNF) were measured following treatment. Based on our data, the Rh1-treated group (5 and 10 mg/kg) showed a significantly improved learning and memory ability in the passive avoidance tests compared with the control group; however, only treatment with 10 mg/kg ginsenoside Rh1 significantly promoted spatial learning ability in the Morris water maze test. Ginsenoside Rh1 significantly enhanced cell survival in the dentate gyrus of mice, although it did not enhance hippocampal cell proliferation. In addition, ginsenoside Rh1 upregulated the expression of BDNF. These findings address the potential therapeutic significance of ginsenoside Rh1 as a nutritional supplement in memory loss and neurodegenerative diseases.

  4. Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction

    Xi-sheng XIE; Man YANG; Heng-cuang LIU; Chuan ZUO; Zi LI; Yao DENG; Jun-ming FAN


    Total saponins ofPanax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups:sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperito-neally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition, a-smooth muscle actin (α-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased a-SMA expression and simultaneously enhanced E-eadherin expression. The messenger RNA (mRNA) of transforming growth factor-131 (TGF-β1), a key mediator to regulate TEMT, in the obstructed kidney increased dra-matically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.

  5. Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells.

    Cao, Guoqiong; Su, Ping; Zhang, Shuai; Guo, Limin; Zhang, Haijing; Liang, Yuexia; Qin, Chunxia; Zhang, Wensheng


    Alzheimer's disease (AD) is a neurodegenerative disease characterized by β-amyloid protein (Aβ) deposition. Reducing the Aβ load may be a new perspective for AD treatment. Ginsenoside Re is an extract from Panax notoginseng, which is a well-known traditional Chinese medicine that has been used for the treatment of various diseases for years. Ginsenoside Re has been reported to decrease Aβ in Alzheimer's disease animal models, but the mechanism has not been fully elucidated. In the present study, we investigated the mechanism of ginsenoside Re. Our results showed that ginsenoside Re decreased the Aβ levels in N2a/APP695 cells. Aβ peptides are generated by β-secretase (β-site amyloid precursor protein cleaving enzyme 1 (BACE1)) and γ-secretase. We found that ginsenoside Re decreased the BACE1 mRNA and protein levels and inhibited BACE1 activity in the N2a/APP695 cells. Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that regulates the activity of the BACE1 promoter, and activating PPARγ can inhibit BACE1. The results also showed that ginsenoside Re significantly increased the PPARγ protein and mRNA levels. These effects of ginsenoside Re on BACE1 could be effectively inhibited by the PPARγ antagonist GW9662. These findings indicate that ginsenoside Re inhibits BACE1 through activation of PPARγ, which ultimately reduces the generation of Aβ1-40 and Aβ1-42. Therefore, ginsenoside Re may be a promising agent for the modulation of Aβ-related pathology in AD.

  6. 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.

    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


    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Study on Interaction of Ginsenosides with Bovine or Human Serum Albumin Using Wavelength Modulation Surface Plasmon Resonance Biosensor

    LIU Xia; SUN Ying; SONG Da-Qian; LI Xu-Wen; ZHANG Qing-Lin; TIAN Yuan; LIU Zhong-Ying; ZHANG Han-Qi


    To use a newly developed wavelength modulation surface plasmon resonance (SPR) biosensor, an experimental protocol was developed to investigate the interaction of ginsenosides with serum albumin. With a known concentration of the ginsenosides, bound percentages of the ginsenosides with human serum albumin (HSA) or bovine serum albumin (BSA) were obtained. SPR technique could require no labeling and this method provided the detailed information on association and disassociation of molecules in real time. The results indicate that the sensitivity of wavelength modulation SPR biosensor is sufficient for detection and characterization of binding events involving low-molecular weight compounds and their immobilized protein targets.

  8. Red notoginseng: higher ginsenoside content and stronger anticancer potential than Asian and American ginseng.

    Sun, Shi; Qi, Lian-Wen; Du, Guang-Jian; Mehendale, Sangeeta R; Wang, Chong-Zhi; Yuan, Chun-Su


    A systematic comparison of the ginsenosides and anticancer activities was performed among white (air-dried) and red (steamed) roots of notoginseng (NG, Panax notoginseng), Asian ginseng (AG, P. ginseng), and American ginseng (AmG, P. quinquefolius). Chemical profiles of different ginseng species were characterized, through simultaneous quantification of nineteen major ginsenosides, by HPLC-UV at 202 nm. The antiproliferative and pro-apoptotic effects on human colorectal cancer cells were determined by MTS method and flow cytometry, respectively. Chemical analysis indicated that white NG possessed the most abundant ginsenosides, i.e., two- and five-fold higher than white AmG and AG. During the steaming process, extensive conversion of the original polar ginsenosides in white ginseng to new, less polar, degradation compounds in red ginseng was observed. White ginsengs produced weak antiproliferative effects, while red ginsengs exhibited a significant increase in antiproliferative and pro-apoptotic effects (both P ginseng). Among the three red ginsengs, red NG showed the best anticancer activity. Due to the low cost of NG and high bioactivity of red NG, the red NG is promising to be a useful botanical product in cancer chemoprevention.

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

    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.

  10. Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats

    Mallikarjuna Korivi


    Full Text Available Despite regular exercise benefits, acute exhaustive exercise elicits oxidative damage in liver. The present study determined the hepatoprotective properties of ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats. Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1 mg/kg bodyweight. After 10-week treatment, ten rats from each group performed exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric acid reactive substance (TBARS (67% and protein carbonyls (56%, were significantly (P<0.01 elevated after exhaustive exercise but alleviated in ginsenoside-Rg1 pretreated rats. Furthermore, exhaustive exercise drastically decreased glutathione (GSH content (∼79% with concurrent decreased superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px activities. However, these changes were attenuated in Rg1 group. Additionally, increased xanthine oxidase (XO activity and nitric oxide (NO levels after exercise were also inhibited by Rg1 pretreatment. For the first time, our findings provide strong evidence that ginsenoside-Rg1 can protect the liver against exhaustive exercise-induced oxidative damage.

  11. Protective effect of ginsenoside Rg1 on glutamate-induced lung injury

    Li SHEN; Jian-zhong HAN; Chen LI; Shao-jie YUE; Yong LIU; Xiao-qun QIN; Hui-jun LIU; Zi-qiang LUO


    Aim: To examine the possible protective effect of ginsenoside Rg1, an active component of ginseng, on lung injury caused by glutamate in vivo. Methods: The lungs of mice receiving glutamate (0.5 g/kg) and/or ginsenoside Rg1 (0.03 g/kg) via intraperitoneal administration were collected. The indexes of lung wet weight/body weight ratios (LW/BW), lung wet/dry weight ratios (W/D), heart rate (HR),and breathing rate (BR) were determined. The activity of nitric oxide synthase(NOS), xanthine oxidase (XOD), superoxide dismutase (SOD), catalase (CAT), the content of NO, and malondialdehyde in the lung homogenate were measured.Results: Treatment with glutamate for 2 h increased LW/BW, W/D, HR, and BR.These changes were nearly abolished by pretreatment with ginsenoside Rg1 for 30 min before glutamate injection. An analysis of the lung homogenate demon-strated the protective effect as evidenced by the inhibition of NOS (12%) and XOD (50%) inactivity, the enhanced activity of SOD (20%) and CAT (25%).Conclusion: Ginsenoside Rg1 has a potential protective role in lung diseases associated with glutamate toxicity.

  12. Protopanaxadiol aglycone ginsenoside-polyethylene glycol conjugates: synthesis, physicochemical characterizations, and in vitro studies.

    Mathiyalagan, Ramya; Kim, Yeon Ju; Wang, Chao; Jin, Yan; Subramaniyam, Sathiyamoorthy; Singh, Priyanka; Wang, Dandan; Yang, Deok Chun


    Ginsenosides are triterpenoid saponins, which is an active compound responsible for most of the pharmacological effects of ginseng (Panax ginseng Meyer). It is known to have numerous structural and pharmacological properties. However, aqueous solubility and delivery of ginsenosides in targeted region by avoiding undesirable toxicity to normal cell is also of prime importance. The aim of this study was to obtain amphiphilic ginsenoside derivatives in which hydrophilic polymers were conjugated to ginsenosides to enhance the water solubility and targeted delivery. To this end, the hydrophobic protopanaxadiol ginsenoside aglycone (aPPD) was covalently conjugated to the backbone of hydrophilic polyethylene glycol (PEG) through a pH sensitive ester linkage, which was confirmed by (1)H NMR and FTIR. The resultant PPD is covalently conjugated to hydrophilic PEG through esterification (PEG-PPD) forming self-assembled spherical nanoparticles, whose average particle diameter was 189 nm as observed by FE-TEM and particle size analyzer respectively. In vitro release experiments revealed that the release rate of PPD was rapidly increased from the self-assembled nanoparticles under acidic conditions (pH 5.0) than in a physiological buffer (pH 7.4) condition. Furthermore, in vitro cytotoxicity assays revealed that PEG-PPD conjugates exhibited lower cytotoxicity in HT-29 cancer cells compared with PPD alone. Since the slow release of PPD from conjugates is triggered only by acidic environmental conditions, such as those found in extracellular solid tumor tissues, intracellular endosomes, and intracellular lysosomes, the conjugation of PPD may aid its selective delivery to these targets. Overall, results suggest that pH-dependent release of PPD, which expected in reduced cytotoxicity to non-targeted regions, may enhance the overall efficacy of PPD.

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

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


    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.

  14. Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells

    Hye Lim Lee


    Conclusion: These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.

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

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


    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.

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

    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


    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

  17. Ginsenoside Rg1 inhibits proliferation of vascular smooth muscle cells stimulated by tumor necrosis factor-α

    Zeng-chun MA; Yue GAO; Yu-guang WANG; Hong-ling TAN; Cheng-rong XIAO; Sheng-qi WANG


    Aim: To investigate the proliferation of vascular smooth muscle cells (VSMC) affected by ginsenoside Rg1 and further explore the molecular mechanism of ginsenoside Rg1 using proteomics. Methods: The proliferation of VSMC was measured by MTS assay kit and flow cytometry. Proteomic alterations were analyzed using two-dimensional electrophoresis and peptide mass fingerprinting. Differential proteins found in proteomics were confirmed by RT-PCR. Results: The proliferation of VSMC was enhanced significantly after tumor necrosis factor-α (TNF-α) treatment, and ginsenoside Rg1 treatment inhibited proliferation in a dose-dependent manner. Proteomic analysis showed 24 protein spots were changed, including 17 spots that were increased and 7 spots that were decreased. Ginsenoside Rg1 could restore the expression levels of these proteins, at least partly, to basic levels of untreated cells. The expression of G-protein coupled receptor kinase, protein kinase C (PKC)-ζ, N-ras protein were decreased, while cycle related protein p21 was increased by ginsenoside Rg1 in TNF-α treated VSMC. Conclusion: PKC-ζ, and p21 pathway might be the mechanism for inhibitory effects of ginsenoside Rg1 on proliferation of VSMC.

  18. Skin anti-photoaging properties of ginsenoside Rh2 epimers in UV-B-irradiated human keratinocyte cells

    Sun-Joo Oh; Sihyeong Lee; Woo-Yong Choi; Chang-Jin Lim


    Ginseng, one of the most widely used herbal medicines, has a wide range of therapeutic and pharmacological applications. Ginsenosides are the major bioactive ingredients of ginseng, which are responsible for various pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour ginsenoside, exists as two different stereoisomeric forms, 20()-ginsenoside Rh2 [20()-Rh2] and 20()-ginsenoside Rh2 [20()-Rh2]. This work aimed to assess and compare skin anti-photoaging activities of 20()-Rh2 and 20()-Rh2 in UV-B-irradiated HaCat cells. 20()-Rh2, but not 20()-Rh2, was able to suppress UV-B-induced ROS production in HaCat cells. Both stereoisomeric forms could not modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both 20()-Rh2 and 20()-Rh2 exhibited suppressive effects on UV-B-induced MMP-2 activity and expression in HaCat cells. In brief, the two stereoisomers of ginsenoside Rh2, 20()-Rh2 and 20()-Rh2, possess skin anti-photoaging effects but possibly in different fashions.



    Objective To study the therapeutic effects of Ginsenoside Rg-1 and Gastrodine on rats model of Alzheimer's disease(AD). Methods Aggregated β-Amyloid peptide (25-35) was injected into the lateral ventricle of rats to establish AD models. Ginsenoside Rg-1, Gastrodine and Ginsenoside Rg-1+Gastrodine were intraperitoneally injected into rats of each test group(Ginsenoside Rg-1∶10mg/kg·day; Gastrodine 100mg/kg·day) for 4 weeks, the rats of control group received equal volume of saline. Passive avoidance task and Morris maze test were done to assess the ability of learning and memory. The content of superoxide dismutase (SOD), malondiadehyde (MDA), total-antioxidative capability (T-AOC), Choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissue were measured. Results Ginsenoside Rg-1 and Gastrodine significantly improved learning and memory deficits in the rats with AD induced by β-Amyloid peptide (25-35) (P<0.05). Ginsenoside Rg-1+Gastrodine group were better than Ginsenoside Rg-1 group and Gastrodine group (P<0.05). Ginsenoside Rg-1 reduced the increase of SOD, MDA, but inhibited the decrease of T-AOC, AchE and ChAT; Gastrodine reduced the increase of SOD, MDA, while inhibited the decrease of T-AOC. Gastrodine could also prevent the activity of ChAT and AchE decline in AD rats. Conclusion Both Ginsenoside Rg-1 and Gastrodine have therapeutic effects on rats with AD; Ginsenoside Rg-1 and Gastrodine injection at the same time were better than only using one of them. Their mechanisms might different. Ginsenoside Rg-1 can not only inhibit peroxidation but also increase the activity of AchE and ChAT in brain tissue, while Gastrodine can inhibit peroxidation only, but it can't prevent the decline of ChAT and AchE activity in AD rats.

  20. [Ginsenoside Rh₂-induced inhibition of histone deacetylase 6 promotes K562 cells autophagy and apoptosis in vivo].

    Liu, Ze-Hong; Chen, Di-Long; Jiang, Rong; Chen, Yi; Xiong, Wei; Wang, Fen; Shi, Xue-Ping; Li, Hai-Xing; Li, Jing


    To study the in vivo inhibition effect of ginsenoside Rh₂ on humanleukemia cells, and explore its mechanism from autophagy and apoptosis aspects, human leukemia K562 cells allograft tumor models were applied, and after administration of ginsenosides Rh₂ by gavage, the tumor diameter, volume and inhibitory rate were measured, and the anti-tumor activity of ginsenosides Rh₂ was observed. The levels of HAT and HDAC in tumor tissues were detected by chemical colorimetry assay, and expressions of HDAC1, HDAC2, HDAC3, HDAC4, HDAC5 and HDAC6 were detected by Western blotting assay. The expression levels of vital genes closely associated with autophagy and mRNA expressions of HDAC6 and Hsp90 were detected by Real time-PCR. HE staining was used to observe apoptosis, and immunohistochemistry was used to detect the protein expressions of HDAC6, Hsp90 and activated caspases 3. The results showed that ginsenoside Rh₂ could inhibit the growth of k562 cells allograft tumor, with a tumor inhibition rate up to 53.10%. Ginsenoside Rh₂ could significantly decrease HDAC activity and decrease the expressions of HDAC1, HDAC2 and HDAC6, and inhibit the expressions of HDAC6 and HSP90, increase the expressions of vital autophagy genes (beclin-1, LC3A and LC3B). Histopathological results showed that ginsenosides Rh₂ could significantly increase the tumor apoptosis. Therefore, ginsenoside Rh₂ had good anti-tumor effect in vivo, and the mechanism maybe associated with regulating autophagy and apoptosis through HDAC6 and Hsp90 pathways and inhibiting the in vivo proliferation of tumor cells. Copyright© by the Chinese Pharmaceutical Association.

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

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


    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.

  2. Whole-Cell Biocatalysis for Producing Ginsenoside Rd from Rb1 Using Lactobacillus rhamnosus GG.

    Ku, Seockmo; You, Hyun Ju; Park, Myeong Soo; Ji, Geun Eog


    Ginsenosides are the major active ingredients in ginseng used for human therapeutic plant medicines. One of the most well-known probiotic bacteria among the various strains on the functional food market is Lactobacillus rhamnosus GG. Biocatalytic methods using probiotic enzymes for producing deglycosylated ginsenosides such as Rd have a growing significance in the functional food industry. The addition of 2% cellobiose (w/v) to glucose-free de Man-Rogosa-Sharpe broths notably induced β-glucosidase production from L. rhamnosus GG. Enzyme production and activity were optimized at a pH, temperature, and cellobiose concentration of 6.0, 40°C, and 2% (w/v), respectively. Under these controlled conditions, β-glucosidase production in L. rhamnosus GG was enhanced by 25-fold. Additionally, whole-cell homogenates showed the highest β-glucosidase activity when compared with disrupted cell suspensions; the cell disruption step significantly decreased the β-glucosidase activity. Based on the optimized enzyme conditions, whole-cell L. rhamnosus GG was successfully used to convert ginsenoside Rb1 into Rd.

  3. Therapeutic potential of Panax ginseng and ginsenosides in the treatment of chronic obstructive pulmonary disease.

    Shergis, J L; Di, Y M; Zhang, A L; Vlahos, R; Helliwell, R; Ye, J M; Xue, C C


    Chronic obstructive pulmonary disease (COPD) is a major global health burden and will become the third largest cause of death in the world by 2030. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, cause progressive airflow limitation. This inflammation, where macrophages, neutrophils and lymphocytes are prominent, leads to oxidative stress, emphysema, airways fibrosis and mucus hypersecretion. COPD responds poorly to current anti-inflammatory treatments including corticosteroids, which produce little or no benefit. Panax ginseng has a long history of use in Chinese medicine for respiratory conditions, including asthma and COPD. In this perspective we consider the therapeutic potential of Panax ginseng for the treatment of COPD. Panax ginseng and its compounds, ginsenosides, have reported effects through multiple mechanisms but primarily have anti-inflammatory and anti-oxidative effects. Ginsenosides are functional ligands of glucocorticoid receptors and appear to inhibit kinase phosphorylation including MAPK and ERK1/2, NF-κB transcription factor induction/translocation, and DNA binding. They also inhibit pro-inflammatory mediators, TNF-α, IL-6, IL-8, ROS, and proteases such as MMP-9. Panax ginseng protects against oxidative stress by increasing anti-oxidative enzymes and reducing the production of oxidants. Given that Panax ginseng and ginsenosides appear to inhibit processes related to COPD pathogenesis, they represent an attractive therapeutic target for the treatment of COPD. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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


    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.

  5. 扣子七中人参皂苷的HPLC-MS-MS方法研究%Research of ginsenosides in Kou zi qi using HPLC-MS-MS

    邹坤; 刘朝霞; 朱姝; 蔡少青; 小松かつ子


    Aim To analyze the ginsenosides in Kou zi qi (rhizomes of Panax japonicus C.A. Mey. var. major (Burkill) C.Y.Wu et K. M. Feng), and to supply evidences for chemotaxanology of Panax species and clinical uses of Kou zi qi. Methods The ginsenosides were isolated by HPLC, then the positive- and negativeion API-MS/MS of constituents collected from HPLC were measured. Results Eight ginsenosides were identified as ginsenoside Re, ginsenoside Ro, chikuseksusaponins IV, IVa, notoginsenoside R2, ginsenosides Rb1 , Rc and Rd, respectively, based on comparison of retention time with those of standards by HPLC, and analysis on their API-MS/MS data. Ginsenoside Ro and chikuseksusaponin IVa are the major components of Kouzi qi. Conclusion This plant had a close relationship to P. stipuleanatns, P. zinginensis and P .japonicns var major; a relatively remote relationship to P. ginseng and P. quinquefolins, in a view of chemotaxanology. Ginsenoside Ro and chikuseksusaponin IVa might be the anti-inflammatory constituents of Kou zi qi.

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

    Christensen, Lars P; Jensen, Martin


    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 falcarinol (r = 0.9904, P falcarinol were found to be important selection parameters for identifying superior genotypes with the highest content of bioactive compounds.

  7. Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats

    Jing SHI; Wei XUE; Wen-jie ZHAO; Ke-xin LI


    Aim: To investigate the pharmacokinetics and dopamine/acetylcholine-releasing effects of ginsenoside Re (Re) in brain regions related to learning and memory,and to clarify the neurochemical mechanisms underlying its anti-dementia activity.Methods: Microdialysis was conducted on awake,freely moving adult male SD rats with dialysis probes implanted into the hippocampus,medial prefrontal cortex (mPFC) or the third ventricle.The concentrations of Re,dopamine (DA) and acetylcholine (ACh) in dialysates were determined using LC-MS/MS.Results: Subcutaneous administration of a single dose of Re (12.5,25 or 50 mg/kg) rapidly distributed to the cerebrospinal fluid and exhibited linear pharmacokinetics.The peak concentration (Cmax) occurred at 60 min for all doses.Re was not detectable after 240 min in the dialysates for the low dose of 12.5 mg/kg.At the same time,Re dose-dependently increased extracellular levels of DA and ACh in the hippocampus and mPFC,and more prominent effects were observed in the hippocampus.Conclusion: The combined study of the pharmacokinetics and pharmacodynamics of Re demonstrate that increase of extracellular levels of DA and ACh,particularly in the hippocampus,may contribute,at least in part,to the anti-dementia activity of Re.

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

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


    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.

  9. Highly selective biotransformation of ginsenoside Rb1 to Rd by the phytopathogenic fungus Cladosporium fulvum (syn. Fulvia fulva).

    Zhao, Xuesong; Wang, Juan; Li, Jie; Fu, Ling; Gao, Juan; Du, Xiuli; Bi, Hongtao; Zhou, Yifa; Tai, Guihua


    Fourteen phytopathogenic fungi were tested for their ability to transform the major ginsenosides to the active minor ginsenoside Rd. The transformation products were identified by TLC and HPLC, and their structures were assigned by NMR analysis. Cladosporium fulvum, a tomato pathogen, was found to transform major ginsenoside Rb(1) to Rd as the sole product. The following optimum conditions for transforming Rd by C. fulvum were determined: the time of substrate addition, 24 h; substrate concentration, 0.25 mg ml(-1); temperature, 37 degrees C; pH 5.0; and biotransformation period, 8 days. At these optimum conditions, the maximum yield was 86% (molar ratio). Further, a preparative scale transformation with C. fulvum was performed at a dose of 100 mg of Rb(1) by a yield of 80%. This fungus has potential to be applied on the preparation for Rd in pharmaceutical industry.

  10. Simultaneous analysis method for polar and non-polar ginsenosides in red ginseng by reversed-phase HPLC-PAD.

    Lee, Sa-Im; Kwon, Ha-Jeong; Lee, Yong-Moon; Lee, Je-Hyun; Hong, Seon-Pyo


    The paper describes the development of a simultaneous determination method for polar and non-polar ginsenosides in red ginseng with a reversed-phase high-performance liquid chromatography-pulsed amperometric detection method. This method could be applied directly without any pretreatment steps and enabled the performance of highly sensitive analysis within 1h. The detection (S/N=3) and quantification (S/N=10) limits for the ginsenosides ranged 0.02-0.10 ng and 0.1-0.3 ng, respectively. The linear regression coefficients ranged 0.9975-0.9998. Intra- and inter-day precisions were <9.91%. The mean recoveries ranged 98.08-103.06%. The total amount of ginsenosides in the hairy root of red ginseng was higher than that in the main root.

  11. Systematic development of a group quantification method using evaporative light scattering detector for relative quantification of ginsenosides in ginseng products.

    Lee, Gwang Jin; Shin, Byong-Kyu; Yu, Yun-Hyun; Ahn, Jongsung; Kwon, Sung Won; Park, Jeong Hill


    The determination for the contents of multi-components in ginseng products has come to the fore by demands of in-depth information, but the associated industries confront the high cost of securing pure standards for the continuous quality evaluation of the products. This study aimed to develop a prospective high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method for relative quantification of ginsenosides in ginseng products without a considerable change from the conventional gradient analysis. We investigated the effects of mobile phase composition and elution bandwidth, which are potential variables affecting the ELSD response in the gradient analysis. Similar ELSD response curves of nine major ginsenosides were obtained under the identical flow injection conditions, and the response increased as the percentage of organic solvent increased. The nine ginsenosides were divided into three groups to confirm the effect of elution bandwidth. The ELSD response significantly decreased in case of the late eluted ginsenoside in the individual groups under the isocratic conditions. With the consideration of the two important effects, stepwise changes of the gradient condition were carried out to reach a group quantification method. The inconsistent responses of the nine ginsenosides were reconstituted to three normalized responses by the stepwise changes of the gradient condition, and this result actualized relative quantification in the individual groups. The availability was confirmed by comparing the ginsenoside contents in a base material of ginseng products determined by the direct and group quantification method. The largest difference in the determination results from the two methods was 8.26%, and the difference of total contents was only 0.91%. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Antiviral Effect of Korean Red Ginseng Extract and Ginsenosides on Murine Norovirus and Feline Calicivirus as Surrogates for Human Norovirus

    Lee, Min Hwa; Lee, Bog-Hieu; Jung, Ji-Youn; Cheon, Doo-Sung; Kim, Kyung-Tack; Choi, Changsun


    Korean red ginseng has been studied various biological activities such as immune, anti-oxidative, anti-microbial, and anticancer activities but antiviral mechanism needs further studies. In this study, we aimed to examine the antiviral effects of Korea red ginseng extract and ginsenosides on norovirus surrogate, including murine norovirus (MNV) and feline calicivirus (FCV). We evaluated the pre-, co-, and post-treatment effects of Korean red ginseng (KRG), ginsenosides Rb1 and Rg1. To measure the antiviral effect and cytotoxicity of KRG extract, and ginsenosides Rb1 and Rg1, we treated Crandell-Reese Feline Kidney for FCV or RAW264.7 cells for MNV with concentrations of 0, 5, 6.7, 10, 20 ug/mL total saponin. There was cytotoxic effect in the highest concentration 20 ug/mL of KRG extract so this concentration was excluded in this study. The FCV titer was significantly reduced to 0.23-0.83 log10 50% tissue culture infectious dose (TCID50)/mL in groups pre-treated with red ginseng extract or ginsenosides. The titer of MNV was significantly reduced to 0.37-1.48 log10 TCID50/mL in groups pre-treated with red ginseng extract or ginsenosides. However, there was no observed antiviral effect in groups co-treated or post-treated with KRG and its constituents. Our data suggest that KRG extract has an antiviral effect against norovirus surrogates. The antiviral mechanisms of KRG and ginsenosides should be addressed in future studies. PMID:23717088

  13. Comparative analysis of the gut microbiota in people with different levels of ginsenoside Rb1 degradation to compound K.

    Kyung-Ah Kim

    Full Text Available Panax ginseng (family Araliaceae which contains ginsenoside Rb1 as a main constituent is traditionally used as a remedy for cancer, inflammation, stress, and ageing. The ginsenoside Rb1 in orally administered ginseng is metabolized to bioactive compounds by gut microbiota before their absorptions to the blood. However, its metabolizing activities in individuals are significantly different as we previously demonstrated. Here, we selected 5 samples with fecal activity potently metabolizing ginsenoside Rb1 to compound K (FPG; metabolic activity, 0.058±0.029 pmol/min/mg and 5 samples with fecal activity non-metabolizing ginsenoside Rb1 to compound K (FNG from a pool of 100 subjects investigated in a previous study and analyzed fecal microbiota by 16S rRNA gene pyrosequencing. Taxonomy-based analysis showed that the population levels of Firmicutes and Proteobacteria in FPG were lower than in FNG, but those of Bacteroidetes and Tenericutes in FPG were higher than in FNG. At the genus level, the population levels of Clostridiales_uc_g, Oscillibacter, Ruminococcus, Holdemania, and Sutterella in FPG were significantly higher than in FNG, but that of Leuconostoc in FPG was lower than in FNG. The population levels of Bacteroides and Bifidobacterium, which potently metabolizes ginsenoside Rb1 to compound K were dramatically increased in FPG. The gut microbiota compositions of FPG and FNG were segregated on PCO2 by Principal Coordinate Analysis. Intestinal bacterial metabolism of ginseng, particularly ginsenoside Rb1, may be dependent on the composition of gut microbiota, such as Ruminococcus spp., Bacteroides spp. and Bifidobacterium spp.

  14. Determination of ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 from different regions by HPLC%HPLC法测定不同产地西洋参中人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1含量

    李岚; 陈华


    Objective: To detect ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 of three active principles in American ginseng from different regions by HPLC. Methods: A C18 column was used by gradient elution of acetonitrile -0.1% H3PO4 solution as the mobile phase, the flow rate was 1.1 ml/min and the detective wavelength was set at 203 nm. the column temperature was seL at 30℃. Results: All of the three compounds showed good linearities and recoveries were in the range of 97.2%-99.0% with RSD of 1.61%-2.03%. Conclusion: The method is accurate and suitable for the determination of ginsenoside Rg1, ginsenoside Re, ginsenoside Rh1.%目的:对不同产地西洋参中人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1三种主要药效成分进行高效液相色谱的含量测定.方法:采用C18柱,以乙腈-0.1%磷酸溶液为流动相进行梯度洗脱,流速为1.1 ml/min,检测波长为203 nm,柱温为30℃.结果:人参皂苷Rg1、Re、Rb1、在测定范围内有良好的线性关系,其平均回收率为97.2%~99.0%,RSD为1.61%~2.03%.结论:该方法准确可靠,重现性好,应用性强.

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

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


    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.

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

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


    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.

  17. Long-term ginsenoside consumption prevents memory loss in aged SAMP8 mice by decreasing oxidative stress and up-regulating the plasticity-related proteins in hippocampus.

    Zhao, Haifeng; Li, Qiong; Zhang, Zhaofeng; Pei, Xinrong; Wang, Junbo; Li, Yong


    Ginsenoside, the effective component of ginseng, has been reported to have a neuron protective effect, but the preventive effect on Alzheimer's disease (AD) related memory loss and the underlying mechanisms have not been well determined. The senescence-accelerated mouse (SAM) is a useful model of AD-related memory impairment. In the present study, SAMP8 mice aged 4 months were chronically treated with ginsenoside (3 dose groups were given ginsenoside in drinking water for 7 months). The three groups were treated with ginsenoside 50, 100 and 200 mg/kg per day, respectively. Placebo-treated aged mice and young ones (4 months old) were used as controls. In addition, SAMR1 mice were used as "normal aging" control. The beneficial role of ginsenoside was manifested in the prevention of memory loss in aged SAMP8 mice. The optimal dose of ginsenoside is 100 or 200 mg/kg per day. In ginsenoside treated groups, the Abeta level markedly decreased in hippocampus and antioxidase level significantly increased in serum. In addition, the plasticity-related proteins in hippocampus significantly increased in the two ginsenoside treated groups. The plasticity-related proteins were checked in the present study including postsynaptic density-95 (PSD-95), phosphor-N-methyl-D-aspartate receptor 1 (p-NMDAR1), phospho-calcium-calmodulin dependent kinase II (p-CaMKII), phospho-protein kinase A Catalyticbeta subunit (p-PKA Cbeta) and protein kinase Cgamma subunit (PKCgamma), phospho-CREB (p-CREB) and brain derived neurotrophic factor (BDNF) etc. These findings suggest that the increase of antioxidation and up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms of ginsenoside on the memory loss prevention in aged SAMP8 mice.

  18. Roles and mechanisms of ginsenoside in cardiovascular diseases: progress and perspectives.

    Sun, Yingying; Liu, Yue; Chen, Keji


    Ginseng is among the oldest traditional Chinese medicinal herbs and is widely used in China and Southeast Asia. Over the past 50 years, considerable research has focused on the chemical constituents, pharmacological action, and clinical applications of ginseng. In this review, we examine the current state of research on ginseng, including the main active ingredient ginsenoside, its pharmacological effects on the cardiovascular system, and mechanisms of action. We focus on what is known of the effects of ginseng against atherosclerosis, arrhythmia, myocardial ischemia, and its inhibition of ventricular remodeling, providing a basis for expanding the clinical applications of ginseng.

  19. Isolation and Characterization of a New Ginsenoside from the Fresh Root of Panax Ginseng

    Chang-Chun Ruan


    Full Text Available A new saponin, malonylginsenoside Ra3, was isolated from the fresh root of Panax ginseng, along with four known ginsenosides. The new compound was identified as (20S-protopanaxadiol-3-O-(6-O-malonyl-β-D-glucopyranosyl(1→2-β-D-glucopyranoside-20-O-β-D-xylopyranosyl(1→3-β-D-glucopyranosyl(1→6-β-D-glucopyranoside on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis.

  20. 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.

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


    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. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Spatio-Temporal Expression Pattern of Six Novel Candidate Genes in Ginsenoside Biosynthesis from Panax ginseng C.A. Meyer

    Zhi-Yong LUO; Shui-Ping LIU; Xiang-Hui CHEN; Ying RUAN; Jian-Qing LUO; Bin WEN; Chun-Lin LIU; Wei-Xin HU


    To explore the mode of the spatio-temporal expression of six newly discovered ginsenoside biosynthesis candidate gene transcripts, both Northern blotting and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to elucidate the mRNA expression levels of the transcripts in various tissues and organs of Panax ginseng C. A. Meyer during different growth development stages. The six gene transcripts were all differentially expressed in cultured callus, root, stem, leaf, and seed.The mRNA expression levels were significantly higher in four-year-old roots than in one-year-old roots, and results of semi-quantitative RT-PCR assays were in accordance with those of Northern blotting analyses.The results strongly suggest that all six genes were differentially expressed at root-specific developmental stages. In particular, when a quiescent early stage culture suspension of P. ginseng cells was exposed to the ginsenoside biosynthesis-promoting elicitor Aspergillus niger polysaccharide, the GBR6 gene transcript response showed time-dependent increments and was parallel with ginsenoside productivity (P < 0.01).Overexpression of the GBR6 gene is likely to play a critically important role in the biosynthesis of ginsenosides.The results of the present study provided a background for the further elucidation of the structure and physiological function of these six candidate genes.

  2. Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action

    Subhasree Ashok Nag


    Full Text Available Conventional chemotherapeutic agents are often toxic not only to tumor cells but also to normal cells, limiting their therapeutic use in the clinic. Novel natural product anticancer compounds present an attractive alternative to synthetic compounds, based on their favorable safety and efficacy profiles. Several pre-clinical and clinical studies have demonstrated the anticancer potential of Panax ginseng, a widely used traditional Chinese medicine. The anti-tumor efficacy of ginseng is attributed mainly to the presence of saponins, known as ginsenosides. In this review, we focus on how ginsenosides exert their anticancer effects by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins, growth factors (c-myc, EGFR, and VEGF, tumor suppressors (p53 and p21, oncogenes (MDM2, cell death mediators (Bcl-2, Bcl-xL, XIAP, caspases, and death receptors, inflammatory response molecules (NF-κB and COX2, and protein kinases (JNK, Akt, and AMPK. We also discuss the structure-activity relationship (SAR of various ginsenosides and their potential in the treatment of various human cancers. In summary, recent advances in the discovery and evaluation of ginsenosides as cancer therapeutic agents support further preclinical and clinical development of these agents for the treatment of primary and metastatic tumors.

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

    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. ...

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

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


    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

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

    Jiahong Zhu

    Full Text Available 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

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

    Li-Yuan Ma


    Full Text Available 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.

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

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


    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.

  8. Rk1, a ginsenoside, is a new blocker of vascular leakage acting through actin structure remodeling.

    Yong-Sun Maeng

    Full Text Available Endothelial barrier integrity is essential for vascular homeostasis and increased vascular permeability and has been implicated in many pathological processes, including diabetic retinopathy. Here, we investigated the effect of Rk1, a ginsenoside extracted from sun ginseng, on regulation of endothelial barrier function. In human retinal endothelial cells, Rk1 strongly inhibited permeability induced by VEGF, advanced glycation end-product, thrombin, or histamine. Furthermore, Rk1 significantly reduced the vessel leakiness of retina in a diabetic mouse model. This anti-permeability activity of Rk1 is correlated with enhanced stability and positioning of tight junction proteins at the boundary between cells. Signaling experiments revealed that Rk1 induces phosphorylation of myosin light chain and cortactin, which are critical regulators for the formation of the cortical actin ring structure and endothelial barrier. These findings raise the possibility that ginsenoside Rk1 could be exploited as a novel prototype compound for the prevention of human diseases that are characterized by vascular leakage.

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

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


    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 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.

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

    Xiao-Jia Chen


    Full Text Available 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.

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

    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


    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

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

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


    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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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


    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.

  14. Ginsenoside Rg1 Attenuates Cigarette Smoke-Induced Pulmonary Epithelial-Mesenchymal Transition via Inhibition of the TGF-β1/Smad Pathway

    Sibin Guan


    Full Text Available Epithelial-mesenchymal transition (EMT is a process associated with airway remodeling in chronic obstructive pulmonary disease (COPD, which leads to progressive pulmonary destruction. Panax ginseng is a traditional herbal medicine that has been shown to improve pulmonary function and exercise capacity in patients with COPD. Ginsenoside Rg1 is one of the main active components and was shown to inhibit oxidative stress and inflammation. The present study investigated the hypothesis that ginsenoside Rg1 attenuates EMT in COPD rats induced by cigarette smoke (CS and human bronchial epithelial (HBE cells exposed to cigarette smoke extract (CSE. Our data showed that CS or CSE exposure increased expression of the mesenchymal marker α-smooth muscle actin (α-SMA and decreased expression of the epithelial marker epithelial cadherin (E-cad in both lung tissues and HBE cells, which was markedly suppressed by ginsenoside Rg1. Importantly, CS-induced upregulation of TGF-β1/Smad pathway components, including TGF-β1, TGF-βR1, phospho-Smad2, and phospho-Smad3, was also inhibited by ginsenoside Rg1. Additionally, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-βR1-Smad2/3 inhibitor, on suppression of EMT in CSE-induced HBE cells. Collectively, we concluded that ginsenoside Rg1 alleviates CS-induced pulmonary EMT, in both COPD rats and HBE cells, via inhibition of the TGF-β1/Smad pathway.

  15. Enhancement of ginsenoside Rg(1) in Panax ginseng hairy root by overexpressing the α-L-rhamnosidase gene from Bifidobacterium breve.

    Zhang, Ru; Zhang, Bian-Ling; Li, Gu-Cai; Xie, Tao; Hu, Teng; Luo, Zhi-Yong


    To improve the production of ginsenoside Rg1 in Panax ginseng. The α-L-rhamnosidase gene from Bifidobacterium breve (BbRha) was overexpressed into hairy root culture system using Agrobacterium rhizogenes A4. Ginsenoside Rg1 in hairy roots was obtained following transformation via overexpressed gene representing 2.2-fold higher than those of control lines. Several overexpression transgenic hairy root lines were obtained exhibiting markedly increased levels of the corresponding α-L-rhamnosidase enzymatic activity relative to control. Ginsenoside Rg1 levels in the transgenic lines were higher (2.2-fold) than those of control after following 30 days culturing, while ginsenoside Re contents in tested transgenic lines were found to be lower. The transgenic hairy roots harboring α-L-rhamnosidase gene improved the accumulation of ginsenoside Rg1 up to 3.6 mg g(-1) dry weight. BbRha gene selectively enhances the production of ginsenoside Rg1 in P. ginseng hairy roots.

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

    Noh, Kyeong-Hwan; Oh, Deok-Kun


    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.

  17. Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

    Rui-Xing Wang


    Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

  18. Caspase-mediated anti-apoptotic effect of Ginsenoside Rg5, a main rare ginsenoside, on Acetaminophen-induced Hepatotoxicity in Mice.

    Wang, Zi; Hu, Junnan; Yan, Menghan; Xing, Jingjing; Liu, Wencong; Li, Wei


    Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group has confirmed that black ginseng (Panax ginseng, BG) showed powerful protective effects on APAP-induced ALI. However, it is not clear which kind of individual ginsenoside from BG to play such liver protection effect. The objective of current investigation was to evaluate whether ginsenoside Rg5 (G-Rg5) protected against APAP-induced hepatotoxicity and the involved action mechanisms. Mice were administrated with G-Rg5 at two dosages of 10 or 20 mg/kg for 7 consecutive days. After the last treatment, all the animals received a single intraperitoneally injection of APAP (250 mg/kg) showed severe liver toxicity after 24 h, and the liver protection effects of G-Rg5 was examined. The results clearly indicated that pre-treatment with G-Rg5 remarkably inhibited the production of serum tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) compared with the APAP group. Meanwhile, G-Rg5 decreased the hepatic malondialdehyde (MDA) content, the protein expression levels of 4-hydroxynonenal (4-HNE) and cytochrome P450 2E1 (CYP2E1) in the liver tissues. G-Rg5 decreased APAP-caused the hepatic overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, analysis of immunohistochemistry and western blotting also indicated that G-Rg5 pretreatment inhibited activation of apoptotic pathways mainly via increasing the expression of Bcl-2 protein, decreasing the expression of Bax protein, proliferating cell nuclear antigen (PCNA), cytochrome c, caspase 3, caspase 8 and caspase 9. Liver histopathological observation provided further evidence that pretreatment with G-Rg5 could significantly inhibit hepatocyte necrosis, inflammatory cell infiltration and apoptosis caused by APAP. In conclusion, the present study clearly demonstrates that G-Rg5 exerts a liver protection effect against APAP

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

    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


    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.

  20. Antihyperglycemic effects of total ginsenosides from leaves and stem of Panax ginseng

    Jing-tian XIE; Chong-zhi WANG; An-bao WANG; Jian WU; Daniel BASILA; Chun-su YUAN


    Aim: The antihyperglycemic effects of the total ginsenosides in Chinese ginseng (TGCG), extracted from leaves and the stem, were evaluated in diabetic C57BL/6J ob/ob mice. Methods: Animals received daily intraperitoneal injections of TGCG (100 and 200 mg/kg) or oral administration (150 and 300 mg/kg) for 12 d. Fasting blood glucose levels and body weight were measured after fasting the animals for 4 h. Peripheral glucose use was also measured using an intraperitoneal glucose tolerance test. Results: In the injection group, a high dose of TGCG (200 mg/kg)significantly lowered the fasting blood glucose levels in ob/ob mice on d 12 (153±16 mg/dL vs 203±9.8 mg/dL, P<0.01, compared to vehicle-treated group). In the oral group, blood glucose decreased notably with a dose of TGCG (300 mg/kg) on d 12 (169.1±12.6 mg/dL vs 211.6±13.8 mg/dL, P<0.05, compared to the vehicletreated group). Glucose tolerance was also improved markedly in ob/ob mice.Furthermore, a significant reduction in bodyweight (P<0.05) was observed after 12 d of TGCG (300 mg/kg) treatment in mice from the oral group. Conclusion: The results indicated that in a diabetic ob/ob mouse model TGCG was endowed with significant anti-hyperglycemic and anti-obesity properties. Therefore, the total ginsenosides extracted from Chinese ginseng leaves and the stem may have some potential for treating diabetes.

  1. [Ginsenoside Rh₂ induces apoptosis and autophagy of K562 cells by activating p38].

    Liu, Xiao-Xia; Xia, Jing; Tang, Jia-Feng; Zhou, Ming-Hua; Chen, Di-Long; Liu, Ze-Hong


    To study the effect of ginseng saponin Rh₂ in inducing apoptosis of human leukemia K562 cells, and explore its mechanism from the aspect of autophagy pathway. CCK-8 assay was used to examine the growth inhibition of human leukemia cell lines K562 treated with ginsenoside Rh₂; flow cytometry (FCM) was used to detect cell apoptosis; Hoechst staining was used to observe the changes of cell morphological apoptosis; Acridine and MDC staining were used to detect the effects of the Rh₂ on autophagy; Western blot and RT-PCR were used to detect the expression levels of the proteins closely associated with autophagy and apoptosis. In order to study the effect of autophagy in proliferation and apoptosis, we used the autophagy inhibitor (3-MA).CCK-8 indicated that Rh₂ at low concentration could effectively inhibit the proliferation of leukemia cellsin dose- and time-dependent manners in K562 cells; FCM indicated that Rh₂ induced apoptosis; Hoechest staining showed that K562 cells had typical apoptotic morphological changes by treated Rh₂; Acridine and MDC staining showed that Rh₂ enhanced the green fluorescence and a large number of acidic autophagy vesicles were present; Western blot and RT-PCR results showed that Rh₂ increased the expression levels of Beclin-1, LC3A, LC3B, activated Caspase-3 and p-p38 in K562 cells; application of autophagy inhibitors(3-MA) could weaken the inhibition effect of Rh₂ on proliferation and induction effect on apoptosis in K562 cells. Ginsenoside Rh₂ inhibited the proliferation and induced apoptosis probably through activating p-p38, and inducing cell autophagy signaling pathway in K562 cells. Copyright© by the Chinese Pharmaceutical Association.

  2. Determination of Contents of Ginsenoside Rg1 , Ginsenoside Rb1 and Notoginsenoside R1 in Notoginseng Hemostasis Tablet%三七止血片中三七含量测定

    沙延淳; 叶小辉; 杨祝仁; 姚建华


    目的:对三七止血片中三七的主要成分进行测定,提高质控标准.方法:采用液相梯度法以人参皂苷Rg1、人参皂苷Rb1和三七皂苷R1的含量为指标.结果:测定三七止血片中人参皂苷Rg1 2.42 mg/片,人参皂苷Rb11.37 mg/片,三七皂苷R10.15 mg/片,含皂苷总量为3.94 mg/片.结论:液相梯度法方法可控,可以达到提高药品质量控制的目的.%Objective:Determination of the contents of main components in notoginseng hemostasis tablet was made to improve the standard of quality.Methods:The contents of ginsenoside Rg1,ginsenoside Rb1 and the notoginsenoside R1 were set up as the indexes by HPLC gradient profile.Results:The contents of ginsenoside Rg1,ginsenoside Rbland the notoginsenoside R1 were 2.42 mg per tablet,1.37 mg per tablet and 0.15 mg per tablet respectively.3.94 mg per tablet was the total saponin content.Conclusion:The experiment of HPLC gradient profile could reach the goal by improving quality control of the drug.

  3. Qualitative and Quantitative Evaluation of Epimedium and Ginseng Contained Combinations Using HPLC

    MAYuan-chun; LUOMai; SarahWittenberg; CliveBarwell; ZHOUYu-xin; WEILu-xue


    Aim:To develop a rapid,effective method for the detemination of flavonoids and ginsenosides in one injection and evaluate the flavonoids and ginsenosides content to control the ratio of Epimedium and Ginseng herbs in botanical combinations.Methods: The quality evaluation was determinatted using reversed-phase high performance liquid chromatog raphy(HPLC),referred by the major flovonoids from Epimedium,epimedin A,epimedin B,epimedin C,and icariin as the standards,and the major ginsenosides Rg1,Re,Rf,Rb1,Rb2,and Rd as the standards,included Epimedium brevicornum Maxim.,E.sagittatum( Zucc)Maxim.,E.koreanum NaKai,P.ginseng C.A.Meyer,P.quinquefolium L.,P.notoginseng and some products containing the above herbs.Results:The main flavonoids and ginsenosides could be clearly resolved in the single analysis.Conclusion.The results can be effectively used in evaluating qualitatively and quantitatively the ration of Epimdium and Ginseng contained products.

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

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


    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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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


    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. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

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

    Wei Li


    Full Text Available 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.

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

    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


    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.

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

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


    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 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 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 ginseng leaves, but benefits for accumulation of secondary metabolism (total content of ginsenoside) in ginseng root.

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

    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


    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.

  10. Inhibition of Autophagy via Activation of PI3K/Akt Pathway Contributes to the Protection of Ginsenoside Rb1 against Neuronal Death Caused by Ischemic Insults

    Tianfei Luo


    Full Text Available 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.

  11. Influence of ginsenoside on expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in the medial septum of aged rats

    Liang Zeng; Haihua Zhao; Yongli Lü; Wenbo Dai


    BACKGROUND: It has been shown that ginsenoside, the effective component of ginseng, can enhance expression of choline acetyl transferase, as well as brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB), in cholinergic neurons of the basal forebrain.OBJECTIVE: To qualitatively and quantitatively verify the influence of ginsenoside on expression of BDNF and its receptor, TrkB, in the medial septum of aged rats, and to provide a molecular basis for clinical application.DESIGN, TIME AND SETTING: A contrast study, which was performed in the Department of Anatomy, China Medical University, and the Department of Anatomy, Shenyang Medical College between December 2005 and May 2007.MATERIALS: Thirty-five, healthy, female, Sprague Dawley rats were selected for this study. Ginsenoside (81% purity) was provided by Jilin Ji'an Wantai Chinese Medicine Factory; anti-BDNF antibody, anti-TrkB antibody, and their kits were provided by Wuhan Boster Company.METHODS: A total of 35 rats were divided into three groups: young (four months old), aging (26 months old), and ginsenoside. Rats in the ginsenoside group were administered ginsenoside (25mg/kg/d) between 17 months and 26 months.MAIN OUTCOME MEASURES: Immunohistochemistry and in situ hybridization were used to measure expression of BDNF and TrkB in the medial septum of aged rats, and the detected results were expressed as gray values.RESULTS: ①Qualitative detection: using microscopy, degenerative neurons were visible in the medial septum in the aging group. However, neuronal morphology in the ginsenoside group was similar to neurons in the young group.②Quantitative detection: the mean gray value of BDNF-positive and TrkB-positive products in the aging group were significantly higher than in the young group (t=3.346,4.169, P<0.01); however, the mean gray value in the ginsenoside group was significantly lower than in the aging group (t=2.432,2.651, P<0.01).CONCLUSION: Ginsenoside can increase

  12. Ginsenoside Rg1 changes brain-derived neurotrophic factor expression in the facial nucleus of rats after ovariectomy:A semiquantitative analysis

    Cuiying Zhou; Wenlong Luo; Dong Wang


    BACKGROUND: Estrogen is neuroprotective, but long-term estrogen treatment can induce side effects such as breast carcinoma, endometrial cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects.OBJECTIVE: To study the effects of Ginsenoside Rg1 on facial neurons and brain-derived neurotrophic factor (BDNF) expression in the facial nucleus in ovariectomized rats.DESIGN, TIME AND SETTING: The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008.MATERIALS: Ginsenoside Rg1 (Sigma, USA), rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG (Boster, China), and a TUNEL kit (Roche, Germany) were used in this study.METHODS: A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation (n=8), model (n=20), and Ginsenoside Rg1 (n=20) groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rg1 group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rg1; other groups received 2 mL saline, once a day, for 14 days.MAIN OUTCOME MEASURES: Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry.RESULTS: At 3-14 days following facial nerve damage, Ginsenoside Rg1 increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths (P< 0.05). Ginsenoside Rg1 also gradually increased Bcl-2 protein expression and decreased Bax protein expression (P < 0.05). By

  13. Absorption of Ginsenosides of Ginseng Preparations in Rat Small Intestine%人参制剂中人参皂甙在大鼠小肠中的吸收

    赵浩如; 李振泉


    AIM Since bioavailability of ginsenosides is small by oral administration, the absorption of ginsenosides in the small intestine was studied. METHODS The absorption action was investigated in an in situ perfusion model of rat small intestine. A ginseng (root of Panax ginseng C. A. Meyer) decoction and a ginsenosides liquor was used as perfusion solution. RESULT AND CONCLUSION A mean value for ginsenosides absorbed in 3 hours per rat was 21. 79 mg and 18.41 mg, respectively. Absorption of ginsenosides in the ginsenosides liquor basically followed first-order reaction of kinet-ics. The absorption of ginsenosides in the decoction was delayed in the second hour. The results confirm that the small intes tine has normal ability to absorb ginsenosides. It is suggested that the preparations containing ginsenosides should be protect-ed from acid hydrolysis in stomach and absorbed as completely as possible in small intestine.%目的 由于口服人参皂甙的生物利用度较小,本文研究了小肠对人参皂苷甙的吸收功能.方法 采用在体大鼠小肠吸收模型,以人参煎剂和人参总皂甙溶液剂作为灌流液.结果与讨论 在3小时中每只大鼠吸收的人参皂甙平均值分别为21.79mg和平共处8.41mg.大鼠小肠对人参总皂甙溶液中人参皂甙的吸收基本遵循动力学一级反应; 对人参煎剂中人参皂甙的吸收在第二小时时受到阻滞.该结果显示大鼠小肠对人参皂甙具有正常吸收功能,建议含人参制剂应参避免胃酸水解,并尽可能在小肠得到完全的吸收.

  14. Structure-activity relationship and substrate-dependent phenomena in effects of ginsenosides on activities of drug-metabolizing P450 enzymes.

    Miao Hao

    Full Text Available Ginseng, a traditional herbal medicine, may interact with several co-administered drugs in clinical settings, and ginsenosides, the major active components of ginseng, may be responsible for these ginseng-drug interactions (GDIs. Results from previous studies on ginsenosides' effects on human drug-metabolizing P450 enzymes are inconsistent and confusing. Herein, we first evaluated the inhibitory effects of fifteen ginsenosides and sapogenins on human CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 enzymes by using commercially available fluorescent probes. The structure-activity relationship of their effects on the P450s was also explored and a pharmacophore model was established for CYP3A4. Moreover, substrate-dependent phenomena were found in ginsenosides' effects on CYP3A4 when another fluorescent probe was used, and were further confirmed in tests with conventional drug probes and human liver microsomes. These substrate-dependent effects of the ginsenosides may provide an explanation for the inconsistent results obtained in previous GDI reports.

  15. Determination of ginsenosides (ginseng saponins) in dry root powder from Panax ginseng, Panax quinquefolius, and selected commercial products by liquid chromatography: interlaboratory study.

    Asafu-Adjaye, Ebenezer B; Wong, Siu Kay


    Twelve collaborating laboratories assayed 4 products, namely, Panax ginseng, Panax quinquefolius, and 2 ginseng products, for 6 ginsenosides: Rb1, Rb2, Rc, Rd, Re, and Rg1. Collaborators also received a negative control for the recovery study. Pure ginsenosides were provided as reference standards for the liquid chromatography (LC) analysis and the system suitability tests. The LC analyses were performed on the methanol extract using UV detection at 203 nm. For P. ginseng, individual ginsenosides were consistent in their means; repeatability standard deviations (RSDr) ranged from 4.17 to 5.09% and reproducibility standard deviations (RSDR) ranged from 7.27 to 11.3%. For P. quinquefolius, the Rb1 and Rb2 ginsenosides were higher and lower in concentration than P. ginseng, with RSDr values of 3.44 and 6.60% and RSDR values of 5.91 and 12.6% respectively, and other analytes at intermediate precisions. For ginseng commercial products, RSDr values ranged from 3.39 to 8.12%, and RSDR values ranged from 7.65 to 16.5%. A recovery study was also conducted for 3 ginsenosides: Rg1, Re, and Rb1. The average recoveries were 99.9, 96.2, and 92.3%, respectively. The method is not applicable for the determination of Rg1 and Re in ginseng product at levels <300 mg/kg.

  16. Screening of plant pathogenic fungi by ginsenoside compound K production%人参皂苷compound K转化菌株的筛选

    杨元超; 王英平; 闫梅霞; 孙成贺; 郑培和


    目的:筛选具有人参皂苷转化能力的真菌菌株,用于生产稀有人参皂苷compound K.方法:通过液态发酵,以三七茎叶总皂苷为底物,采用TLC和HPLC-ELSD检测转化产物,从12株植物病原真菌中筛选能够转化产生人参皂苷compoundK的最佳菌株.结果:获得一株高效人参皂苷转化真菌,可以转化产生人参皂苷compound K,该菌株为镰刀属真菌串珠镰孢Fusarium moniliforme.结论:串珠镰孢对三七茎叶总皂苷具有较高的转化效率,有望用于生产制备compound K等低含量高活性的稀有人参皂苷.%Objective:To screen a new strain which can transform panaxadiol saponins into the rare ginsenoside compound K.Method:The total saponins in stems and leaves of Panax notoginseng was used as a substrate in the liquid state fermentation process.and the results were detected by TCL and HPLC-ELSD to screen a strain from twelve plant pathogenic fungi which can produce ginsenoside compound K.Result:Fusarium moniliforme was found to transform the total saponins to ginsenoside compound K efficiently in the all twelve fungal strains.In the fermentation process, ginsenoside Rb1 was transformed almost completely,and the content of ginsenoside Rd was decreasing evidently.Conclusion:F.moniliforme is selected as a new high-yield strain.It is expected to be used to produce the high activity infrequent ginsenoside compound K and to improve the content of active principles in medicinal plants.

  17. Evaluation of the adaptogenic potential exerted by ginsenosides Rb1 and Rg1 against oxidative stress-mediated neurotoxicity in an in vitro neuronal model.

    Fernández-Moriano, Carlos; González-Burgos, Elena; Iglesias, Irene; Lozano, Rafael; Gómez-Serranillos, M Pilar


    Ginseng (Panax sp.) is a drug with multiple pharmacological actions that has been largely used in traditional medicines for the treatment of many health problems. In the therapy of neurodegenerative disorders, it has been employed due to its capacity to strengthen mental processes by enhancing cognitive performance and psychological function. Current work aimed at evaluating the adaptogenic potential of Rb1 and Rg1 against oxidative-stress mediated degeneration in a model of nervous cells. Oxidative stress and mitochondrial dysfunction were achieved by exposing SH-SY5Y cells to the mitochondrial complex I inhibitor rotenone. The cytoprotective activity of pre-treatments with ginsenosides Rb1 and Rg1 against rotenone was assessed by determining biochemical markers regarding oxidative stress (ROS scavenging, glutathione and lipid peroxidation levels, SOD activity and Nrf2 activation) and apoptosis-related alterations (mitochondrial membrane potential, calcium levels, aconitase activity and pro/antiapoptotic proteins). Their capacity to cross the blood brain barrier was also estimated. At their optimal doses, ginsenosides Rb1 and Rg1 significantly ameliorated redox status within the cells; they reduced ROS and TBARS levels and improved the glutathione system, as well as they enhanced SOD activity and Nrf2 pathway activation. They protected neuronal cells against MMP loss, calcium homeostasis disruption and aconitase inhibition. Consequently, apoptotic cell death was attenuated by the pre-treatment with ginsenosides, as evidenced by the reduction in caspase-3 and Bax, and the increase in Bcl-2 expressions; also, lower levels of cytochrome C were found in the cytosol. Poor BBB permeation was demonstrated for both ginsenosides. In conclusion, ginsenosides Rb1 and Rg1 exhibit neuroprotective potential which is achieved, at least in part, via mitochondrial protection and the plausible involvement of Nrf2 pathway activation. Our results contribute to validate the

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

    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


    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

  19. Involvement of serotonergic, noradrenergic and dopaminergic systems in the antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax ginseng C.A. Meyer.

    Wang, Guo-Li; He, Zhong-Mei; Zhu, Hong-Yan; Gao, Yu-Gang; Zhao, Yan; Yang, He; Zhang, Lian-Xue


    Ginsenoside Rb1, a 20 (S)-protopanaxadiol, is a major active ingredient of Panax ginseng C.A. Meyer, which as the King of Chinese herbs, has been wildly used for the treatment of central nervous system diseases. Previous studies have shown that 20 (S)-protopanaxadiol possesses a novel antidepressant-like effect in the treatment of depression, whereas ginsenoside Rb1 in depression has been rarely reported. The present study was to investigate the antidepressant-like effect of ginsenoside Rb1 and its relevant mechanisms. The whole experiment was divided into two parts: one part we examined the antidepressant-like effect of ginsenoside Rb1 with open-field test (OFT), tail suspension test (TST), forced swim test (FST), 5-HTP induced head-twitch and reserpine response in mice, another part we used chronic unpredicted mild stress (CUMS) model to further explore the antidepressant-like effect of ginsenoside Rb1 with caffeine, fluoxetine and p-Chlorophenylalanine (PCPA) in rats. Furthermore, the levels of monoamine neurotransmitters of NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, HVA were all measured by ELISA kits after the CUMS protocol. Our data indicated that 7 days treatment with ginsenoside Rb1 (4, 8, 10mg/kg, p.o.) significantly decreased immobility time in the FST and TST in mice, and played important roles in mice which were induced by 5-HTP (200mg/kg, i.p.) and reserpine (4mg/kg, i.p.). On the basis of CUMS model, 21 days treatment with ginsenoside Rb1 not only had effective interactions with caffeine (5mg/kg, i.p.), fluoxetine (1mg/kg, i.p.) and PCPA (100mg/kg, i.p.), but also significantly up-regulated the 5-HT, 5-HIAA, NE and DA levels in CUMS rats' brain, whereas HVA and DOPAC had no significant difference. Moreover, there was no alteration in spontaneous locomotion in any experimental group. These results suggest that ginsenoside Rb1 exhibits significant antidepressant-like effect in behavioral tests, chronic animal model and drug interactions, its

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

    Yi, Jae-Sung; Choo, Hyo-Jung [College of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-gu, Seoul 136-701 (Korea, Republic of); Cho, Bong-Rae [Department of Chemistry, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Hwan-Myung [Department of Chemistry, Ajou University, Suwon, Kyunggi-Do 443-749 (Korea, Republic of); Kim, Yong-Nyun [Division of Specific Organs Center, National Cancer Center, Kyunggi-Do 411-769 (Korea, Republic of); Ham, Young-Mi, E-mail: [College of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-gu, Seoul 136-701 (Korea, Republic of); Ko, Young-Gyu, E-mail: [College of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-gu, Seoul 136-701 (Korea, Republic of)


    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.

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

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


    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 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 TNBS-induced recurrent UC by inhibiting neutrophil infiltration and promoting the antioxidant capacity of the damaged colonic tissue.

  2. [Ultrasound assisted the enzymolysis of ginsenosides to prepare pare ginseng saponin Compound K].

    Yu, Zhao-Hui; Liu, Qi-Yuan; Cui, Li; Jia, Xiao-Bin; Jin, Xin; Zhang, Zhen-Hai


    To prepare ginseng saponin Compound K with ultrasound-assisted total zymolytic ginseng saponins. The conversion rate was taken as the index to detect the pre-treatment factors such as ultrasonic power and ultrasonic time, as well as the impact of enzymatic factors, such as pH value, temperature, concentration of substrate, dosage of enzyme and reaction time, on the conversion rate. The response surface method was used to optimize the preparation conditions. The enzymolytic products were identified with MS, 1H-NMR and 13C-NMR. The results showed that the optimum conditions of the ultrasound-assisted enzymolysis were 250 W for ultrasonic power, 15 min for ultrasonic time, 5.5 for enzymolytic pH, 50 degrees C for enzymolytic temperature, 36 h for enzymolytic time, 4:5 for enzymolytic dosage: substrate and 1.0 g x L(-1) for concentration of substrate. The relative molecular mass of reaction products was 622.4. Therefore, the nuclear magnetic map verified that the reaction product was rare ginseng saponin Compound K. Under the above conditions, based on the total zymolytic ginseng saponins, the conversion rate of rare ginseng saponin Compound K was 6.91% in proportion to the total of ginsenosides. The process features gentle reaction conditions, high conversion rate and simple and reliable process, which is suitable for industrial production.

  3. Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury

    Yang Liu


    Full Text Available Ginsenoside Rd (GSRd, one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+, an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Our results, from the addition of different concentrations of GSRd (1, 10 and 50 μM, showed that GSRd at 1 and 10 μM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation.

  4. Panax ginseng modulates cytokines in bone marrow toxicity and myelopoiesis: ginsenoside Rg1 partially supports myelopoiesis.

    Hanumantha Rao Balaji Raghavendran

    Full Text Available In this study, we have demonstrated that Korean Panax ginseng (KG significantly enhances myelopoiesis in vitro and reconstitutes bone marrow after 5-flurouracil-induced (5FU myelosuppression in mice. KG promoted total white blood cell, lymphocyte, neutrophil and platelet counts and improved body weight, spleen weight, and thymus weight. The number of CFU-GM in bone marrow cells of mice and serum levels of IL-3 and GM-CSF were significantly improved after KG treatment. KG induced significant c-Kit, SCF and IL-1 mRNA expression in spleen. Moreover, treatment with KG led to marked improvements in 5FU-induced histopathological changes in bone marrow and spleen, and partial suppression of thymus damage. The levels of IL-3 and GM-CSF in cultured bone marrow cells after 24 h stimulation with KG were considerably increased. The mechanism underlying promotion of myelopoiesis by KG was assessed by monitoring gene expression at two time-points of 4 and 8 h. Treatment with Rg1 (0.5, 1 and 1.5 µmol specifically enhanced c-Kit, IL-6 and TNF-α mRNA expression in cultured bone marrow cells. Our results collectively suggest that the anti-myelotoxicity activity and promotion of myelopoiesis by KG are mediated through cytokines. Moreover, the ginsenoside, Rg1, supports the role of KG in myelopoiesis to some extent.

  5. Ginsenoside Rh2 Showing Ability to Induce Apoptosis in HeLa Cells


    This paper deals with the inhibitory mechanisms of ginsenoside G-Rh2 on the growth of tumor cells. G-Rh2 significantly inhibited the proliferation of human cervical adenocarcinoma HeLa cells in a time- and dose-dependent manner. G-Rh2 induced apoptotic manifestations in HeLa cells as evidenced by the changes in the cell morphology, the DNA fragmentation and the activation of caspases. Caspase inhibitors, caspase family inhibitor, z-Val-Ala-Asp-fmk(z-VAD-fmk); caspase-1 inhibitor, Ac-Tyr-Val-Ala-Asp-chloromethyl-ketone(Ac-YVAD-cmk); caspase-3 inhibitor, z-Asp-Glu-Val-Asp-fmk(z-DEVE-fmk) and caspase-8 inhibitor, z-Ile-Glu-Asp-fmk(z-IETD-fmk) effectively attenuated G-Rh2-induced cell death. The activities of caspase-1 and caspase-3 were increased in the G-Rh2-induced apoptotic process. However, caspase inhibitors can not inhibit G-Rh-2 induced cell death completely. These results suggest that G-Rh2-induced cell death is mediated by the activation of caspase cascade, but there might be some other pathways for induction of this apoptosis.

  6. Ginsenoside Rb1 Protects Rat Neural Progenitor Cells against Oxidative Injury

    Na Ni


    Full Text Available Ginseng, the root of Panax ginseng C.A. Meyer, has been used as a tonic to enhance bodily functions against various ailments for hundreds of years in Far Eastern countries without apparent adverse effects. Ginsenoside Rb1, one of the most active ingredients of ginseng, has been shown to possess various pharmacological activities. Here we report that Rb1 exhibits potent neuroprotective effects against oxidative injury induced by tert-butylhydroperoxide (t-BHP. Lactate dehydrogenase (LDH assay demonstrated that incubation with 300 µm t-BHP for 2.5 h led to a significant cell loss of cultured rat embryonic cortex-derived neural progenitor cells (NPCs and the cell viability was pronouncedly increased by 24 h pretreatment of 10 µm Rb1. TUNEL staining further confirmed that pretreatment of Rb1 significantly reduced the cell apoptosis in t-BHP-induced oxidative injury. Real time PCR revealed that pretreatment with Rb1 activated Nrf2 pathway in cultured NPCs and led to an elevated expression of HO-1. The results of the present study demonstrate that Rb1 shows a potent anti-oxidative effect on cultured NPCs by activating Nrf2 pathway.

  7. Inhibitory Effects of Ginsenoside Rb1 on Apoptosis Caused by HSV-1 in Human Glioma Cells

    Yuan-Yuan Liang; Bin Wang; Dong-Meng Qian; Ling Li; Zhi-Hao Wang; Ming Hu; Xu-Xia Song


    To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1 (HSV-1) in Human Glioma Cells (U251),U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRb1,GRb1+HSV-1,HSV-1 and control groups.MTT and cell apoptosis assays were used to detect the inhibitory effects of GRbl on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay.We found that in the 400 μg/mL GRbl and 400 μg/mL GRbl+HSV-1 groups,MTT values were higher than control group at all times (P<0.05).Moreover,the apoptosis rate in the 400 μg/mL GRb1+HSV-1 group was lower than the HSV-1 group (P<0.05).These results confirmed that,at appropriate concentrations,GRb 1 could inhibit nerve cell apoptosis in HSV-1 infections.

  8. The integration of GC-MS and LC-MS to assay the metabolomics profiling in Panax ginseng and Panax quinquefolius reveals a tissue- and species-specific connectivity of primary metabolites and ginsenosides accumulation.

    Liu, Jia; Liu, Yang; Wang, Yu; Abozeid, Ann; Zu, Yuan-Gang; Tang, Zhong-Hua


    The traditional medicine Ginseng mainly including Panax ginseng and Panax quinquefolius is the most widely consumed herbal product in the world. Despite the extensive investigation of biosynthetic pathway of the active compounds ginsenosides, our current understanding of the metabolic interlink between ginsenosides synthesis and primary metabolism at the whole-plant level. In this study, the tissue-specific profiling of primary and the secondary metabolites in two different species of ginseng were investigated by gas chromatography- and liquid chromatography coupled to mass spectrometry. A complex continuous coordination of primary- and secondary-metabolic network was modulated by tissues and species factors during growth. The results showed that altogether 149 primary compounds and 10 ginsenosides were identified from main roots, lateral roots, stems, petioles and leaves in P. ginseng and P. quinquefolius. The partial least squares-discriminate analysis (PLS-DA) revealed obvious compounds distinction among tissue-specific districts relative to species. To survey the dedication of carbon and nitrogen metabolism in different tissues to the accumulation of ginsenosides, we inspected the tissue-specific metabolic changes. Our study testified that the ginsenosides content was dependent on main roots and lateral roots energy metabolism, whereas independent of leaves and petiole photosynthesis during ginsenosides accumulation. When tow species were compared, the results indicated that high rates of C assimilation to C accumulation are closely associated with ginsenosides accumulation in P. ginseng main roots and P. quinquefolius lateral roots, respectively. Taken together, our results suggest that tissue-specific metabolites profiling dynamically changed in process of ginsenosides biosynthesis, which may offer a new train of thoughts to the mechanisms of the ginsenosides biosynthesis at the metabolite level. Copyright © 2016 The Author(s). Published by Elsevier B.V. All

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

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


    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

  10. Component Analysis of Cultivated Ginseng, Red Ginseng, Cultivated Wild Ginseng, and Red Wild Ginseng Using HPLC Method

    Jang Ho, Lee


    Full Text Available Objectives : The aim of this experiment is to provide an differentiation of ginseng, red ginseng, cultivated wild ginseng(CWG, and red wild ginseng(RWG through component analysis using HPLC(High Performance Liquid Chromatography, hereafter HPLC. Methods : Comparative analyses of ginsenoside Rg3, ginsenoside Rh2, and ginsenosides Rb1 and Rg1 of various ginsengs were conducted using HPLC. Results : 1. CWG was relatively heat-resistant and showed slow change in color during the process of steaming and drying, compared to cultivated ginseng. 2. Ginsenoside Rg3 was not detected in cultivated ginseng and CWG, whereas it was high in red ginseng and RWG. Ginsenoside Rg3 was more generated in red ginseng than in RWG. 3. Ginsenoside Rh2 appreared during steaming and drying of cultivated ginseng, whereas it was more increased during steaming and drying of CWG. 4. Ginsenoside Rg1 content was more increased during steaming and drying of cultivated ginseng, whereas it was more decreased during steaming and drying of CWG. 5. Ginsenoside Rb1 content was increased about 500% during steaming and drying of cultivated ginseng, whereas it was increased about 30% during steaming and drying of CWG, indicating that ginsenoside Rb1 was more generated in red ginseng than in RWG. 6. Ginsenoside Rg3 content was higher, whereas ginsenoside Rg1 content was lower in 11th RWG than in 9th RWG, indicating that ginsenoside Rg3 content was increased and Rg1 content was decreased as steaming and drying continued to proceed. Ginsenoside Rh2 and Rb1 contents began to be increased, followed by decreased after 9th steaming and drying process. Conclusions : Above experiment data can be an important indicator for the identification of ginseng, red ginseng, CWG, and RWG. And the following studies will be need for making good product using CWG.

  11. An ultra performance liquid chromatography-time-of-flight-mass spectrometric method for fast analysis of ginsenosides in Panax ginseng root

    Hu, C.; Kong, H.; Zhu, C.; Wei, H.; Hankemeier, T.; Greef, J. van der; Wang, M.; Xu, G.


    A method for fast analysis of ginsenosides in Panax ginseng roots was developed using ultra performance liquid chromatography-time-of-flight-mass spectrometry (UPLC-TOF-MS). The column used was HSS T3 (100 mm × 2.1 mm, 1.8 µm). The mobile phase consisted of 15 mmol/L ammonium formate and acetonitril

  12. An ultra performance liquid chromatography-time-of-flight-mass spectrometric method for fast analysis of ginsenosides in Panax ginseng root

    Hu, C.; Kong, H.; Zhu, C.; Wei, H.; Hankemeier, T.; Greef, J. van der; Wang, M.; Xu, G.


    A method for fast analysis of ginsenosides in Panax ginseng roots was developed using ultra performance liquid chromatography-time-of-flight-mass spectrometry (UPLC-TOF-MS). The column used was HSS T3 (100 mm × 2.1 mm, 1.8 µm). The mobile phase consisted of 15 mmol/L ammonium formate and

  13. Ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury.

    Ma, Junxiong; Li, Wenxian; Tian, Ruifeng; Lei, Wei


    Searching for effective drugs which are capable of promoting nerve regeneration after nerve injuries has gained extensive attention. Ginsenoside Rg1 (GRg1) is one of the bioactive compounds extracted from ginseng. GRg1 has been shown to be neuroprotective in many in vitro studies, which raises the possibility of using GRg1 as a neuroprotective agent after nerve injuries. However, such a possibility has never been tested in in vivo studies. The present study was designed to investigate the efficacy of GRg1 in promoting nerve regeneration after nerve crush injury in rats. All rats were randomly divided into four groups (n=8 in each group) after crush injury and were intraperitoneally administrated daily for 4 weeks with 1mg/kg, or 5mg/kg GRg1 (low or high dose GRg1 groups), or 100mug/kg mecobalamin or normal saline, respectively. The axonal regeneration was investigated by retrograde labeling and morphometric analysis. The motor functional recovery was evaluated by electrophysiological studies, behavioral tests and histological appearance of the target muscles. Our data showed that high dose GRg1 achieved better axonal regeneration and functional recovery than those achieved by low dose GRg1 and mecobalamin. The final outcome of low dose GRg1 and mecobalamin was similar in both morphological and functional items, which was significantly better than that in saline group. These findings show that GRg1 is capable of promoting nerve regeneration after nerve injuries, suggesting the possibility of developing GRg1 a neuroprotective drug for peripheral nerve repair applications.

  14. Ginsenoside Rh2 inhibits glioma cell proliferation by targeting microRNA-128

    Nan WU; Guo-cai WU; Rong HU; Mei LI; Hua FENG


    Aim: To examine the influence of ginsenoside Rh2 (Rh2), a triterpene saponin extracted from the traditional medicinal plant ginseng,on the expression of miRNAs in human glioma cells.Methods: The expression profile of miRNA (miR) was analyzed in human U251, T98MG and A172 glioma cells using a miRNA array and quantitative real-time PCR. Cell viability was assessed using a colorimetric assay (cell counting kit-8). Transfection of miR-128was performed using Lipofectamine 2000. Caspase 3 activity was determined using a caspase colorimetric assay kit. Apoptosis was assessed using annexin V and propidium iodide staining. Protein expression was determined with Western blot analysis. miRNA-128targeting activity was measured using a luciferase reporter assay.Results: In U251 cells treated with Rh2 (12 μg/mL), 14 of 452 human miRNAs were up-regulated and 12 were down-regulated as detected with the miRNA array assay. The up-regulation of miR-128 by Rh2 was further verified in human U251, T98MG and A172 cells using quantitative real-time PCR. In U251 cells, transfection of a miR-128 inhibitor (50 nmol/L) prevented the overexpression of miR128 by Rh2, and significantly blunted Rh2-induced cytotoxicity, apoptosis, caspase 3 activation, transcriptional activation of E2F3a, a miR-128 target gene, as well as E2F3a protein expression.Conclusion: The anti-proliferative effect of Rh2 in human glioma cells was mediated in part through up-regulation of miRNA-128 expression.

  15. Ginsenoside Rh2 Mitigates Pediatric Leukemia Through Suppression of Bcl-2 in Leukemia Cells

    Xiaoru Wang


    Full Text Available Background/Aims: Acute myeloid leukemia (AML is a severe malignant cancer worldwide, in both adult and pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia remains challenging. Ginsenoside Rh2 (GRh2 is a well-characterized component in red ginseng, and has established therapeutic effects for different diseases, although whether GRh2 may have a therapeutic effect on pediatric leukemia has not been investigated. Methods: We examined the effects of GRh2 on the survival of mice in an acute leukemia model. We analyzed the effects of GRh2 on the cell viability of leukemia cell lines in vitro, using a CCK-8 assay and an MTT assay. We analyzed the effects of GRh2 on the apoptosis of leukemia cell lines in vitro, by flow cytometry. We analyzed the levels of Bcl-2 and microRNA-21 (miR-21 in GRh2-treated leukemia cells. Prediction of binding between miR-21 and 3'-UTR of Bcl-2 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: GRh2 significantly prolonged the survival of mice with pediatric leukemia. GRh2 significantly decreased the viability of leukemia cells in vitro, through induction of apoptosis. GRh2 significantly decreased the levels of an anti-apoptotic protein Bcl-2 in leukemia cells, possibly through induction of miR-21, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. Conclusion: GRh2 may be an effective treatment for pediatric leukemia, and GRh2 may induce apoptosis of leukemia cells through miR-21-modulated suppression of Bcl-2.

  16. Difference in oral absorption of ginsenoside Rg1 between in vitro and in vivo models

    Min HAN; Xiao-ling FANG


    Aim:To clarify the cause of poor oral absorption of ginsenoside Rg1 (Rg1) ,the active ingredient in Panax notoginseng saponins (PNS) used for treating hemorrhage.Methods:Caco-2 cell monolayers were used as an in vitro model to study the transport mechanism of Rg1 across the intestinal mucosa.Moreover,the serum concentration-time profiles after peroral (po) ,intraduodenal (id) ,portal venous (pv) and tail venous (iv) administration of Rg1 in rats were compared to evaluate the first-pass effects in the stomach.intestine,and liver.Results:Uptake of Rg1 by Caco-2 cell monolayers was temperature-dependent,but was not influenced by cyclosporin A.The change in the apical pH produced no obvious effect on the uptake of Rg1.The uptake and transport of Rg1 was non-saturable;whereas the flux from the apical compartment to the basolateral compartment (A-B) increased in a linear manner with the increase in concentration,indicating passive transport.An apparent permeability coefficient of (2.59±0.17)×10-7 cm/s (C0=1mg/mL) predicted incomplete absorption.A significant difference was observed between the po (Fpo was 3.29% at a dose of 1500 mg/kg) ,id (Fid was 6.60% at a dose of 1200 mg/kg) and pv (Fpv was 50.56%) administration methods,and the barrier function of the intestine was more significant than those of the stomach and liver in the absorption process.Conclusion:Elimination in the stomach.large intestine and liver contributed to the low oral bioavailability of Rg,but low membrane permeability might be a more important factor in determining the extent of absorption.

  17. Oral absorption of ginsenoside Rb1 using in vitro and in vivo models.

    Han, Min; Sha, Xianyi; Wu, Yunjuan; Fang, Xiaoling


    This research attempts to clarify the cause for poor oral absorption of ginsenoside Rb1 (Rb1), one main ingredient of the well known Panax notoginseng saponins (PNS) for curing hemorrhage. Caco-2 cell monolayers were used as an in vitro model to reveal the transport mechanism of Rb1 across the intestinal mucosa. Moreover, the serum concentration-time profiles of Rb1 after tail venous (IV), portal venous (PV), intraduodenal (ID) and peroral (PO) administration to rats were compared to evaluate the first-pass effects of stomach, intestine and liver. In vitro experiments showed that uptake by Caco-2 cell monolayers was temperature dependent, but was not influenced by cyclosporine A and ketoconazole. The change in the apical pH showed no obvious effects on the uptake of Rb1. The uptake and transport were non-saturable, and flux from the apical compartment to the basolateral compartment (A-B) increased linearly with increasing concentration, which indicated a passive transport. Meanwhile, an apparent permeability coefficient of (5.90 +/- 1.02) x 10(-8) cm/s (C0 = 1 mg/mL) predicted an incomplete absorption. The investigation on the pharmacokinetic behavior of Rb1 after different routes of administration to rats showed a significant difference between PO (F(PO) was 0.64%), ID (F(ID) was 2.46%) and PV (F(PV) was 59.49%) administration, and the first-pass effect of the intestine is more significant than that of the stomach and liver in the absorption process. In summary, elimination in the stomach, large intestine and liver contributed to the poor absorption of Rb1, but the low membrane permeability might be a more important factor dominating the extent of absorption.

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

    Xu, Linqiang [China Pharmaceutical University, Department of Pharmaceutics, State Key Laboratory of Natural Medicines (China); Yu, Hua [University of Macao, Institute of Chinese Medical Sciences (China); Yin, Shaoping; Zhang, Ruixia; Zhou, Yudan; Li, Juan, E-mail: [China Pharmaceutical University, Department of Pharmaceutics, State Key Laboratory of Natural Medicines (China)


    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.

  19. Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model.

    Fang, Fang; Chen, Xiaochun; Huang, Tianwen; Lue, Lih-Fen; Luddy, John S; Yan, Shirley Shidu


    There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer's disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/Aβ (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral Aβ levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of γ-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to Aβ or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral Aβ accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12-13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Saponins (Ginsenosides) from the Leaves of Panax quinquefolius Ameliorated Acetaminophen-Induced Hepatotoxicity in Mice.

    Xu, Xing-Yue; Hu, Jun-Nan; Liu, Zhi; Zhang, Rui; He, Yu-Fang; Hou, Wei; Wang, Zhi-Qing; Yang, Ge; Li, Wei


    Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and hepatotoxicity was assessed. Our results showed that pretreatment with PQS significantly decreased the serum alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β) levels in a dose-dependent manner as compared to the APAP administration. Meanwhile, compared with that in the APAP group, PQS decreased hepatic malondialdehyde (MDA) contents and 4-hydroxynonenal (4-HNE) expression and restored reduced glutathione (GSH) content and superoxide dismutase (SOD) activity in livers of mice. PQS inhibited the overexpression of pro-inflammatory factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the liver tissues. Furthermore, Western blotting analysis revealed that PQS pretreatment inhibited the activation of apoptotic signaling pathways via increase of Bcl-2 and decrease of Bax and caspase-3 protein expression levels. Liver histopathological observation provided further evidence that PQS pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration, and congestion. Biological indicators of nitrative stress such as 3-nitrotyrosine (3-NT) were inhibited after PQS pretreatment, compared to the APAP group. The present study clearly demonstrates that PQS exerts a protective effect against APAP-induced hepatic injury because of its antioxidant, anti-apoptotic, and anti-inflammatory activities. The findings from

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

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


    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.

  2. Ginsenoside Rh2 Inhibits Cancer Stem-Like Cells in Skin Squamous Cell Carcinoma

    Shunli Liu


    Full Text Available Background/Aims: Treatments targeting cancer stem cells (CSCs are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs in human skin squamous cell carcinoma (SCC. Ginsenoside Rh2 (GRh2 has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined. Methods: Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and β-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA for Atg7 and β-catenin were used to inhibit autophagy and β-catenin signaling pathway, respectively, as loss-of-function experiments. Results: We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced β-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on β-catenin and cell viability, while increasing β-catenin abolished the effects of GRh2 on autophagy and cell viability. Conclusion: Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and β-catenin signaling.

  3. Effects of ginsenoside on brain-derived neurotrophic factor and tyrosine kinase B mRNA expression in the hippocampal formation of aged rats

    Hong Lai; Wensu Liu; Zhaosheng Li; Haihua Zhao; Yongli Lü


    BACKGROUND:There are a limited number of studies involving the effects of ginsenosides,the active component of ginseng,on expression of hippocampal TrkB mRNA in aged rats.OBJECTIVE:To observe expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase B (TrkB)mRNA in the hippocampal formation of aged rats,as well as changes after ginsenoside administrated.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Department of Anatomy,College of Basic Medical Sciences,China Medical University in March 2005.MATERIALS:A total of 39 female,Wistar rats were randomly divided into 3 groups (n=13 each):young (3-5 months old),aged(27 months old),and ginsenoside group(received 25mg/kg/d ginsenoside in the drinking water between 17 and 27 months of age).METHODS:Following anesthesia,the rats were exsanguinated and perfused transcardially with chilled,heparinized,0.9% saline.The brains were removed and post-fixed in 40 g/L paraformaldehyde/phosphate buffer for 20 minutes,and further incubated in 30% sucrose/phosphate buffer overnight.MAIN OUTCOME MEASURES:In situ hybridization,immunohistochemistry,and image analysis were used to investigate expression of BDNF and Trk(B mRNA in the hippocampal formation.RESULTS:The expression levels of BDNF in the hippocampal CA3 and CA1 of aged rats was significantly less than the young group(t=2.879,1.814,1.984,P<0.05).BDNF expression was significantly greater in the dentate gyrus of the ginsenoside group,compared with the aging group(t=1.943,P<0.01).The expression of TrkB mRNA in the hippocampal CA3,CA1,and dentate gyrus of aged rats was less than the young group(t=3.540,3.629,17.905,P<0.01).TrkB mRNA expression in the CA3 region and dentate gyrus of the ginsenoside group was significantly greater compared with the aging group(t=1.293,3.386,P< and TrkB mRNA expression in the hippocampal formation were reduced in the aged group.However,ginsenosides can increase BDNF and TrkB m

  4. [Effect of ginsenoside Rb1 in ameliorating insulin resistance and ectopic fat deposition in obese mice induced by high fat diet].

    Shang, Wen-Bin; Yu, Xi-Zhong; Wang, Guo-Qiang; Zhao, Juan


    Ginsenoside Rb1 is an active component in ginseng. Previous in vitro experiments showed that ginsenoside Rb1, could inhibit lipolysis and promote glucose transporter in adipocytes. This study focused on the effect of ginsenoside Rb1 in insulin resistance and ectopic fat deposit in obese mice induced by high fat diet and its molecular mechanism. Obese male C57/L mice induced by high fat diet were randomly divided into the diet-induced obesity group (DIO group), the ginsenoside Rb1 group (Rb1 group) and the rosiglitazone group (Rog group), and continuously fed with high fat diet. In addition, male C57/L mice fed with normal diet were selected as the normal group (NC group). Mice in Rb1 group and Rog groups were intraperitoneally injected with ginsenoside Rb1 and rosiglitazone with the dosage of 20 mg x kg(-1) and 10 mg x kg(-1), respectively. NC and DIO groups were intraperitoneally injected with the same amount of saline. Two weeks later, the intraperitoneal glucose tolerance test (IPGTT) was performed. Three days later, the mice were killed, and their serum samples were collected to detect insulin and free fatty acid (FFA). Their livers were weighed to examine the triglyceride content, and a pathological detection was performed. Epididymal adipose tissues were weighed, and PDE3B, HSL and perilipin were detected by Western blotting. The results showed that the treatment with ginsenoside Rb1 for two weeks could improve the glucose tolerance of obese mice. Except for 0-120 min, the areas under the glucose tolerance curve (0-30 min, 0-60 min and 0-90 min) in the Rb1 group were less than that in the DIO group (P fat level of obese mice was significantly reduced by Rbl (P tissues, but without obvious change in the expressions of PDE3B and HSL and the phosphorylated activation. The above findings indicated that ginsenoside Rb1 could reduce the release of FFA and alleviate the ectopic deposit of triglyceride by up-regulating the expression of perilipin in adipose tissue

  5. 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.

    Wu, Chunwei; Zhao, Lu; Rong, Yueying; Zhu, Guoxue; Liang, Shengwang; Wang, Shumei


    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

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

    Kim, Jin Hee; Choi, Jae-Sun


    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.

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

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


    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. 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. 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. The ginsenoside Rf appears to be promising compound that could prove useful in antiobesity treatments.

  8. Transcriptome Analysis of Methyl Jasmonate-Elicited Panax ginseng Adventitious Roots to Discover Putative Ginsenoside Biosynthesis and Transport Genes

    Cao, Hongzhe; Nuruzzaman, Mohammed; Xiu, Hao; Huang, Jingjia; Wu, Kunlu; Chen, Xianghui; Li, Jijia; Wang, Li; Jeong, Ji-Hak; Park, Sun-Jin; Yang, Fang; Luo, Junli; Luo, Zhiyong


    The Panax ginseng C.A. Meyer belonging to the Araliaceae has long been used as an herbal medicine. Although public databases are presently available for this family, no methyl jasmonate (MeJA) elicited transcriptomic information was previously reported on this species, with the exception of a few expressed sequence tags (ESTs) using the traditional Sanger method. Here, approximately 53 million clean reads of adventitious root transcriptome were separately filtered via Illumina HiSeq™2000 from two samples treated with MeJA (Pg-MeJA) and equal volumes of solvent, ethanol (Pg-Con). Jointly, a total of 71,095 all-unigenes from both samples were assembled and annotated, and based on sequence similarity search with known proteins, a total of 56,668 unigenes was obtained. Out of these annotated unigenes, 54,920 were assigned to the NCBI non-redundant protein (Nr) database, 35,448 to the Swiss-prot database, 43,051 to gene ontology (GO), and 19,986 to clusters of orthologous groups (COG). Searching in the Kyoto encyclopedia of genes and genomes (KEGG) pathway database indicated that 32,200 unigenes were mapped to 128 KEGG pathways. Moreover, we obtained several genes showing a wide range of expression levels. We also identified a total of 749 ginsenoside biosynthetic enzyme genes and 12 promising pleiotropic drug resistance (PDR) genes related to ginsenoside transport. PMID:25642758

  9. Transcriptome Analysis of Methyl Jasmonate-Elicited Panax ginseng Adventitious Roots to Discover Putative Ginsenoside Biosynthesis and Transport Genes

    Hongzhe Cao


    Full Text Available The Panax ginseng C.A. Meyer belonging to the Araliaceae has long been used as an herbal medicine. Although public databases are presently available for this family, no methyl jasmonate (MeJA elicited transcriptomic information was previously reported on this species, with the exception of a few expressed sequence tags (ESTs using the traditional Sanger method. Here, approximately 53 million clean reads of adventitious root transcriptome were separately filtered via Illumina HiSeq™2000 from two samples treated with MeJA (Pg-MeJA and equal volumes of solvent, ethanol (Pg-Con. Jointly, a total of 71,095 all-unigenes from both samples were assembled and annotated, and based on sequence similarity search with known proteins, a total of 56,668 unigenes was obtained. Out of these annotated unigenes, 54,920 were assigned to the NCBI non-redundant protein (Nr database, 35,448 to the Swiss-prot database, 43,051 to gene ontology (GO, and 19,986 to clusters of orthologous groups (COG. Searching in the Kyoto encyclopedia of genes and genomes (KEGG pathway database indicated that 32,200 unigenes were mapped to 128 KEGG pathways. Moreover, we obtained several genes showing a wide range of expression levels. We also identified a total of 749 ginsenoside biosynthetic enzyme genes and 12 promising pleiotropic drug resistance (PDR genes related to ginsenoside transport.

  10. Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling

    Mao Lin


    Full Text Available Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB, which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF, and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.

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

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


    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.

  12. Inhibitory Effects of Ginsenoside-Rb2 on Nicotinic Stimulation-Evoked Catecholamine Secretion

    Lim, Hyo-Jeong; Lee, Hyun-Young


    The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 µM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 µM) also time-dependently inhibited the CA secretion evoked by DMPP (100 µM, a selective neuronal nicotinic receptor agonist) and high K+ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 µg/mL), the secretory responses of CA evoked by veratridine (a selective Na+ channel activator (50 µM), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 µM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 µM) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 µM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca2+ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca2+ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade. PMID:25352764

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

    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


    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

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

    Kwok, Hoi-Hin [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Chan, Lai-Sheung [Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Poon, Po-Ying [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Yue, Patrick Ying-Kit [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Wong, Ricky Ngok-Shun, E-mail: [Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China); Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR (China)


    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

  15. De novo sequencing and analysis of the American ginseng root transcriptome using a GS FLX Titanium platform to discover putative genes involved in ginsenoside biosynthesis

    Lui Edmund MK


    Full Text Available Abstract Background American ginseng (Panax quinquefolius L. is one of the most widely used herbal remedies in the world. Its major bioactive constituents are the triterpene saponins known as ginsenosides. However, little is known about ginsenoside biosynthesis in American ginseng, especially the late steps of the pathway. Results In this study, a one-quarter 454 sequencing run produced 209,747 high-quality reads with an average sequence length of 427 bases. De novo assembly generated 31,088 unique sequences containing 16,592 contigs and 14,496 singletons. About 93.1% of the high-quality reads were assembled into contigs with an average 8-fold coverage. A total of 21,684 (69.8% unique sequences were annotated by a BLAST similarity search against four public sequence databases, and 4,097 of the unique sequences were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes. Based on the bioinformatic analysis described above, we found all of the known enzymes involved in ginsenoside backbone synthesis, starting from acetyl-CoA via the isoprenoid pathway. Additionally, a total of 150 cytochrome P450 (CYP450 and 235 glycosyltransferase unique sequences were found in the 454 cDNA library, some of which encode enzymes responsible for the conversion of the ginsenoside backbone into the various ginsenosides. Finally, one CYP450 and four UDP-glycosyltransferases were selected as the candidates most likely to be involved in ginsenoside biosynthesis through a methyl jasmonate (MeJA inducibility experiment and tissue-specific expression pattern analysis based on a real-time PCR assay. Conclusions We demonstrated, with the assistance of the MeJA inducibility experiment and tissue-specific expression pattern analysis, that transcriptome analysis based on 454 pyrosequencing is a powerful tool for determining the genes encoding enzymes responsible for the biosynthesis of secondary metabolites in non-model plants. Additionally, the

  16. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action

    Yong CHENG; Li-hong SHEN; Jun-tian ZHANG


    In the present paper, we overview the discovery of new biological activities induced by ginsenoside Rg1 and Rb1 and discuss possible mechanisms of action. Both compounds could increase neural plasticity in efficacy and structure; espe cially Rg1, as one small molecular drug, can increase proliferation and differentia tion of neural progenitor cells in dentate gyms of hippocampus of normal adult mice and global ischemia model in gerbils. This finding has great value for treat ment of Alzheimer's disease and other neurodegenerative disorders which is characterized by neurons loss. Increase of expression of brain derived neurotrophic factor, Bcl-2 and antioxidant enzyme, enhanced new synapse formation, inhibition of apoptosis and calcium overload are also important neuron protective factors. Rg1 and Rb1 have common effects, but there are some differences in pharmacol ogy and mechanism. These differences may attribute to their different chemical structure. Rg1 is panaxtriol with two sugars, while Rb1 is panaxtriol with four sugars.

  17. The Role of Nerve Growth Factor in Ginsenoside Rg1-Induced Regeneration of Injured Rat Sciatic Nerve.

    Huo, Dong-Sheng; Zhang, Ming; Cai, Zhi-Ping; Dong, Chao-Xuan; Wang, He; Yang, Zhan-Jun


    Sciatic nerve injury is commonly seen in clinical practice predominantly associated with trauma or sports injuries. Recent studies indicated that ginsenoside Rg1 (Gs Rg1), extracted from Chinese herbs, was found to promote regeneration of injured rat sciatic nerve and that nerve growth factor (NGF) may be involved in this process. The aim of this study was to examine the role that NGF may play in ginsenoside Rg1-induced regeneration of rat sciatic nerve following injury. Animals following surgical right sciatic nerve injury were subsequently administered intraperitoneally either saline (sham control) or different doses of 2, 4, 8, or 12 mg/kg daily GsRg1 for 2 to 8 wk. In addition, 100 μg/kg mecobalamin, a drug utilized to treat nerve injuries, was employed as a positive control. After 2, 4, or 8 wk, sciatic functional index (SFI) and mean nerve conduction velocity (MNCV), markers of sciatic nerve function, were assessed to determine whether recovery of injured sciatic nerve occurred. In addition, immunohistochemistry and Western blot methods were used to examine NGF protein expression changes. Results showed that all doses of GsRg1 significantly increased SFI and MNCV in injured sciatic-nerve-damaged rats in a manner similar to that noted with mecobalamin. It is of interest that the intermediate 4- and 8-mg/kg doses were more effective in restoring nerve functions. Immunohistochemistry and Western blot results also demonstrated a similar pattern with enhanced NGF protein expression at all doses, but greater effects were noted at 4 and 8 mg/kg GsRg1. Data suggest that GsRg1 promotes recovery of injured sciatic nerve functions within a specific dose range and that NGF may be involved in this physiological process.

  18. Ginsenoside Rg1, a novel glucocorticoid receptor agonist of plant origin, maintains glucocorticoid efficacy with reduced side effects.

    Du, Juan; Cheng, Binbin; Zhu, Xiaoyan; Ling, Changquan


    Glucocorticoids (GCs) are widely used to treat inflammatory diseases. However, they cause debilitating side effects, which limit the use of these compounds. In the past decade, many researchers have attempted to find so-called dissociated GCs that have separate distinct transactivation and transrepression activities. Anti-inflammation of GCs is a result of glucocorticoid receptor (GR)-mediated transactivation and transrepression in some tissues, similar to their side effects; therefore, the goal to discover a compound that has anti-inflammatory properties, but lacks the negative side effects seen with GCs, has yet to be achieved. In the present study, we introduce a plant-derived compound, ginsenoside Rg1, which possesses GC and estrogen-like activities. In this study, we show that Rg1 downmodulates LPS-induced proinflammatory cytokine release and inhibits NF-κB nuclear translocation and DNA binding activity. The negative effects on NF-κB activation are due to a decrease in IκB phosphorylation and protein stabilization. Furthermore, the inhibitory effect of Rg1 on NF-κB is GR-dependent, as small interfering RNA knockdown of GR abrogated this function. Rg1 also displayed profound inhibitory effects on LPS-induced MAPK activation. Importantly, Rg1 did not impair proliferation or differentiation of mouse osteoblasts. Finally, we show that Rg1 can effectively inhibit acute and chronic inflammation in vivo, but it does not cause hyperglycemia or osteoporosis as seen with dexamethasone. These results suggest that ginsenoside Rg1 may serve as a novel anti-inflammatory agent and may exhibit a potential profile for therapeutic intervention in inflammatory diseases.

  19. Ginsenoside Rc Promotes Anti-Adipogenic Activity on 3T3-L1 Adipocytes by Down-Regulating C/EBPα and PPARγ

    Ji-Won Yang


    Full Text Available Panax ginseng and its major components, the ginsenosides, are widely used in oriental medicine for the prevention of various disorders. In the present study, the inhibitory activity of ginsenoside Rc on adipogenesis was investigated using the 3T3-L1 cell line. The results obtained showed that Rc reduced the proliferation and viability of 3T3-L1 preadipocytes in a dose-dependent manner. Treatment with Rc decreased the number of adipocytes and reduced lipid accumulation in maturing 3T3-L1 preadipocytes, demonstrating an inhibitory effect on lipogenesis. Moreover, it was found that Rc directly induced lipolysis in adipocytes and down-regulated the expression of major transcription factors of the adipogenesis pathway, such as PPARγ and C/EBPα. These findings indicate that Rc is capable of suppressing adipogenesis and therefore they seem to be natural bioactive factors effective in adipose tissue mass modulation.

  20. Attenuation of TNF-α-Induced Inflammatory Injury in Endothelial Cells by Ginsenoside Rb1 via Inhibiting NF-κB, JNK and p38 Signaling Pathways

    Ping Zhou


    Full Text Available It is currently believed that inflammation plays a central role in the pathophysiology of atherosclerosis. Oxidative stress and redox-sensitive transcription factors are implicated in the process. Ginsenoside Rb1, a major active ingredient in processed Radix notoginseng, has attracted widespread attention because of its potential to improve cardiovascular function. However, the effects of ginsenoside Rb1 on tumor necrosis factor-α (TNF-α-induced vascular endothelial cell injury and the underlying molecular mechanisms have never been studied. This study showed that TNF-α-induced oxidative stress, inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs could be attenuated by ginsenoside Rb1 pretreatment. Using JC-1, Annexin V/PI and TUNEL staining, and a caspase-3 activity assay, we found that Rb1 provided significant protection against TNF-α-induced cell death. Furthermore, Rb1 pretreatment could inhibit TNF-α-induced ROS and MDA production; increase the activities of SOD, CAT, and GSH-Px; and decrease the levels of IL-1β, IL-6, VCAM-1, ICAM-1, VEGF, MMP-2 and MMP-9. Importantly, the cytoprotective effects of Rb1 were correlated with NF-κB signaling pathway inhibition. Additionally, we found that Rb1 may suppress the NF-κB pathway through p-38 and JNK pathway activation, findings supported by the results of our experiments involving anisomycin (AM, a JNK and p38 activator. In conclusion, this study showed that ginsenoside Rb1 protects HUVECs from TNF-α-induced oxidative stress and inflammation by inhibiting JNK and p38. This inhibition suppressed NF-κB signaling and down-regulated the expression of inflammatory factors and apoptosis-related proteins.

  1. Ginsenoside Re Protects Trimethyltin-Induced Neurotoxicity via Activation of IL-6-Mediated Phosphoinositol 3-Kinase/Akt Signaling in Mice.

    Tu, Thu-Hien Thi; Sharma, Naveen; Shin, Eun-Joo; Tran, Hai-Quyen; Lee, Yu Jeung; Jeong, Ji Hoon; Jeong, Jung Hwan; Nah, Seung Yeol; Tran, Hoang-Yen Phi; Byun, Jae Kyung; Ko, Sung Kwon; Kim, Hyoung-Chun


    Ginseng (Panax ginseng), an herbal medicine, has been used to prevent neurodegenerative disorders. Ginsenosides (e.g., Re, Rb1, or Rg1) were obtained from Korean mountain cultivated ginseng. The anticonvulsant activity of ginsenoside Re (20 mg/kg/day × 3) against trimethyltin (TMT) insult was the most pronounced out of ginsenosides (e.g., Re, Rb1, and Rg1). Re itself did not significantly alter tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-ϒ), and interleukin-1β (IL-1β) expression, however, it significantly increases the interleukin-6 (IL-6) expression. In addition, Re attenuated the TMT-induced decreases in IL-6 protein level. Therefore, IL-6 knockout (-/-) mice were employed to investigate whether Re requires IL-6-dependent neuroprotective activity against TMT toxicity. Re significantly attenuated TMT-induced lipid peroxidation, protein peroxidation, and reactive oxygen species in the hippocampus. Re-mediated antioxidant effects were more pronounced in IL-6 (-/-) mice than in WT mice. Consistently, TMT-induced increase in c-Fos-immunoreactivity (c-Fos-IR), TUNEL-positive cells, and nuclear chromatin clumping in the dentate gyrus of the hippocampus were significantly attenuated by Re. Furthermore, Re attenuated TMT-induced proapoptotic changes. Protective potentials by Re were comparable to those by recombinant IL-6 protein (rIL-6) against TMT-insult in IL-6 (-/-) mice. Moreover, treatment with a phosphoinositol 3-kinase (PI3K) inhibitor, LY294002 (1.6 µg, i.c.v) counteracted the protective potential mediated by Re or rIL-6 against TMT insult. The results suggest that ginsenoside Re requires IL-6-dependent PI3K/Akt signaling for its protective potential against TMT-induced neurotoxicity.

  2. The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng.

    Han, Jung-Yeon; Kim, Hyun-Jung; Kwon, Yong-Soo; Choi, Yong-Eui


    Ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs and contains pharmacologically active components, ginsenosides, in its roots. Ginsenosides, a class of tetracyclic triterpene saponins, are thought to be synthesized from dammarenediol-II after hydroxylation by the Cyt P450 (CYP) enzyme and then glycosylation by glycosyltransferase (GT). However, no genes encoding the hydroxylation and glycosylation in ginsenoside biosynthesis have been identified. Here, we identify protopanaxadiol synthase, which is a CYP enzyme (CYP716A47), to be involved in the hydroxylation of dammarenediol-II at the C-12 position to yield protopanaxadiol. Nine putative full CYP sequences were isolated from the expressed sequence tags (ESTs) of methyl jasmonate (MeJA)-treated adventitious ginseng roots. The CYP716A47 gene product was selected as the putative protopanaxadiol synthase because this gene was transcriptionally activated not only by MeJA treatment but also in transgenic ginseng that overexpresses squalene synthase and overproduces ginsenosides. In vitro enzymatic activity assays revealed that CYP716A47 catalyzed the oxidation of dammarenediol-II to produce protopanaxadiol. Ectopic expression of CYP716A47 in recombinant WAT21 yeasts that were fed dammarenediol-II yielded protopanaxadiol. Furthermore, co-expression of the dammarenediol synthase gene (PgDDS) and CYP716A47 in yeast yielded protopanaxadiol without adding dammarenediol-II. The chemical structures of the protopanaxadiol products from dammarenediol-II were confirmed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). Thus, CYP716A47 is a dammarenediol 12-hydroxylase that produces protopanaxadiol from dammarenediol-II.

  3. Ginsenoside 20S-protopanaxatriol (PPT) activates peroxisome proliferator-activated receptor gamma (PPARgamma) in 3T3-L1 adipocytes.

    Han, Kyu Lee; Jung, Myeong Ho; Sohn, Jong Hee; Hwang, Jae-Kwan


    Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor of ligand-activated transcription factors, regulates the expression of key genes involved in lipid and glucose metabolism or adipocyte differentiation. Ligands for this receptor have emerged as potent insulin sensitizers used in the treatment of Type2 diabetes. Ginseng saponins or ginsenosides are reported to provide anti-diabetic activity as well as to modulate glucose metabolism, although the mechanism remains unclear. In this study, we examined the effect of ginsenosides on activation of PPARgamma and adipogenes in 3T3-L1. Using a GAL-4/PPARgamma transactivation assay, 20(S)-protopanaxatriol (PPT), one of the ginsenoside metabolites, was found to increase PPARgamma-transactivation activity dose-dependently with similar activity as troglitazone, a well-known PPARgamma agonist. PPT enhanced adipogenesis by increasing the expression of PPARgamma target genes such as aP2, LPL and PEPCK. Furthermore, PPT significantly increased expression of glucose transporter 4 (GLUT4). These results indicate that PPT can be developed as a PPARgamma agonist for the improvement of insulin resistance associated with diabetes.

  4. Anticancer effect of 20(S)-ginsenoside Rh2 on HepG2 liver carcinoma cells: Activating GSK-3β and degrading β-catenin.

    Shi, Qingqiang; Shi, Xueping; Zuo, Gei; Xiong, Wei; Li, Haixing; Guo, Pei; Wang, Fen; Chen, Yi; Li, Jing; Chen, Di-Long


    20(S)-ginsenoside Rh2 [(S)Rh2] possesses potential to prevent cancer in vitro as well as in vivo, but the underlying mechanism is still unknown. First, we infected HepG2 cells with lentivirus which carries β‑catenin. We detected the pharmacological effects of (S)Rh2 on HepG2 and HepG2‑β‑catenin cells and found that the IC50 of (S)Rh2 exposure on HepG2-β-catenin cells was higher than HepG2 cells. Flow cytometry (FCM) indicated that (S)Rh2 could be arrested in G0/G1 phase and induce early apoptosis in HepG2 and HepG2‑β‑catenin cells. Second, ELISA kit was used to check the activity of glycogen synthase kinase‑3β (GSK‑3β), which was upregulated by (S)Rh2. GSK‑3β inhibitor BIO, was used to verify that (S)Rh2 activated GSK‑3β. PCR and western blotting results indicated that (S)Rh2 could degrade the expression of β‑catenin, which combined with TCF in the nucleus and activate transcription of Wnt target genes, such as Bax, Bcl‑2, cyclin D1, MMP3, which were checked by chromatin immunoprecipitation (ChIP), PCR and western blotting. The results showed that the expression of Bax mRNA and proteins increased, while the cyclin D1, Bcl‑2, MMP3 mRNA and proteins were downregulated in HepG2 and HepG2‑β‑catenin cells which was induced by (S)Rh2. By contrast, with the HepG2-β-catenin + (S)Rh2 group, the expression of other mRNA and proteins in HepG2 + (S)Rh2 group changed significantly. In vivo, experiments were performed using a nude mouse xenograft model to investigate the (S)Rh2 effect. So these results suggested that (S)Rh2 could suppress proliferation, promote apoptosis and inhibit metastasis of HepG2, decrease weight of tumor by downregulating β‑catenin through activating GSK‑3β and the pharmacological effect of (S)Rh2 on HepG2 cells might be weakened by overexpression of β‑catenin.

  5. Long-term ginsenoside administration prevents memory loss in aged female C57BL/6J mice by modulating the redox status and up-regulating the plasticity-related proteins in hippocampus.

    Zhao, H F; Li, Q; Li, Y


    Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. The generation of reactive oxygen species (ROS) and/or free radicals-induced oxidative stress which is the major age-related changes, can lead to hippocampus damage and increase vulnerability to impaired learning and memory. Ginsenoside, the effective ingredient of ginseng, has been reported to have a neuron beneficial effect. In the present study, C57BL/6J mice aged 12 months were chronically treated with ginsenoside (three dose groups were given ginsenoside in drinking water for 8 months, the concentration of ginsenoside in drinking water was 0.028%, 0.056%, and 0.112% (w/v), respectively). Placebo-treated aged mice and young ones (4 months old) were used as controls. The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBARS) have been used as the biomarkers of oxidative stress. In ginsenoside treated groups, the activities of T-SOD and GSH-Px markedly increased, and the levels of TBARS and the content of protein carbonyl decreased significantly in serum and in hippocampus. The activation of lipofuscin formation, disruption or loss of cristae in mitochondria, the irregular nucleus and condensed chromatin laid against the nuclear membrane in pyramidal cells of hippocampal CA1 region, which are all related to oxidative stress, were also reduced after ginsenoside treatment. Processes of memory formation and functional plasticity are associated with postsynaptic density-95 (PSD-95), protein kinase Cγ subunit (PKCγ) and brain derived neurotrophic factor (BDNF). In the present study, we found that long-term ginsenoside treatment prevented age-related reductions of PSD-95, PKCγ, and BDNF in

  6. 人参皂苷 Rd的抗癌机制研究进展%Advances in the Research of Antitumor Mechanism of Ginsenoside Rd

    朱春燕; 张旭; 叶丽红


    Ginsenoside Rd is one of the main metabolites in the human gut , which belongs to the panaxadiol group of dammarane glycosides .Ginsenoside Rd is extracted from notoginseng , ginseng , gynostemma etc , which has extensive biological activity .It has a unique effect on heart cerebrovascular , nervous system , immune system and antitumor .The treatment and prevention of tumour have been a worldwide problem .Due to the diversity and security of the pharmaco-logical effects of Rd , it has become the focus of attention .The chemical synthesis of ginsenoside Rd has not been suc-cessful because of the complicated structure .It is extracted from plants to meet the needs of the medical and scientific research .But because the amount of ginsenoside Rd extracted from plants is low , it is difficult to meet the need .There-fore, both domestic and overseas focus on the effective extracted way ginsenosides and ignore its anti -cancer effect. Therefore , both at home and abroad we focus on the effective access to a lot of work on ginsenoside Rd and ignore its an -ti-cancer effect .Therefore , this paper researches on the antitumor mechanism in detail in order to provide theoretical basis for ginsenoside Rd to treat tumor and the toxic and side effect of radiotherapy and chemotherapy .%人参皂苷Rd是二醇型人参皂苷在人体肠道内的主要代谢产物之一,是三七、人参、绞股蓝等的提取物,具有广泛的生物活性。对心脑血管、神经系统、免疫系统及抗肿瘤方面等作用独特。由于人参皂苷Rd的药理作用的多样性和安全性,已成为人们关注的焦点,但因人参皂苷Rd的结构复杂,化学合成至今尚未成功,需从植物药中提取以满足医疗和科研的需要,但因植物中人参皂苷Rd的量较低,从植物中提取的方法难以满足需要。因此,国内外着重对有效获取人参皂苷Rd方面进行了大量研究,而忽略了其本身的抗癌功效。肿瘤防治现已成

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


    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

  8. Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging

    Bo Teng


    Full Text Available Derived from Panax ginseng, the natural product 20(S-Protopanaxadiol (PPD has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes G2/M cell cycle arrest in human laryngeal carcinoma cells (Hep-2 cells. PPD also decreases the levels of proteins related to cell proliferation. Moreover, PPD-induced apoptosis is characterized by a dose-dependent down-regulation of Bcl-2 expression and up-regulation of Bax, and is accompanied by the activation of Caspase-3 as well. Further molecular mechanism is revealed by direct stochastic optical reconstruction microscopy (dSTORM—a novel high-precision localization microscopy which enables effective resolution down to the order of 10 nm. It shows the expression and spatial arrangement of mTOR and its downstream effectors, demonstrating that this ginsenoside exerts its excellent anticancer effects via down-regulation of mTOR signaling pathway in Hep-2 cells. Taken together, our findings elucidate that the antitumor effect of PPD is associated with its regulation of mTOR expression and distribution, which encourages further studies of PPD as a promising therapeutic agent against laryngeal carcinoma.

  9. Ginsenoside-Rb1 Protects Hypoxic- and Ischemic-Damaged Cardiomyocytes by Regulating Expression of miRNAs

    Xu Yan


    Full Text Available Ginsenoside (GS-Rb1 is one of the most important active compounds of ginseng, with extensive evidence of its cardioprotective properties. However, the miRNA mediated mechanism of GS-Rb1 on cardiomyocytes remains unclear. Here, the roles of miRNAs in cardioprotective activity of GS-Rb1 were investigated in hypoxic- and ischemic-damaged cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs were first isolated, cultured, and then incubated with or without GS-Rb1 (2.5–40 μM in vitro under conditions of hypoxia and ischemia. Cell growth, proliferation, and apoptosis were detected by MTT and flow cytometry. Expressions of various microRNAs were analyzed by real-time PCR. Compared with that of the control group, GS-Rb1 significantly decreased cell death in a dose-dependent manner and expressions of mir-1, mir-29a, and mir-208 obviously increased in the experimental model groups. In contrast, expressions of mir-21 and mir-320 were significantly downregulated and GS-Rb1 could reverse the differences in a certain extent. The miRNAs might be involved in the protective effect of GS-Rb1 on the hypoxia/ischemia injuries in cardiomyocytes. The effect might be based on the upregulation of mir-1, mir-29a, and mir-208 and downregulation of mir-21 and mir-320. This might provide us a new target to explore the novel strategy for ischemic cardioprotection.

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

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


    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

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

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


    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.

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

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


    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.

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

    Wei Wang

    Full Text Available 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.

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

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


    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.

  15. 人参皂苷对脂代谢的调控作用%Regulatory effects of ginsenosides on lipid metabolism

    吕文山; 杨丽丽; 黄海涛


    Total ginsenosides (GS) or GS monomer can improve lipid metabolism through variety of mechanisms,such as suppression of food intake through the ventromedial nucleus,inhibition of intestinal absorption of dietary fat via down regulation of pancreatic lipase activity,or through regulation of adipogenesis transcription factors peroxisome proliferator-activated receptors (PPARs),glucose and lipid metabolic regulation molecular AMP-activated protein kinase (AMPK) and expressions of their target genes,etc.%人参总皂苷或人参皂苷(GS)单体可通过多种机制改善脂代谢,主要包括:通过下丘脑腹内侧核抑制摄食行为;通过下调胰脂肪酶(PL)活性,抑制肠道含脂食物吸收;抑或通过调控脂肪生成转录因子过氧化物酶体增殖物活化受体(PPARs)、糖脂代谢调控分子腺苷酸活化蛋白激酶(AMPK)及其靶基因表达等.

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

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


    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.

  17. The protective effects of ginsenoside Rg1 against hypertension target-organ damage in spontaneously hypertensive rats

    Chen Hui


    Full Text Available Abstract Background Although a number of medicines are available for the management of hypertension, the organ damage induced by hypertension is not resolved. The aim of this study was to investigate the protection of ginsenoside Rg1 (Rg1 against vascular remodeling and organ damage in spontaneously hypertensive rats (SHR. Methods Male SHR were treated with 5, 10 or 20 mg/kg Rg1 through intraperitoneal injection per day for 1 month. SHR or Wistar-Kyoto rats (WKY receiving vehicle (saline was used as control. Blood pressure detection and pathological stain, transmission electron microscope, immunohistochemical assay were used to elucidate the protection of Rg1. Results Blood pressures were not different between control SHR rats and Rg1 treated SHR rats, but Rg1 improved the aortic outward remodeling by lowering the lumen diameter and reducing the media thickness according the histopathological and ultrastructural detections. Rg1 also protected the retinal vessels against inward remodeling detected by immunohistochemical assay. Furthermore, Rg1 attenuated the target heart and kidney damage with improvement on cardiac and glomerular structure. Conclusions These results suggested that Rg1 held beneficial effects on vascular structure and further protected against the organ-damage induced by hypertension. These findings also paved a novel and promising approach to the treatment of hypertensive complications.

  18. 人参皂苷Rg1联合骨髓间充质干细胞移植对痴呆大鼠学习记忆能力的影响%Effect of Ginsenoside Rg1 on the Spatial Learning-memory Ability in Dementia Rats after Transplanted with Bone Marrow Mesenchymal Stem Cells

    邬伟; 杨景全; 何志勇; 王小同


    Objective To study the effect and mechanism of ginsenoside Rg1 on the spatial learning-memory ability in rats with Alzheimer's disease after transplanted with bone marrow mesenchymal stem cells (BMSCs).Methods Using digital randomization table method, seventy-five male SD rats were divided into the bilateral FF transection model group (as the model group: ambi-hippocampal fimbria-fomix transected), the sham-operative control group (the SOC group: receiving the same modeling process as the model group, but without ambi-hippocampal fimbria-fornix transected), the ginsenoside Rg1 treatment group (as the treatment group: Two weeks after modeling ginsenoside Rg1 was peritoneally injected at the dose of 5 mg/kg, once daily for four weeks in total), the BMSCs transplanted treatment group [as the control group: Two weeks after modeling every rat received transplantation of BMSCs (10 μL, 1 ×106cells)], and the ginsenoside Rg1 +BMSCs treatment group (as the combination group: They received both transplantation of BMSCs and peritoneal injection of ginsenoside Rg1 ).The spatial learning-memory ability of rats was detected by Morris water maze and the escape latency (s) was recorded.mRNA expression of nerve growth factor (NGF) was detected using Real-time PCR.Results Six weeks after the hippocampal fimbria-fornix (FF) transection,the escape latency of each medication group was obviously shorter than that of the model group, and the spatial learning-memory ability of dementia rats was somewhat improved.The spatial learning-memory ability of rats in the combination group was (29.95 ±2.03) and the mRNA expression level of NGF was (1.13 ±0.15), better than those in the BMSCs group (44.36 ±1.43, 0.78 ±0.09, P<0.05).Conclusions Ginsenoside Rg1 could strengthen the spatial learningmemory ability in dementia rats after transplanted with BMSCs.Its mechanism might be possibly correlated with up-regulating mRNA expression of NGF in basal forebrain after BMSCs transplantation

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

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


    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

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

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


    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.

  1. 水溶性人参皂苷对秀丽隐杆线虫生物学功能的影响%Effect of Water Soluble Ginsenosides on Biological Functions of Caenorhabditis elegans

    于笑坤; 何潇潇; 付学奇; 马俊锋


    Soluble ginsenosides with gradient concentrations were added into the culture environment of Caenorhabditis elegans. The effects of ginsenosides on C. elegans were further investigated including lifespan, broodsize, and locomotion. Our results show that 200 μg/mL ginsenosides can increase the lifespan and slow the aging of C. elegans. However, 500 (μg/mL ginsenosides induced toxicity to C. elegans.%以秀丽隐杆线虫作模式生物,研究水溶性人参皂苷成分对线虫的寿命、产卵和运动等生命活动的影响.结果表明:质量浓度为200 μg,/mL的人参皂苷可使线虫寿命延长,减缓衰老;质量浓度为500μg/mL的人参皂苷则对线虫具有一定的毒性作用.

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

    Qian Mao


    Full Text Available 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.

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

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


    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.

  4. Ginsenoside Rh2 Improves Cardiac Fibrosis via PPARδ–STAT3 Signaling in Type 1-Like Diabetic Rats

    Shih-Hsiang Lo


    Full Text Available Ginsenoside Rh2 (Rh2 is an active principal ingredient contained in ginseng (Panax ginseng Meyer, a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats, the increased fasting blood glucose levels and heart weight/body weight (HW/BW ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor δ (PPARδ in STZ-diabetic rats. The role of PPARδ was subsequently investigated in vitro. Rh2 restored the decreased PPARδ expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3, connective tissue growth factor (CCN2 and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPARδ Taken together, PPARδ activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPARδ signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis.

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

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


    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

  6. Effects of Ginsenoside Rg1 on the Expression of Toll-Like Receptor 3, 4 and Their Signalling Transduction Factors in the NG108-15 Murine Neuroglial Cell Line

    Bao-Sheng Zhao


    Full Text Available As one of the most important components of Panax ginseng, ginsenoside Rg1 has certain anti-aging effects, improving the activity of learning and memory. Studies have showed that ginsenoside Rg1 improves the memory impairment associated with Alzheimer’s disease (AD. In this study, the effects of ginsenoside Rg1 were investigated through the activity of toll-like receptor (TLR 3, TLR4 and their signaling transduction pathways in amyloid β peptide 25–35 (Aβ25–35 induced AD cell model. Thus we investigated several critical components of the TLR pathway. The neuroglial cell line NG108-15 was stimulated with or without Aβ25–35, while different concentrations of ginsenoside Rg1 were administered. After 24 h, tumor necrosis factor-α (TNF-α, interferon-β (IFN-β in cell supernatant and inducible nitric oxide synthase (iNOS in cell lysate supernatant were measured with enzyme-linked immunosorbent assays (ELISAs. The mRNA and protein expression of TLR3, TLR4, nuclear factor kappa B (NF-κB and tumor necrosis factor receptor-associated factor-6 (TRAF-6 were detected by real-time PCR and western blot methods, respectively. The experimental results showed that Aβ25–35 could markedly raise the level of TNF-α, IFN-β and iNOS, and increase the expressions of mRNA and TLR3, TLR4, NF-κB and TRAF-6 protein in the NG108-15 cells. At the same time, the ginsenoside Rg1 significantly reduced the expressions of proteins and mRNA of TLR3, TLR4, NF-κB and TRAF-6, and down-regulated the levels of TNF-α, IFN-β of cell supernatant and iNOS of cell lysate supernatant in a concentration-dependent manner. In conclusion, ginsenoside Rg1 has good activity for suppressing the signaling transduction pathway of TLR3 and TLR4, and decreasing the inflammation factors induced by Aβ25–35 in NG108-15 cells, and this may be the mechanism of ginsenoside Rg1 action in AD treatment, but more studies are needed to identify its specificity.

  7. Role of epidermal γδ T-cell-derived interleukin 13 in the skin-whitening effect of Ginsenoside F1.

    Han, Jiyeon; Lee, Eunkyung; Kim, EunJoo; Yeom, Myung Hun; Kwon, Ohsang; Yoon, Tae Hong; Lee, Tae Ryong; Kim, Kwangmi


    Ginsenoside F1 (GF1) is a metabolite of ginsenoside Rg1. Although GF1 has several benefits for skin physiology, the effect of GF1 on skin pigmentation has not been reported. We found that a cream containing 0.1% GF1 showed a significant whitening effect on artificially tanned human skin after 8 weeks of application. However, GF1 did not inhibit mRNA expression of tyrosinase or dopachrome tautomerase (DCT) in normal human epidermal melanocytes (NHEMs) or cocultured NHEMs/normal human epidermal keratinocytes. Interestingly, GF1 enhanced production of interleukin 13 (IL-13) from human epidermal γδ T cells. IL-13 significantly reduced the mRNA expression and protein amount of both tyrosinase and DCT and reduced melanin synthesis activities in NHEMs, resulting in visible brightening of NHEM pellet. These results suggest that enhancement of IL-13 production by GF1 from epidermal γδ T cells might play a role in the skin-whitening effect of GF1 via the suppression of tyrosinase and DCT.

  8. Determination of ginsenoside content in Asian and North American ginseng raw materials and finished products by high-performance liquid chromatography: single-laboratory validation.

    Brown, Paula N


    A single-laboratory validation study was conducted for the quantification of Rg1, Re, Rb1, Rc, Rb2, and Rd in Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) raw materials and finished products by RP-HPLC. The extraction with aqueous methanol was optimized for whole root, powdered extract, and finished product (raw, tablet, and capsule matrixes) test articles. Root materials were treated with base to hydrolyze acidic malonyl ginsenosides to their neutral counterparts. Calibration curves for each ginsenoside were linear over the following ranges (microg/g): 5-394 for Rg1, 15-1188 for Re, 39-2981 for Rb1, 6-499 for Rc, 5-406 for Rb2, and 7-600 for Rd, all having a coefficient of determination (r2) of > or = 99.5%. The LOD for Rg1, Re, Rb1, Rc, Rb2, and Rd was determined to be 1.06, 1.25, 2.19, 1.24, 1.27, and 1.70 microg/mL, respectively. Quantitative determinations performed with eight test materials by two analysts over 3 days (n = 12) resulted in RSDr values that ranged from 1.11 to 7.61%.

  9. Simultaneous determination of 2 aconitum alkaloids and 12 ginsenosides in Shenfu injection by ultraperformance liquid chromatography coupled with a photodiode array detector with few markers to determine multicomponents

    Ai-Hua Ge


    Full Text Available A method with few markers to determine multicomponents was established and validated to evaluate the quality of Shenfu injection by ultraperformance liquid chromatography coupled with a photodiode array detector. The separations were performed on an ACQUITY UPLC BEH C18 (2.1 × 50 mm2, 1.7 μm column. Methanol and 0.1% formic acid aqueous solution were used as the mobile phase. The flow rate was 0.3 mL/min. 2 aconitum alkaloids and 12 ginsenosides could be perfectly separated within 15 minutes. Ginsenoside Rg1 and benzoylmesaconine, the easily available active components, were employed as the maker components to calculate the relative correction factors of other components in Shenfu injection, Panax ginseng and Aconitum carmichaeli. The external standard method was also established to validate the feasibility of the method with few markers to determine multicomponents. Parameter p and the principal component analysis method were employed to investigate the disparities among batches for the effective quality control of Shenfu injection. The results demonstrated that the ultraperformance liquid chromatography coupled with a photodiode array detector method with few markers to determine multicomponents could be used as a powerful tool for the quality evaluation of traditional Chinese medicines and their preparations.

  10. 人参皂苷Rb3的药理研究进展%Research Progress on Pharmacology of Ginsenoside Rb3

    王凤; 周亚滨


    人参和三七在临床和日常生活中使用广泛,人参具有益气复脉、补脾益肺、生津安神的功效,三七具有化瘀止血、活血定痛的功效.本文对二者的有效成分人参皂苷Rb3在神经系统、心血管系统、血液系统等方面的药理研究文献资料进行了综述.%Ginseng and Panax are widely used in clinical and daily life. Ginseng can greatly tonify the original qi, tonify spleen and replenish lung , engender fluid and tranquilize. Panax can resolve stasis to stop bleeding and disperse swelling to stop pain. This article is about pharmacological studies on ginsenoside Rb3 which is an active ingredient of Ginseng and Panax in the nervous system, cardiovascular system, hematological system and other aspects. The results show ginsenoside Rb3 has the functions of protecting neurons and cardiomyocytes, anti - platelet aggregation and anti - virus effect .

  11. Effect of Ginsenoside Rd on Chromosome Aberration in Chinese Hamster Lung Cells%人参皂苷Rd对中国仓鼠肺细胞染色体畸变作用

    高梅; 曹冲; 朱春花; 曲保恩


    目的 研究人参皂苷Rd致中国仓鼠肺细胞(Chinese hamster lung cells,CHL)染色体畸变的作用.方法 细胞计数法测定人参皂苷Rd对CHL细胞的半数抑制浓度(IC50),根据IC50设立不同剂量组,进行染色体畸变试验,分别观察人参皂苷Rd染毒6、24h及加S9后染毒6h CHL细胞染色体的数目及结构变化,进行染色体畸变分析.结果 人参皂苷Rd染毒6、24h及加S.后染毒6h CHL细胞染色体畸变为阴性.结论 在本试验条件下,人参皂苷Rd不能引起CHL细胞染色体产生畸变.%Objective To explore the effect of ginsenoside Rd on chromosome aberration in Chinese hamster lung cells(CHL). Methods We used the method of cell counting to determine the IC50, of ginsenoside Rd on CHL cells,then to establish the range of doses according to the IC50 and to do the cell chromosome aberration experiment. When the CHL cells were exposured to ginsenoside Rd at 6h and 24h and plused S9 mixture at 6h respectively, we observed the changes of chromosome number and structure, then to judge the chromosome aberration results. Results Negative response was found at 6h and 24h after the treatment with ginsenoside Rd and at 6h after the addition of S9 mixture. Conclusion Under the condition of this experiment, ginsenoside Rd does not induce chromosome aberration in CHL cells.

  12. Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng.

    Han, Jung-Yeon; Hwang, Hwan-Su; Choi, Su-Wan; Kim, Hyun-Jung; Choi, Yong-Eui


    Ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs, and the root of this plant contains pharmacologically active components, called ginsenosides. Ginsenosides, a class of tetracyclic triterpene saponins, are synthesized from dammarenediol-II after hydroxylation by cytochrome P450 (CYP) and then glycosylation by a glycosyltransferase. Protopanaxadiol synthase, which is a CYP enzyme (CYP716A47) that catalyzes the hydroxylation of dammarenediol-II at the C-12 position to yield protopanaxadiol, was recently characterized. Here, we isolated two additional CYP716A subfamily genes (CYP716A52v2 and CYP716A53v2) and determined that the gene product of CYP716A53v2 is a protopanaxadiol 6-hydroxylase that catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in P. ginseng. Both CYP716A47 and CYP716A53v2 mRNAs accumulated ubiquitously in all organs of ginseng plants. In contrast, CYP716A52v2 mRNA accumulated only in the rhizome. Methyl jasmonate (MeJA) treatment resulted in the obvious accumulation of CYP716A47 mRNA in adventitious roots. However, neither CYP716A52v2 nor CYP716A53v2 mRNA was affected by MeJA treatment during the entire culture period. The ectopic expression of CYP716A53v2 in recombinant WAT21 yeast resulted in protopanaxatriol production after protopanaxadiol was added to the culture medium. In vitro enzymatic activity assays revealed that CYP716A53v2 catalyzed the oxidation of protopanaxadiol to produce protopanaxatriol. The chemical structures of the protopanaxatriol products were confirmed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). Our results indicate that the gene product of CYP716A53v2 is a protopanaxadiol 6-hydroxylase that produces protopanaxatriol from protopanaxadiol, which is an important step in the formation of dammarane-type triterpene aglycones in ginseng saponin biosynthesis.

  13. 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.

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


    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.

  14. Ginsenoside Rg1 decreases Aβ(1-42 level by upregulating PPARγ and IDE expression in the hippocampus of a rat model of Alzheimer's disease.

    QianKun Quan

    Full Text Available 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 (Aβ(1-42 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 Aβ(1-42, PPARγ, and insulin-degrading enzyme (IDE expression in the hippocampus. KEY RESULTS: Injection of soluble Aβ(1-42 into the hippocampus led to significant dysfunction of learning and memory, hippocampal histopathological abnormalities and increased Aβ(1-42 levels in the hippocampus. Rg1 treatment significantly improved learning and memory function, attenuated hippocampal histopathological abnormalities, reduced Aβ(1-42 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 Aβ(1-42, 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.

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

    Yizhen Wu

    Full Text Available 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.

  16. Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

    Zhi-ying LIN; Li-min CHEN; Jing ZHANG; Xiao-dong PAN; Yuan-gui ZHU; Qin-yong YE; Hua-pin HUANG; Xiao-chun CHEN


    Aim:To investigate the effect of ginsenoside Rb1 on voltage-gated calcium currents in cultured rat hippocampal neurons and the modulatory mechanism.Methods:Cultured hippocampal neurons were prepared from Sprague Dawley rat embryos.Whole-cell configuration of the patchclamp technique was used to record the voltage-gated calcium currents (VGCCs)from the hippocampal neurons,and the effect of Rb1 was examined.Results:Rb1 (2-100 μmol/L)inhibited VGCCs in a concentration-dependent manner,and the current was mostly recovered upon wash-out.The specific L-type Ca2+ channel inhibitor nifedipine (10 μmol/L)occluded Rb1-induced inhibition on VGCCs.Neither the selective N-type Ca2+ channel blocker ω-conotoxin-GVlA (1 μmoVL),nor the selective P/Q-type Ca2+ channel blocker ωo-agatoxin IVA (30 nmol/L)diminished Rb1-sensitive VGCCs.Rb1 induced a leftward shift of the steady-state inactivation curve of Ica to a negative potential without affecting its activation kinetics or reversal potential in the I-V curve.The inhibitory effect of Rb1 was neither abolished by the adenylyl cyclase activator forskolin (10 μmol/L),nor by the PKA inhibitor H-89 (10 μmol/L).Conclusion:Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels,without affecting the N-type or P/Q-type Ca2+ channels in hippocampal neurons,cAMP-PKA signaling pathway is not involved in this effect.

  17. 人参皂苷Rg1促进人牙周膜干细胞增殖与成骨分化%Promotion of ginsenoside Rg1 on proliferation and osteogenic potential of human periodontal ligament stem cells

    王萍; 周玥; 王亚平; 屈晨


    目的 观察人参皂苷Rg1对体外培养的人牙周膜干细胞(periodontal ligament stem cells,PDLSCs)增殖和成骨分化的影响.方法 选取第3代PDLSCs,采用MTT法和细胞周期检测不同浓度(0.25、0.5、1、2、4μmol/L)人参皂苷Rg1对PDLSCs增殖的影响;采用碱性磷酸酶(ALP)活性、实时荧光定量RT-PCR和放免法检测人参皂苷Rg1对PDLSCs成骨分化的影响;采用ELISA方法检测人参皂苷Rg1对PDLSCs碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)表达的影响.结果 与对照组比较,浓度为0.5、1、2μmol/L的人参皂苷Rg1能明显提高PDLSCs的增殖能力(P<0.05),其中浓度为1μmol/L的促增殖作用最强,S+G2/M期细胞百分率明显高于对照组(P<0.05);浓度为1μmol/L的人参皂苷Rg1组ALP活性、骨钙素(osteocalcin,OCN)和bFGF的表达水平明显高于对照组(P<0.05).结论 人参皂苷Rg1对体外培养的PDLSCs有促进增殖和成骨分化的作用.%Objective To evaluate the effect of ginsenoside Rgl on the proliferation and osteogenic potential of human periodontal ligament stem cells (PDLSCs).Methods PDLSCs at passage 3 were incubated with different concentrations of ginsenoside Rg1 (0.25,0.5,1,2 and 4 μmol/L).The effect of ginsenoside Rg1 on the proliferative ability of PDLSCs was evaluated by MTT assay,and flow cytometry was used for detecting cell cycle.The osteogenic potential of the cells was assayed by ALP enzymatic activity,realtime RT-PCR and radioimmunoassay,respectively.Basic fibroblast growth factor (bFGF) was detected by enzyme-linked immunosorbent assay.Results Compared with the control group,the proliferative ability of PDLSCs in ginsenoside Rg1 groups (0.5,1 and 2 μmol/L) was significantly enhanced (P <0.05),especially in the ginsenoside Rg1 group (1 μmol/L).Cell cycle analysis showed that ginsenoside Rg1 (1 μmol/L) significantly increased the proportion of PDLSCs in proliferative phase (S + G2/M phase).ALP activity and the

  18. A UFLC-MS/MS method with a switching ionization mode for simultaneous quantitation of polygalaxanthone III, four ginsenosides and tumulosic acid in rat plasma: application to a comparative pharmacokinetic study in normal and Alzheimer's disease rats.

    Lv, Chunxiao; Li, Qing; Zhang, Yaowen; Sui, Zhenyu; He, Bosai; Xu, Huarong; Yin, Yidi; Chen, Xiaohui; Bi, Kaishun


    A fast, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantitation of polygalaxanthone III (POL), ginsenoside Rb1 (GRb1), ginsenoside Rd (GRd), ginsenoside Re (GRe), ginsenoside Rg1 (GRg1) and tumulosic acid (TUM) in rat plasma after oral administration of Kai-Xin-San, which plays an important role for the treatment of Alzheimer's disease (AD). The plasma samples were extracted by liquid-liquid extraction using ethyl acetate-isopropanol (1:1, v/v) with salidrdoside as internal standard (IS). Good chromatographic separation was achieved using gradient elution with the mobile phase consisting of methanol and 0.01% acetic acid in water. The tandem mass spectrometric detection was performed in multiple reaction monitoring mode on 4000Q UFLC-MS/MS system with turbo ion spray source in a negative and positive switching ionization mode. The lower limits of quantification were 0.2-1.5 ng/ml for all the analytes. Both intra-day and inter-day precision and accuracy of analytes were well within acceptance criteria (±15%). The mean absolute extraction recoveries of analytes and IS from rat plasma were all more than 60.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in normal and AD rat plasma. The results indicated that no significant differences in pharmacokinetic parameters of GRe, GRg1 and TUM were observed between the two groups, while the absorption of POL and GRd in AD group were significantly higher than those in normal group; moreover, the GRb1 absorbed more rapidly in model group. The different characters of pharmacokinetics might be caused by pharmacological effects of the analytes.

  19. Dynamic Changes in Ginsenoside Rb 2 and Rb3 Content in Solid-state Fermentation%人参须固态发酵中皂苷 Rb 2与 Rb 3的动态变化

    闫梅霞; 崔丽丽; 许世泉; 刘俊霞; 王英平


    以人参须为发酵基质进行赤芝双向固态发酵,测定发酵过程中人参皂苷Rb2和Rb3的含量,分析固态发酵对其影响。发酵作用使基质中Rb2和Rb3含量发生显著变化,但2种皂苷含量变化不同。Rb2在发酵初期和发酵后期都出现含量先升高后降低的过程,Rb3仅在发酵初期含量先升高后降低,发酵结束时基质中未检测到2种皂苷。%Bidirectional solid-state fermentation was carried out through the strains of Ganoderma lucidum in ginseng .The content of ginseno-side Rb2 and Rb3 was determined and the impact on the ginsenoside by solid -state fermentation was analyzed .The content of Rb2 and Rb3 changed significantly through the fermentation ,but the two kinds of ginsenoside content varied differently .The content of Rb2 increased in the early fermentation stage ,then decreased in the late fermentation stage ,the level of Rb3 increased then decreased only in the early fermentation stage ,the two kinds of ginsenoside content was 0 by the end of the fermentation .

  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.

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


    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. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    Chong-Zhi Wang


    Full Text Available Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  2. Ginsenoside 20(S)-Rh2 Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells: Role of Orphan Nuclear Receptor Nur77.

    Wang, Chengqiang; He, Hui; Dou, Guojun; Li, Juan; Zhang, Xiaomei; Jiang, Mingdong; Li, Pan; Huang, Xiaobo; Chen, Hongxi; Li, Li; Yang, Dajian; Qi, Hongyi


    Ginsenoside 20(S)-Rh2 has been shown to induce apoptosis and differentiation of acute myeloid leukemia (AML) cells. However, the underlying molecular mechanisms are not fully understood. In our study, 20(S)-Rh2 induced the expression of orphan nuclear receptor Nur77 and death receptor proteins Fas, FasL, DR5, and TRAIL, as well as the cleavage of caspase 8 and caspase 3 in HL-60 cells. Importantly, shNur77 attenuated 20(S)-Rh2-induced apoptosis and Fas and DR5 expression. Meanwhile, 20(S)-Rh2 promoted Nur77 translocation from the nucleus to mitochondria and enhanced the interaction between Nur77 and Bcl-2, resulting in the exposure of the BH3 domain of Bcl-2 and activation of Bax. Furthermore, 20(S)-Rh2 promoted the differentiation of HL-60 cells as evidenced by Wright-Giemsa staining, NBT reduction assay, and detection of the myeloid differentiation marker CD11b by flow cytometry. Notably, shNur77 reversed 20(S)-Rh2-mediated HL-60 differentiation. Additionally, 20(S)-Rh2 also exhibited an antileukemic effect and induced Nur77 expression in NOD/SCID mice with the injection of HL-60 cells into the tail vein. Together, our studies suggest that the Nur77-mediated signaling pathway is highly involved in 20(S)-Rh2-induced apoptosis and differentiation of AML cells.

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

    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


    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.

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

    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


    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.

  5. Modulation of Calcium Signaling of Angiotensin AT1, Endothelin ETA, and ETB Receptors by Silibinin, Quercetin, Crocin, Diallyl Sulfides, and Ginsenoside Rb1.

    Bahem, Ruba; Hoffmann, Anja; Azonpi, Arnaud; Caballero-George, Catherina; Vanderheyden, Patrick


    Angiotensin II and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. Both peptides exert their pleiotropic effects via binding to their respective G-protein-coupled receptors, i.e., angiotensin AT1 and endothelin type A and type B receptors. In the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used and validated a cellular luminescence-based read-out system in which we measured intracellular calcium signaling in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Firstly, silibinin, a flavanolignan that occurs in milk thistle (Silybum marianum), was investigated and found to be an antagonist for the human angiotensin AT1 receptor with an affinity constant of about 9 µM, while it had no effect on endothelin type A or type B receptor activation. Quercetin and crocin partially impeded intracellular calcium signaling resulting in a non-receptor-related reduction of the responses recorded for the three investigated G-protein-coupled receptors. Two organosulfur compounds, diallyl disulfide and diallyl trisulfide, as well as the triterpene saponin ginsenoside Rb1 did not affect the activation of the angiotensin AT1 and endothelin type A and type B receptors. In conclusion, we were able, by using a nonradioactive cellular read-out system, to identify a novel pharmacological property of the flavanolignan silibinin.

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

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


    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. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2.

    Yu, Tao; Yang, Yanyan; Kwak, Yi-Seong; Song, Gwan Gyu; Kim, Mi-Yeon; Rhee, Man Hee; Cho, Jae Youl


    Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis factor-α/interferon-γ-treated synovial cells, and HEK293 cells transfected with various inducers of inflammation. G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis factor-α and interleukin-1β. G-Rc also markedly suppressed the activation of TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling.

  8. Ginseng and Its Active Components Ginsenosides Inhibit Adipogenesis in 3T3-L1 Cells by Regulating MMP-2 and MMP-9

    Jaeho Oh


    Full Text Available The growth and development of adipose tissue are believed to require adipogenesis, angiogenesis, and extracellular matrix remodeling. As our previous study revealed that ginseng reduces adipose tissue mass in part by decreasing matrix metalloproteinase (MMP activity in obese mice, we hypothesized that adipogenesis can be inhibited by ginseng and its active components ginsenosides (GSs. Treatment of 3T3-L1 adipocytes with Korean red ginseng extract (GE inhibited lipid accumulation and the expression of adipocyte-specific genes (PPARγ, C/EBPα, aP2, and leptin. GE decreased both the mRNA levels and activity of MMP-2 and MMP-9 in 3T3-L1 cells. These effects were further inhibited by total GSs (TGSs and individual GSs. TGSs and individual GSs also significantly decreased MMP-2 and MMP-9 reporter gene activities in the presence of phorbol 12-myristate 13-acetate (PMA, the MMP inducer. Among the GSs, Rb1 most effectively inhibited MMP activity. In addition, PMA treatment attenuated the inhibitory actions of GE and GSs on adipogenesis. Moreover, GE and GSs reduced the expression of NF-κB and AP-1, the transcription factors of MMP-2 and MMP-9. These results demonstrate that ginseng, in particular GSs, effectively inhibits adipogenesis and that this process may be mediated in part through the suppression of MMP-2 and MMP-9. Thus, ginseng and GSs likely have therapeutic potential for controlling adipogenesis.

  9. Ginsenoside-Rg1 promotes angiogenesis in rats with acute myocardial ischemia%人参皂苷Rg1对大鼠急性缺血心肌血管再生的促进作用

    张庆勇; 陈燕萍; 刘芬; 陈霞


    目的 研究人参皂苷Rg1对急性心肌缺血大鼠心肌血管再生的分子机制.方法 建立大鼠急性心肌缺血模型,48只大鼠随机抽签法分为急性心肌缺血模型组,阳性药组(美托洛尔4.5 mg/kg),人参皂苷Rg1 5、10、15 mg/kg组,假手术组,每组各8只.连续腹腔注射14 d后取材.TTC法测定心肌梗死面积,免疫组化染色法测定心肌梗死边缘区微血管密度,心肌梗死边缘区VEGF、VEGFR1、VEGFR2和p-Akt表达,Griess法测定大鼠心肌组织NO水平.结果 与模型组比较,人参皂苷Rg1 10、15 mg/kg组心肌梗死面积明显减小(P<0.01),微血管密度显著增加(P<0.01).人参皂苷Rg1 10 mg/kg组VEGF、VEGFR1、VEGFR2及p-Akt表达均为次强阳性,Rg1 15 mg/kg组VEGF、VEGFR1、VEGFR2及p-Akt表达则均为强阳性,结果与阳性药物作用相当,其中以Rg1 15 mg/kg剂量效果最佳.此外,与模型组比较,人参皂苷Rg110、15 mg/kg组心肌组织NO水平明显升高(P<0.05,P<0.01).结论 人参皂苷Rg1可促进大鼠急性缺血心肌血管再生,该作用与人参皂苷Rg1增加心肌组织VEGF、VEGFR、p-Akt以及NO的表达有关.%Objective To investigate the role of ginsenoside-Rg1 in the angiogenesis in rats with acute myocardial ischemia (AMI). Methods The acute ischemia model was established by ligation of the left front descending branch of the coronary artery. The rats were divided randomly into the model group, metoprolol treatment (MET, 4.5 mg/kg) group, ginsenoside-Rg1 treatment groups (5, 10, and 15 mg/kg) , 8 rats in each group. Another 8 rats receiving sham operation served as sham operation group. The drugs were administered for 14 d. The myocardial infarction area was measured after 2,3, 5-triphenyltetrazoliumchloride (TTC) staining. The microvascular density (MVD) was observed by immunohistochemistry staining. The expression of myocardial VEGF, VEGFR1, VEGFR2 and p-Akt was examined by immunohistochemical staining. The myocardial NO levels were

  10. 人参皂苷Rg1与氧化苦参碱协同保肝作用及其机制研究%Synergic liver protection effects of Ginsenoside Rg1 and Oxymatrine and its mechanism

    吴涛; 王乐民


    同护肝作用,对肝脏PPARα、PPARγ协同调节、抗氧化作用可能为其作用机制。%Objective To observe the liver protection of Ginsenoside Rg1 and Oxymatrine and research its mechanisms.Methods Nonalcoholic fatty liver disease(NAFLD) model was induced by high-fat diet and hepatic fibrosis(HF) model was caused by CCl4 in rats. Protection effects of Ginsenoside Rg1, Oxymatrine and the combination were obsrved.ResultsBoth Rg1 and OMT significantly reduced serum total cholesterol(TC), triglyceride(TG), alanine aminotransferase(ALT) and aspartate amino transferase (AST) levels of NAFLD rats[Rg1 group (2.76±0.22) mmol/L,(1.24±0.17) mmol/L,(112.39±12.91)U/L, (195.16±12.99) U/L; OMT group (2.35±0.19) mmol/L,(1.09±0.09) mmol/L,(90.57±10.25) U/L, (186.45±13.14) U/L,P<0.05 or 0.01],elevated liver PPARα mRNA and PPARγ mRNA[Rg1 group: (0.64± 0.05),(0.77±0.07);OMT group(0.67±0.07),(0.73±0.06),P<0.05 or 0.01] and alleviated the degree of fatty liver. The effects of the combination group[(1.87±0.21) mmol/L, (0.77±0.10) mmol/L,(58.78± 8.87)U/L,(149.78±11.27)U/L,(0.81±0.09),(0.89±0.05) ] was better than single treatment group (P<0.05 or 0.01). Both Rg1 and OMT significantly reduced the serum ALT, AST levels and liver methane dicarboxylic aldehyde(MDA)content[Rg1 group: (46.75±5.11) U/L,(147.53±7.31) U/L,(5.54±1.06) nmol/g; OMT group:(148.24±4.32) U/L, (93.90±14.22) U/L,(5.85±0.91) nmol/g,P<0.01] in HF model[Rg1 group: (146.75±5.11) U/L,(147.53±7.31)U/L,(5.54±1.06)nmol/g; OMT group:(148.24±4.32) U/L,(93.90±14.22) U/L,(5.85±0.91) nmol/g,P<0.01], enhanced liver SOD activity[Rg1 group:(91.61±9.26) U/mg prot; OM group: (86.19±8.51) U/mg prot,P<0.01] and reduced the semi-quantitative score [Rg1 group:(2.7±0.4); OMT group:(2.9±0.5),P<0.05 or 0.01], the effect of the combination group[(92.21±4.36) U/L,(52.08±7.56) U/L,(3.68±0.54) nmol/g,(99.67±13.13) U/mg prot, (1.2±0.4)] was better than single treatment group.Conclusion Ginsenoside

  11. Studies on the chemical transformation of 20(S)-protopanaxatriol (PPT)-type ginsenosides R(e), R(g2), and R(f) using rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS).

    Wu, Wei; Qin, Qiujie; Guo, Yingying; Sun, Jinghui; Liu, Shuying


    A rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method was developed for analysis of chemical transformation of 20(S)-protopanaxatriol (PPT)-type ginsenosides Re, Rg2, and Rf in acidic conditions. The transformation products were identified by comparing the retention time of the standard compounds, the accurate mass measurement, and the fragment ions obtained from RRLC-Q-TOF-tandem mass spectrometry (MS/MS) analyses. The specific product ions of aglycone PPT (m/z 475), C-24- and C-25-hydrated PPT (m/z 493), and Δ20(21) or Δ20(22) dehydration PPT (m/z 457) by MS/MS were discussed for structural characterization. Experiments demonstrated that chemical transformation mechanisms of 20(S)-PPT-type ginsenosides in acidic conditions include hydrolysis of saccharide substitution, Δ20(21) or Δ20(22) dehydration, and hydration addition reactions at C-24 and C-25. The chemical transformation pathway for 20(S)-PPT-type ginsenosides was summarized. The developed RRLC-Q-TOF-MS method was also applied for comparative analysis of 20(S)-PPT ginsenoside and related chemical transformation products in ginseng products.

  12. Ginsenoside Rb1 Protects Neonatal Rat Cardiomyocytes from Hypoxia/Ischemia Induced Apoptosis and Inhibits Activation of the Mitochondrial Apoptotic Pathway

    Xu Yan


    Full Text Available Aim. To investigate the effect of Ginsenoside Rb1 (GS-Rb1 on hypoxia/ischemia (H/I injury in cardiomyocytes in vitro and the mitochondrial apoptotic pathway mediated mechanism. Methods. Neonatal rat cardiomyocytes (NRCMs for the H/I groups were kept in DMEM without glucose and serum, and were placed into a hypoxic jar for 24 h. GS-Rb1 at concentrations from 2.5 to 40 µM was given during hypoxic period for 24 h. NRCMs injury was determined by MTT and lactate dehydrogenase (LDH leakage assay. Cell apoptosis, ROS accumulation, and mitochondrial membrane potential (MMP were assessed by flow cytometry. Cytosolic translocation of mitochondrial cytochrome c and Bcl-2 family proteins were determined by Western blot. Caspase-3 and caspase-9 activities were determined by the assay kit. Results. GS-Rb1 significantly reduced cell death and LDH leakage induced by H/I. It also reduced H/I induced NRCMs apoptosis induced by H/I, in accordance with a minimal reactive oxygen species (ROS burst. Moreover, GS-Rb1 markedly decreased the translocation of cytochrome c from the mitochondria to the cytosol, increased the Bcl-2/ Bax ratio, and preserved mitochondrial transmembrane potential (ΔΨm. Its administration also inhibited activities of caspase-9 and caspase-3. Conclusion. Administration of GS-Rb1 during H/I in vitro is involved in cardioprotection by inhibiting apoptosis, which may be due to inhibition of the mitochondrial apoptotic pathway.

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

    Hyuk-Woo Kwon


    Full Text Available 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.

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

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


    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.

  15. Protective and anti‑angiopathy effects of ginsenoside Re against diabetes mellitus via the activation of p38 MAPK, ERK1/2 and JNK signaling.

    Shi, Yawei; Wan, Xuesi; Shao, Nan; Ye, Runyi; Zhang, Ning; Zhang, Yunjian


    The present study aimed to determine the protective and anti-angiopathy effects of ginsenoside (GSS) on Wistar rats with diabetes mellitus (DM). Diabetic angiopathy occurs during the early stage of diabetes, and in type 1 DM (T1DM) and type 2 DM (T2DM). In the present study, early DM, T1DM and T2DM were induced by treatment with a high‑sucrose‑high‑fat diet, alloxan monohydrate or streptozocin, respectively. The levels of blood glucose, insulin, lipid metabolism markers [total cholesterol (TC), triglyceride (TG), high‑density lipoprotein (HDL) and lipoprotein(a) (Lp‑a)], and endothelial cell function markers [endothelin, nitric oxide, vascular endothelial growth factor (VEGF) and interleukin‑6 (IL‑6)] were determined following treatment with GSS. In addition, oral glucose tolerance test and insulin tolerance test were performed. The phosphorylation levels of p38 mitogen‑activated protein kinase (MAPK), extracellular signal‑regulated kinase 1/2 (ERK1/2) and c‑Jun N‑terminal kinase (JNK) were detected in aorta samples harvested from T2DM rats by western blot analysis. The present study determined that GSS treatment effectively decreased the levels of blood glucose, TC, TG, Lp‑a, VEGF, IL‑6, phosphorylated (p)‑p38, p‑ERK1/2 and p‑JNK; however, treatment with GSS increased insulin and HDL levels. Therefore, it is possible that GSS exerts protective and anti‑angiopathy effects against the early stage of diabetes, T1DM and T2DM in vivo via the activation of p38 MAPK, ERK1/2 and JNK signaling.

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

    Jin-Song Zhou


    Full Text Available 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(PH 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.

  17. Mechanisms of ginsenoside and oridonin inducing cancer cell apoptosis%人参皂苷和冬凌草甲素诱导癌细胞凋亡的作用机制

    李小记; 米志宽; 符兆英


    细胞凋亡在肿瘤的发生发展中起重要作用,用中药诱导癌细胞凋亡是当前肿瘤治疗的研究热点之一.已经发现许多中药活性成分能够诱导癌细胞凋亡,人参皂苷和冬凌草甲素是其中研究较为深入的两种.人参皂苷和冬凌草甲素诱导癌细胞凋亡的作用机制包括阻滞细胞周期进展、上调凋亡促进蛋白表达、下调凋亡抑制蛋白表达和激活caspase级联反应等多个方面.%Apoptosis plays a critical role in tumor genesis and progression. Induction of cancer cell apoptosis with traditional Chinese medicines is at present a hot topic in the research of cancer therapy. It has been found that many active components of traditional Chinese medicines can induce cancer cell apoptosis; ginsenoside and oridonin are two of them that have been studied relatively thoroughly. The mechanisms that ginsenoside and oridonin induce cancer cell apoptosis include arresting cell cycle progression, up-regulating expression of apoptotic promoting proteins, down-regulating expression of apoptotic inhibiting proteins, and activating caspase cascade.

  18. Effects of different penetration enhancers on transdermal absorption of ginsenoside Rg1 in vitro%不同促透剂对人参皂苷 Rg1体外透皮吸收的影响

    韩莉; 王平; 刘善新; 苏酩; 孙虎


    Objective To investigate the effects of different penetration enhancers on transdermal absorption of ginsen-oside rg1 in vitro through skin - penetrating experiments in mice,and determine the best penetration enhancer for laying the foundation for researching new transdermal absorption preparations. Methods Using the modified Franz diffusion pool method,with mice skin as transdermal barrier,physiological saline as accept medium,adding different penetration enhancers to make samples,with ginsenoside rg1 as quantitative indexes for transdermal absorption in vitro tests,measured by high performance liquid chromatography( HPLC) method,inspects the accumulation of ginsenoside rg1 through the vol-ume. Results Without penetration enhancers,ginsenoside rg1 had no accumulation;In single penetration enhancers,7%propylene glycol had the best effect,7% azone came second,borneol in aqueous solution had more lower effect;In compound penetration enhancers,the accumulation of azone ﹢ propylene glycol groups was closing at any concentrations;Effect of azone﹢ borneol group was better when both concentrations were at 2. 5% . Conclusion Common penetration enhancers as azone,propylene glycol and borneol can increase the accumulation of ginsenoside rg1 ,among them,7% propylene glycol was the best.%目的:通过小鼠体外透皮实验,探讨不同促透剂对人参皂苷 rg1体外透皮吸收的影响,确定最佳促透剂,为研制新型透皮吸收制剂奠定基础。方法采用改良 Franz 扩散池法,以离体小鼠皮肤为透皮屏障,以生理盐水为接受介质,加入不同促透剂制备药液样品,以人参皂苷 rg1为定量指标成分进行体外透皮吸收检测,考察人参皂苷 rg1累计透过量。结果无促透剂条件下,人参皂苷 rg1未能透过;单一促透剂中以7%丙二醇效果最好,7%氮酮效果次之,冰片促透作用较小;复合促透剂中,氮酮﹢丙二醇组各浓度下累计透过量接近,氮酮﹢

  19. Effects of ginsenoside Rb1 on behaviors and memory of lead-exposed mice%人参皂苷Rb1对染铅小鼠行为记忆的影响

    刘微; 王艳春; 范红艳; 沈楠; 任旷


    AIM: To explore the effects of ginsenoside Rb1 on the blood lead levels and behaviors of lesd-exposed mice. METHODS: Lead-exposed models of mice were established with lead acetate drinking water, and different doses of ginsenoside Rb1 (100, 50, 25 mg/kg) were fed. Morris water maze test was employed to evaluate the effects of ginsenoside Rb1 on the learning and memory functions of the lead-exposed mice. The blood lead content and the activity of superoxide dismutase(SOD) and nitric oxide synthase ( NOS ) were detected. RESULTS : Morris water maze test showed that the searching distance and the latent periods were extended in lead-exposure mice. The activity of SOD decreased while the activity of NOS increased compared with those in control group (P<0.05 or P<0.01). Ginsenoside Rb1 markedly shortened the searching distance and latent periods, decreased the blood lead content, promoted the activity of SOD, and lowered the activity of NOS (P<0.05 or P<0.01). CONCLUSION: The results suggest that ginsenoside Rb1 reduces the blood lead concentration and alleviates the learning and memory obstacles of lead-expesed mice by restoring the vitality of the antioxidant system.%目的:研究人参皂苷Rb1对染铅小鼠血铅水平及行为记忆的影响.方法:以醋酸铅饮水制备染铅小鼠模型,灌胃给予100,50,25 mg/kg不同剂量的人参皂苷Rb1,采用Mor-ris水迷宫实验评价人参皂苷Rb1对小鼠学习记忆的影响,并测定小鼠血中铅含量、脑组织中超氧化物歧化酶(SOD)活性和一氧化氮合酶(NOS)活性.结果:染铅可导致小鼠水迷宫实验搜索路程及潜伏期延长;SOD活性降低及NOS活性升高,与空白对照组相比较差异显著(P<0.05或P<0.01).给予人参皂苷Rb1后,染铅小鼠水迷宫实验搜索路程及潜伏期缩短;血铅含量降低;SOD活性升高;NOS活性降低,与染铅模型组相比较差异显著(P<0.05或P<0.01).结论:人参皂苷Rb1能明显降低血铅浓度;通过提高染铅小鼠体内

  20. Inhibitory Effect of Ginsenoside Rg1 on Vascular Smooth Muscle Cell Proliferation Induced by PDGF-BB Is Involved in Nitric Oxide Formation

    Jing Huang


    Full Text Available Ginsenoside Rg1 (Rg1 has been reported to suppress the proliferation of vascular smooth muscle cells (VSMCs. This study aimed to observe the role of nitric oxide (NO in Rg1-antiproliferative effect. VSMCs from the thoracic aorta of SD rats were cultured by tissue explant method, and the effect of Rg1 (20 mg⋅L-1, 60 mg⋅L-1, and 180 mg⋅L-1 on platelet-derived growth factor-BB (PDGF-BB-induced proliferation was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. For probing the mechanisms, the content of NO in supernatant and cGMP level in VSMCs was measured by nitric oxide kit and cGMP radio-immunity kit, respectively; the expressions of protooncogene c-fos and endothelial NO synthase (eNOS mRNA in the VSMCs were detected by real-time RT-PCR; the intracellular free calcium concentration ([Ca2+]i was detected with Fura-2/AM-loaded VSMCs. Comparing with that in normal group, Rg1 180 mg⋅L-1 did not change the absorbance of MTT and cell percent of G0/G1, G2/M, and S phase in normal cells (P>0.05. Contrarily, PDGF-BB could increase the absorbance of MTT (P<0.01 and the percent of the S phase cells but decrease the G0/G1 phase cell percent in the cell cycle, accompanied with an upregulating c-fos mRNA expression (P<0.01, which was reversed by additions of Rg1(20 mg⋅L-1, 60 mg⋅L-1, and 180 mg⋅L-1. Rg1 administration could also significantly increase the NO content in supernatant and the cGMP level in VSMCs, as well as the eNOS mRNA expression in the cells, in comparison of that in the group treated with PDGF-BB alone (P<0.01. Furthermore, Rg1 caused a further increase in the elevated [Ca2+]i induced by PDGF-BB. It was concluded that Rg1 could inhibit the VSMC proliferation induced by PDGF-BB through restricting the G0/G1 phase to S-phase progression in cell cycle. The mechanisms may be related to the upregulation of eNOS mRNA and the increase of the formation of NO and cGMP.

  1. Impact of miR-208 and its Target Gene Nemo-Like Kinase on the Protective Effect of Ginsenoside Rb1 in Hypoxia/Ischemia Injuried Cardiomyocytes

    Xu Yan


    Full Text Available Background/Aims: Ginsenoside Rb1 (GS-Rb1 is one of the most important active pharmacological extracts of the Traditional Chinese Medicine ginseng, with extensive evidence of its cardioprotective properties. Mir-208 has been shown to act as a biomarker of acute myocardial infarction in vivo studies including man. However the impact of miR-208 on the protective effect of GS-Rb1 in hypoxia/ischemia injured cardiomyocytes remains unclear. The current study aims to investigate the target gene of miR-208 and the impact on the protective effect of GS-Rb1 in hypoxia/ischemia (H/I injuried cardiomyocytes. Materials and Methods: Primary cultures of neonatal rat cardiomyocytes (NRCMs was subjected to the H/I conditions with or without GS-Rb1. Cell viability was calculated by MTT assay and confirmed by flow cytometry analysis. Mir-208 was then detected by qRT-PCR. Luciferase reporter assay was carried out to detect the target gene of Mir-208. Then the NRCMs were transfected with miR-208 mimics and inhibitors to evaluate the impact on cardioprotective properties of Rb1. Results: The miR-208 expression level was clearly upregulated in the H/I treated NRCMs accompanied by the percentage of the apoptotic cells which could be reversed by GS-Rb1 pretreatment. The nemo-like kinase (NLK mRNA and protein expression levels were decreased in H/I group measured by RT-PCR and western blotting. Luciferase activity assay was then carried out to identify that NLK may be a direct target of mir-208. MTT assay showed that miR-208 inhibitor slightly decreased the protective effect of Rb1 on the H/I impaired NRCMs. However, results showed no statistical difference. Conclusions: These findings proved that NLK was a direct target of mir-208 and miR-208 act indirectly during Rb1 protecting H/I impaired NRCMs and further researches were needed to explore the relationship that microRNAs and other signal pathways in the protective effect of GS-Rb1 on the hypoxia/ischemia injuries in

  2. In vitro studies on the oxidative metabolism of 20(s)-ginsenoside Rh2 in human, monkey, dog, rat, and mouse liver microsomes, and human liver s9.

    Li, Liang; Chen, Xiaoyan; Zhou, Jialan; Zhong, Dafang


    20(S)-Ginsenoside Rh2 (Rh2)-containing products are widely used in Asia, Europe, and North America. However, extremely limited metabolism information greatly impedes the complete understanding of its clinical safety and effectiveness. The present study aims to systematically investigate the oxidative metabolism of Rh2 using a complementary set of in vitro models. Twenty-five oxidative metabolites were found using liquid chromatography-electrospray ionization ion-trap mass spectrometry. Six metabolites and a metabolic intermediate were synthesized. The metabolites were structurally identified as 26-hydroxy Rh2 (M1-1), (20S,24S)-epoxydammarane-12,25-diol-3-β-d-glucopyranoside (M1-3), (20S,24R)-epoxydammarane-12,25-diol-3-β-d-glucopyranoside (M1-5), 26,27-dihydroxy Rh2 (M3-6), (20S,24S)-epoxydammarane-12,25,26-triol-3-β-d-glucopyranoside (M3-10), (20S,24R)-epoxydammarane-12,25,26-triol-3-β-d-glucopyranoside (M3-11), and 26-aldehyde Rh2 on the basis of detailed mass spectrometry and nuclear magnetic resonance data analysis. Double-bond epoxidation followed by rearrangement and vinyl-methyl group hydroxylation represent the initial metabolic pathways generating monooxygenated metabolites M1-1 to M1-5. Further sequential metabolites (M2-M5) from the dehydrogenation and/or oxygenation of M1 were also detected. CYP3A4 was the predominant enzyme involved in the oxidative metabolism of Rh2, whereas alcohol dehydrogenase and aldehyde dehydrogenase mainly catalyzed the metabolic conversion of alcohol to the corresponding carboxylic acid. No significant differences were observed in the phase I metabolite profiles of Rh2 among the five species tested. Reactive epoxide metabolite formation in both humans and animals was evident. However, GSH conjugate M6 was detected only in cynomolgus monkey liver microsomal incubations. In conclusion, Rh2 is a good substrate for CYP3A4 and could undergo extensive oxidative metabolism under the catalysis of CYP3A4.

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

    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


    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. Extraction of Ginsenoside with Orthogonal Experiment and Preparation of Supple Ginseng Shampoo%人参活性物质的提取及人参柔顺洗发水的研制

    万玉华; 蒋日琼; 刘丹丹; 徐静; 张榕文; 吴志强


    为优化人参活性物质Rg1、Re、Rb1的提取工艺,研制人参柔顺洗发水,采用L9(33)正交试验表设计人参皂苷的提取工艺,选用药粉目数、溶剂倍量、提取时间为考察因素,以人参皂苷Rg1、Re、Rb1为测定指标筛选最佳工艺参数;结合头发梳理测试,研究人参提取液在洗发水中的最佳添加量.结果发现:人参提取液最佳制备工艺为24目粉末,7倍量水,提取1 h;人参提取液在洗发水中的最佳添加量为15%.可以得出:人参活性物质--皂苷类成分的提取工艺方便且结果可靠,洗发水研制路线全面、合理,可为产业化生产提供实验数据.%To optimize the technology for extraction of ginsenoside Rg1 , Re and Rbi , prepare the supple ginseng shampoo, the ginsenoside Rg, , Re and Rb, were used as the evaluation indexes, L9(33) orthogonal experiment was designed to study the effect of concentration of mesh powder , solvent quantity and extraction time on extraction rate of alkaloids; the best concentration of ginseng extract used in shampoo was also studied through hair combing test. The best extracting conditions were as follows s 24 mesh ginseng powder, adding 7-fold amount of water and extracting for an hour; The best concentration for ginseng extract used in shampoo was 15%. This technology for extracting ginsenoside is convenient and feasible, the preparation of shampoo is comprehensive and reasonable, it produces beneficial data for industrial production.

  5. 人参皂苷Rd干预体外培养肝储脂细胞胶原的表达%Effect of ginsenoside Rd on collagen expression in liver fat-storing cells

    谯时文; 王继丰; 黄勤; 朱宗贵; 张知贵


    背景:肝储脂细胞产生胶原是导致肝硬化的直接原因,调控肝储脂细胞产生胶原的能力即可以防治肝硬化.目的:观察人参皂苷Rd 对体外培养肝储脂细胞Ⅰ,Ⅲ型胶原表达的影响.方法:体外培养肝储脂细胞,随机分为对照组和实验组,实验组用100 mg/L 人参皂苷Rd 进行培养干扰,用免疫组织化学、免疫荧光技术检测Ⅰ,Ⅲ型胶原基因的表达.结果与结论:实验组比对照组,Ⅰ,Ⅲ型胶原阳性产物吸光度和面积比值明显降低(P < 0.05),说明人参皂苷Rd 对体外培养肝储脂细胞Ⅰ,Ⅲ型胶原的表达有明显调节作用,影响肝储脂细胞产生胶原纤维.%BACKGROUND: Collagens produced by liver fat-storing cells are the directly reasons for cirrhosis, thus, regulating capacity of fat-storing cells producing collagens can prevent cirrhosis. OBJECTIVE: To explore effect of ginsenoside Rd on expression of type anⅠ d Ⅲ collagens in liver fat-storing cells in vitro. METHODS: The liver fat-storing cells were cultured in vitro and interfered with ginsenoside Rd. The expression of type Ⅰ and Ⅲ collagens was detected by immunohistochemistry and immunofluorescent.RESULTS AND CONCLUSION: Compared with the control group, the positive/negative-area and the absorbance of the experimental group were obviously decreased (P < 0.05), suggesting that ginsenoside Rd regulates the expression of type Ⅰ and Ⅲ collagens in liver fat-storing cells in vitro, which affects liver fat-storing cells producing collagens.

  6. Synergistic effects of ginseng stem and leaf-extracted ginsenoside and choline on improving learning and memory in rats Association verification experiment in animals with multiple learning and memory Disorders

    Xiaomin Zhao; Hongxia Gu; Qing Li; Xianglin Xie; Zuoli Xia; Hongxin Cai; Ling Zhang; Dawei Li; Xinnong Wang


    BACKGROUND:Ginsenoside extracted from the stem and leaf of ginseng(GSL)and choline have both been shown to improve learning and memory functions; however,further studies are needed to understand the synergistic effects of a combination of both.OBJECTIVE:To verify the combined improved synergistic effects of GSL and choline on learning and memory disorders in rats.DESIGN:Control observation.SETTING:Taishan Medical College.MATERIALS:A total of 150 male Kunming mice weighing(20±2)g and 40 healthy male Wistar rats weighing(220±20)g were provided by the Experimental Animal Department of Jilin University.Animal experimentation received confirmed consent from the local ethic committee.GSL was provided by the Department of Chemistry,Norman Bethune Medical University,and choline was provided by the Third Experiment Factory,Shanghai.METHODS:This study was performed at the Life Science Institute,Taishan Medical College from October 2006 to February 2007.①Scopolamine-induced learning and memory disorders in rats:Forty rats were randomly divided into control group,model group,combination group(400 mg/kg GSL + 200 mg/kg choline),GSL(400 mg/kg)group,and choline(200 mg/kg)group,8 rats/group.Rats were perfused and administrated in the morning,once a day for 14 successive days.Rats in the control group and model group were perfused with 20 mL/kg distilled water and underwent Morris water maze spatial resolution test 1 hour after perfusion on the 10th,11th,and 12th days after administration.Rats also underwent passive step-down avoidance test 1 hour after reperfusion on the 13th and 14th days after administration.Thirty minutes prior to experimentation,rats in the remaining three groups were intraperitoneally(I.p)injected with 2 mg/kg scopolamine,and rats in the control group were I.p.injected with 2 mL/kg saline.②Scopolamine-induced learning disorder and memory acquired disorder in mice:Fifty mice were randomly divided into control group,model group,combination group(400 mg

  7. 人参皂苷Rg1对体外培养C2C12成肌细胞凋亡的影响%Effect of ginsenoside Rg1 during serum-deprivation induced apoptosis in C2C12 myoblasts cultured in vitro

    叶东明; 余磊; 王乐禹; 邱小忠; 欧阳钧


    Objective: To investigate the effect and possible mechanism of ginsenoside Rgl during serum-deprivation induced apoptosis in C2C12 myoblasts cultured in vitro. Methods: The effect of different concentrations of ginsenoside Rgl during the cell apoptosis was assessed by MTT assay, Hoechst 33258-PI double staining and RT-PCR analysis. Results: After 48 h treatment, various doses of ginsenoside Rgl increased cell viability in serum-deprived C2C12 myoblasts using MTT assay. Hoechst 33258-PI double staining showed that the rate of apoptosis cells significantly decreased after being treated by ginsenoside Rgl. RT-PCR showed that ginsenoside Rgl caused the downregulation of pro-apoptotic caspase-3, Bax and AIF genes, while caused the up-regulation of anti-apoptotic Bcl-2 gene. Conclusion: Ginsenoside Rgl can protect the serum-deprived apoptosis in C2C12 myoblasts.%目的:研究人参皂苷Rg1对体外无血清诱导培养的C2C12成肌细胞凋亡的影响及其可能机制.方法:采用MTT法、人参皂苷Rg1处理48 h后hoechst 33258-PI染色,以及RT-PCR方法观察不同浓度人参皂苷Rg1对C2C12成肌细胞凋亡的影响.结果:MTT法结果显示人参皂苷Rg1处理48 h后可抑制C2C12成肌细胞凋亡;Hoechst 33258-PI染色可见C2C12成肌细胞凋亡率人参皂苷处理前后差异有统计学意义,人参皂苷处理后C2C12成肌细胞凋亡率显著下降;RT-PCR法结果显示人参皂苷Rg1可抑制Caspase-3、Bax和AIF mRNA表达,并能诱导Bcl-2 mRNA表达.结论:人参皂苷Rg1对C2C12成肌细胞凋亡具有保护作用.

  8. Gene expression of the p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) signaling pathways in the regulation of hematopoietic stem cell aging by ginsenoside Rg1.

    Yue, Z; Rong, J; Ping, W; Bing, Y; Xin, Y; Feng, L D; Yaping, W


    The elucidation of the molecular mechanisms underlying the effects of traditional Chinese medicines in clinical practice is a key step toward their worldwide application, and this topic is currently a subject of intense research interest. Rg1, a component of ginsenoside, has recently been shown to perform several pharmacological functions; however, the underlying mechanisms of these effects remain unclear. In the present study, we investigated whether Rg1 has an anti-senescence effect on hematopoietic stem cells (HSCs) and the possible molecular mechanisms driving any effects. The results showed that Rg1 could effectively delay tert-butyl hydroperoxide (t-BHP)-induced senescence and inhibit gene expression in the p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) signaling pathways in HSCs. Our study suggested that these two signaling pathways might be potential targets for elucidating the molecular mechanisms of the Rg1 anti-senescence effect.

  9. 蛹虫草固态发酵对3种皂苷含量的影响分析%Study on Three Ginsenoside Contents Changed in Solid-state Fermentation by Cordycepsmilitaris

    闫梅霞; 逄世峰; 张瑞; 侯微; 王英平


    研究蛹虫草固态发酵人参须,超高效液相色谱仪测定单体人参皂苷Rb1、Rc、Rd含量,分析发酵过程中其含量变化。固态发酵过程中3种人参皂苷含量变化显著,同一皂苷不同时期含量相差较大。%To Study ginseng Cordyceps solid state fermentation by cordycepsmilitaris ,ultra high-performance liquid chromatograph was used to analyze monomer ginsenosides Rb1 ,Rc ,Rd content ,and its content in the fermentation process .Solid state fermentation process caused three kinds of ginseng saponin content changes significantly ,the same saponin content in different periods was quite different .

  10. Effects of ginsenoside Rb1 on melanogenesis in human epidermal melanocytes%人参皂苷Rb1对人表皮黑素细胞黑素生成的影响

    卢珊珊; 李国艳; 赵丹; 张微; 林茂; 涂彩霞


    [目的]探讨人参皂苷Rb1对体外培养的人黑素细胞黑素生成的影响及其作用机制.[方法]人表皮黑素细胞取自小儿包皮环切术标本,取第2~5代细胞进行实验.采用MTT法测定体外培养的人黑素细胞增殖情况,分光光度计法测定酪氨酸酶的多巴氧化酶活性,氢氧化钠裂解法测定黑素含量,免疫蛋白印记法测定黑素细胞酪氨酸酶、小眼畸形相关转录因子(MITF)的表达及cAMP应答元件结合蛋白(CREB)的磷酸化.[结果]体外培养的人黑素细胞分别加入25、50、100 μ mol/L人参皂苷Rbl作用72 h后,黑素细胞存活率3组间差异无统计学意义(P>0.05),黑素含量呈浓度依赖性增加(与溶剂对照组相比的相对黑素含量分别为112.4%±5.7%、155.7%±6.3%、217.2%±11.7%),酪氨酸酶活性增加(相对酪氨酸酶活性分别为117.9%±5.7%、158.2%±9.6%、182.6%±10.0%).100 μmol/L人参皂苷Rb1作用72 h,黑素细胞酪氨酸酶(225.4%±12.8%)、MITF(313.5%±16.7%)蛋白表达明显升高(与溶剂对照组相比,P值均< 0.01),CREB磷酸化明显增加(322.5%±21.1%)(与溶剂对照组相比,P< 0.01).100 μmol/L人参皂苷Rb1作用黑素细胞8h,MITF蛋白表达无明显变化;作用24h后,MITF表达明显增加,与0时间点相比,P< 0.01.10 μmol/L的蛋白激酶A(PKA)抑制剂H-89预处理细胞,可明显抑制100 μmol/L人参皂苷Rbl引起的CREB激活、酪氨酸酶及MITF蛋白表达的增加,与100 μmol/L人参皂苷Rb1作用72 h比较,P值均< 0.01,进而抑制人参皂苷Rb1引起的酪氨酸酶活性作用增强及黑素合成增加.[结论]人参皂苷Rb1可促进正常人黑素细胞的黑素合成和酪氨酸酶活性.PKA/CREB/MITF/酪氨酸酶信号通路可能参与了人参皂苷Rb1的促黑素生成机制.%[Objective] To estimate the effects of ginsenoside Rb1 on melanogenesis in human melanocytes and underlying mechanisms.[Methods] Epidermal melanocytes were obtained

  11. 人参皂甙对阿尔茨海默病治疗机制的实验研究%Experimental study on therapeutic effects of Ginsenoside on Alzheimer's disease

    王龙安; 马瑜红; 李玮


    Objective To study the effects of ginsenoside on expression of inducible nitric oxide synthase and concentration of NO in THP-1 induced by amyloid beta(Aβ) in Alzheimer's disease. Methods The concentra- tion of nitric oxide was determined by Griess Reagent in supernatant of THP-1. The content of iNOS was measured by western blotting. Results The expression of iNOS of model group was significantly higher than those of control group. Compared with model group, the ginseng could reduce expression of iNOS and concentration of NO significant- ly in THP-1. Conclusion Ginsenoside can significantly inhibit the expression of iNOS, and reduce secretions of NO, so it may provide a novel therapy for AD.%目的 研究人参皂甙对阿尔茨海默病(AD)相关β淀粉样蛋白(AB)诱导THP-1细胞表达诱导性一氧化氮合酶(iNOS)和一氧化氮的影响.方法 用免疫印迹法测定THP-1细胞iNOS表达,用Griess法测定细胞上清中一氧化氮的浓度.结果 模型组iNOS的表达明显高于对照组,与模型组比较,人参皂甙可明显减少THP-1细胞iNOS的表达和一氧化氮的产生.结论 人参皂甙可以抑制THP-1细胞iNOS的表达,进一步影响一氧化氮的产生而用于AD的治疗.

  12. 人参皂苷Rb1、Re对Aβ25-35诱导SK-N-SH细胞损伤的保护作用%Protective effects of ginsenoside Rbl and Re on SK-N-SH cells injured by Aβ25-35

    贾立云; 潘晓华; 刘晶; 崔行; 王墨林


    Objective To investigate protective effects of ginsenoside Rbl and Re against injury of SK-N-SH cells induced by Aβ25-35 and the possible mechanism. Methods Aβ25-35 was added to the medium for cell culture to make a cell model of Alzheimer disease, and ginsenoside Rb1 or Re were used to treat the injured cells. Cell survival rates were determined by the MTr assay, intracellular ROS levels were determined by fluorescence probes, and expressions of phosphorylated tau and active glycogen synthase kinase 3β(GSK-3β) were determined by Western blot. Results The survival ratio of SK-N-SH cells were significantly decreased after exposure to Aβ25-35, and treatment with ginsenoside Rbl or Re significantly increased the survival ratio and decreased the cellular ROS level. Ginsenoside Rbl and Re decreased expressions of phosphorylated tau and active GSK-3β, respectively. Conclusion Ginsenoside Rbl and Re may exert a neuroprotective effect on SH-N-SH neural cells induced by neurotoxic Aβ25-35.%目的 观察人参皂苷Rb1和Re对Aβ25-35诱导损伤SK-N-SH细胞的保护作用进而研究其内在机制.方法 用Aβ25-35处理人神经母细胞瘤细胞(SK-N-SH细胞),模拟阿尔茨海默病的神经元损伤,并以适当浓度人参皂苷Rb1或Re处理.采用MTT法测定细胞存活率,荧光探针法检测细胞内ROS水平变化,Western blot法检测tau蛋白磷酸化水平及活性GSK-3β蛋白表达.结果 培养基中添加Aβ25-35后SK-N-SH细胞存活率明显下降,而人参皂苷Rb1和Re均能显著提高损伤细胞的存活率,降低细胞内ROS水平,降低活性GSK-3β的表达,造成tau蛋白396位点的磷酸化程度下降,缓解tau蛋白的过度磷酸化.结论 人参皂苷Rb1和Re对Aβ25-35诱导损伤的SK-N-SH细胞具有一定的保护作用.

  13. Effects of Ginsenoside Rh2 on oxytocin-induced transformation of bone marrow mesenchymal stem cells into myocardial cells%人参皂苷Rh2干预催产素诱导骨髓间充质干细胞向心肌细胞的转化

    王乐; 田立; 郑明奇; 刘刚; 吉立双; 马国平


    背景:课题组前期实验已证明了10μmol/L催产素能诱导大鼠骨髓间充质干细胞向心肌细胞转化。目的:观察人参皂苷Rh2在催产素诱导大鼠骨髓间充质干细胞向心肌细胞转化过程中的作用。方法:采用贴壁法分离培养大鼠骨髓间充质干细胞。实验共分为5组,空白对照组细胞常规培养2周;催产素诱导组:10μmol/L催产素连续诱导培养2周;人参皂苷Rh2低、中、高剂量组:分别加入0.5,1,2μmol/L人参皂苷Rh2,培养24 h后加入10μmol/L催产素,连续诱导培养2周。结果与结论:光学显微镜下观察显示,与空白对照组相比,催产素诱导组的细胞部分细胞体积变大,部分细胞密集重叠生长,随人参皂苷Rh2剂量增大细胞密集重叠生长的范围增大。免疫组织化学染色和免疫印迹法结果显示,催产素诱导组和人参皂苷Rh2低、中、高剂量组中心肌肌钙蛋白T,连接蛋白43的蛋白表达均显著高于空白对照组(P <0.05);人参皂苷Rh2剂量增大而阳性表达增强,并显著高于催产素诱导组(P <0.05)。激光共聚焦检测结果显示,催产素诱导2周后,催产素诱导组骨髓间充质干细胞中游离钙的相对荧光强度显著升高(P <0.05),而人参皂苷Rh2处理组的荧光强度高于催产素诱导组,与剂量呈正相关(P <0.05)。结果证实,人参皂苷Rh2在体外可显著增强催产素诱导大鼠骨髓间充质干细胞向心肌细胞转化的作用。%BACKGROUND:Our prior experiments have confirmed that 10 μmol/L oxytocin can induce transformation of bone marrow mesenchymal stem cels into myocardial cels. OBJECTIVE: To investigate the effects of Ginsenoside Rh2 on oxytocin-induced transformation of bone marrow mesenchymal stem cels into myocardial cels. METHODS:Rat bone marrow mesenchymal stem cels were isolated by differential adherence method. These isolated cels were randomly divided into five groups. In

  14. Mechanisms underlie ginsenosides regulating spontaneous sleep architecture in rats%人参皂甙调节大鼠自发睡眠脑电结构的机制

    洪芬芳; 王新; 杨树龙; 张大雷; 杨蓓; 吴磊


    Objective To study the underling mechanism of the effect of ginsenosides(GS) on spontaneous sleep. Methods Adult SD rats were randomly divided into the control, GS 10 mg/kg (low dose) and 100 mg/kg (high dose ) groups. Rats were instrumented with sleep-wake recording electrodes. After recovery front surgical operation, rats were orally administered GS 10 mg/kg and 100 mg/kg or water once per day for 6 days. On GS administration day 1 and day 6, Polygraphic signs of undisturbed sleep-wake activities were recorded for 12 h (07:30 ~ 19:30) after GS administration. Results On GS administration day 1 (acute) , 10 mg/kg GS slightly (P >0.05) but 100 mg/kg GS significantly (P 0. 05 ) but enhanced the expressions of GABAA receptor α, β not γ subunits in rat hy-pothalamus ( P 0. 05) but high dose GS significantly (P 0. 05 ). Conclusions These primary results suggest that GS can regulate spontaneous sleep architecture in time and dose-dependent manner in which acute GS treatment is related to its up-regulating GABAA receptor α,β subtypes whereas chronic GS administration involved in the raised GABA product produced by its over-expressing GAD in rat hypothalamus.%目的 初步探索人参皂甙(GS)调节自发睡眠的作用机制.方法 大鼠随机分为对照、GS低和高(10和100 mg/kg)剂量组.在大鼠体内植入无线发射器,术后每日1次灌胃给药,共6 d.第1(急性)和6天(慢性)给药后记录自由活动大鼠脑电活动12 h.于第1和6天取下丘脑组织用免疫印迹方法检测GABAAergic系统蛋白表达.结果GS灌胃给药第1天,高剂量GS显著增加非快动眼睡眠(NREM)[(8.002±0.427)hvs (6.363±0.542)h,P<0.05]和总睡眠时间[(9.397±0.313)h vs (7.548±0.562)h,P<0.01],减少觉醒[(2.463±0.288)h vs (4.376±0.572)h,P<0.01];GS低和高剂量都增强了下丘脑GABAA受体a、β亚型表达(P<0.05).第6天,低、高剂量GS均显著提高NREM睡眠[(7.587±0.174)h,(7.610±0.204)h vs (6.799±0.302)h,P<0.05]

  15. Experimental Study on Pharmacodynamics of Ginsenoside Rg1 Nasal Spray%人参皂苷Rg1鼻腔喷雾剂的药效学研究



    Objective: To investigate the pharmacodynamics of ginsenoside Rg1 ( GRg1 ) nasal spray.Method:Water maze was used to observe the ability of learning and memory in the mice administrated with GRg1 nasal spray(30 mg· kg-1 ).Step-down test was used to observe the impairment of memory acquisition, memory consolidation and memory retrieval induced by scopolamine, NaNO2 or ethanol.Result:The time required to the safe area and the error times were shortened in the normal mice administrated with GRg1 nasal spray.The error number was decreased and the latency was extended by the treatment of GRg1 nasal spray in the model mice with impaired memory acquisition, memory consolidation and memory retrieval.Conclusion: The ability of learning and memory in normal mice and in model mice can be improved to different degrees after administration of GRg1 nasal spray.%目的:考察人参皂苷Rg1(GRg1)鼻腔喷雾剂的药效学.方法:采用水迷宫考察GRg1鼻腔喷雾剂对正常小鼠空间学习能力的影响:小鼠随机分成空白组、GRg1生理盐水溶液鼻腔给药组、GRg1鼻腔喷雾剂组.每组16只,每天给药2次,连续7 d.GRg1生理盐水溶液鼻腔给药组、GRg1鼻腔喷雾剂组给药剂量均为30 mg·kg-1;空白组给予等体积的生理盐水.采用跳台法考察GRg1鼻腔喷雾剂对模型小鼠记忆获得障碍、记忆巩固障碍和记忆再现障碍的影响:小鼠随机分为5组:正常组、模型组、GRg1生理盐水溶液ig组、GRg1生理盐水溶液鼻腔给药组、GRg1鼻腔喷雾剂组,每组14只,每天给药2次,连续7 d.GRg1生理盐水溶液ig组、GRg1生理盐水溶液鼻腔给药组、GRg1鼻腔喷雾剂组给药剂量均为30 mg·kg-1;正常组和模型组鼻腔给予等体积的生理盐水.于末次给药30 min后,除正常组外各组均造模,用跳台法测试.结果:GRg1鼻腔喷雾剂使正常小鼠第3天和第7天在水迷宫中到达平台时间缩短(P<0.05)、在水迷宫中5 min内错误次数减少(P<0.05);对

  16. Combination analysis.

    Tallarida, Ronald J


    This chapter describes quantitative methodology that is directed toward assessing interactions between a combination of agonist drugs that individually produce overtly similar effects. Drugs administered in combination may show exaggerated, reduced or predictable effects that are dependent on the specific drug pair and the doses of t h e constituents. The basisfor quantitating these unusual interactions is the concept of dose equivalence which, in turn, is determined from the individual drug dose-effect relations. A common analytical procedure that follows from dose equivalence uses a graph termed an isobologram. We present here an overview of the isobologram, its use and certain related methods that apply to classifying various drug interactions.

  17. Ginsenoside Rb1 Attenuates Oxygen-Glucose Deprivation-Induced Apoptosis in SH-SY5Y Cells via Protection of Mitochondria and Inhibition of AIF and Cytochrome c Release

    Pengfei Ge


    Full Text Available To investigate the role of mitochondria in the protective effects of ginsenoside Rb1 on cellular apoptosis caused by oxygen-glucose deprivation, in this study, MTT assay, TUNEL staining, flow cytometry, immunocytochemistry and western blotting were used to examine the cellular viability, apoptosis, ROS level, mitochondrial membrane potential, and the distribution of apoptosis inducing factor, cytochrome c, Bax and Bcl-2 in nucleus, mitochondria and cytoplasm. We found that pretreatment with GRb1 improved the cellular viability damaged by OGD. Moreover, GRb1 inhibited apoptosis in SH-SY5Y cells induced by OGD. Further studies showed that the elevation of cellular reactive oxygen species levels and the reduction of mitochondrial membrane potential caused by OGD were both counteracted by GRb1. Additionally, GRb1 not only suppressed the translocation of apoptosis inducing factor into nucleus and cytochrome c into cytoplasm, but also inhibited the increase of Bax within mitochondria and alleviated the decrease of mitochondrial Bcl-2. Our study indicates that the protection of GRb1 on OGD-induced apoptosis in SH-SY5Y cells is associated with its protection on mitochondrial function and inhibition of release of AIF and cytochrome c.

  18. Comparison of pharmacological effects of ginsenoside Rg1 and Rb1%人参皂甙Rg1和Rb1药理作用的比较



    Ginseng has long been used as a tonic and agent for prolonging life span in chinese traditional medicine. Using morden technology,ginsenoside Rgl and Rbl were proved to be main active principles of ginseng.Both conpounds showed the same effect in improving learning and memory, increasing Bmax of M-cholinergic receptors and accelerating cerebral protein and acetylcholine biosynthesis.However,Rgl but not Rbl had immunoregulatory action in aged rats and anti-osteoporosis effect in ovariectomized rats as well as enhanced basic synaptic transmission and magnitude of LTP induced by HFS. On the other hand,Rbl had anti-stress effects in antagonizing acute,chronic and repeated stress induced reduction of sexual behaviour and decrease of plasma andogen or estrogen.Rgl showed no such effect even aggravate stress induced damage.Rhl possessed anti-oxidant activity and prolong survival time of mice in cold(-10℃) condition.There was no any anti-cold effect with Rgl .These diference of biological activities between Rgl and Rbl may be arributed to their structures containing different number of glucoses.

  19. 人参皂苷和丹参注射液对犬食管大剂量辐射损伤的影响%Effects of Ginsenosides and Salviae Miltiorrhizae on Canine Esophagus after Intrathoracic 20 Gy Electron Beam Radiation

    丁保国; 朱桂; 孙玉鹗; 赵海潞; 林善文


    Objectives \\ To observe the effects of Ginsenosides and Salviae Miltiorrhizae on canine esophagus after in-trathoracic 20 Gy electron beam radiation. Methods: 12 healthy mongrel dogs were randomly divided into three groups with 4 in each group. A single dose of 20Gy electronic beam radiation was given to the mid segment of the esophagus. Before the intrathoracic radiation, Ginsenosides solution (25mg/kg body weight) was injected intra-peritoneally 6 hours and 30 minutes in one group and Salviae Miltiorrhizae administered intravenously in the same manner in the second group and the third group received no medications. The dogs were sacrificed on 15th day after the radiation for pathological ex-amination. Results; Dogs in control group showed delayed recovery, body weight changed from (17.4 ±0. 7)kg to (14.4 ±0.7)kg on day 14, LDF value from 52.4 ±11. 1 on day 0 to 64. 9 ±11.2 on day 3, 47.4 ±7.4 on day 14. CEC count changed from 0. 25 ± 0.5 on day 0 to 10 ± 1. 83 on day 14; blood vascular size 10μm, with surrounding scattered blood red cells. HE staining showed esophageal mucosa had erosion and blood congestion, microvasculature much dilat-ed. Electron microscopic examination found membranal organells swelling such as loss of parallel arrays of endoplasmic reticulum and vacuolation and loss of ribosomal particles, swelling of mitochondria, phagosomes containing membranous structures. Ginsenosides group showed that bodyweight from 17. 3 ±0. 8kg on day 0 to 18. 4 ± 0. 6kg on day 14, LDF val-ue 50. 1 ±10.5 on day 0, 45.6 ±5.7 on day 3, 47.4 ±7.4 on day 14, CEC count 0. 25 ±0.5 on day 0, 3 ±0.96 on day 14, vascular size 4 ~ 6μm on day 0, 8u,m on day 14. HE staining and electronic microscopic examination showed significantly less damage than control group. Salviae Miltiorrhizae showed similar changes as control group. Conclusion; Advance administration of Ginsenosides will significantly alleviate the damage of the esophagus receiving a single large

  20. Combination rules

    Holicky, M.; Vrouwenvelder, A.C.W.M.


    Load combinations specified in EN 1990 for verification of ultimate limit and serviceability limit states in conjunction with the partial factor method are discussed and illustrated by practical examples of typical civil structures. Alternative procedures to identify critical load cases are reviewed

  1. Antifungal combinations.

    Vitale, Roxana G; Afeltra, Javier; Dannaoui, Eric


    The increase in fungal infections and the change in fungal epidemiology is caused by the extensive use of antifungal agents to treat fungal infections that are being diagnosed in severly immunocompromised hosts. In addition, opportunistic fungal infections resistant to antifungal drugs have become increasingly common, and the armamentarium for treatment remains limited. A possible approach to overcoming these problems is to combine antifungal drugs, especially if the mechanisms of action are different. The in vitro test is the first step to evaluate possible antifungal combinations. In this chapter, the three most frequently used metholodologies are described: checkerboard, E-test, and time-kill curves. The description of each technique and intrepretaion of the results are addressed in detail.

  2. Combining haplotypers

    Kääriäinen, Matti; Lappalainen, Sampsa; Mielikäinen, Taneli


    Statistically resolving the underlying haplotype pair for a genotype measurement is an important intermediate step in gene mapping studies, and has received much attention recently. Consequently, a variety of methods for this problem have been developed. Different methods employ different statistical models, and thus implicitly encode different assumptions about the nature of the underlying haplotype structure. Depending on the population sample in question, their relative performance can vary greatly, and it is unclear which method to choose for a particular sample. Instead of choosing a single method, we explore combining predictions returned by different methods in a principled way, and thereby circumvent the problem of method selection. We propose several techniques for combining haplotype reconstructions and analyze their computational properties. In an experimental study on real-world haplotype data we show that such techniques can provide more accurate and robust reconstructions, and are useful for out...

  3. Combination Light


    The Rayovac TANDEM is an advanced technology combination work light and general purpose flashlight that incorporates several NASA technologies. The TANDEM functions as two lights in one. It features a long range spotlight and wide angle floodlight; simple one-hand electrical switching changes the beam from spot to flood. TANDEM developers made particular use of NASA's extensive research in ergonomics in the TANDEM's angled handle, convenient shape and different orientations. The shatterproof, water resistant plastic casing also draws on NASA technology, as does the shape and beam distance of the square diffused flood. TANDEM's heavy duty magnet that permits the light to be affixed to any metal object borrows from NASA research on rare earth magnets that combine strong magnetic capability with low cost. Developers used a NASA-developed ultrasonic welding technique in the light's interior.

  4. Search Combinators

    Schrijvers, Tom; Wuille, Pieter; Samulowitz, Horst; Stuckey, Peter J


    The ability to model search in a constraint solver can be an essential asset for solving combinatorial problems. However, existing infrastructure for defining search heuristics is often inadequate. Either modeling capabilities are extremely limited or users are faced with a general-purpose programming language whose features are not tailored towards writing search heuristics. As a result, major improvements in performance may remain unexplored. This article introduces search combinators, a lightweight and solver-independent method that bridges the gap between a conceptually simple modeling language for search (high-level, functional and naturally compositional) and an efficient implementation (low-level, imperative and highly non-modular). By allowing the user to define application-tailored search strategies from a small set of primitives, search combinators effectively provide a rich domain-specific language (DSL) for modeling search to the user. Remarkably, this DSL comes at a low implementation cost to the...

  5. 人参皂苷对K562细胞增殖与分化相关基因表达的影响%The effect of ginsenoside on mRNA expression of proliferation and differentiationrelated genes in K562 cells

    危建安; 胡永珍; 韩凌


    Objective To explore the potential mechanisms of ginsenosides on K562 cell proliferation and differentiation. Methods Relative quantification RT-PCR with SYBR Green dye was used to determine the expression of Lif, Ccndl, Mdm2, Erbb2 ,p53 and myc mRNA in K562 cells treated with ginsenoside (20 μg/mL) at 36 h. Results mRNA expression of Lif was significantly up-regulated(P < 0.05 ), and that of myc was markedly down-regulated (P < 0.05) in K562 cells when treated with traginsenoside。 mRNA levels of Mdm2,Erbb2 and Ccndl were not significantly changed after treatment of ginsenoside (P > 0. 05 ). mRNA expression of p53 was very weak in K562 cells, so that was not statistically analysed. Conclusion The effect of ginsenoside on proliferative inhibition and differential induction of K562 cells is related to up-regulation of Lif mRNA and down - regulation of myc mRNA respectively.%目的 探讨人参皂苷影响K562细胞增殖、分化的可能分子机制.方法 采用real-time PCR技术和SYBR Green染料法检测人参皂苷(20 μg/mL)作用于K562细胞36 h时间点Lif、Ccnd1、Mdm2、Erbb2、p53和myc等6个基因mRNA相对表达水平.结果 人参皂苷能显著促进K562细胞Lif mRNA的表达(P<0.05),对myc mRNA表达有显著抑制作用(P<0.05),对Mdm2、Erbb2和Ccnd1等mRNA表达无显著影响.结论 人参皂苷对K562细胞的诱导分化和增殖抑制作用可能分别与Lif mRNA表达上调和mycmRNA表达下调相关.

  6. Analgesic combinations

    Raffa, Robert B.; Pergolizzi, Joseph V.; Tallarida, Ronald J.


    When the pathophysiology of a medical condition is multi-modal, i.e., related to multiple physiological causes or mediated by multiple pathways, the optimal strategy can be to use a drug or a combination of drugs that contribute multiple mechanisms to the therapeutic endpoint. In such situations, a rational multi-modal approach can also result in the fewest adverse effects. We discuss the quantitative analysis of multi-modal action using the treatment of pain as a practical example and give examples of its application to some widely used analgesic drugs. PMID:20338825

  7. 人参皂苷Rg1人工抗原的合成及免疫原性鉴定%Synthesis and immunogenicity indentification of artificial antigen of ginsenoside Rg1

    刘洋; 屈会化; 任燕; 吴婷婷; 薛瑾; 孙晔; 赵琰; 王庆国


    目的 合成人参皂苷Rg1的人工免疫原和包被原,为后续制备人参皂苷Rg1的单克隆抗体及建立相应的免疫分析方法奠定基础.方法 采用NaIO4氧化法分别合成人参皂苷Rg1免疫抗原(Rg1-BSA)和包被抗原(Rg1-PLL);紫外光谱和薄层色谱法鉴定人工抗原偶联是否成功;用间接ELISA方法检测免疫小鼠血清中抗体效价,用间接竞争ELISA检测抗体特异性.结果 经紫外光谱和薄层色谱法检测,人参皂苷Rg1与BSA/PLL偶联成功;免疫小鼠后Rg1-BSA可以使小鼠体内产生抗Rg1抗体;利用合成的偶联物成功建立间接ELISA和间接竞争ELISA方法,测得小鼠血清抗体效价在1∶80 000以上,并且所得抗体能特异性结合人参皂苷Rg1.结论 成功合成了人参皂苷Rg1人工免疫原和包被原,可用于下一步的人参皂苷Rg1单克隆抗体制备及建立相应免疫分析方法.%Objective To synthesize the artificial antigen of ginsenoside Rg1-bovine serum albumin (Rg1-BSA) and the artificial coated antigen of ginsenoside Rg1-polylysine (Rg1-PLL),and to provide the basis for the preparation of monoclonal antibody (MAb)and the establishment of immunoassay method.Methods Rg1-BSA and Rg1-PLL were synthesized by sodium periodate oxidation method.The characterization of the synthesis was examined by UV spectrometry and TLC method.The titer and specificity of the antibody in serum of immunised mice were detected by indirect enzyme-linked immunosorbent assay (I-ELISA) and indirect competitive enzyme-linked immunosorbent assay (I-CELISA),respectively.Results According to the UV and TLC,the Rg1 was successfully conjugated with BSA and PLL.I-ELISA and IC-ELISA methods were developed using Rg1-PLL.The anti-Rg1 antibodyobtained from immunized mice could bind to Rg1 specially and the titer was up to 1 ∶ 80 000.Conclusion The artificial immunogen Rg1-BSA and coated antigen Rg1-PLL are successfully synthesized,which could be used to prepare the MAb of Rg1 and

  8. 人参皂甙Rd在脑缺血亚急性期的脑保护效应%Neuroprotective effect of ginsenoside Rd during the subacute stage of the cerebral ischemia

    赵海波; 张云霞; 韩军良; 史明; 赵钢


    Objective; To investigate neuroprotective effect of ginsenoside Rd (GSRd) during the subacute stage of cerebral ischemia. Methods:Eighty-four male SD rats were randomly divided into four groups;a sham-operated group with PG treatment; a sham-operated group with Rd treatment; a MCAO group with PG treatment;and a MCAO group with Rd treatment (n — 18 in each sham-operated group, n = 24 in each MCAO group). Focal transient middle cerebral artery occlusion (MCAO) models were builded according to the suture-occluded method. GSRd and PG were administered intrap-eritoneally 1 d after MCAO onset respectively. The neurological behavior scores (NBS) were assessed prior to administration, 3 d and 7 d after administration, The brain tissues were stained with 2% 2,3 ,5-triphenyltetrazolium chloride (TTC) to evaluate the percentages of infarct volume by ImageJ software. Identify the effect of GSRd to inflammation response after brain ischemic by investigate the microglic changes by immunohistochemical of Iba 1 in ischemic area or penumbra. Results; Compared with PG treatment groups,GSRd treatment could significantly improve the NBS, reduce the infarct volume and attenuate microglia cells activation in MCAO rats (P < 0. 05) . Conclusion; GSRd exerts neuroprotective effect during the subacute stage of cerebral ischemia.%目的:探讨人参皂甙Rd(Ginsenoside Rd,GSRd)在脑缺血亚急性期的脑保护效应.方法:84只雄性SD大鼠随机分为四组,其中假手术+丙二醇(propylene glycol,PG)组和假手术+GSRd组各18只,脑缺血+PG组和脑缺血+ GSRd组各24只.线栓法建立局灶性短暂性大脑中动脉栓塞模型(focal transient middle cerebral artery occlusion,MCAO),栓塞后1d经腹腔注射GSRd和PG.在用药前、用药后3d和7d分别进行神经功能评分(neurological behavior scores,NBS),每次评分后取脑进行2,3,5-氯化三苯基四氮唑(TTC)染色,用ImageJ图像分析软件计算出梗死体积百分比,并且对

  9. Antidepressive-like Effect of Ginsenoside Rg1 and Its Mechanism%人参皂苷Rg1的抗抑郁作用及其作用机制

    黄倩; 楚世峰; 连晓媛; 张均田


    Objective:To investigate the anti-depressive-like effects and mechanisms of Ginsenoside Rg1. Methods:Antidepressant-like effect of Ginsenoside Rg1 was assessed in mice tail suspension test and forced swim test,and trat chronic unpredictable mild stress (CUMS)(28 days)test. Rg1(5,10,20 mg·kg-1·d-1)and duloxetine(10 mg·kg-1·d-1)were studied. Results:Rg1(5,10,20 mg·kg-1)significantly reduced the immobility time in both forced swimming and tail suspension tests. In animals receiving CUMS,they showed an increased immobility in the forced swimming test and decreased sucrose preference test,and Rg1 produced a significant decrease of immobility time and an increase of sucrose intake percentage. The anti-depressive-like mechanisms of Rg1 involved the activation of cAMP signal transduction pathways induced by PDE4,and the increase of androgens level as well as the promotion of the synaptogenesis. Conclusion:Ginsenoside Rg1 has robust antidepressant-like effects in acute and chronic models of depression,and the underlying mechanisms could involve regulating neurotransmitter release,reducing glucocorticoid levels and increasing the expression of neurotrophic factors as well as enhancing synaptic plasticity.%目的:观察人参皂苷Rg1的抗抑郁作用,探讨其抗抑郁机制。方法:采用小鼠悬尾实验(tail suspension test,TST)和强迫游泳实验(forced swim test,FST)建立急性应激模型,选择大鼠慢性温和不可预见性应激(chronic unpredictable mild stress,CUMS)的方法建立长期抑郁模型。同时给予人参皂苷Rg1(5,10,20 mg·kg-1·d-1)和度洛西汀(10 mg·kg-1·d-1),观察Rg1的抗抑郁作用。结果:在急性应激实验中,Rg1三个剂量组(5,10,20 mg·kg-1)均能够显著减少动物的不动时间。慢性应激后,采用强迫游泳和糖水消耗实验进行行为学检测,与模型组相比,Rg1三个剂量均能够显著减少大鼠在强迫游泳实验中的

  10. Effect of Ginsenosides on Memory Retention of Rats in Sleep Deprivation%人参皂甙对睡眠剥夺大鼠记忆保持的影响

    杨国愉; 皇甫恩; 苗丹民; 王家同; 李强; 谢小平; 陈足怀; 齐建林


    目的:探讨人参皂甙(Ginsenosides,GS)对睡眠剥夺(sleep deprivation,SD)大鼠记忆保持的影响。方法:用小平台水环境法(Flower Pot)建立大鼠SD模型。选用Sprague-Dawley大鼠24只。根据SD时间的不同,将大鼠随机分为三组:24SD(24小时SD组),48SD(48小时SD组)和72SD(72小时SD组),每组又设实验组和对照组。其中,实验组用GS连续灌胃5天,对照组以同样方式给予等量生理盐水,然后给予不同时间的SD。观察各组SD前后在跳台实验中的行为变化。结果:SD后各组大鼠跳台测试第一次触电潜伏期均下降,触电次数和触电时间均增加。SD前实验组和对照组的第一次触电潜伏期、触电次数和触电时间无显著差别(p>0.05);72SD大鼠的第一次触电潜伏期实验组显著大于对照组(p<0.05),触电次数和触电时间,实验组显著低于对照组(p<0.05);24SD、48SD的第一次触电潜伏期、触电次数和触电时间,实验组和对照组无显著差别。结论:连续口服GS对SD造成的大鼠记忆保持能力受损有明显保护作用。在一定睡眠剥夺时间内,这种保护作用随SD时间的延长而增强。%Objective: To explore the effect of ginsenosides (GS) on the memory retention of rats in sleep deprivation (SD). Methods: SD was induced in male Sprague-Dawlay rats by employing “Flower Pot”technique. According to the time difference of being deprived of sleep, 24 rats were divided into three groups randomly: 24 SD (being deprived of sleep for 24 hours), 48 SD (being deprived of sleep for 48 hours), 72 SD (being deprived of sleep for 72 hours). And every group was also divided into two subgroups: experimental group and control group. Ginsenosides were forced fed to the experimental groups continuously for 5 days, and normal saline in equal volume to the controls, then the rats were being deprived of sleep for different time. Before and after SD immediately, the

  11. Study on mechanism of ginsenoside Rg1-induced human neural stem cells differentiation by genechip%构建芯片技术探讨人参皂苷Rg1促进人神经干细胞分化的机制

    赵香琴; 李英博; 姜英虹; 陈笛; 姜蓉; 王莎莉


    目的:采用基因芯片技术筛选出入参皂苷Rg1促进NSCs分化的主要分子靶点.方法:通过基因芯片技术,观察Rg1诱导人神经干细胞(neural stem cells,NSCs)向神经元分化7d时靶基因表达,通过数据演算筛选出Rg1促进NSCs分化的最主要的靶基因和信号转导途径,然后采用Western blot和免疫组化的方法对其中的ERK信号分子进行验证.结果:在Rg1诱导NSCs分化第7天时,获得差异基因675个,其中显著上调的基因255个,显著下调的基因420个;MAPK(丝裂原活化蛋白激酶)通路中的ERK1/2(细胞外信号调节蛋白激酶)信号分子与NSCs分化直接相关.经Western blot和免疫组化证实,在Rg1诱导NSCs分化中,ERK1/2蛋白明显上调,磷酸化水平也明显增强,此作用能够被PD98059(ERK1/2阻断剂)所阻断,同时PD98059也可以明显阻断NSCs的分化.结论:ERK1/2是人参皂苷Rg1促进NSCs分化的重要分子靶点.基因芯片筛选出的差异表达基因可能为研究Rg1促进NSCs分化的分子机制提供线索.%Objective: The molecular targets of ginsenoside Rg1 -induced neural stem cells ( NSCs ) differentiation were screened by genechip. Method; 7th day following ginsenoside Rg, induced human neural stem cells to neurons the gene expression was observed by genechip. The purpose gene and signal transduction pathways were selected by the data calculations, and then confirmed by western blot and immunohistochemical method. Result; 7th day following Rg,-induced NSCs differentiation, there were about 675 different genes, 255 genes of which were up-regulated and 420 genes down-regulated obviously. Meanwhile the ERK1/2 (extracellular signal-regulated protein kinase) in MAPK ( mitogen-activated protein kinase) pathway was related with the NSCs differentiation. The Western blot and immunohistochemistry detection confirmed that ERK 1/2 protein and its phosphorylation were significantly increased, which can be blocked by PD98059 (ERK1 / 2 inhibitor). In

  12. 人参总皂苷对粘虫体内蛋白质含量及消化酶活性的影响%Effect of total ginsenoside on content of protein and activity of digestive enzyme of Mythimna separata larvae

    谭世强; 张爱华; 许永华; 张连学


    目的:测定人参总皂苷对粘虫Mythimna separata体内蛋白质总含量及消化酶(纤维素酶和α-淀粉酶)活性的影响,探讨人参总皂苷的生态学作用.方法:在室内模拟粘虫的自然生长条件,采用载毒叶碟法饲喂4龄粘虫,通过Folin-酚试剂盒法测定粘虫体内蛋白质总含量,二硝基水杨酸法测定α-淀粉酶活性,滤纸法测定纤维素酶活性.结果:人参总皂苷能够显著降低粘虫体内蛋白质总含量,对粘虫体内消化酶(纤维素酶和α-淀粉酶)活性具有抑制作用,并且差异性显著.处理组蛋白质总含量、纤维素酶和α-淀粉酶活性显著低于对照组,且参总皂苷对α-淀粉酶和纤维素酶活性的抑制率与人参总皂苷浓度呈正相关,即20 g·L-1组>l0g· L-1组>5 g·L-1组.结论:人参总皂苷对粘虫体内蛋白质含量和消化酶活性的抑制,可能是引起粘虫表现拒食和生长发育不良的重要原因之一.%Objective:This study aims to reveal the effect of total ginsenoside on the protein content and digestive enzyme activities of 4th-instar Mythimna separata larvae,including α-amylase and cellulose,and explore the ecological function of total ginsenoside.Method:While simulating natural growing condition indoors,4th-instar M.separata larvae were fed by poison leaf disk method.The protein content was tested by Lowry Protein Assay Kit method,the activity of α-amylase was measured by dinitrosalicylic acid test,and the activity of cellulase was determined by the filter paper method.Result:The total ginsenoside could reduce the content of protein of 4th-instar M.separata larvae significantly,and the activity of digestive enzyme,including α-amylase and cellulase.The protein content,α-amylase and cellulase activity of treatments were obviously lower than that of the control.Inhibition ratio of α-amylase and cellulase activity was positively correlated with total ginsenoside concentration:i.e.20 g · L-1 > 10 g · L-1 >5

  13. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    刘丽琴; 罗艳; 张瑞睿; 郭建友


    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  14. A combination of four effective components derived from Sheng-mai san attenuates hydrogen peroxide-induced injury in PC12 cells through inhibiting Akt and MAPK signaling pathways.

    Cao, Guo-Sheng; Li, Shao-Xia; Wang, Yan; Xu, Ying-Qiong; Lv, Yan-Ni; Kou, Jun-Ping; Yu, Bo-Yang


    The present study was designed to investigate whether a combination of four effective components derived from Sheng-mai san (SMXZF; ginsenoside Rb1: ginsenoside Rg1: DT-13: Schizandrol A as 6 : 9 : 4 : 5) could attenuate hydrogen peroxide (H2O2)-induced injury in PC12 cells, focusing on the Akt and MAPK pathways . The PC12 cells were exposed to H2O2 (400 μmol·L(-1)) for 1 h in the presence or absence of SMXZF pre-treatment for 24 h. Cell viability was measured by MTT assay. The efflux of lactate dehydrogenase (LDH), the intracellular content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), and caspase-3 were also determined. Cell apoptosis was measured by Hoechst 33342 staining and Annexin V-FITC/PI staining method. The expression of Bcl-2, Bax, cleaved caspase-3, Akt, and MAPKs were detected by Western blotting analyses. SMXZF pretreatment significantly increased the cell viability and SOD activity and improved the cell morphological changes, while reduced the levels of LDH and MDA at the concentrations of 0.1, 1 and 10 μg·mL(-1). SMXZF also inhibited H2O2-induced apoptosis in PC12 cells. Moreover, SMXZF reduced the activity of caspase-3, up-regulated the protein ratio of Bcl-2 and Bax and inhibited the expression of cleaved caspase-3, p-Akt, p-p38, p-JNK and p-ERK1/2 in H2O2-induced PC12 cells. Co-incubation of Akt inhibitor or p38 inhibitor partly attenuated the protection of SMXZF against H2O2-injured PC12 cells. In conclusion, our findings suggested that SMXZF attenuated H2O2-induced injury in PC12 cells by inhibiting Akt and MAPKs signaling pathways, which might shed insights on its neuroprotective mechanism.

  15. Inhibitory Effect of Triterpenoids from Panax ginseng on Coagulation Factor X

    Lingxin Xiong


    Full Text Available Enzymes involved in the coagulation process have received great attention as potential targets for the development of oral anti-coagulants. Among these enzymes, coagulation factor Xa (FXa has remained the center of attention in the last decade. In this study, 16 ginsenosides and two sapogenins were isolated, identified and quantified. To determine the inhibitory potential on FXa, the chromogenic substrates method was used. The assay suggested that compounds 5, 13 and 18 were mainly responsible for the anti-coagulant effect. Furthermore, these three compounds also possessed high thrombin selectivity in the thrombin inhibition assay. Furthermore, Glide XP from Schrödinger was employed for molecular docking to clarify the interaction between the bioactive compounds and FXa. Therefore, the chemical and biological results indicate that compounds 5 (ginsenoside Rg2, 13 (ginsenoside Rg3 and 18 (protopanaxtriol, PPT are potential natural inhibitors against FXa.

  16. Research on the Transformation of Ginsenoside Rg1 by Intestinal Flora%肠内菌群对人参皂苷Rg1的代谢转化作用的研究

    王毅; 刘铁汉; 王巍; 王本祥


    Objective:The decomposition of Ginsenoside Rg1 (Rg1) byintestinal bacteria in rats or human was investigated both in vitro and in vivo. Method: The decompositions were investigated by means of thin-layer chromatography and Electron spurt ion mass.Result:It was found that Rg1 was converted into two metabolites [Rh1 and 20(S)-protopanaxatriol(20S-Ppt)]by human intestinal bacteria in vitro, while three compounds [Rh1, F1, and 20(S)-Ppt] were detected in rat intestinal bacteria metabolism in vitro and in vivo. Conclusion:The decomposition and/or metabolism of Rg1 in rat and human digestive tract was confirmed. The mode of metabolism in rat is Rg1→ Rh1 (F1)→Ppt, while in human it is Rg1→Rh1→Ppt.%目的:通过离体和整体实验研究大鼠及人的肠道内细菌对人参皂苷Rg1的代谢作用。方法:用薄层层析及电喷雾质谱检测Rg1的代谢产物。结果:Rg1在大鼠体内被代谢成一对同分异构体(Rh1及F1)及苷元[20(S)Protopanaxatriol,Ppt]。但在人的肠道内,则代谢物为Rh1及苷元。结论:Rg1在人和大鼠肠内菌作用下均被代谢,但沿不同的代谢途径进行代谢。在大鼠体内,代谢模式为:Rg1→Rh1(F1)→Ppt;在人体内,代谢模式为Rg1→Rh1→Ppt。

  17. Determination of Notoginsenoside R1,Ginsenoside Rg1 in Xinkeshu Capsule by HPLC-ELSD%HPLC-ELSD测定心可舒胶囊中三七皂苷R1、人参皂苷Rg1的含量

    黄秋妹; 曹智启; 丁沐淦


    OBJECTIVE To determine the content of notoginsenoside R1, ginsenoside Rg1 in Xinkeshu capsule. METHODS The notoginsenoside R1, ginsenoside Rg1 in Xinkeshu capsule were separated on a COSMOSIL 5C18-PAQ Packed column(250 mm × 4.6 mm, 5μm). The mobile phase was acetonitrile-water(27 : 73) at the flow rate of 1 mL·min-1. The analytes were detected using ELSD. The drift tube temperature was 41 ℃, and gas press was 350 kPa. RESULTS The responses of notoginsenoside R1, ginsenoside Rgl were linear in the ranges of 0.123 2-6.16 ug and 0.327 2-16.36 ug, respectively. The average recoveries were 98.7% and 99.2% with RSD 2.72% and 1.54%, respectively. CONCLUSION The described method is simple and accurate. It can be used for the quality control of Xinkeshu capsule.%目的 建立心可舒胶囊中三七皂苷R1、人参皂苷Pg1的含量测定方法.方法 以COSMOSIL 5C18-PAQ Packed Column(250 mm×4.6 mm,5 μm)为色谱柱,以乙腈-水(27∶73)为流动相,流速为1 mL·min-1,ELSD为检测器,漂移管温度:41℃;雾化器(氮气)压力∶350 kPa.结果 三七皂苷R1、人参皂苷Rg1的线性范围分别为0.1232~6.16,0.3272~16.36μg,r值分别为0.9999,0.9997;回收率分别为98.7%,99.2%,RSD分别为2.72%,1.54%.结论 该方法简便,准确,灵敏度高,重复性好,可作为心可舒胶囊的含量测定方法.

  18. Neutral Loss Ion Mapping Experiment Combined with Precursor Mass List and Dynamic Exclusion for Screening Unstable Malonyl Glucoside Conjugates

    Yang, Min; Zhou, Zhe; Yao, Shuai; Li, Shangrong; Yang, Wenzhi; Jiang, Baohong; Liu, Xuan; Wu, Wanying; Qv, Hua; Guo, De-an


    Malonates are one type of the acylation conjugates and found abundantly in ginseng and soybean. Malonyl conjugates of ginsenosides and isoflavone glycosides were often considered as the characteristic components to evaluate various species and different forms of ginseng and soybean products because of their thermal instability. Another famous isoflavonoid-rich leguminous traditional Chinese medicine (TCM), named Puerarin lobata (Gegen), has also been reported to contain malonyl daidzin and malonyl genistin. However, the conjugates were found to present in very low amount and particularly unstable in the negative ion mode scan using LTQ Orbitrap mass spectrometry with electrospray ionization (ESI). In order to screen and characterize the malonyl conjugates in Gegen, a specific method was designed and developed combining neutral loss ion mapping (NLIM) experiment and precursor mass list (PL) triggered data dependent acquisition (DDA). Along with the activation of dynamic exclusion (DE), the method was proven to be specific and efficient for searching the malonate derivatives from Gegen. Two samples were examined by the established method. A total of 66 compounds were found, and 43 of them were malonates of isoflavone glycoside. Very few compounds were reported previously in Gegen. The results are helpful to understand the constituents of Gegen with more insight. The study not only provided a method for analyzing the malonyl conjugates from complex matrices but also explored a way to trace other low amount components in TCMs.

  19. 人参皂苷Rg1延缓造血干细胞衰老及其相关机制%Mechanism of ginsenoside Rg1 in the delayed senescence of hematopoietic stem cell

    周玥; 杨斌; 姜蓉; 姚欣; 王亚平


    Objective To investigate the underlying mechanism of ginsenoside Rg1 in the regulation of hematopoietic stem cell (HSC) senescence so as to provide the theoretic and experimental foundations for searching the methods of how to delay its senescence. Methods Sca-1 + HSC was isolated by magnetic cell sorting (MACS) and divided into control, aged, Rg1, Rg1 treatment aged and Rg1 delayed aged groups. The cellular changes were observed by senescence-associated β-galactosidase ( SA-β-Gal ) staining. And cell cycle assay and culture of mixed hematopoietic progenitor cell were used to investigate the effect of ginsenoside Rg1 to delay Sca-1 + HSC senescence. The expressions of p16INK4a, p19Arf, p53 and p21Cipl/Wafl mRNA were detected by reverse transcription-polymerase chain reaction ( RT-PCR ). The expressions of p16INK4a, p21Cipl/Wafl , cyclinD1, cyclinE, CDK2 and CDK4 protein were examined by Western blot. Results In the Rg1 treatment and delayed aged groups, the percentage of positive SA-β-Gal-expressing cells was lower than that of the aged group [30. 1% ± 2. 4%, 21.5% ± 2. 8% vs 69. 5% ± 5. 0%]; the number of cells in G1 phase was lower than that of the aged group [81.4% ± 1. 2%, 78.2% ± 1. 4% vs 87. 5% ±4. 0%]; but the number of colony for the mixed hematopoietic progenitor was higher than that of the aged group [(8. 0 ±2. 2)/104 Sca-1 + HSC, (9. 2 ± 1. 8)/104 Sca-1 + HSC vs (3.0 ± 1. 6)/104 Sca-1 +HSC].As compared with the aged group, the expressions of p16INK4a, p19Arf, p53, p21cipl/Wafl mRNA and p16INK4a,p21Cipl/Wafl, cyclinD1 protein were down-regulated (all P < 0. 01 ) while the expressions of CDK4, CDK2and cyclinE protein up-regulated in Rg1 treatment aged and Rg1 delayed aged groups ( all P <0. 01 ). The changes of the Rg1 delayed aged group were significantly marked than those of the Rg1 treatment aged group. Conclusions Rg1 can effectively delay the t-BHP-induced senescence of HSCs. Both p16INK4a-Rb and p19Arf-p53-p21Crp/Wafl may play an

  20. 人参皂甙Rd预处理对大鼠局灶性脑缺血再灌注损伤后多聚ADP核糖聚合物的影响%The effect of Ginsenoside Rd pretreatment on the level of poly (ADP-ribose) polymer after focal ischemia reperfusion injury in rats

    胡耿瑶; 史明; 周林甫; 张云霞; 赵钢


    目的:观察人参皂甙Rd缺血前预给药对大鼠局灶性脑缺血/再灌注损伤后多聚ADP核糖聚合物含量的影响.方法:60只健康雄性Sprague-Dawley大鼠,体重280 ~ 300 g,随机分为假手术组(Sham组)、丙二醇组(Vehicle组)和人参皂甙Rd处理组(Rd组),每组20只.Vehicle组和Rd组大鼠采用MCAO线栓法阻塞大鼠右侧大脑中动脉,2h后拔出栓线达到再灌注目的,建立急性局灶性脑缺血/再灌注模型.Vehicle组和Rd组分别于造模前30 min腹腔注射丙二醇(人参皂甙Rd稀释液)和人参皂甙Rd( 10 mg/kg).Sham组手术操作同前,但线栓未阻塞大脑中动脉.Western Blot和免疫组织化学方法检测大鼠大脑中动脉阻塞4h后多聚ADP核糖聚合物的含量.结果:与Sham组相比,Vehicle组和Rd组缺血侧脑组织PAR聚合物含量增加(P<0.01);与Vehicle组相比,Rd组缺血侧脑组织PAR聚合物含量明显上调(P<0.01).结论:10 mg/kg人参皂甙Rd预处理可能通过.增加PAR聚合物的含量起到脑缺血损伤早期神经保护作用.%Objective: To investigate the effect of Ginsenoside Rd pretreatment on poly (ADP-ribose) (PAR) polymer expression in rats after focal cerebral ischemia. Methods: A total of 60 male Sprague-Dawley rats weighing 280-300 g were randomly divided into sham operation group (Sham group) , propanediol group (Vehicle group) and ginsenoside Rd pretreatment group ( Rd group) , with 20 in each group. The focal cerebral ischemia/reperfusion was induced by intervening a MCAO monofilament from the right external carotid artery into the origin of the middle cerebral artery and removing it after 2 h. In Vehicle group and Rd group, rats were respectively exposed to propanediol and ginsenoside Rd (10 mg/ kg) for 30 min before the occlusion of the right middle cerebral artery. The rats in Sham group were operated the same as propanediol group, but cerebral artery was not blocked. The expression of poly (ADP-ribose) polymer was detected by Westem

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

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


    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.

  2. Ginsenoside Rb1, Rg1 and three extracts of traditional Chinese medicine attenuate ultraviolet B-induced G1 growth arrest in HaCaT cells and dermal fibroblasts involve down-regulating the expression of p16, p21 and p53.

    Wang, Xiao-Yong; Wang, Yun-Gui; Wang, Yan-Fei


    The aims of this study were to confirm whether traditional Chinese medicine ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1), polygonum multiflorum (PM), ginkgo extract (GE) and lycium barbarum polysaccharide (LBP) can attenuate G1 growth arrest of HaCaT cells and dermal fibroblasts induced by 10 subcytotoxic ultraviolet B (UVB) exposures, and to explore the possible mechanism in terms of the expression of cell-cycle regulatory proteins p16, p21 and p53. Ten subcytotoxic exposures to UVB induced G1 growth arrest of HaCaT cells and dermal fibroblasts. Cell-cycle analysis was performed using flow cytometry, and mRNA levels of p16, p21 and p53 were detected by a reverse transcription-polymerase chain reaction (RT-PCR), and protein levels were detected using Western blot analysis. Five types of traditional Chinese medicine attenuated UVB-induced G1 growth arrest. The mRNA and protein levels of p16, p21 and p53 in HaCaT cells and dermal fibroblasts increased after UVB irradiation, but pretreatment with five types of traditional Chinese medicine decreased the expression of p16, p21 and p53. These results indicated that five types of traditional Chinese medicine can attenuate G1 growth arrest of HaCaT cells and dermal fibroblasts induced by UVB exposures, which was caused by down-regulating the expression of cell-cycle regulatory proteins p16, p21 and p53. © 2011 John Wiley & Sons A/S.

  3. 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.

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


    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.

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

    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


    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.

  5. Comparative Study of Enhancing Effect on mRNA Expression of Hematopoietic Growth Factors in Rat Bone Marrow Mesenchymal Stem Cells by Ginseng Polysaccharide and Ginsenoside%人参多糖与人参皂苷诱导大鼠骨髓间充质干细胞造血细胞因子表达的作用比较

    危建安; 程志安; 温建炫; 戴韵峰; 莫嘉强


    目的 了解骨髓多能间充质干细胞(BM-MSC) 主要造血因子mRNA表达水平,比较人参多糖和人参皂苷对BM-MSC造血因子mRNA表达的影响.方法采用Real-time PCR技术,观察人参多糖(20 μg/mL)或人参皂苷(20 μg/mL)作用于大鼠BM-MSC 12、24、36 h时间点造血因子IL4、Csf2、Kitlg、Csf1、IL6、Lif、Csf3、IL11、Epo和IL3等10个基因mRNA相对表达水平.结果 正常大鼠BM-MSC未检测到IL4和Csf2 mRNA表达,以内参基因Gapdh mRNA作参比, Kitlg、Csf1、IL6、Lif、Csf3、IL11、Epo和IL3等mRNA相对表达量依次减弱.Epo和IL3 mRNA表达在人参多糖与人参皂苷作用后各个时间点均无明显影响(P>0.05).人参多糖在12 h和36 h时间点对BM-MSC的Csf1、IL6、Lif、Csf3和IL11等5个造血因子mRNA表达有显著促进作用(P<0.05),在24 h时间点对Csf1、IL6、Lif、Csf3和Kitlg等5个造血因子mRNA表达有显著促进作用(P<0.05).人参皂苷在12、24和36 h时间点对BM-MSC有促进表达的基因分别为1个(Csf3),3个(Csf3、IL6和Lif),5个(Csf3、IL6、Lif、IL11和Kitlg).结论 在药物作用早期人参多糖对BM-MSC造血细胞因子mRNA表达的促进作用强于人参皂苷;随着作用时间延长,人参皂苷的促进作用逐渐增强并超过人参多糖的作用.%Objective To study mRNA expression levels of main hematopoietic growth factors in bone marrow mesenchymal stem cells ( BM-MSC), and to compare effect on mRNA expression levels treated by ginseng polysaccharide and ginsenoside. Methods Relative quantification Real-time polymerase chain reaction (RT-PCR) was used to observe mRNA expression levels of IL4, Csf2, Kitlg, Csf1, IL6, Lif, Csf3, IL11, Epo,and IL3, etc. in rat BM-MSC treated with ginseng polysaccharide (20 μg/mL) or ginsenoside (20 μg/mL) at 12,24, and 36 h. Results IL4 and Csf2 mRNA expressions were not detected. Relative expression of Kitlg, Csf1,IL6, Lif, Csf3, IL11, Epo and IL3 mRNA ranked in an attenuating order when compared with Gapdh

  6. Role of NO in reduction of myocardial ischemia-reperfusion injury by ginsenoside Rb1 preconditioning in diabetic rats%一氧化氮在人参皂甙Rb1预处理减轻糖尿病大鼠心肌缺血再灌注损伤中的作用

    张力; 夏中元; 吴洋; 库玛


    Objective To evaluate the role of by NO in reduction of myocardial ischemia-reperfusion (IR)injury by ginsenoside Rb1 preconditioning in diabetic rats. Methods Forty healthy adult male SD rats weighing 220-280 g were used in this study. Diabetes mellitus was induced by intraperitoneal streptozotocin 65 mg/kg and confirmed by fasting blood glucose > 16.7 mmol/L. The animals were randomly divided into 4 groups ( n = 10each): sham operation group (group S), group IR, ginsenoside Rb1 group (group R) and L-NAME + ginsenoside Rb1 group (group LR). IR was produced by occlusion of the anterior descending branch of left coronary artery (LAD) for 30 min followed by 120 min reperfusion in group IR, R and LR. In group S, LAD was exposed but not occluded. In group LR, L-NAME 10 mg/kg was injected iv 25 min before ischemia. In group R and LR, ginsenoside Rb1 40 mg/kg was injected iv 10 min before ischemia. In group S and IR, eaqual volume of normal saline was injected instead of ginsenoside Rb1. The blood sample was taken from carotid artery at 120 min of reperfusion for determination of serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH). Then the animals were sacrificed and myocadial tissues were obtained for determination of infarct size, endothelial nitric oxide synthase (eNOS) expression, MDA and NO contents, SOD activity and microscopic examination. Results The serum activities of CK and LDH were significantly increased and the myocardial infarct size was enlarged in group IR, R and LR, and eNOS expression was significantly down-regulated, MDA content was increased, and SOD activity and NO content was significantly decreased in group IR and LR compared with group S ( P < 0.05). The serum activities of CK and LDH, and MDA content were significantly decreased, the myocardial infarct size was reduced, the expression of eNOS was up-regulated and the activity of SOD was increased in group R compared with group IR and LR ( P < 0.05). There was no

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  8. Effects of Panax ginseng on Tumor Necrosis Factor-α-Mediated Inflammation: A Mini-Review

    Davy CW Lee


    Full Text Available Panax ginseng is one of the most commonly used Chinese medicines in China, Asia and Western countries. The beneficial effects of ginseng have been attributed to the biological activities of its constituents, the ginsenosides. In this review, we summarize recent publications on the anti-inflammatory effects of ginseng extracts and ginsenosides on cellular responses triggered by different inducers including endotoxin, tumor necrosis factor-alpha (TNF-α, interferon-gamma and other stimuli. Proinflammatory cytokines, chemokines, adhesion molecules and mediators of inflammation including inducible nitric oxide synthase, cyclooxygenase-2 and nitric oxide orchestrate the inflammatory response. Ginseng extracts and ginsenosides including Rb1, Rd, Rg1, Rg3, Rh1, Rh2, Rh3 and Rp1 have been reported to have anti-inflammatory properties in different studies related to inflammation. Ginsenosides inhibit different inducers-activated signaling protein kinases and transcription factor nuclear factor-kappaB leading to decreases in the production of cytokines and mediators of inflammation. The therapeutic potential of ginseng on TNF-α-mediated inflammatory diseases is also discussed. Taken together, this summary provides evidences for the anti-inflammatory effects of ginseng extracts and ginsenosides as well as the underlying mechanisms of their effects on inflammatory diseases.

  9. Cardioprotection by combination of three compounds from ShengMai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission

    Li, Fang; Fan, Xiaoxue; Zhang, Yu; Pang, Lizhi; Ma, Xiaonan; Song, Meijia; Kou, Junping; Yu, Boyang


    GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index. Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3 activity, normalization of Bcl-2/Bax levels and improved mitochondrial function. Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated AMPKα phosphorylation. Interestingly, AMPK activation prevented hypoxia and reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions were significantly attenuated by knockdown of AMPKα. Collectively, these data show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission, thereby providing a rationale for future clinical applications and potential therapeutic strategy for MI/R injury. PMID:27869201

  10. Effects of Zinc Concentration on Growth, Ginsenoside Content and Zinc Content of Panax ginseng by Foliar Application%叶面喷施锌对农田人参锌营养、生长发育及皂苷含量的影响

    杨鹤; 张浩; 郜玉钢; 张连学


    为确定适宜人参Panax ginseng叶面喷施的Zn浓度范围,采用田间试验的方法,研究喷Zn浓度对人参生长、皂苷含量及叶片吸收Zn速率的影响.结果表明,人参叶片可有效吸收叶面供给的无机态Zn2+,并可运至根部.在20~20000 mg/L质量浓度范围内,人参叶片吸收Zn的速率和数量与喷施浓度呈显著正相关(P<0.01,R2>0.9),而且随着喷施浓度的升高,从叶片向根部运输Zn的数量也升高.喷施适宜质量浓度(200和2000 mg/L)Zn2+可显著改善人参的Zn营养状况,促进人参生长和皂苷积累,增强叶片过氧化物酶(POD)和过氧化氢酶(CAT)活性.喷施浓度过高,人参叶片受到伤害,丙二醛(MDA)含量增加,CAT活性降低,但人参根皂苷含量显著升高,可能与环境胁迫刺激次生代谢产物积累有关.适宜人参叶面喷施的Zn质量浓度范围是200~2000 mg/L.%In order to identify appropriate Zn concentration range of foliar spraying for ginseng, effects of zinc spraying concentration on growth, ginsenoside content and zinc absorption efficiency by leaves of ginseng were studied through field experiments. Results showed that ginseng leaves can efficiently uptake Zn2 + of foliar applied, and transformation of Zn from leaves to roots was found. The amount of Zn uptake by leaves had significant (P 0. 9) positive correlation with applied Zn mass concentration range from 20 - 20 000 mg/L. As spraying concentration increased, the amount of zinc transferred from leaves to roots was also enhanced. Increment of fresh mass and ginsenoside content of root were found when appropriate Zn nutrient solution(200 and 2 000 mg/L) was applied, and peroxidases (POD) and catalase (CAT) activities increased when applied rate was 200 mg/L, but spraying 2 000 mg/L Zn2+ led to POD activity increase and CAT activity decrease compared to control. Although malondialdehyde ( MDA) content increased, CAT activity decrease and leaf burn were observed when 2 000 mg/L was

  11. The bioavailability of red ginseng extract fermented by Phellinus linteus.

    Ryu, Jae Sik; Lee, Hyun Jung; Bae, Song Hwan; Kim, Sun Young; Park, Yooheon; Suh, Hyung Joo; Jeong, Yoon Hwa


    For the improvement of ginsenoside bioavailability, the ginsenosides of fermented red ginseng by Phellinus linteus (FRG) were examined with respect to bioavailability and physiological activity. The polyphenol content of FRG (19.14±0.50 mg/g) was significantly higher (p<0.05) compared with that of non-fermented red ginseng (NFRG, 11.31±1.15 mg/g). The antioxidant activities in FRG, such as 2,2'-diphenyl-1-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and ferric reducing antioxidant power, were significantly higher (p<0.05) than those in NFRG. The HPLC analysis results showed that the FRG had a high level of ginsenoside metabolites. The total ginsenoside contents in NFRG and FRG were 41.65±1.53 mg/g and 50.12±1.43 mg/g, respectively. However, FRG had a significantly higher content (33.90±0.97 mg/g) of ginsenoside metabolites (Rg3, Rg5, Rk1, compound K, Rh1, F2, and Rg2) compared with NFRG (14.75±0.46 mg/g). The skin permeability of FRG was higher than that of NFRG using Franz diffusion cell models. In particular, after 3 h, the skin permeability of FRG was significantly higher (p<0.05) than that of NFRG. Using a rat everted intestinal sac model, FRG showed a high transport level compared with NFRG after 1 h. FRG had dramatically improved bioavailability compared with NFRG as indicated by skin permeation and intestinal permeability. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

  12. Effect of ginsenoside-Rg1 on the proliferation of paraurethral fascia fibroblasts derived from women suffering from stress urinary incontinence%人参皂甙Rg1对压力性尿失禁患者尿道旁筋膜成纤维细胞增殖的影响

    吴冬梅; 宋岩峰


    Objective To investigate the effect of ginsenoside-Rgl on paraurethral fascia fibroblastsmultiplication and the expression of proliferation cell nuclear antigen (PCNA) of stress urinary incontinence(SUI) women in vitro. Methods Specimens of human paraurethral fascia were obtained from 4 SUI womenduring tension-free vaginal tape (TVT) or tension-free vaginal tape-obturator (TVT-O) procedure.Fibroblasts were isolated and cultured by outgrowth technique. After reaching confluency fibroblasts weresubcultured every 5 days and cells after passage number 3 to 5 were used for assessment. The paraurethralfascia fibroblasts were treated with ginsenoside-Rgl at different concentrations (5, 10, 20 μmol/L) andfibroblnsts without Rgl were used as controL The multiplication conditions of paraurethral fascia fibroblastswere respectively detected by methyl thiazolyl tetrazolium (MTr) assay and the expression of PCNA byhistochemistry. Results ( 1 ) Compared with the control group, the growth rate of cells treated with differentconcentrations of Rgl after 72h [ (29±5 )%, (40±5 )%, (26±4)% respectively ] was significantly higher(P0.05).(2)同一浓度人参皂甙Rg1组培养48 h后的细胞增殖率与培养24 h时比较,差异均有统计学意义(P<0.01);培养72 h后与培养48 h时比较,差异也均有统计学意义(P<0.01).(3)5 μmoL/L组、10 μmol/L组及20 μmol/L组培养48 h后的PCNA阳性率分别为49.24%、83.48%和54.50%,分别与对照组(28.77%)比较,差异均有统计学意义(P<0.01);10 μmol/L组与5μmol/L组、20 μmol/L组分别比较,差异也有统计学意义(P<0.01).结论 人参皂甙Rg1可促进体外培养的SUI患者尿道旁筋膜成纤维细胞的增殖.

  13. Actions of ginsenosides on sleep architecture and cortical electroencephalogram power spectrum in rats%人参皂甙对大鼠睡眠结构和皮质脑电功率谱的作用

    洪芬芳; 贺长生; 涂桂林; 杨树龙


    Objective To study the effects of ginsenosides (GS) on spontaneous sleep architecture and Cortical EEG power spectrum. Methods 24 adult SD rats were randomly divided into the control, GS 10 and 100mg/kg groups ( n = 8). Rats were instrumented with sleep-wake recording electrodes. After recovery from surgical operation,rats were orally administered GS 10 and 100mg/kg or distilled water once per day for 6 days. On GS administration day 1 and 6,Polygraphic signs of undisturbed sleep-wake activities were recorded for 12 h after GS administration. Results On GS administration day 1 ,only 100mg/kg GS increased significantly total sleep and the non-rapid eye movement ( NREM ) sleep but decreased wakefulness [(9.40 ± 0.88 ) h, ( 8.00 ± 1. 21 ) h,(2.46 ±0.81)h s (7.55 ±1.59)h,(6.36±1.54)h,(4.38 ±1.62)h,(P<0.01, P<0.05, P<0.01),respectively] ;Low and high dose GS enhanced δ-wave power of NREM sleep and wakefulness (P< 0.05 ) but reduced θ-wave power of wakefulness (P<0.01) and-wave power during NREM, REM sleep and wakefulness (P < 0.01 ),moreover,Low and high dose GS lowered θ-wave power of REM and NREM stage(P<0.05 ) ,respectively. After 6days of GS administration, Low and high dose GS increased markedly total sleep(P<0.05 ) and NREM sleep(P<0.05 ) but decreased wakefulness (P <0.05 ) and sleep-wake cycles (P < 0.05, P < 0.01 ); moreover, Low and high dose GS enhanced δ-wave power during NREM sleep and wakefulness (P < 0. 05 ) but reduced θ-wave power of wakefulness(P < 0.05 ) and -wave power during NREM, NEM sleep and wakefulness (P < 0. 05 ), 10mg/kg GS also lowered θ-wave power of NREM sleep (P<0.01). Conclusion These results demonstrate that GS can regulate spontaneous sleep architecture in time dependent manner,as well as cortical EEG power spectrum in rats.%目的 研究人参皂甙(GS)调节自发睡眠结构和皮质脑电功率谱的作用.方法 SD大鼠24只随机分为对照、低(GS 10mg/kg)和高剂量(100mg

  14. Birth control pills - combination

    ... page: // Birth control pills - combination To use the sharing features on ... both progestin and estrogen. What Are Combination Birth Control Pills? Birth control pills help keep you from ...

  15. Severe Combined Immunodeficiency (SCID)

    ... with facebook share with twitter share with linkedin Severe Combined Immunodeficiency (SCID) SCID is a group of rare disorders ... life-saving treatments. Why Is the Study of Severe Combined Immunodeficiency (SCID) a Priority for NIAID? SCID is a ...

  16. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

    Ike dela Peña


    Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.

  17. COMBINE 2 seminar

    Sørensen, Lars Schiøtt; Jacobsen, Kim


    A seminar about the COMBINE project was described. Further, the project was described in generel, i.e. the COMBINE´s data model (IDM), the data exchange system (DES) and the different I/O-systems included in COMBINE 2......A seminar about the COMBINE project was described. Further, the project was described in generel, i.e. the COMBINE´s data model (IDM), the data exchange system (DES) and the different I/O-systems included in COMBINE 2...

  18. The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

    Li, Fang; Zhang, Yu; Zeng, Donglin; Xia, Yu; Fan, Xiaoxue; Tan, Yisha; Kou, Junping; Yu, Boyang


    GRS is a drug combination of three components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula Sheng MaiSan, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study illuminates its underlying mechanisms against myocardial ischemic diseases based on the combined methods of bioinformatic prediction and experimental verification. A protein database was established through constructing the drug-protein network. And the target-pathway interaction network clustered the potential signaling pathways and targets of GRS in treatment of myocardial ischemic diseases. Several target proteins, such as NFKB1, STAT3 and MAPK14, were identified as the candidate key proteins, and MAPKs and JAK-STAT signaling pathway were suggested as the most related pathways, which were in accordance with the gene ontology analysis. Then, the predictive results were further validated and we found that GRS treatment alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury via suppression of MDA levels and ROS generation, and potential mechanisms might related to the suppression of activation of MAPKs and JAK2-STAT3 signaling pathways. Conclusively, our results offer the evidence that GRS attenuates myocardial ischemia injury via regulating oxidative stress and MAPKs and JAK2-STAT3 signaling pathways, which supplied some new insights for its prevention and treatment of myocardial ischemia diseases.

  19. Effects of ginsenoside Rg2 on hemodynamics and oxygen metabolism in narco-canine with acute cardiogenic shock%人参皂苷Rg2对麻醉犬急性心源性休克血流动力学和氧代谢的影响

    吕文伟; 刘洁; 赵丽娟; 田建明; 李龙云; 杨世杰


    目的:观察人参皂苷Rg2(ginsenoside Rg2)对犬急性心源性休克血流动力学和氧代谢的影响.方法:结扎犬冠状动脉左前降支(LAD)复制心源性休克模型,观察人参皂苷Rg2(2和1 mg·kg-1)对麻醉犬血流动力学和氧代谢各项指标的作用.结果:人参皂苷Rg2可升高平均血压(MBP)、左室内压(LVSP)、±dp/dtmax和心排出量(CO),降低心肌耗氧指数、心肌氧摄取率.结论:人参皂苷Rg2对犬急性心源性休克具有一定的治疗作用.

  20. Mechanism of ginsenoside Rg1 regulating the activity of β secretase in N2a/APP695 cells%人参皂苷Rg1调节N2a/APP695细胞β分泌酶活性的可能机制

    陈丽敏; 林楠; 张静; 朱元贵; 陈晓春


    Objective To explore whether or not ginsenoside Rg1 can modify the metabolism of amyloid precursor protein (APP) and the generation of amyloid beta (Aβ) by nuclear factor-kappa B (NF-κB).Methods N2a/APP695 cells,a mutated APP-overexpressing neuronal cell line,was used to mimic the APP metabolism and Aβ generation in vitro.The BACE1 mRNA and protein levels were detected by RTPCR (reverse transcription-polymerase chain reaction) and Western blot respectively.Then the expression levels and subcellular localization of NF-κB were detected by Western blot and confocal laser scanning microscope respectively.Results The treatment of ginsenoside Rg1 at a dose of 2.5 μmol/L decreased the levels of Aβ1-40 and Aβ1-42 ( 13.3 ± 4.3 ) ng/ml vs ( 12.0 ± 5.4 ) ng/ml in N2a/APP695 cells,decreased the protein level of BACE1 ( BACE1/β -actin 0.26 ± 0.05),increased the protein level of NF-κB p65 (p-p65/p65 0.93 ± 0.02) and resulted in the translocation of NF-κB from cytoplasm to nucleus.Quinazoline inhibited the activation of NF-κB with a reduction of p-p65 and p-p65/p65 in N2a/APP695 cells and increased the BACE1 protein level.And the treatment of ginsenoside Rg1 showed similar changes in N2a/APP695 cells when compared with the treatment of quinazoline alone.Conclusion Ginsenoside Rg1 may modify the metabolism of APP by enhancing the nuclear binding of NF-κB to BACE1 promoter and inhibiting the transcription and translation of BACE1.%目的 观察人参皂苷Rg1能否通过核蛋白因子κB(NF-κB)影响N2a/APP695细胞β淀粉样肽(Aβ)的生成和代谢,从源头上缓解和(或)减轻阿尔茨海默病(AD)病人的神经病理改变.方法 利用稳定表达突变型APP695的N2a细胞(N2a/APP695),通过RT-PCR、蛋白免疫印迹、激光共聚焦显微镜等方法检测人参皂苷Rg1对β分泌酶活性及上游转录因子NF-κB活性的影响.结果 2.5 mol/L人参皂苷Rg1作用6~12 h后,N2a/APP695细胞外液Aβ1-40和Aβ1-42水平较Rg1作用前均有不

  1. Combination of HPLC-MS and QAMS as a new analytical approach for determination of saponins in ginseng containing products.

    Stavrianidi, Andrey; Stekolshchikova, Elena; Porotova, Anna; Rodin, Igor; Shpigun, Oleg


    Conventional liquid chromatographic methods coupled with ultraviolet detection with low-wavelength range are lacking selectivity and sensitivity to determine both polar and less polar ginsenosides. Also the lack of standard substances for such quality control methods is leading to development of the approaches using single standard for quantitative analysis of multi-component system (QAMS). The objective of present study was to establish and compare for the first time liquid chromatography-ultraviolet detection and liquid chromatography-mass spectrometry QAMS methods for the simultaneous determination of protopanaxatriol-type and protopanaxadiol-type ginsenosides in a variety of ginseng products. Sixteen polar and less polar ginsenosides were separated on a reversed-phase C18-column (150mm×2.0mm, 2.2μm) with a mobile phase consisting of 0.1% formic acid in water and acetonitrile. Components were then detected by means of ultraviolet and mass spectrometry detection. Characteristic sapogenin fragmentation signals with m/z 423 and 425 for two major groups of ginseng saponins allowed their simultaneous determination in a single chromatographic run, while the use of ultraviolet detection tends to give overvalued results. Structural correlation between the relative response factors and saponin structure was demonstrated. The method was linear (R(2) >0.999) and sensitive (LODs, 0.01-0.03mg/mL) within the concentration range tested. Concentrations of individual ginsenosides and several quality control parameters were determined in ginseng root extracts and commercial ginseng products of different types (root slices, tablets and tea samples), and results showed that ginsenoside content can be successfully measured by means of QAMS approach.

  2. Embodied Conceptual Combination

    Dermot eLynott


    Full Text Available Conceptual combination research investigates the processes involved in creating new meaning from old referents. It is therefore essential that embodied theories of cognition are able to explain this constructive ability and predict the resultant behaviour. However, by failing to take an embodied or grounded view of the conceptual system, existing theories of conceptual combination cannot account for the role of perceptual, motor and affective information in conceptual combination. In the present paper, we propose the Embodied Conceptual Combination (ECCo model to address this oversight. In ECCo, conceptual combination is the result of the interaction of the linguistic and simulation systems, such that linguistic distributional information guides or facilitates the combination process, but the new concept is fundamentally a situated, simulated entity. So, for example, a cactus beetle is represented as a multimodal simulation that includes visual (e.g., the shiny appearance of a beetle and haptic (e.g., the prickliness of the cactus information, all situated in the broader location of a desert environment under a hot sun, and with (at least for some people an element of creepy-crawly revulsion. The ECCo theory differentiates interpretations according to whether the constituent concepts are destructively, or nondestructively, combined in the situated simulation. We compare ECCo to other theories of conceptual combination, and discuss how it accounts for classic effects in the literature.

  3. Effective Nutritional Supplement Combinations

    Cooke, Matt; Cribb, Paul J.

    Few supplement combinations that are marketed to athletes are supported by scientific evidence of their effectiveness. Quite often, under the rigor of scientific investigation, the patented combination fails to provide any greater benefit than a group given the active (generic) ingredient. The focus of this chapter is supplement combinations and dosing strategies that are effective at promoting an acute physiological response that may improve/enhance exercise performance or influence chronic adaptations desired from training. In recent years, there has been a particular focus on two nutritional ergogenic aids—creatine monohydrate and protein/amino acids—in combination with specific nutrients in an effort to augment or add to their already established independent ergogenic effects. These combinations and others are discussed in this chapter.

  4. Resonant High Power Combiners

    Langlois, Michel; Peillex-Delphe, Guy


    Particle accelerators need radio frequency sources. Above 300 MHz, the amplifiers mostly used high power klystrons developed for this sole purpose. As for military equipment, users are drawn to buy "off the shelf" components rather than dedicated devices. IOTs have replaced most klystrons in TV transmitters and find their way in particle accelerators. They are less bulky, easier to replace, more efficient at reduced power. They are also far less powerful. What is the benefit of very compact sources if huge 3 dB couplers are needed to combine the power? To alleviate this drawback, we investigated a resonant combiner, operating in TM010 mode, able to combine 3 to 5 IOTs. Our IOTs being able to deliver 80 kW C.W. apiece, combined power would reach 400 kW minus the minor insertion loss. Values for matching and insertion loss are given. The behavior of the system in case of IOT failure is analyzed.

  5. Qualitative and quantitative analysis on aroma characteristics of ginseng at different ages using E-nose and GC-MS combined with chemometrics.

    Cui, Shaoqing; Wang, Jun; Yang, Liangcheng; Wu, Jianfeng; Wang, Xinlei


    Aroma profiles of ginseng samples at different ages were investigated using electronic nose (E-nose) and GC-MS techniques combined with chemometrics analysis. The bioactive ginsenoside and volatile oil content increased with age. E-nose performed well in the qualitative analyses. Both Principal Component Analysis (PCA) and Discriminant Functions Analysis (DFA) performed well when used to analyze ginseng samples, with the first two principal components (PCs) explaining 85.51% and the first two factors explaining 95.51% of the variations. Hierarchical Cluster Analysis (HCA) successfully clustered the different types of ginsengs into four groups. A total of 91 volatile constituents were identified. 50 of them were calculated and compared using GC-MS. The main fragrance ingredients were terpenes and alcohols, followed by aromatics and ester. The changes in terpenes, alcohols, aromatics, esters, and acids during the growth year once again confirmed the dominant role of terpenes. The Partial Least Squares (PLS) loading plot of gas sensors and aroma ingredients indicated that particular sensors were closely related to terpenes. The scores plot indicated that terpenes and its corresponding sensors contributed the most in grouping. As regards to quantitative analyze, 7 constituent of terpenes could be accurately explained and predicted by using gas sensors in PLS models. In predicting ginseng age using Back Propagation-Artificial Neural Networks (BP-ANN), E-nose data was found to predict more accurately than GC-MS data. E-nose measurement may be a potential method for determining ginseng age. The combination of GC-MS can help explain the hidden correlation between sensors and fragrance ingredients from two different viewpoints. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Effects of ginsenoside Rg1 on c-fos gene expression and cAMP levels in rat hippocampus%人参皂苷Rg1对大鼠海马c-fos基因表达和cAMP含量的影响

    刘忞; 张均田


    To study the mechanisms of Rg1 antiaging and nootropic function. METHODS: Using Northern and Western blot analyses, the levels of cfos mRNA and fos protein were determined in the hippocampus of young and old rats treated with or without ginsenoside Rg1. RESULTS: The expression of c-fos gene and protein was decreased in the hippocampus of aged rats, but dose-dependently increased in young and aged rats after the administration of Rg1. Furthermore, Rg1 increased the level of cAMP in the hippocampus of both young and old rats. CONCLUSION: The changes at the genomic and protein levels, arisen from the increase of cAMP, provide an explanation of the mechanisms of Rg1 nootropic and antiaging function.%探讨Rg1对神经系统作用的机制.方法:采用Northern和Western印迹分析法,检测了Rg1处理前后大鼠海马组织的c-fos基因和蛋白的表达.结果:老年鼠c-fos基因和蛋白的表达明显低于青年鼠,但给Rg1后老年鼠和青年鼠均呈现显著性增强效应.此外,Rg1还明显增加青年鼠和老年鼠海马组织的cAMP含量.结论:Rg1升高cAMP水平及促进c-fos基因和蛋白的表达有助于阐明其促智和抗衰老作用的机制.

  7. 人参皂苷Rg1对lactacystin诱导SH-SY5Y细胞损伤的保护作用%Protective effects of ginsenoside Rg1 on lactacystin-induced cell death in SH-SY5Y cells

    陈瑛; 梁海燕; 李海军


    目的:探讨人参皂苷Rg1(ginsenoside Rg1,Rg1)对lactacystin所致SH-SY5Y细胞损伤的保护作用及可能机制.方法:实验分正常对照组、lactacystin组、lactacystin和Rg1联合处理组(0.1,1,10 μmol/L),分别用CCK-8检测细胞活力,免疫荧光法、流式细胞术测定法检测二价金属离子转运蛋白1 (divalent metal transporter 1,DMT1)表达情况,calcein-AM荧光检测细胞的摄铁能力,JC-1染色检测细胞线粒体膜电位,荧光探针carboxy-H2DCFDA检测胞内氧化应激水平.结果:与lactacystin组相比,lactacystin和Rg1联合处理组的细胞活力显著增加,细胞DMT1表达减少,细胞摄铁能力下降,线粒体膜电位增加,胞内氧化应激水平降低,差异均有统计学意义(P<0.05).结论:Rgl对lactacystin诱导损伤的SHSY5Y细胞具有一定的神经保护作用,其作用机制可能与下调DMT1介导的细胞摄铁能力,稳定线粒体膜电位,降低氧化应激反应有关.

  8. 过度运动对大鼠肾损伤敏感标志物的影响及人参总皂苷的干预研究%Excessive-exercise Induced Kidney Injury Sensitive Biomarker Change in Rats and the Effects of Ginsenoside

    王会玲; 李俊彦; 许烨; 张金元


    Objective : We investigate the changes of some sensitive hiomarkers in rats undertaking excessive - exercise, and the effects of Ginsenoside ( GS ) which was a product from a plant herb - Ginsen.Methods : Male Sprague - Dawley rats divided into five groups: control group( CTL ), over - exercise group( two sub - group : M2 and M24 ); Ginsenoside group ( two sub - group: G2 and C24 ).The animal model of excessive - exercise induced AKI was established by exhaustively running on the treadmill according protocol.We administrated with GS ( 100g/kg· d ) intragastric ahead the G2 and G24 rats took exhausting running.We collected urine 2h or 24h after excessive - exercise , and measured their albumin, neutrophil gelatinase - associated lipocalin ( NGAL ) and N - acetyl - d - glucosaminidase( NAG ).We collected blood to test the renal function ( BUN, serum creatinine ), superoxide dismutase ( SOD ) and malondialdehyde ( MDA ).The hlood and kidney Angiotensin Ⅱ ( Ang Ⅱ ) were measured by radioimmunoassay ( RIA ).We observed the renal pathology by Microscope after HE staining.Results : Over - exercise induced the urine albumin and NAG excretion increasing, the BUN and blood NGAL increased too.Compared with the blood and kidney Ang Ⅱ increased, the serum and kidney tissue SOD decreased, but MDA increased at the same time.We ohserved a part of the renal tuhular epithelial cells swelling and ablating.After treatment by GS, the excretion of urine albumin and NAC reduced.BUN and NGAL in hlood decreased.GS decreased the kidney Angiotensin Ⅱ and MDA level, but increased the SOD level in blood or kidney tissue, thus, ameliorate the tubular injury.Conclusion : Ginsenoside protect the tuhular injury induced by the over - exercise in rats, which mechanism might reduce the Ang Ⅱ and anti - oxidative stress in the kidney.%目的:探讨过度运动对大鼠肾组织及肾损伤敏感标志物的影响,及人参总皂苷的防治作用.方法:SD大鼠随机分为对

  9. 人参皂苷Rg1对非酒精性脂肪肝病大鼠脂肪酸β-氧化的改善作用研究%Study on the improvement effect of Ginsenoside Rg1 on nonalcoholic fatty liver phenotype by regulation ofβ-oxidation

    廖文云; 徐丹


    Objective To investigate the role of Ginsenosides Rg1 for non-alcoholic fatty liver disease by β-oxidation.Methods 120 SD rats were randomly divided into control group(CON),model group(HFD),Ginsenosides Rg1low,medium and high dose group (GLD ,GMD and GHD) ,sodium deoxycholate of bear treatment group (PDT ) ,20 rats in each group .After 4 and 8 weeks treatment ,the rats were sacrificed ,Pathology of hepatic tissue was tested by HE staining ,and liver function ,lipid levels ,hepatic ac-yl-CoA synthetase (CoASH1) ,carnitine acyl transferase I(CATI) and acetyl coenzyme A oxidase 1 (ACOX1) mRNA and protein expression were tested .Results After 4 weeks of treatment ,the liver function tested by HE staining only improved in GHD group . After 8 weeks ,there′s a little fat particles aggregation in PDT and GLD groups ,but no infiltration of fat in GMD and GHD groups . After 4 weeks ,AST ,ALT and AKP ,CHOL ,TG and LDL-C levels were significantly lower in PDT ,GLD ,GMD and GHD groups compared with HFD group (P<0 .05) ,which were significant declined 8 weeks later .After 4 weeks ,HDL-C level in four groups was significantly increased ,then reached the normal level 8 weeks later .After 4 weeks ,CoASH1 ,CATI and ACOX1 expressions in hepatic tissue of four groups were significantly increased ,which improved more obviously after eight weeks .Conclusion Ginsen-oside Rg1 can improves nonalcoholic fatty liver phenotype by regulation of β-oxidation .%目的:研究人参皂苷Rg1对非酒精性脂肪肝病(NAFLD)大鼠β-氧化的作用。方法将120只SD大鼠分为对照组(CON组)、模型组(HFD组)及人参皂苷Rg1低、中、高剂量组(GLD、GMD、GHD组)和熊去氧胆酸钠治疗组(PDT组),每组20只,分别于治疗4、8周后处死大鼠各半,肝脏切片 HE染色,检测肝功能、血脂、肝脏脂酰CoA合成酶1(CoASH1)、脂酰肉毒碱转移酶I(CATI)及酰基辅酶A氧化酶1(ACOX1) mRNA和蛋白表达。结果治疗4

  10. Tissue Distribution of Ginsenoside Re in Rats by Rapid Resolution Liquid Chromatography Coupled With Quadrupole-Time-of Flight Mass Spectrometry%高分离快速液相色谱-四极杆飞行时间质谱法检测人参皂苷 Re 在大鼠体内的分布

    王恩鹏; 斋藤哲男; 孙岩; 陈长宝; 刘淑莹


    A method of rapid resolution liquid chromatography coupled with quadrupole-time-of flight mass spectrometry (RRLC-Q-TOF MS)was established to investigate the distribution of ginsenoside Re (G-Re)in rat various tissues (heart,liver,spleen,lung,kidney and brarin)after a single administration by intravenous injection.The biological samples were prepared by protein precipitation. Chromatographic separations was achieved on a Supelco Ascentis® Express C18 column (50 mm×3.0 mm×2.7 μm)with a mobile phase consisting of solvent A (0.1% formic acid in water)and solvent B (ace-tonitrile)at a flow rate of 0.3 mL/min.Gradient elution was as follows:0-15 min, 20%-40%B;15-20 min,40%-50%B;20-22 min,50%-100%B.Ginsenoside Rc (G-Rc) was used as internal standard (IS).All mass spectrometric experiments were performed on RRLC-Q-TOF MS equipped with an electrospray ionization (ESI)source operated in negative mode.The result shows that the calibration curve is linear in the range of 10-20 000 μg/L for tissue homogenates (r>0.99),the lower limit of detection (LLOD) is 3 μg/L,and the lower limit of quantification (LLOQ)is 10 μg/L.The accuracy,in-tra-day,inter-day precision and recovery ratio can meet the requirements of the biologi-cal samples analysis.As a result,G-Re could be widely distributed in organizations with 20 mg/kg solution by caudal vein injection,which could be detected in different organs and distributed mainly in the lung,spleen,kidney and heart.Lung had a highest affinity to G-Re,which was not easy to pass through the blood-brain barrier and hard to accumulate.This method is simple,sensitive and rapid,which is suitable for analyzing ginsenosides Re in vivo.%建立了高分离快速液相色谱-四极杆飞行时间质谱(RRLC-Q-TOF MS)法检测大鼠尾静脉注射人参皂苷 Re(G-Re)后,不同组织(心、肝、脾、肺、肾、脑)中 G-Re 的分布情况。样本经蛋白沉淀处理, Supelco Ascentis® Express C18色谱柱(50 mm×3.0 mm×2.7

  11. Severe Combined Immunodeficiency Disorders.

    Chinn, Ivan K; Shearer, William T


    Severe combined immunodeficiency disorders represent pediatric emergencies due to absence of adaptive immune responses to infections. The conditions result from either intrinsic defects in T-cell development (ie, severe combined immunodeficiency disease [SCID]) or congenital athymia (eg, complete DiGeorge anomaly). Hematopoietic stem cell transplant provides the only clinically approved cure for SCID, although gene therapy research trials are showing significant promise. For greatest survival, patients should undergo transplant before 3.5 months of age and before the onset of infections. Newborn screening programs have yielded successful early identification and treatment of infants with SCID and congenital athymia in the United States.

  12. Combinators for Paraconsistent Attitudes

    Villadsen, Jørgen


    In order to analyse the semantics of natural language sentences a translation into a partial type logic using lexical and logical combinators is presented. The sentences cover a fragment of English with propositional attitudes like knowledge, belief and assertion. A combinator is a closed term...... used for embedded sentences expressing propositional attitudes, thereby allowing for inconsistency without explosion (also called paraconsistency), and is based on a few key equalities for the connectives giving four truth values (truth, falsehood, and undefinedness with negative and positive polarity...

  13. Lefunomide in combination therapy

    Kalden, J.R.; Smolen, J.S.; Emery, P.; Riel, P.L.C.M. van; Dougados, M.; Strand, C.V.; Breedveld, F.C.


    In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficaci

  14. Combination treatment for hypertension

    On average, one in four adults has hypertension.1 This figure is higher in certain regions of the world, .... doses favours the development of diabetes and should be ... New and old evidence strongly supports combination treatment .... cardiovascular death, stroke and myocardial infarction, cognitive function and dementia.

  15. Coherently combining antennas

    Dybdal, Robert B. (Inventor); Curry, Samuel J. (Inventor)


    An apparatus includes antenna elements configured to receive a signal including pseudo-random code, and electronics configured to use the pseudo-random code to determine time delays of signals incident upon the antenna elements and to compensate the signals to coherently combine the antenna elements.

  16. Why combine logics?

    Blackburn, P.; Rijke, M. de


    Combining logics has become a rapidly expanding enterprise that is inspired mainly by concerns about modularity and the wish to join together tailored made logical tools into more powerful but still manageable ones. A natural question is whether it offers anything new over and above existing standar

  17. Combination Chemotherapy for Influenza

    Robert G. Webster


    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  18. Combined XRD and XAS

    Ehrlich, S.N.; Hanson, J.C.; Lopez Camara, A.; Barrio, L.; Estrella, M.; Zhou, G.; Si, R.; Khalid, S. & Wang, Q.


    X-ray diffraction (XRD) and X-ray absorption fine structure (XAFS) are complementary techniques for investigating the structure of materials. XRD probes long range order and XAFS probes short range order. We have combined the two techniques at one synchrotron beamline, X18A at the NSLS, allowing samples to be studied in a single experiment. This beamline will allow for coordinated measurements of local and long range structural changes in chemical transformations and phase transitions using both techniques.

  19. Combined XRD and XAS

    Ehrlich, S.N., E-mail: [NSLS, Brookhaven National Laboratory, Upton, NY 11973 (United States); Hanson, J.C.; Lopez Camara, A.; Barrio, L.; Estrella, M.; Zhou, G.; Si, R. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Khalid, S. [NSLS, Brookhaven National Laboratory, Upton, NY 11973 (United States); Wang, Q. [Synchrotron Catalysis Consortium, University of Delaware, Newark, DE 19716 (United States)


    X-ray diffraction (XRD) and X-ray absorption fine structure (XAFS) are complementary techniques for investigating the structure of materials. XRD probes long range order and XAFS probes short range order. We have combined the two techniques at one synchrotron beamline, X18A at the NSLS, allowing samples to be studied in a single experiment. This beamline will allow for coordinated measurements of local and long range structural changes in chemical transformations and phase transitions using both techniques.

  20. Transfer function combinations

    Zhou, Liang


    Direct volume rendering has been an active area of research for over two decades. Transfer function design remains a difficult task since current methods, such as traditional 1D and 2D transfer functions, are not always effective for all data sets. Various 1D or 2D transfer function spaces have been proposed to improve classification exploiting different aspects, such as using the gradient magnitude for boundary location and statistical, occlusion, or size metrics. In this paper, we present a novel transfer function method which can provide more specificity for data classification by combining different transfer function spaces. In this work, a 2D transfer function can be combined with 1D transfer functions which improve the classification. Specifically, we use the traditional 2D scalar/gradient magnitude, 2D statistical, and 2D occlusion spectrum transfer functions and combine these with occlusion and/or size-based transfer functions to provide better specificity. We demonstrate the usefulness of the new method by comparing to the following previous techniques: 2D gradient magnitude, 2D occlusion spectrum, 2D statistical transfer functions and 2D size based transfer functions. © 2012 Elsevier Ltd.


    王晓英; 陈霁; 张均田


    目的 观察人参皂苷Rg1对β-淀粉样肽[β-AP,(25-35)]所致小鼠拟阿尔茨海默(AD)学习记忆功能障碍的改善作用及其作用机制。方法 小鼠侧脑室注射凝聚态β-AP 4 nmol,次日,ip Rg1 5和10 mg*kg-1,10 d后,测试各组被动回避、空间学习记忆能力,及皮层、海马组织胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AchE)活性变化。结果 人参皂苷Rg1可明显改善β-AP所致小鼠被动回避、空间学习记忆能力及皮层海马组织ChAT活性的下降。β-AP对小鼠AchE活性无显著性影响,但与对照、模型组相比,Rg1明显抑制AchE活性。结论 Rg1对β-AP(25-35)所致的小鼠学习记忆障碍有显著改善作用,其对胆碱能系统的影响是Rg1重要作用机制之一。%AIM To study the effect of ginsenoside Rg1 on the learning and memory impairment in mice induced by aggregated β-AP(25-35). METHODS Mice were administered Rg1 (5, 10 mg*kg-1, ip) for 10 d and control mice received daily ip injections of saline after the intracerebroventricular injection of aggregated β-AP(25-35). After the final treatment, passive avoidance and performance in the Morris water maze (MWM) were assessed. and the activity of cortical and hippocampal ChAT and AchE were detected after the final behavior test. RESULTS Ginsenoside Rg1 (5, 10 mg*kg-1, ip) significantly ameliorated the learning and memory impairment induced by β-AP(25-35). Rg1 (5, 10 mg*kg-1) decreased the latencies and swim distances of mice to reach a hidden platform and improved the corresponding changes in search strategies occurred in the Morris water maze, and Rg1 (10 mg*kg-1, ip), increased step-through latencies also. Biochemical analysis showed that Rg1 (5, 10 mg*kg-1, ip) prevented the cortical and hippocampal ChAT activity decline induced by β- AP(25-35), and showed inhibition of the activity of AchE, although β-AP(25-35) showed no effect on the cortical and hippocampal AchE activity

  2. Wind-hydro combinations

    Stregger, D.L.; Fisher, W.H.


    A study was undertaken to investigate the technical and economic viability of a generalized system composed of a wind-electric and hydroelectric system interacting together to provide firm power to a grid, and to determine limits in the extent to which such a combination can be effected. Several scenarios were considered, including: a farm of horizontal axis wind turbines with various generator ratings, generating into a grid; the same wind turbine generator used to pump water into a hydroelectric plant reservoir; and a cursory examination of mechanical pumping with wind energy to increase the water supply of a hydroelectric project. The review of the state-of-the-art indicated that the scenarios investigated represent the most practical utility applications of wind-hydro combinations. The present state-of-the-art is more advanced for multi-megawatt horizontal axis tubines than for vertical axis wind turbines. The utilization factor, on a monthly determination, of the firm wind energy varies with the shape of the hydrograph, load and the wind regimes. Across Canada it was found to vary from a low of 79% to a maximum of 100%. The most important parameter in the economic evaluation of the break-even costs of wind-hydro generation is the cost of alternative supplies of energy. The regions of Canada where wind-hydro combinations appear to be within economic limits at present cost levels are Newfoundland, assuming a oil-fired thermal alternative, and isolated areas such as the Northwest Territories, assuming a diesel alternative. 67 refs., 12 figs., 13 tabs.

  3. Coherent laser beam combining

    Brignon, Arnaud


    Recently, the improvement of diode pumping in solid state lasers and the development of double clad fiber lasers have allowed to maintain excellent laser beam quality with single mode fibers. However, the fiber output power if often limited below a power damage threshold. Coherent laser beam combining (CLBC) brings a solution to these limitations by identifying the most efficient architectures and allowing for excellent spectral and spatial quality. This knowledge will become critical for the design of the next generation high-power lasers and is of major interest to many industrial, environme

  4. Combine Harvester Simulator

    Vilmann, Ole; Sørlie, James Arnold


    A simulator for training pilots in the operation of a modern high-tech combine harvester is presented. The new simulator application is based on DMI´s well-known DMS maritime simulator architecture. Two major challenges have been encountered in the development of the simulator: 1) interfacing...... the simulator software and the harvester hardware, and 2) the visual image generation system. Aims of the project have been to promote technology transfer from DMI´s maritime simulator to new application areas, to develop a state-of-the-art pilot training environment, and to utilise the state......-of-the-art in objec-oriented graphics programming technologies....

  5. Optimal Antihypertensive Combination Treatments

    Massimo Volpe


    Full Text Available Over the past three decades it has been consistently shown that optimal blood pressure (BP control significantly reduced cardiovascular (CV morbidity and mortality [1]. Despite solid evidence in favour of benefits derived from BP reductions, however, hypertension control in treated hypertensive patients remains suboptimal worldwide [2, 3]. In addition, proportions of diagnosed and treated hypertensive patients remain largely unchanged over the last two decades[4]. Multiple factors may be advocated to explain this observation, including variation in healthcare access and availability [5, 6], attitudes amongst clinicians towards hypertension [7, 8], inaccuracy in BP measurements [9] and underuse or under dosage of antihypertensive drugs in both monotherapy and in combination therapy [10, 11].On the basis of these considerations, it is beyond the aim of this article to discuss the socioeconomic impact on healthcare and BP measurement techniques. Instead it will seek to explain the importance of attaining early optimal BP control and the use of combination therapy as a new paradigm for the modern clinical management of hypertension.

  6. Combined solar collector

    Voznyak, O.; Shapoval, S.; Pona, O.; Vengryn, I.


    In this article was analyzing the efficiency of the combined solar collector for heating buildings. This enhances the efficiency of solar system by increasing the area of the absorption of solar energy. There are describes the results of the research on solar radiation input on a combined solar collector. Проаналізовано ефективність використання комбінованого сонячного колектора для теплопостачання будівель. Він забезпечує підвищення ефективності геліосистеми за рахунок збільшення площі погли...

  7. 剂型因素和给药途径对人参皂苷Rg1在大鼠血清和脑组织中分布的影响%Effect of Dosage Form and Administration Route to Distribution of Ginsenoside Rg1 in Serum and Brain of Rats



    Objective:To discuss the effect of dosage form and administration route on the distribution of ginsenoside Rg1 ( GRg1 ) in serum and brain of the rats.Method: Compared with GRg1 saline solution administrated from nasal route and oral route, GRg1 nasal spray was administrated from nasal route in rats.The concentration of GRg1 in the serum and brain was detected by HPLC-UV.The data was analyzed by the Wagner-Nelson method.Result: The distribution and transport efficiency of GRg1 was improved 5.05 and 2.50 times respectively by nasal administration route.The distribution and transport efficiency of GRg1 was improved 11.80 and 3.35 times respectively by nasal spray.Conclusion: The bio-availability of GRg1 can be improved dramatically by the nasal administration route and nasal spray.%目的:考察剂型因素和给药途径对人参皂苷Rg1(GRg1)在大鼠血清和脑组织中分布的影响.方法:大鼠鼻腔给GRg1鼻腔喷雾剂,以大鼠口服和鼻腔给GRg1生理盐水为对照,给药后测定各组大鼠脑和血清中的GRg1的含量.采用Wagner-Nelson法处理数据.结果:鼻腔给药途径使GRg1在血清和脑组织中的分布和转运效率分别提高了5.05,2.50倍;喷雾剂的剂型因素使GRg1在血清和脑组织中的吸收和转运效率分别提高了11.80,3.35倍.结论:GRg1鼻腔给药途径和喷雾剂都能显著提高其生物利用度.

  8. Combining classical metrology models

    Francisco Roldán


    Full Text Available The results obtained in the graphic analysis of the modulation of the Cuarto Real de Santo Domingo building in Granada, Spain, (ROLDÁN, 2011 have provided new insights to further approach the research on possible use the double-scale in historical monumental architecture. We propose the characterization of the singularities of the system, from the implications and graphic representation required by the metrological scheme identified, as well as the variety of typologies that are presented in their modular frames, and the iterative combination of two-scale modules which allow operational approximations to fractions and ratios not explicitly present in the system.

  9. Combined Heat and Power



    At their 2007 Summit in Heiligendamm, G8 leaders called on countries to 'adopt instruments and measures to significantly increase the share of combined heat and power (CHP) in the generation of electricity.' As a result, energy, economic, environmental and utility regulators are looking for tools and information to understand the potential of CHP and to identify appropriate policies for their national circumstances. This report forms the first part of the response. It includes answers to policy makers' questions about the potential economic, energy and environmental benefits of an increased policy commitment to CHP. It also includes for the first time integrated IEA data on global CHP installations, and analyses the benefits of increased CHP investment in the G8+5 countries. A companion report will be produced later in 2008 to document best practice policy approaches that have been used to expand the use of CHP in a variety of countries.

  10. Combined PET/MRI

    Bailey, D. L.; Pichler, B. J.; Gückel, B.


    This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from...... February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology......, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both...

  11. Combination of external loads

    Frandsen, S.; Tarp Johansen, N.J.; Joergensen, H. [Forskningscenter Risoe, Roskilde (Denmark); Gravesen, H.; Soerensen, S.L. [Carl Bro, Glostrup (Denmark); Pedersen, J. [Elsam Engineering, Fredericia (Denmark); Zorn, R.; Hvidberg Knudsen, M. [DHI Water and Environment, Hoersholm (Denmark); Voelund, P. [Energi E2, Koebenhavn (Denmark)


    The project onbectives have been: To improve and consequently opimise the basis for design of offshore wind turbines. This is done through 1) mapping the wind, wave ice and current as well as correlations of these, and 2) by clarifyring how these external conditions transform into loads. A comprehensive effort has been made to get a thorough understanding of the uncertainties that govern the reliability of wind turbines with respect to wind and wave loading. One of the conclusions is that the reliability of wind turbines is generally lower, than the average reliability of building structures that are subject not only to environmental loads, which are very uncertain, but also imposed loads and self weight, which are less uncertain than the environmental loads. The implication is that, at the moment lower load partial safety factors for onshore wind turbines cannot be recommended. For the combination of wind and wave design loads the problem is twofold: 1). A very conservative design will be generated by simply adding the individual wind and wave design loads disregarding the independence of the short-term fluctuations of wind and wave loads. 2). Characteristic values and partial safety factors for wind and wave loads are not defined similarly. This implies that the reliability levels of turbine support structures subject to purely aerodynamic loads and subject to purely hydrodynamic loads are not identical. For the problem of combining aerodynamic design loads and hydrodynamic design loads two results have been obtained in the project: 1). By simple means a site specific wave load safety factor rendering the same safety level for hydrodynamic loads as for aerodynamic loads is derived, and next, by direct square summation of extreme fluctuations, the wind and wave load safety factors are weighted. 2). Under the assumptions that a deep water site is considered and that the wave loading is a fifty-fifty mix of drag and inertia the same wind and wave load safety factor

  12. Biomass Gasification Combined Cycle

    Judith A. Kieffer


    Gasification combined cycle continues to represent an important defining technology area for the forest products industry. The ''Forest Products Gasification Initiative'', organized under the Industry's Agenda 2020 technology vision and supported by the DOE ''Industries of the Future'' program, is well positioned to guide these technologies to commercial success within a five-to ten-year timeframe given supportive federal budgets and public policy. Commercial success will result in significant environmental and renewable energy goals that are shared by the Industry and the Nation. The Battelle/FERCO LIVG technology, which is the technology of choice for the application reported here, remains of high interest due to characteristics that make it well suited for integration with the infrastructure of a pulp production facility. The capital cost, operating economics and long-term demonstration of this technology area key input to future economically sustainable projects and must be verified by the 200 BDT/day demonstration facility currently operating in Burlington, Vermont. The New Bern application that was the initial objective of this project is not currently economically viable and will not be implemented at this time due to several changes at and around the mill which have occurred since the inception of the project in 1995. The analysis shows that for this technology, and likely other gasification technologies as well, the first few installations will require unique circumstances, or supportive public policies, or both to attract host sites and investors.

  13. Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry.

    Wan, Jin-Yi; Liu, Peng; Wang, Huai-You; Qi, Lian-Wen; Wang, Chong-Zhi; Li, Ping; Yuan, Chun-Su


    American ginseng is a widely used natural product. Ginseng products are usually taken orally, and human intestinal microflora may metabolize ginsenosides. Existing publications report the metabolite fates of ginsenosides. However, investigations on the comprehensive metabolic profile of American ginseng extract are absent because of the chemical complexity and limitation of analytical methods. In this work, we studied the biotransformation and metabolic profile of American ginseng extract by human intestinal microflora. Human fecal microflora was prepared from a healthy Chinese man and then anaerobically incubated with American ginseng sample at 37 °C for 24 h. A rapid and simple liquid-liquid extraction method was used for sample pretreatment. A highly sensitive and selective liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) method was used to characterize ginsenosides and related metabolites in the reaction samples. The LC-Q-TOF-MS provides superior data quality and advanced analytical capabilities for profiling, identifying, and characterizing complex metabolites in matrix-based biological samples. A total of 25 metabolites were detected, 13 of which were undoubtedly assigned by comparison with reference compounds, and 12 others were tentatively identified. The three most abundant metabolites are 20S-ginsenoside Rg3, ginsenoside F2 and compound K. The main metabolic pathways of ginseng saponins are deglycosylation reactions by intestinal microflora through stepwise cleavage of sugar moieties. Subsequent dehydration reactions also occur. Protopanaxadiol- and oleanane-type triterpenoids are easy to metabolize. The intestinal microbiota may play an important role in mediating the metabolism bioactivity of American ginseng. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 三七块根紫色素的花色苷本质及其含量和总皂苷含量的正相关性%Anthocyanin essence of the purple pigment and positive correlation of the anthocyanin content and the total ginsenoside content of the root tuber of Panax notoginseng

    赵昶灵; 王颖; 段承俐; 陈中坚; 萧凤回


    三七是中国云南省的"第一药材",云南文山三七是三七的道地药材.三七块根的横截面为黄白色至紫色.紫色块根约占研究块根总数的28.21%,其中柱鞘、内皮层、皮层或表皮为紫色.特征颜色反应和紫外--可见光谱表明:三七块根紫色素属于黄酮类化合物,可能含有酚性邻位二羟基,不含类胡萝卜素、查耳酮、噢哢、异黄酮、儿茶素.花色苷和/或其苷元花色素奠定了紫色块根着色的基础,其他的非红色的黄酮类化合物起共色素的作用.块根的平均花色苷含量和平均总皂苷含量均以纯紫色块根的为最高,其次是黄紫混合色块根的,纯黄色的最低.块根的花色苷含量差异达到极显著水平,但总皂苷含量差异却没有达到显著水平.每个块根都含有不同量的花色苷,随花色苷量的增加,块根的紫色一般逐渐明显.块根的花色苷含量与其总皂苷含量之间呈显著正相关,相关系数r=0.355.本文可为三七块根颜色呈现的机理探索及其色素的分子结构鉴定提供参考.%Panax Notoginseng is"the first medinal mateial"in Yunnan of China and P. notoginseng produced in the Wenshan eparchy of Yunnan is the Genuine Medicinal Material of P. Notoginseng. The transverse sections of the root tubers of P. notoginseng range from yelowish white to purple. The root tubers with pure purple occupy about 28.21% of the root tubers researched,and their pericycles, endodermises cortexes or epidermises are purple. Specific color reactions and UV-vis spectra indicated that the purple pigment of the root tuber of P. notoginseng belongs to flavonoids,probably holding phenolic o-dihydroxyls, excluding carotenoids, chalcones, aurones,isoflavones and cate-chins. Anthocyanins and/or their aglycones,namely anthocyanidinsunderlay the pigmentation of the purple root tu-ber and other non-red flavonoids function as co-pigments. The average anthocyanin content and the average total gin-senoside

  15. 人参皂苷Rg1经线粒体通路抗Aβ25-35致原代大鼠皮层神经元凋亡%Ginsenoside Rg1 antagonizes β-amyloid peptide-induced apoptosis in primarily cultured rat neurons via mitochondrial pathway

    吴佳莹; 沈圆圆; 朱闻杰; 程梅园; 王志强; 刘琰; 朱丹雁; 楼宜嘉


    Objective; To assess the neuroprotective effects of ginsenoside Rgl against p-amyloid peptide ( Aβ25-35) -induced apoptosis in primarily cultured rat cortical neurons. Methods; Primarily cultured cortical neurons were obtained from embryonic (E18d) rat fetus and maintained in neurobasal medium for 7d. Primary neurons pretreated with 1 (μmol/L, 10 μmol/L or 20 μmol/L Rg1 for 24 h were challenged with 10 μmol/L Aβ25-35 for 72 h. Morphological changes of neurons were evaluated; mitochondrial membrane potential (ΔΨm) was measured; with JC-1 staining and the expression of neural apoptosis-related proteins was detected by Western blot analysis. Results; Exposure to Aβ25-35 for 72 h caused serious neural cell insults. A pretreatment with Rgl significantly reduced Aβ25-35-induced cell death in a dose-dependent manner, with a maximal effect ( -90% ) obtained at 20 |xmol/L. The JC-1 staining results demonstrated the loss of ΔΨm after Aβ25-35 treatment, while Rgl maintained the normal level of ΔΨm. A series of mitochondrion-mediated apoptotic events happened after Aβ25-35 treatment, such as decrease of Bcl-2/Bax, release of cytoehrome C and activation of caspase 9 and caspase 3, which were all blocked by Rgl pretreatment. Both estrogen receptor ( ER) antagonist IC1182, 780 and glucocorticoid receptor (GR) antagonist RU486 blocked the antiapoptotic effects of Rgl. Conclusions; Ginsenoside Rgl protects primary cultured rat cortical neurons from Aβ25-35-induced injury, which may be associated with mitochondrion-mediated antiapoptosis pathway.%目的:通过人参皂苷Rg1与原代培养大鼠皮层神经元预培养,评价抗β淀粉样肽(β-amy1oid peptide,Aβ)所致神经元损伤,并探讨Rg1的神经保护作用及相关分子机制.方法:原代神经元培养7d成熟后,分别以1、10、20 μmol/L Rg1处理24 h,加入Aβ毒性片段Aβ25.35 10 μmoL/L模拟阿尔茨海默病( Alzheimer's Disease,AD)脑组织局部微环境.孵育72 h后,光镜观察

  16. Toxicology and antioxidation ability of ginsenoside and epimedium pubescen-s incariine Astragalus Membranaceus Composite in rats%人参皂甙与淫羊藿苷复方制剂安全性及抗氧化功能实验研究

    田辉; 田洁; 王玉娥; 付少华; 杨文祥; 孙凡中; 樊柏林; 卢笑丛


    目的 研究人参皂甙与淫羊藿苷复方制剂作为特殊食品的安全性及其抗氧化作用.方法 安全性实验:进行了小鼠急性经口毒性试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验和大鼠30 d喂养试验;抗氧化作用试验采用老龄小鼠作为抗氧化低下动物模型,进行干预性试验,检测各试验组小鼠的血液中MDA含量及GSH-PX活力,测定肝匀浆中SOD活力.结果 小鼠急性毒性试验MTD值>20g/kg bw;人群推荐剂量395倍剂量对小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验结果 均为阴性;人群推荐剂量100倍剂量给予大鼠30d口服未发现临床症状、血液临床检查指标、动物脏器以及病理组织学等指标的改变.与老龄小鼠对照组相比,受试样品中、高剂量组可显著减少老龄小鼠血液MDA含量(P<0.05);中剂量组可显著升高老龄小鼠肝匀浆中SOD活性(P<0.05)以及血液GSH-PX活性(P<0.01).结论 人参皂甙、淫羊藿苷复方制剂具有抗氧化功能,并符合特殊食品安全毒理学要求.%Objective To test the safety and the effect on anti-oxidation of ginsenoside and epimedium pubesceus incariine Astragalis Membranaceus Composite as a kind of health food. Methods Toxicology results were obtained through acute toxicity test,micronucleus test of bone marrow ceil,sperm shape abnormality test,and thirty-day feeding tests. Antioxidation indexes were through determination of MDA content,GSH-Px activity and SOD activity. Results ① The amount of 20 g/kg BW (Ginseneside and epimedium pubeseens incariine Astragalus Membranaceus Composite) was fed each time to SPF Kunming mice (female and male) ,no toxic phenomenon and death were found in animals within two weeks. In the experiment of micronucleus test of bone marrow cell and sperm shape abnormality test in mice, the result was negative. In the thirty-day feeding test, the following dosage was given to the experienced

  17. Effect of Combination of Berberine and Ginsenosides Rb1 on Inflammatory Adipocytokines and Inflammatory Signaling Pathways in Adipocytes%小檗碱和人参皂苷Rb1合用对脂肪细胞炎症因子表达和炎症信号通路的影响

    张红霞; 赵娟; 于希忠; 郭超; 潘扬; 尚文斌



  18. Propagating Class and Method Combination

    Ernst, Erik


    This paper presents a mixin based class and method combination mechanism with block structure propagation. Traditionally, mixins can be composed to form new classes, possibly merging the implementations of methods (as in CLOS). In our approach, a class or method combination operation may cause any...... number of implicit combinations. For example, it is possible to specify separate aspects of a family of classes, and then combine several aspects into a full-fledged class family. The combination expressions would explicitly combine whole-family aspects, and by propagation implicitly combine the aspects...... for each member of the class family, and again by propagation implicitly compose each method from its aspects. As opposed to CLOS, this is type-checked statically; and as opposed to other systems for advanced class combination/ merging/weaving, it is integrated directly in the language, ensuring a clear...


    V. V. Elizarov


    Full Text Available Subject of Research. The results of lidar combined scanning unit development for locating leaks of hydrocarbons are presented The unit enables to perform high-speed scanning of the investigated space in wide and narrow angle fields. Method. Scanning in a wide angular field is produced by one-line scanning path by means of the movable aluminum mirror with a frequency of 20Hz and amplitude of 20 degrees of swing. Narrowband scanning is performed along a spiral path by the deflector. The deflection of the beam is done by rotation of the optical wedges forming part of the deflector at an angle of ±50. The control function of the scanning node is performed by a specialized software product written in C# programming language. Main Results. This scanning unit allows scanning the investigated area at a distance of 50-100 m with spatial resolution at the level of 3 cm. The positioning accuracy of the laser beam in space is 15'. The developed scanning unit gives the possibility to browse the entire investigated area for the time not more than 1 ms at a rotation frequency of each wedge from 50 to 200 Hz. The problem of unambiguous definition of the beam geographical coordinates in space is solved at the software level according to the rotation angles of the mirrors and optical wedges. Lidar system coordinates are determined by means of GPS. Practical Relevance. Development results open the possibility for increasing the spatial resolution of scanning systems of a wide range of lidars and can provide high positioning accuracy of the laser beam in space.

  20. Combination strategies for pain management.

    Raffa, Robert B; Clark-Vetri, Rachel; Tallarida, Ronald J; Wertheimer, Albert I


    At least two factors relating to pain management using oral analgesics suggest that combination strategies merit consideration: many pains arise from more than one physiological cause and current analgesics have adverse effect profiles that might be reduced by combination with another agent in smaller doses or with less frequent dosing. In addition to increased convenience, combinations sometimes also result in the unexpected benefit of synergy. But not all pains, clinical settings or combinations merit the extra expense or other potential negative features of fixed-ratio products. This review examines the multiple basic science, clinical and pharmacoeconomic issues relating to analgesic combinations and the methodologies available for assessing these issues.

  1. Integrated coal gasification combined cycle

    Richards, P. C.; Wijffels, J.-B.; Zuideveld, P. L.

    Features of the integrated coal gasification combined cycle power plants are described against the backdrop of the development and first commercial application of the shell coal gasification process. Focus is on the efficiency and excellent environmental performance of the integrated coal gasification combined power plants. Current IGCC projects are given together with an outline of some of the options for integrating coal gasification with combined cycles and also other applications of synthesis gas.

  2. Combined Environment Acoustic Chamber (CEAC)

    Federal Laboratory Consortium — Purpose: The CEAC imposes combined acoustic, thermal and mechanical loads on aerospace structures. The CEAC is employed to measure structural response and determine...

  3. Chemical Diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng

    Kim, Dong-Hyun


    The major commercial ginsengs are Panax ginseng Meyer (Korean ginseng), P. quinquifolium L. (American ginseng), and P. notoginseng (Burk.) FH Chen (Notoginseng). P. ginseng is the most commonly used as an adaptogenic agent and has been shown to enhance physical performance, promote vitality, increase resistance to stress and aging, and have immunomodulatory activity. These ginsengs contain saponins, which can be classified as dammarane-type, ocotillol-type and oleanane-type oligoglycosides, and polysaccharides as main constituents. Dammarane ginsenosides are transformed into compounds such as the ginsenosides Rg3, Rg5, and Rk1 by steaming and heating and are metabolized into metabolites such as compound K, ginsenoside Rh1, protoand panaxatriol by intestinal microflora. These metabolites are nonpolar, pharmacologically active and easily absorbed from the gastrointestinal tract. However, the activities metabolizing these constituents into bioactive compounds differ significantly among individuals because all individuals possess characteristic indigenous strains of intestinal bacteria. To overcome this difference, ginsengs fermented with enzymes or microbes have been developed. PMID:23717099

  4. Effects of Temperature variations on the Super Fine Powderization of Korean Cultivated Wild Ginseng

    Jin Ho Kim


    Full Text Available Objectives : The aim of this study was to find optimal conditions for producing red ginseng from cultivated wild ginseng using the Turbo Mill. Methods : Characteristics of powdered cultivated wild ginseng based on various temperature settings of the Turbo Mill were observed, and changes in the content was measured by HPLC for various ginsenosides. Results : 1. The diameter of cultivated wild ginseng powder ground by the Turbo Mill was around 10㎛. 2. As the temperature rose, presusre, Specific Mechanical Energy(SME, and density decreased, whileas Water Solubility Index(WSI increased. 3. As the temperature rose, super fine powder showed tendency to turn into dark brown. 4. Measuring content changes by HPLC, there was no detection of ginsenoside Rg3 and ginsenosideRg1, Rb1, and Rh2 concentrations decreased with increase in temperature. Conclusions : Super fine powder of cultivated wild ginseng produced by the Turbo Mill promotes easy absorption of effective ingredients by breaking the cell walls. Using this mechanism to produce red ginseng from cultivated wild ginseng, it yielded less than satisfactory results under the current experiment setup. Furtherresearches are needed to verify more suitable condition for the production of red ginseng.

  5. 发根农杆菌诱导人参产生发根及离体发根中人参皂甙含量的测定%Formation of Ginseng Hairy Roots Mediated by Agrobacterium rhizogenes and Analysis of Ginsenosides in Hairy Roots In Vitro

    赵寿经; 杨振堂; 李昌禹; 臧埔; 申玉华


    发根农杆菌A4菌株诱导人参(Panax ginseng C.A.Meyer)产生发根,诱导率31.6%。转化发根可在无任何激素的MS培养基上快速生长,且具有分枝性强、丛生、无向地性等特点。通过对液体培养条件的选择,发现人参发根在1/2MS液体培养基上(25℃、110r/min摇床上暗培养)获得最大生长速率,经14 d培养,人参发根鲜重增加了7.97倍。利用高效液相色谱法测定发根中人参皂甙含量发现,发根系R9923中人参单体皂甙Rb1含量达到10.38mg/g,超过栽培六年生人参根中Rb1含量(6.45mg/g)。用高压纸电泳方法在人参发根中检测到农杆碱及甘露碱的存在。Southern点杂交证明:本研究获得的人参发根确已被A4菌株Ri质粒的T-DNA所转化,并被整合到人参发根DNA上。%Hairy roots of ginseng (Panax ginseng C. A. Meyer) were induced by strain A4 of Agrobacterium rhizogenes and the induction rate was 31.6%. The transformed hairy roots grew rapidly on MS medium without phytohormones and were characterized by strongly branching, clustering and non-geotropism, etc. The hairy roots of ginseng achieved the highest growth rate on MS liquid medium (shaked at 110 r/min at 25℃ in darkness) and their fresh weight was increased by 7.97 times after culture for 14 days. Determined by HPLC, the content of ginsenoside-Rb1 in hairy root clone R9923 was found to be 10.38 mg/g, higher than that of 6-year-old cultivated ginseng (6.45mg/g). Agropine and mannopine were detected in the hairy roots of ginseng by the high-voltage paper electrophoresis. Southern dot blotting proved that the hairy roots of ginseng had been indeed transformed by the strain A4 and the T-DNA of Ri plasmid had been integrated into the DNA of hairy roots.

  6. Effects of ginsenoside on synaptic plasticity of freely moving rats and its mechanism of action%人参皂甙Rg1对自由活动大鼠突触可塑性的影响及其作用机制

    王晓英; 张均田


    目的:研究人参皂甙Rg1对自由活动大鼠突触功能可塑性的影响及作用机制.方法:应用细胞外微电极记录技术,大鼠埋植电极后d 6予以Rg1(10,30 mg/kg,ip)12 d,记录(直至停药后d 3)其齿状回群体峰电位(PS).大鼠给予Rg1(10,30mg/kg,ip)12 d,据Timm染色法观察海马CA3区苔藓纤维出芽情况.以免疫组化技术检测齿状回颗粒细胞层GAP-43表达水平.结果:1)Rg1可显著降低诱发PS的阈值,提高清醒自由活动大鼠的突触传递效能,诱导LTP形成,停药3 d后,LTP仍可维持.2)Rg1组大鼠齿状回颗粒细胞层及齿状回门区GAP-43表达显著增加.3)Timm染色显示海马CA3区苔藓纤维出芽增加.结论:Rg1可使自由活动大鼠PP-DG突触传递效能发生以LTP为主的可塑性变化,其机制为齿状回颗粒细胞GAP-43表达增加,其投射靶区海马CA3苔藓纤维明显出芽增加,这呈正反馈性增强了突触传递效能.%AIM: To investigate the effect and mechanism of gin senoside Rg1 on synaptic plasticity of freely moving rats. METHODS: SD rats were chronically implanted with a stimulation electrode in the perforant path (PP) of hip pocampus and a recording electrode in the granule cell of dentate gyrus. After administration of ginsenoside Rg1 (10, 30 mg/kg, ip) for 12 d, extracellular recording technique was used to record the population spike (PS). Mossy fiber (MF) sprouting was measured using Timm's staining, and an immunohistochemical technique was used to detect the expression of presynaptic growth-associated protein 43 (GAP-43). RESULTS: Rg1 could signifi cantly increase the sensitivity of evoking PS, the ampli tude of PS and induce PP-DG long-term potentiation (LTP) in the dentate gyms (DG) of freely moving rats. In the meantime, Rg1 accelerated MF sprouting in CA3 cell field of hippocampus. The expression level of GAP-43 was elevated in granule cell layer and hilus of DG of Rgb-treated rats. CONCLUSION: The

  7. 人参皂甙Rd对匹罗卡品致(癎)大鼠模型中netrin-1表达及神经元凋亡的影响%Effects of ginsenoside-Rd on expression levels of netrin-1 and neuron apoptosis in epilepsy model

    郑佳丽; 杨金升; 刘学娟; 马亚杰


    目的 探讨人参皂甙Rd(GSRd)对大鼠癫(癎)持续状态后齿状回netrin-1表达及海马神经元凋亡的影响.方法 健康Wistar大鼠30只,随机分为颞叶癫(癎)组、GSRd组和对照组,每组10只.氯化锂-匹罗卡品建立大鼠颞叶癫(癎)模型,采用免疫组织化学法及TUNEL法观察颞叶癫(癎)组、GSRd组和对照组齿状回netrin-1蛋白表达及海马神经元凋亡细胞数情况.结果 与对照组比较,颞叶癫(癎)组大鼠30 d齿状回netrin-1蛋白表达明显增高,海马CA3区TUNEL阳性细胞数在癫(癎)持续状态后7d明显增高,差异有统计学意义(P< 0.05);与颞叶癫(癎)组比较,GSRd组大鼠30 d齿状回netrin-1蛋白表达明显降低,海马CA3区TUNEL阳性细胞数在癫(癎)持续状态后7d明显降低,差异有统计学意义(P< 0.05).结论 GSRd可能通过下调netrin-1的表达,并使神经元凋亡数目减少,从而发挥对神经元的保护作用.%Objective To investigate the effects of ginsenoside-Rd(GSRd) on the expression levels of netrin-1 and neuron apoptosis in the rat hippocampus after lithium-pilocarpine induced epilepsy.Methods Thirty Wistar rats were randomly divided into the NS control group,temporal lobe epilepsy(TLE) group and GSRd group.The TLE animal model was established using lithium-pilocarpine.Netrin-1 proteins were detected with immunohistochemical method.The neuron apoptosis was observed with TdT-mediated dUTP nick end labeling(TUNEL) method.Results The expression of netrin-1 in GSRd group was notably lower than that of TLE group (P < 0.05).The TUNEL positive cells in hippocampus CA3 of TLE group were more than those of NS control group (P < 0.05).TUNEL positive cells in TLE group were significantly more than those in NS control group (P < 0.05).TUNEL positive cells in GSRd treated group significantly decreased as compared with TLE group (P < 0.05).Conclusions GSRd may serve as an effective agent for curing the brain damage after TLE in vivo.The mechanism

  8. [Antilipemic agents in combined therapy].

    Márk, László; Császár, Albert


    In the prevention of coronary heart disease the aim to achieve the target cholesterol and triglyceride levels and the maximal risk reduction leads to the combination of lipid lowering agents. The importance of the combination is supported by the fact that in monotherapy use of the high dose of the drugs, the lipid lowering effect is modest and the side effects are more frequent. The combined therapy is expected to be used more frequently despite the fact, that the improperly applied combination could have serious unfavourable effects. The authors review the advantages and drawbacks of the fibrate-statin combination, which could be used in the most frequent lipid abnormality, the high cholesterol and high triglyceride level, when the combination of micronized fenofibrate and fluvastatin is recommended. Beside the co-administration of other lipid lowering drugs (nicotine acid and resins), it is discussed the combination of statins and fibrates with a new, cholesterol absorption inhibitor, ezetimibe, a well tolerated drug with advantageous safety profile. Considering further metabolic risks the combination of lipid lowering drugs with glitazones, hormone replacement therapy, homocysteine reducing agents is as well highlighted.

  9. Revised Accounting for Business Combinations

    Wilson, Arlette C.; Key, Kimberly


    The Financial Accounting Standards Board (FASB) has recently issued Statement of Financial Accounting Standards No. 141 (Revised 2007) Business Combinations. The object of this Statement is to improve the relevance, representational faithfulness, and comparability of reported information about a business combination and its effects. This Statement…

  10. Combination moisture and hydrogen getter

    Harrah, L.A.; Mead, K.E.; Smith, H.M.


    A combination moisture and hydrogen getter comprises (a) a moisture getter comprising a readily oxidizable metal; and (b) a hydrogen getter comprising (1) a solid acetylenic compound and (2) a hydrogenation catalyst. A method of scavenging moisture from a closed container uses the combination moisture and hydrogen getter to irreversibly chemically reduce the moisture and chemically bind the resultant hydrogen.

  11. Oxycodone combinations for pain relief.

    Raffa, R B; Pergolizzi, J V; Segarnick, D J; Tallarida, R J


    No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment.

  12. Multidimensional Datawarehouse with Combination Formula

    Warnars, Spits


    Multidimensional in data warehouse is a compulsion and become the most important for information delivery, without multidimensional Multidimensional in data warehouse is a compulsion and become the most important for information delivery, without multidimensional datawarehouse is incomplete. Multidimensional give ability to analyze business measurement in many different ways. Multidimensional is also synonymous with online analytical processing (OLAP). By using some concepts in datawarehouse like slice-dice,drill down and roll up will increase the ability of multidimensional datawarehouse. The research question and the discussing for this paper are how much deepest the multidimensional ability from each fact table in datawarehouse. By using the statistic combination formula we try to explore the combination that can be yielded from each dimension in hypercubes, the entire of dimensi combination, minimum combination and maximum combination.

  13. Combining norms to prove termination

    Genaim, S.; Codish, M.; Gallagher, John Patrick;


    of deriving automatically a candidate norm with which to prove termination. Instead of deriving a single, complex norm function, it is sufficient to determine a collection of simpler norms, some combination of which, leads to a proof of termination. We propose that a collection of simple norms, one for each...... of the recursive data-types in the program, is often a suitable choice. We first demonstrate the power of combining norm functions and then the adequacy of combining norms based on regular types....

  14. New combinations in African Sapindaceae

    Friis, Ib; Vollesen, Kaj; Verdcourt, Bernard


    Three new combinations are formally made: Allophylus rubifolius (A. Rich.) Engl. var. alnifolius (Baker) Friis & Vollesen, Allophylus rubifolius (A. Rich.) Engl. var. rhusiphyllus (Balf.f.) Froos & Vollesen and Haplocoelum folosum (Hiern) Bullock subsp. mombasense (Bullock) Verdc....

  15. The efficiency of combined machinings


    This paper analyses the efficiency of the finish process applied in machining of hard surfaces, completed by grinding, hard turning and also by the combination of these two procedures, on the basis of time consumption.

  16. Autonomous grain combine control system

    Hoskinson, Reed L.; Kenney, Kevin L.; Lucas, James R.; Prickel, Marvin A.


    A system for controlling a grain combine having a rotor/cylinder, a sieve, a fan, a concave, a feeder, a header, an engine, and a control system. The feeder of the grain combine is engaged and the header is lowered. A separator loss target, engine load target, and a sieve loss target are selected. Grain is harvested with the lowered header passing the grain through the engaged feeder. Separator loss, sieve loss, engine load and ground speed of the grain combine are continuously monitored during the harvesting. If the monitored separator loss exceeds the selected separator loss target, the speed of the rotor/cylinder, the concave setting, the engine load target, or a combination thereof is adjusted. If the monitored sieve loss exceeds the selected sieve loss target, the speed of the fan, the size of the sieve openings, or the engine load target is adjusted.

  17. Combined radar and telemetry system

    Rodenbeck, Christopher T.; Young, Derek; Chou, Tina; Hsieh, Lung-Hwa; Conover, Kurt; Heintzleman, Richard


    A combined radar and telemetry system is described. The combined radar and telemetry system includes a processing unit that executes instructions, where the instructions define a radar waveform and a telemetry waveform. The processor outputs a digital baseband signal based upon the instructions, where the digital baseband signal is based upon the radar waveform and the telemetry waveform. A radar and telemetry circuit transmits, simultaneously, a radar signal and telemetry signal based upon the digital baseband signal.

  18. Combined cataract and strabismus surgery.

    Gayton, J L; Ledford, J K


    A patient with cataracts and congenital exotropia underwent combined cataract and strabismus surgery OU. A lateral rectus recession plus an extracapsular cataract extraction with intraocular lens implantation was done OD first; three months later, this procedure was repeated OS. The patient's postoperative course was benign in both cases, and her strabismus resolved after the second operation. A combined surgical approach to cataracts and strabismus (where only a single muscle is involved) was safe and useful in restoring this patient's vision, binocularity, and appearance.


    V. N. Poptsov


    Combined heart-kidney transplantation may be performed in carefully selected patients with end-stage heart disease and renal failure. There are two types of combined transplantation of heart and kidney: 1) simultaneous heart-kidney transplantation (SHKT) from the same donor; 2) staged transplantation of heart and kidneys from two genetically different donors. The ISHLT registry in 2014 reported an increase in the number of SHKT over the years: from 22 in 1994 to 97 in 2012. World experience d...

  20. Intelligence Fusion for Combined Operations


    doctrine on intelligence in combined operations, the lessons learned from the most recent combined operations, the current state of intelligence fision ...control of nuclear weapons and arms proliferation in the former Soviet Union.’ In Asia, the United States maintains a military presence in support of...emanating from other than nuclear or radioactive sources. Individual Reports Database - The portion of the LOCE database consisting of entity data records

  1. Chemical characteristics combined with bioactivity for comprehensive evaluation of Panax ginseng C.A. Meyer in different ages and seasons based on HPLC-DAD and chemometric methods.

    Shan, Si-Ming; Luo, Jian-Guang; Huang, Fang; Kong, Ling-Yi


    Panax ginseng C.A. Meyer has been known as a valuable traditional Chinese medicines for thousands years of history. Ginsenosides, the main active constituents, exhibit prominent immunoregulation effect. The present study first describes a holistic method based on chemical characteristic and lymphocyte proliferative capacity to evaluate systematically the quality of P. ginseng in thirty samples from different seasons during 2-6 years. The HPLC fingerprints were evaluated using principle component analysis (PCA) and hierarchical clustering analysis (HCA). The spectrum-efficacy model between HPLC fingerprints and T-lymphocyte proliferative activities was investigated by principal component regression (PCR) and partial least squares (PLS). The results indicated that the growth of the ginsenosides could be grouped into three periods and from August of the fifth year, P. ginseng appeared significant lymphocyte proliferative capacity. Close correlation existed between the spectrum-efficacy relationship and ginsenosides Rb1, Ro, Rc, Rb2 and Re were the main contributive components to the lymphocyte proliferative capacity. This comprehensive strategy, providing reliable and adequate scientific evidence, could be applied to other TCMs to ameliorate their quality control.

  2. Combined sensor noise-immunity

    Vladimir A. Shchurov; Alexander V. Shchurov


    The paper presents statistical analysis of combined sensor noise-immunity while recording fluctuating tone against underwater dynamic noise background. The experimental data used for the analysis have been collected by a pair of four-component combined sensors centered at two depths, 150 and 300 m in deep water. Expressions for combined sensor signalto-noise ratio (SNR) for cross-spectral levels of signal and noise for both wide and narrow frequency bands have been derived. A combined sensor gain has been introduced in terms of ordinary single-point coherence function between acoustic pressure and particle velocity in acoustic wave. The estimates obtained experimentally evidence that SNR for a combined sensor with multiplicative data processing may exceed SNR for a hydrophone-based sensor by 15 to 16 dB at most for the horizontal channel of the combined sensor, and by 30 dB at most for the vertical channel (when opposite energy flows of signal and noise compensate one another).

  3. COMBINE Archive Specification Version 1.

    Bergmann, Frank T; Rodriguez, Nicolas; Le Novère, Nicolas


    Several standard formats have been proposed that can be used to describe models, simulations, data or other essential information in a consistent fashion. These constitute various separate components required to reproduce a given published scientific result. The Open Modeling EXchange format (OMEX) supports the exchange of all the information necessary for a modeling and simulation experiment in biology. An OMEX file is a ZIP container that includes a manifest file, an optional metadata file, and the files describing the model. The manifest is an XML file listing all files included in the archive and their type. The metadata file provides additional information about the archive and its content. Although any format can be used, we recommend an XML serialization of the Resource Description Framework. Together with the other standard formats from the Computational Modeling in Biology Network (COMBINE), OMEX is the basis of the COMBINE Archive. The content of a COMBINE Archive consists of files encoded in COMBINE standards whenever possible, but may include additional files defined by an Internet Media Type. The COMBINE Archive facilitates the reproduction of modeling and simulation experiments in biology by embedding all the relevant information in one file. Having all the information stored and exchanged at once also helps in building activity logs and audit trails.

  4. Combination trading with limit orders

    Henry Schellhorn


    Full Text Available We model the exchange of commodities that are contingent upon each other, when traders place mostly limit orders. Examples include: 1 a market of financial futures where future spreads are also traded, 2 a market of mutual funds and stocks, 3 a market of options and stocks, under the viewpoint that they are both combinations of Arrow-Debreu securities. We prove that consistent prices are optimal. We develop a fixed-point algorithm to compute an optimal price and allocation. The algorithm combines ideas from contraction mapping theory and from homotopy theory. It is much faster than a traditional linear programming approach.


    Ilya Levin


    Full Text Available DDoS attacks have become one of the most dangerous issues in the Internet today. Because of theseattacks, legitimate users can not access the resources they need. In [1] authors proposeda combined method for tracing and blocking the sources of DDoS-attacks. The essence of the method isthat each router marks the network packet that passes through it using a random hash function from theset. At the receiving side this information is stored and used to filter unwanted traffic and traceback thesource of distributed attack. This article describes the simulation and its results of the combined method.

  6. Determining Covers in Combinational Circuits

    Ljubomir Cvetkovic


    Full Text Available In this paper we propose a procedure for determining 0- or 1-cover of an arbitrary line in a combinational circuit. When determining a cover we do not need Boolean expression for the line; only the circuit structure is used. Within the proposed procedure we use the tools of the cube theory, in particular, some operations defined on cubes. The procedure can be applied for determining 0- and 1- covers of output lines in programmable logic devices. Basically, this procedure is a method for the analysis of a combinational circuit.

  7. Identification of the molecular genetic basis of the low palmitic acid seed oil trait in soybean mutant line RG3 and association analysis of molecular markers with elevated seed stearic acid and reduced seed palmitic acid

    The fatty acid composition of vegetable oil is becoming increasingly critical for the ultimate functionality and utilization in foods and industrial products. Partial chemical hydrogenation of soybean oil increases oxidative stability and shelf life but also results in the introduction of trans fats...

  8. H gas turbine combined cycle

    Corman, J. [General Electric Co., Schenectady, NY (United States)


    A major step has been taken in the development of the Next Power Generation System - {open_quotes}H{close_quotes} Technology Combined Cycle. This new gas turbine combined-cycle system increases thermal performance to the 60% level by increasing gas turbine operating temperature to 1430 C (2600 F) at a pressure ratio of 23 to 1. Although this represents a significant increase in operating temperature for the gas turbine, the potential for single digit NOx levels (based upon 15% O{sub 2}, in the exhaust) has been retained. The combined effect of performance increase and environmental control is achieved by an innovative closed loop steam cooling system which tightly integrates the gas turbine and steam turbine cycles. The {open_quotes}H{close_quotes} Gas Turbine Combined Cycle System meets the goals and objectives of the DOE Advanced Turbine System Program. The development and demonstration of this new system is being carried out as part of the Industrial/Government cooperative agreement under the ATS Program. This program will achieve first commercial operation of this new system before the end of the century.

  9. Property Attribution in Combined Concepts

    Spalding, Thomas L.; Gagné, Christina L.


    Recent research shows that the judged likelihood of properties of modified nouns ("baby ducks have webbed feet") is reduced relative to judgments for unmodified nouns ("ducks have webbed feet"). This modification effect has been taken as evidence both for and against the idea that combined concepts automatically inherit…

  10. Mode Combinations and International Operations

    Benito, Gabriel R. G.; Petersen, Bent; Welch, Lawrence S.


    reveals that companies tend to combine modes of operation; thereby producing unique foreign operation mode “packages” for given activities and/or countries, and that the packages are liable to be modified over time – providing a potentially important optional path for international expansion. Our data...

  11. Mode Combinations and International Operations

    Benito, Gabriel R. G.; Petersen, Bent; Welch, Lawrence S.


    reveals that companies tend to combine modes of operation; thereby producing unique foreign operation mode “packages” for given activities and/or countries, and that the packages are liable to be modified over time—providing a potentially important optional path for international expansion. The data show...

  12. A Radix-10 Combinational Multiplier

    Lang, Tomas; Nannarelli, Alberto


    reduces the number of partial product precomputations and uses counters to eliminate the need of the decimal equivalent of a 4:2 adder. The results of the implementation show that the combinational decimal multiplier offers a good compromise between latency and area when compared to other decimal multiply...

  13. Property Attribution in Combined Concepts

    Spalding, Thomas L.; Gagné, Christina L.


    Recent research shows that the judged likelihood of properties of modified nouns ("baby ducks have webbed feet") is reduced relative to judgments for unmodified nouns ("ducks have webbed feet"). This modification effect has been taken as evidence both for and against the idea that combined concepts automatically inherit…

  14. Combined scleral buckling and phacoemulsification

    Pukhraj Rishi


    Conclusion: Combined scleral buckling and phacoemulsification is a safe and effective procedure that spares the patient the burden of repeated surgeries. It may be considered as a treatment option in selected cases of rhegmatogenous retinal detachment with significant cataract with/without early PVR.

  15. Combination throttle and shutoff valve

    Carriker, J. W.


    Combination of translating sleeve throttle valve and conventional poppet valve provides capability of shutting off flow completely by poppet and sleeve control of the rate of flow. Integration of the two concepts can be accomplished without difficulty and in a manner that requires a minimum of development.

  16. Diagnosis of severe combined immunodeficiency

    Gennery, A; Cant, A


    Early diagnosis of severe combined immunodeficiency (SCID) is important to enable prompt referral to a supraregional centre for bone marrow transplantation before the occurrence of end organ damage secondary to infective complications. This review outlines clinical, microbiological, and immunopathological clues that aid the diagnosis of SCID and emphasises the multidisciplinary approach needed to diagnose and treat these infants.

  17. Airbreathing combined cycle engine systems

    Rohde, John


    The Air Force and NASA share a common interest in developing advanced propulsion systems for commercial and military aerospace vehicles which require efficient acceleration and cruise operation in the Mach 4 to 6 flight regime. The principle engine of interest is the turboramjet; however, other combined cycles such as the turboscramjet, air turborocket, supercharged ejector ramjet, ejector ramjet, and air liquefaction based propulsion are also of interest. Over the past months careful planning and program implementation have resulted in a number of development efforts that will lead to a broad technology base for those combined cycle propulsion systems. Individual development programs are underway in thermal management, controls materials, endothermic hydrocarbon fuels, air intake systems, nozzle exhaust systems, gas turbines and ramjet ramburners.

  18. Pattern Recognition by Combined Invariants

    WANG Xiaohong; ZHAO Rongchun


    A feature-based recognition of objectsor patterns independent of their position, size, orien-tation and other variations has been the goal of muchrecent research. The existing approaches to invarianttwo-dimensional pattern recognition are useless whenpattern is blurred. In this paper, we present a novelpattern recognition system which can solve the prob-lem by using combined invariants as image features.The classification technique we choose for our systemis weighted normalized cross correlation. The mean ofthe intraclass standard deviations of the kth featureover the total number of prototypes for each class isused as a weighting factor during the classification pro-cess to improve recognition accuracy. The feasibilityof our pattern recognition system and the invarianceof the combined features with respect to translation,scaling, rotation and blurring are approved by numer-ical experiments on head images.

  19. Combined fertility and embryotoxicity study.

    Reynaud, Lucie; Marsden, Edward


    Under normal circumstances, fertility and embryotoxicity studies are run separately according to the ICH S5(R2) guideline for the detection of toxicity to reproduction of medicinal products (1). However, the flexible approach of the S5(R2) guideline also allows the reproduction stages covered in the fertility and embryo-fetal development studies (stages A to D) to be combined into a single study design. The administration period covers the pre-mating and gestation phases through to closure of the hard palate. The principal advantages of the combined study include reductions in the number of animals required and cost. Although the rat is the routine species of choice, the mouse may also be used.

  20. Run 1 Higgs legacy combination

    Donato, Silvio


    The total Higgs boson cross-section has been measured to be $1.09 \\pm 0.11$ the Standard Model prediction. The combination of the ATLAS and CMS results gives observed significances for the vector boson fusion production process and for the $H\\rightarrow \\tau \\tau$~decay of~$5.4$ and $5.5$~standard deviations, respectively. The data are consistent with the Standa...

  1. Combining different types of classifiers

    Gatnar, Eugeniusz


    Model fusion has proved to be a very successful strategy for obtaining accurate models in classification and regression. The key issue, however, is the diversity of the component classifiers because classification error of an ensemble depends on the correlation between its members. The majority of existing ensemble methods combine the same type of models, e.g. trees. In order to promote the diversity of the ensemble members, we propose to aggregate classifiers of different t...

  2. Combining activity and economic efficiency

    Fersch, Barbara

    In the Danish welfare state, long-term care is a universal service that is run by the municipalities. The municipalities, although bound by a national legal framework, do have considerable autonomy concerning the concrete definition and organization of long-term care services. One of the newest “....... The paper provides a discourse analysis of the interviewees’ accounts, that shows how discourses on activity and economic efficiency have been combined in the Danish context....

  3. Radiosensitive Severe Combined Immunodeficiency Disease

    Dvorak, Christopher C.; Cowan, Morton J.


    Inherited defects in components of the non-homologous end joining DNA repair mechanism produce a T-B-NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation. Patients with the radiosensitive form of SCID may also have increased short- and long-term sensitivity to the alkylator-based chemotherapy regimens traditionally utilized for conditioning prior to allogeneic hematopoietic cell transplantation (HCT). Known etiologies of radiosensit...

  4. Combination chemoprevention with grape antioxidants.

    Singh, Chandra K; Siddiqui, Imtiaz A; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal


    Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Imagining a Stata / Python Combination

    Fiedler, James


    There are occasions when a task is difficult in Stata, but fairly easy in a more general programming language. Python is a popular language for a range of uses. It is easy to use, has many high ]quality packages, and programs can be written relatively quickly. Is there any advantage in combining Stata and Python within a single interface? Stata already offers support for user-written programs, which allow extensive control over calculations, but somewhat less control over graphics. Also, except for specifying output, the user has minimal programmatic control over the user interface. Python can be used in a way that allows more control over the interface and graphics, and in so doing provide a roundabout method for satisfying some user requests (e.g., transparency levels in graphics and the ability to clear the results window). My talk will explore these ideas, present a possible method for combining Stata and Python, and give examples to demonstrate how this combination might be useful.

  6. Ginsenosides-Rbl inhibits ET-1-induced cardiomyocyte hypertrophy via PKC pathway in neonatal rats%人参皂甙 Rbl 通过 PKC 途径抑制 ET-1诱发的乳鼠心肌肥大

    孔宏亮; 黄带发; 王聿杰


    Objective:To explore whether ginsenosides-Rb1 (Gs-Rb1)can relieve cardiomyocyte hypertrophy induced by endothelin-1 (ET-1)via protein kinase C (PKC)system.Methods:Cardiomyocytes of neonatal rat were random-ly divided into blank control group,Gs-Rb1 group,ET-1 group,Gs-Rb1+ET-1 group,ET-1+CHE (chelerythrine, PKC blocker)group and Gs-Rb1 +ET-1 +CHE group.After 96h intervention,cardiomyocyte surface area,total protein content,PKC activity,c-fos and p-c-jun expressions were measured.Results: (1)Cardiomyocyte surface area and total protein content in Gs-Rb1+ET-1 group were significantly lower than those of ET-1 group (P <0.05~<0.001),but not significant different with those of Gs-Rb1+ET-1+CHE group,P =0.569;(2)PKC activity in Gs-Rb1+ET-1 group was significantly lower than that of ET-1 group [(9.3±0.6)pmol·min-1 ·mg-1 vs.(14.1± 0.9)pmol·min-1 ·mg-1 ],but significantly higher than that of Gs-Rb1+ET-1+CHE group [(2.7±0.2)pmol· min-1 ·mg-1 ],P <0.001 all;(3)Expressions of c-fos and p-c-jun gene and protein in ET-1 group were significant-ly higher than those of blank control group (P <0.001 all);compared with ET-1 group,there were significant re-ductions in expressions of c-fos [mRNA/protein:(0.53±0.05/0.39±0.02)vs.(0.43±0.03/0.31±0.03)]and p-c-jun [mRNA/protein:(0.64±0.04/0.44±0.02)vs.(0.33±0.05/0.37±0.03)]in Gs-Rb1+ET-1 group and ex-pressions of c-fos [mRNA/protein:0.41 ± 0.05/0.31 ± 0.02]and p-c-jun [mRNA/protein:0.31 ± 0.05/0.36 ±0.03]in ET-1+CHE group (P <0.05 or <0.001),expressions of c-fos and p-c-jun gene and protein in Gs-Rb1+ET-1+CHE group were significantly lower than those of Gs-Rb1+ET-1 group and ET-1+CHE group (P <0.05 or<0.001).Conclusion:Gs-Rb1 can significantly inhibit cardiomyocyte hypertrophy induced by ET-1 and PKC system is one of pathways mediating this biological effect.%目的:探讨人参皂甙 Rb1(Gs-Rb1)是否可通过蛋白激酶 C (PKC)系统减轻内皮素-1(ET-1)诱导的乳鼠心肌细胞肥大。方法:

  7. Combining Alphas via Bounded Regression

    Zura Kakushadze


    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  8. [Combination chemotherapy of experimental leukemia].

    Emanuel', N M; Konovalova, N P; D'iachkovskaia, R F


    In the present work an attempt was made to gain greater therapeutic effect of diazane coupled with adriamycin and sarcolysin. Leucemias L-1210 and La served as a model. In leucosis La diazane was injected once in 5 days. Either an additional injection of adriamycin two days prior to diazane injection or sarcolysin injected simultaneously with diazane enabled the authors to obtain a distinct synergestic effect. In leucemia L-1210 a simultaneous administration of diazane and sarcolysin also contributes to considerably longer survival of leucemic animals. Such combinations are likely to be promising in their clinical use.

  9. Anti-cancer natural products isolated from chinese medicinal herbs

    Wu Guosheng


    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  10. Radiation tolerant combinational logic cell

    Maki, Gary R. (Inventor); Gambles, Jody W. (Inventor); Whitaker, Sterling (Inventor)


    A system has a reduced sensitivity to Single Event Upset and/or Single Event Transient(s) compared to traditional logic devices. In a particular embodiment, the system includes an input, a logic block, a bias stage, a state machine, and an output. The logic block is coupled to the input. The logic block is for implementing a logic function, receiving a data set via the input, and generating a result f by applying the data set to the logic function. The bias stage is coupled to the logic block. The bias stage is for receiving the result from the logic block and presenting it to the state machine. The state machine is coupled to the bias stage. The state machine is for receiving, via the bias stage, the result generated by the logic block. The state machine is configured to retain a state value for the system. The state value is typically based on the result generated by the logic block. The output is coupled to the state machine. The output is for providing the value stored by the state machine. Some embodiments of the invention produce dual rail outputs Q and Q'. The logic block typically contains combinational logic and is similar, in size and transistor configuration, to a conventional CMOS combinational logic design. However, only a very small portion of the circuits of these embodiments, is sensitive to Single Event Upset and/or Single Event Transients.

  11. Combination therapies in iron chelation

    Raffaella Origa


    Full Text Available The availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with b thalassemia major. However, monotherapy is not effective in all patients for a variety of reasons. We analyzed the most relevant reports recently published on alternating or combined chelation therapies in thalassemia major with special attention to safety aspects and to their effects in terms of reduction of iron overload in different organs, improvement of complications, and survival. When adverse effects, such as gastrointestinal upset with deferasirox or infusional site reactions with deferoxamine are not tolerable and organ iron is in an acceptable range, alternating use of two chelators (drugs taken sequentially on different days, but not taken on the same day together may be a winning choice. The association deferiprone and deferoxamine should be the first choice in case of heart failure and when dangerously high levels of cardiac iron exist. Further research regarding the safety and efficacy of the most appealing combination treatment, deferiprone and deferasirox, is needed before recommendations for routine clinical practice can be made.

  12. Performance of lazy combinator graph reduction

    Hartel, Pieter H.; Hartel, P.H.

    The performance of program-derived combinator graph reduction is known to be superior to that of graph reduction based on a fixed set of standard combinators. The major advantage of program-derived combinator reduction is that it uses less transient store than standard combinator reduction. We show

  13. Beam combination modes of the VLT

    Merkle, Fritz

    The optical configuration of the ESO Very Large Telescope (VLT) is based on a linear array of 4 independently mounted 8-m telescopes. This concept allows a flexible and versatile use of the telescopes. They can be operated either independently or in various combination schemes. In the latter case, the light collected with the unit telescopes is fed via beam combination optics to the combined focus. The incoherent combination with a combined coude focus offers the light collecting power approximately equivalent to a 16-m single dish telescope. The efficiency of the combined foci operation is only given if the losses in the combining train are minimized.

  14. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium

    Chieh-fu CHEN; Wen-fei CHIOU; Jun-tian ZHANG


    Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic" around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive compo-nents contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For antican-cer effects, P quinquefolium is better.

  15. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium.

    Chen, Chieh-fu; Chiou, Wen-fei; Zhang, Jun-tian


    Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic"around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive components contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For anticancer effects, P quinquefolium is better.

  16. Combined processing of lead concentrates

    Kubasov, V. L.; Paretskii, V. M.; Sidorin, G. N.; Travkin, V. F.


    A combined scheme of processing of lead concentrates with the production of pure metallic lead and the important components containing in these concentrates is considered. This scheme includes sulfating roasting of the lead concentrates and two-stage leaching of the formed cinder with the formation of a sulfate solution and lead sulfate. When transformed into a carbonate form, lead sulfate is used for the production of pure metallic lead. Silver, indium, copper, cadmium, nickel, cobalt, and other important components are separately extracted from a solution. At the last stage, zinc is extracted by either extraction followed by electrolytic extraction of a metal or the return of the forming solution of sulfuric acid to cinder leaching.

  17. Combined photoacoustic and ultrasound biomicroscopy.

    Harrison, Tyler; Ranasinghesagara, Janaka C; Lu, Huihong; Mathewson, Kory; Walsh, Andrew; Zemp, Roger J


    We report on the development of an imaging system capable of combined ultrasound and photoacoustic imaging based on a fast-scanning single-element 25-MHz ultrasound transducer and a unique light-delivery system. The system is capable of 20 ultrasound frames per second and slower photoacoustic frame rates limited by laser pulse-repetition rates. Laser and ultrasound pulses are interlaced for co-registration of photoacoustic and ultrasound images. In vivo imaging of a human finger permits ultrasonic visualization of vessel structures and speckle changes indicative of blood flow, while overlaid photoacoustic images highlight some small vessels that are not clear from the ultrasound scan. Photoacoustic images provide optical absorption contrast co-registered in the structural and blood-flow context of ultrasound with high-spatial resolution and may prove important for clinical diagnostics and basic science of the microvasculature.

  18. Chemical and natural stressors combined:

    Gergs, André; Zenker, Armin; Grimm, Volker


    In addition to natural stressors, populations are increasingly exposed to chemical pollutants released into the environment. We experimentally demonstrate the loss of resilience for Daphnia magna populations that are exposed to a combination of natural and chemical stressors even though effects...... on population size of a single stressor were cryptic, i.e. hard to detect statistically. Data on Daphnia population demography and along with model-based exploration of our predator-prey system revealed that direct trophic interactions changed the population size-structure and thereby increased population...... vulnerability to the toxicant which acts in a size selective manner. Moreover, population vulnerability to the toxicant increases with predator size and predation intensity whereas indirect trait-mediated interactions via predator kairomones may buffer chemical effects to a certain extent. Our study...

  19. How rats combine temporal cues.

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M


    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  20. Combining supramolecular chemistry with biology.

    Uhlenheuer, Dana A; Petkau, Katja; Brunsveld, Luc


    Supramolecular chemistry has primarily found its inspiration in biological molecules, such as proteins and lipids, and their interactions. Currently the supramolecular assembly of designed compounds can be controlled to great extent. This provides the opportunity to combine these synthetic supramolecular elements with biomolecules for the study of biological phenomena. This tutorial review focuses on the possibilities of the marriage of synthetic supramolecular architectures and biological systems. It highlights that synthetic supramolecular elements are for example ideal platforms for the recognition and modulation of proteins and cells. The unique features of synthetic supramolecular systems with control over size, shape, valency, and interaction strength allow the generation of structures fitting the demands to approach the biological problems at hand. Supramolecular chemistry has come full circle, studying the biology and its molecules which initially inspired its conception.

  1. Combined PET/MRI scanner

    Schlyer, David; Woody, Craig L.; Rooney, William; Vaska, Paul; Stoll, Sean; Pratte, Jean-Francois; O'Connor, Paul


    A combined PET/MRI scanner generally includes a magnet for producing a magnetic field suitable for magnetic resonance imaging, a radiofrequency (RF) coil disposed within the magnetic field produced by the magnet and a ring tomograph disposed within the magnetic field produced by the magnet. The ring tomograph includes a scintillator layer for outputting at least one photon in response to an annihilation event, a detection array coupled to the scintillator layer for detecting the at least one photon outputted by the scintillator layer and for outputting a detection signal in response to the detected photon and a front-end electronic array coupled to the detection array for receiving the detection signal, wherein the front-end array has a preamplifier and a shaper network for conditioning the detection signal.

  2. Combined Shape and Topology Optimization

    Christiansen, Asger Nyman

    Shape and topology optimization seeks to compute the optimal shape and topology of a structure such that one or more properties, for example stiffness, balance or volume, are improved. The goal of the thesis is to develop a method for shape and topology optimization which uses the Deformable...... Simplicial Complex (DSC) method. Consequently, we present a novel method which combines current shape and topology optimization methods. This method represents the surface of the structure explicitly and discretizes the structure into non-overlapping elements, i.e. a simplicial complex. An explicit surface...... representation usually limits the optimization to minor shape changes. However, the DSC method uses a single explicit representation and still allows for large shape and topology changes. It does so by constantly applying a set of mesh operations during deformations of the structure. Using an explicit instead...

  3. Food combinations for cholesterol lowering.

    Harland, Janice I


    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful foo