Ginsenoside Rg1 protects rat bone marrow mesenchymal stem cells against ischemia induced apoptosis through miR-494-3p and ROCK-1.

PubMed

Zheng, Hui-Zhen; Fu, Xue-Kun; Shang, Jiu-Long; Lu, Rong-Xi; Ou, Yong-Fang; Chen, Chun-Ling

2018-03-05

This study aimed to verify the cytoprotective effect of ginsenoside Rg1 in vivo, and to elucidate the mechanism of Rg1 in the ischemic microenvironment. Male rat bone marrow mesenchymal stem cells (rBMSCs) or rBMSCs treated with Rg1 were injected into ischemic region of the arterial embolism hind limb in female rats. Behavioral and histological data, obtained one-week post injection, showed that rBMSCs with Rg1 could improve the survival rate of BMSCs and enhance the therapeutic effects. rBMSCs treated with hypoxia and serum deprivation for 24h (H/SD-rBMSCs) showed the up-regulated expression of ras homolog family member A (RhoA), Rho associated coiled-coil containing protein kinase 1 (ROCK-1), myosin light chain 2 (MLC-2), Bcl2 associated agonist of cell death (Bad) and Bcl2 associated X, apoptosis regulator (Bax); while the expression of miR-148b-3p, miR-148b-5p and miR-494-3p was down-regulated. H/SD with Rg1 treatment (H/SD+Rg1-rBMSCs) inhibited the expression of ROCK-1, MLC-2, Bad and Bax, increased the expression of Bcl-2, miR-494-3p. After ROCK-1 knockout, the expression of Bad and Bax were downregulated and Bcl-2 upregulated, but Rg1 no longer altered their expression. Mir-494-3p functional study established that miR-494-3 mimic downregulated and miR-494-3 inhibitor upregulated ROCK-1 gene expression, Rg1 did not have the ability to change the ROCK gene expression after loss of function of miR-494-3p. Also, the function loss of mir-494-3p promoted apoptosis; otherwise reduced apoptosis. The anti-apoptotic effect of Rg1 disappeared after mir-494-3p loss or gain function. In conclusion, Ginsenoside Rg1 has shown to have protective effects on ischemic-induced rBMSCs apoptosis through mir-494-3p→ROCK-1→Bcl-2 signaling pathway. Copyright © 2018. Published by Elsevier B.V.

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

PubMed Central

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

2016-01-01

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

Ginsenoside Rg1 nanoparticle penetrating the blood-brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction.

PubMed

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood-brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

PubMed Central

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction. PMID:28919749

Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA‑155‑5p inhibition.

PubMed

Wang, Jun; Li, Dan; Hou, Jincai; Lei, Hongtao

2018-02-01

Geniposide, an active component of Gardenia, has been reported to protect against cerebral ischemia in animals. Ginsenoside Rg1, a component of Panax notoginseng, is usually administered in combination with Gardenia for the treatment of acute ischemic stroke; however, there are unknown effects of ginsenoside Rg1 that require further investigation. In the present study, the effects of geniposide and ginsensoide Rg1 combination treatment on focal cerebral ischemic stroke were investigated. For in vivo analysis, male rats were separated into three groups, including the (control), model and geniposide + ginsenoside Rg1 groups (n=8 per group). A middle cerebral artery occlusion model was established as the model group. The treatment group was treated with geniposide (30 mg/kg, tail vein injection) + ginsenoside Rg1 (6 mg/kg, tail vein injection), and the model group received saline instead. Neurobehavioral deficits, infarct volume, brain edema, and the expression of microRNA (miR)‑155‑5p and CD11b by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry, were assessed following 24 h of ischemia. For in vitro analysis, BV2 mouse microglial cells were cultured and exposed to geniposide (40 µg/ml) + ginsenoside Rg1 (8 µg/ml) during various durations of oxygen‑glucose deprivation (OGD). The expression levels of miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 were detected by RT‑qPCR. The results demonstrated that increases in brain infarct volume, edema volume, CD11b‑positive cells and miR‑155‑5p levels were alleviated following geniposide + ginsenoside administration in rats exposed to ischemia. Furthermore, geniposide + ginsenoside Rg1 treatment suppressed the miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 expression levels in OGD‑injured BV2 microglial cells. The results of the present study demonstrated that tail vein administration of geniposide in combination with ginsenoside Rg1

Ginsenoside Rg1 improves fertility and reduces ovarian pathological damages in premature ovarian failure model of mice.

PubMed

He, Lianli; Ling, Li; Wei, Tianqin; Wang, Yaping; Xiong, Zhengai

2017-04-01

This study aims to investigate the effect as well as mechanism of ginsenoside Rg1 (Rg1) on premature ovarian failure (POF) induced by d-galactose (d-gal) in mice. C57BL/6 female mice were divided into four groups randomly, which were the saline group, the d-gal group, the d-gal + Rg1 group, and the Rg1 group. Body weight was recorded. Overall ovarian function including estrous cycles, sex hormone secretion, ovarian follicle development, and ovarian morphology was analyzed by H&E staining and ELISA. Effect of Rg1 on aging was determined by analyzing the activities of oxidation-associated biomarkers, pro-inflammatory cytokine secretion, expression of senescence-associated proteins, and fertility. Compared with the d-gal group, in Rg1 + d-gal group, body weight was increased significantly, estrous cycle block was released, and fertility and the morphology of ovaries were restored. And, Rg1 treatment after d-gal administration significantly reduced senescence-associated protein expression, increased the activity of total superoxide dismutase and glutathione peroxidase from bovine erythrocyte, and induced higher follicle stimulating hormone receptor protein expression. Additionally, the expression levels of malondialdehyde, interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased. Together, Rg1 improves mouse fertility and reduces ovarian pathological damage in d-gal-induced POF model possibly through enhancing anti-inflammatory and antioxidant capacities and reducing expression of senescence signal pathway proteins. Impact statement Ginsenoside Rg1 (Rg1) is a kind of natural estrogen and it has antioxidation and antiaging effects. However, whether Rg1 has effects on premature ovarian failure (POF) is still not clear. In this study, aging model induced by d-galactose was used to mimic POF. The effect and possible mechanism of Rg1 on ovary aging was investigated. We found that Rg1 treatment up-regulated the expression of follicle

Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

PubMed

Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

2013-12-01

Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

PubMed Central

Jiang, Bo; Xiong, Zhe; Yang, Jun; Wang, Wei; Wang, Yue; Hu, Zhuang-Li; Wang, Fang; Chen, Jian-Guo

2012-01-01

BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis. PMID:22335772

Effect of enzyme on extraction of ginsenoside Rb1 and Rg3 from Panax notoginseng roots

NASA Astrophysics Data System (ADS)

Phuong, Nguyen Tran Xuan; Thy, Lu Thi Mong; Khang, Nguyen Luu Vinh; My, Huynh Thi Kieu; Tam, Nguyen Le Phuong; Hieu, Nguyen Huu

2018-04-01

Panax notoginseng is distributed throughout the north and northwest of Vietnam, especially Ha Giang, Lao Cai, and Cao Bang provinces. The root of this plant contains ginsenosides (Rb1, Rb2, Rd, Rg3), flavonoids, polyacetylene, polysaccharides, amino acids, fatty acids, and peptides. In this study, the ratios of enzyme (Viscozyme, Termamyl, Cellulase), solvent of components, and time extraction were investigated. The results showed that the highest contents of Rb1 and Rg3 were achieved in the sample extracted with the ratio of enzymes V:C:T = 1:0:0, ethanol:water (60:40, v/v) as extracting solvent in 45 minutes. Then, conditions of high performance liquid chromatography with diode array detector method to determine the content of ginsenosides Rb1 and Rg3 in the roots of Panax notoginseng were studied, including wavelength, mobile phase, and flow rate. The separation was subjected on a reversed-phase C18 column using acetonitrile (A) and water (B) as mobile phase. The gradient elution was set as follow: 0-10 min, 15-25% A; 10-20 min, 25-30% A; 20-40 min, 30-60% A; 40-60 min, 60-80% A; and 60-65 min back to 15% A before the next injection, at a flow rate of 0.5 mL/min, and the wavelength was set at 202 nm. The linear range was from 298.59 to 696.72 µg/mL for Rb1 and from 8.19 to 19.10 µg/L for Rg3. The limits of detection for Rb1 and Rg3 obtained were 0.31 µg/mL and 0.33 µg/mL, respectively. The limits of quantification were 0.95 µg/mL and 1.01 µg/mL for Rb1 and Rg3, respectively. Consequently, the high performance liquid chromatography demonstrated the highly sensitive and accurate method for determination of Rb1 and Rg3 in Panax notoginseng.

Anti-Inflammatory Effect of Ginsenoside Rg5 in Lipopolysaccharide-Stimulated BV2 Microglial Cells

PubMed Central

Lee, Yu Young; Park, Jin-Sun; Jung, Ji-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

2013-01-01

Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-α, IL-1β, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-κB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders. PMID:23698769

Caspase-Mediated Anti-Apoptotic Effect of Ginsenoside Rg5, a Main Rare Ginsenoside, on Acetaminophen-Induced Hepatotoxicity in Mice.

PubMed

Wang, Zi; Hu, Jun-Nan; Yan, Meng-Han; Xing, Jing-Jing; Liu, Wen-Cong; Li, Wei

2017-10-25

Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group 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 plays such a liver protection effect. The objective of the 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 of the animals that received a single intraperitoneal injection of APAP (250 mg/kg) showed severe liver toxicity after 24 h, and the liver protection effects of G-Rg5 were examined. The results clearly indicated that pretreatment 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

[Effect of ginsenoside Rg3 on hepatic fibrosis in murine schistosomiasis japonica].

PubMed

Zeng, Jin; Wang, Hong; Jia, Xue-mei; Li, Cui-ying; Li, Fei

2011-04-30

[(11.08 +/- 4.43)%] and D [(11.19 +/- 4.91)%] (P < 0.05). The SSS scores of hepatic fibrosis in group C (2.83 +/- 1.09) was lower than that of groups B (7.42 +/- 1.16) and D (8.08 +/- 1.76) (P < 0.05). Ginsenoside Rg3 shows anti-hepatofibrosis effects in murine schistosomiasis japonica after praziquantel treatment.

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen

PubMed Central

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-01-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin−) Sca-1+ c-Kit+ haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit+ HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit+ HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit+/CD45+ HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. PMID:26153045

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

PubMed Central

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

2015-01-01

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

Ginsenoside Rg3 attenuates sepsis-induced injury and mitochondrial dysfunction in liver via AMPK-mediated autophagy flux.

PubMed

Xing, Wei; Yang, Lei; Peng, Yue; Wang, Qianlu; Gao, Min; Yang, Mingshi; Xiao, Xianzhong

2017-08-31

Sepsis-led mitochondrial dysfunction has become a critical pathophysiological procedure in sepsis. Since ginsenosides have been applied in the treatment of mitochondrial dysfunction, ginsenoside Rg3 was employed to study its effects on the mitochondrial dysfunction induced by sepsis. The apoptosis rate, oxygen consumption rate (OCR), reactive oxygen species (ROS), antioxidant glutathione (GSH) pools, and mitochondrial transmembrane potential (MTP) were determined in LPS-induced sepsis hepatocytes treated with different concentrations of Rg3. Then, the protein expression levels of mitochondrial biogenesis related transcription factors, autophagy-related proteins, and AMP-activated protein kinase (AMPK) signal pathway related proteins were determined by Western blotting in both in vitro and in vivo sepsis models. Rg3 shows functions of promotion of OCR, attenuation of ROS, and maintenance of GSH pools, and its conjugating activity in the in vitro sepsis models. Rg3-treated cells were observed to have a higher MTP value compared with the LPS only induced cells. Moreover, Rg3 treatment can inhibit mitochondrial dysfunction via increasing the protein expression levels of mitochondrial biogenesis related transcription factors. Rg3 treatment has the function of inhibitor of apoptosis of human primary hepatocytes, and Rg3 can up-regulate the autophagy-related proteins and activate AMPK signal pathway in sepsis models. Meanwhile, the mitochondrial protective function exerted by Rg3 decreased after the autophagy inhibitors or AMPK inhibitor treatment in LPS-induced human primary hepatocytes. Rg3 can improve mitochondrial dysfunction by regulating autophagy in mitochondria via activating the AMPK signal pathway, thus protecting cell and organ injuries caused by sepsis. © 2017 The Author(s).

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

PubMed

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-11-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

PubMed

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

2015-01-01

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

Inhibitory effect of ginsenoside Rg1 on extracellular matrix production via extracellular signal-regulated protein kinase/activator protein 1 pathway in nasal polyp-derived fibroblasts.

PubMed

Cho, Jung-Sun; Moon, You-Mi; Um, Ji-Young; Moon, Jun-Hyeok; Park, Il-Ho; Lee, Heung-Man

2012-06-01

Nasal polyps are associated with chronic inflammation of the sinonasal mucosa and are involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. Ginsenoside Rg1, a compound derived from Panax ginseng, shows antifibrotic and anticancer effects. However, the molecular effects of Rg1 on myofibroblast differentiation and ECM production remain unknown. The aims of this study were to investigate the effect of Rg1 on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and ECM production and to determine the molecular mechanism of Rg1 in nasal polyp-derived fibroblasts (NPDFs). NPDFs were isolated from nasal polyps of seven patients who had chronic rhinosinusitis with nasal polyp. NPDFs were exposed to TGF-β1 with or without Rg1. Expression levels of α-smooth muscle actin (SMA), fibronectin and collagen type Iα1 were determined by reverse transcription polymerase chain reaction, Western blot and immunofluorescent staining. TGF-β1 signaling molecules, including Smad2/3, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were analyzed by Western blotting. Transcription factors involved with TGF-β1 signaling, nuclear factor (NF)-κB and activator protein 1 (AP-1) were also assessed by Western blot. The cytotoxic effect of Rg1 was measured by an established viability assay. The mRNA and protein expression levels of α-SMA, fibronectin and collagen type Iα1 were increased in TGF-β1-induced NPDFs. Rg1 inhibited these effects. The inhibitory molecular mechanism of Rg1 was involved in the ERK pathway. Rg1 inhibited the transcription factor activation of AP-1. Rg1 itself was not cytotoxic. The ginsenoside Rg1 has inhibitory effects on myofibroblast differentiation and ECM production. The inhibitory mechanism of Rg1 is involved with the ERK and AP-1 signaling pathways. Rg1 may be useful as an inhibitor of ECM deposition, and has potential to be used as a novel treatment option for nasal

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

PubMed Central

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

2015-01-01

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

The protective effects of ginsenosides on human erythrocytes against hemin-induced hemolysis.

PubMed

Li, Guo-Xiang; Liu, Zai-Qun

2008-03-01

Panax ginseng has been used in traditional Chinese medicine to enhance stamina and capacity to deal with fatigue and physical stress. Many reports have been devoted to the effects of ginsenosides on many in vitro or in vivo experimental systems. The major aim of this work is to investigate the protective effects of 12 individual ginsenosides including Rb1, Rb3, Rc, Rd, Re, Rg1, Rg2, Rg3, Rh1, Rh2, R1 and pseudoginsenoside F11, together with the central structures of aforementioned ginsenosides, 20(S)-protopanaxadiol (PD) and 20(S)-protopanaxatriol (PT), on hemin-induced hemolysis of human erythrocytes. This is because hemin can induce hemolysis by accelerating the potassium leakage, dissociating skeletal proteins and prohibiting some enzymes in the membrane of erythrocyte. Thus, the structure-activity-relationship (SAR) between ginsenosides and protective effects has been screened in this in vitro experimental system. It is found that Rh2 and Rg3 intensify hemolysis in the presence of hemin, and initiate hemolysis even in the absence of hemin. All the other ginsenosides protect human erythrocytes against hemin-induced hemolysis more or less. The overall sequence is Rc>Rd>Re approximately Rb1>Rg1 approximately Rh1>Rb3 approximately Rg2 approximately R1 approximately F11 approximately PT. In addition, the protective effects of PD and PT have been detected, and found that PD promotes hemolysis appreciably, whereas PT protects erythrocytes efficiently. Moreover, the protective effects of PT ginsenosides are similar to PT itself, and the protective effects of PD ginsenosides vary remarkably, demonstrating that the positions of the sugar moieties make the protective activities of ginsenosides complicated. Especially, sugar moiety at 20-position is critical for PD ginsenosides to inhibit hemolysis, whereas hydroxyl group at 3-position is important for PT ginsenosides. The present result may be useful for understanding the SAR of ginsenosides.

Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Mengwei; Huang, Chenglin; Wang, Cheng

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 tissuemore » 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.« less

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

PubMed

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

2016-12-30

Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-01-01

The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg(-1)d(-1) or 20 mg kg(-1) d(-1)). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A literature update elucidating production of Panax ginsenosides with a special focus on strategies enriching the anti-neoplastic minor ginsenosides in ginseng preparations.

PubMed

Biswas, Tanya; Mathur, A K; Mathur, Archana

2017-05-01

Ginseng, an oriental gift to the world of healthcare and preventive medicine, is among the top ten medicinal herbs globally. The constitutive triterpene saponins, ginsenosides, or panaxosides are attributed to ginseng's miraculous efficacy towards anti-aging, rejuvenating, and immune-potentiating benefits. The major ginsenosides such as Rb1, Rb2, Rc, Rd., Re, and Rg1, formed after extensive glycosylations of the aglycone "dammaranediol," dominate the chemical profile of this genus in vivo and in vitro. Elicitations have successfully led to appreciable enhancements in the production of these major ginsenosides. However, current research on ginseng biotechnology has been focusing on the enrichment or production of the minor ginsenosides (the less glycosylated precursors of the major ginsenosides) in ginseng preparations, which are either absent or are produced in very low amounts in nature or via cell cultures. The minor ginsenosides under current scientific scrutiny include diol ginsenosides such as Rg3, Rh2, compound K, and triol ginsenosides Rg2 and Rh1, which are being touted as the next "anti-neoplastic pharmacophores," with better bioavailability and potency as compared to the major ginsenosides. This review aims at describing the strategies for ginsenoside production with special attention towards production of the minor ginsenosides from the major ginsenosides via microbial biotransformation, elicitations, and from heterologous expression systems.

Ginsenoside Rb1 promotes browning through regulation of PPARγ in 3T3-L1 adipocytes.

PubMed

Mu, Qianqian; Fang, Xin; Li, Xiaoke; Zhao, Dandan; Mo, Fangfang; Jiang, Guangjian; Yu, Na; Zhang, Yi; Guo, Yubo; Fu, Min; Liu, Jun-Li; Zhang, Dongwei; Gao, Sihua

2015-10-23

Browning of white adipocyte tissue (WAT) has received considerable attention due to its potential implication in preventing obesity and related comorbidities. Ginsenoside Rb1 is reported to improve glycolipid metabolism and reduce body weight in obese animals. However whether the body reducing effect mediates by browning effect remains unclear. For this purpose, 3T3-L1 adipocytes were used to study the effect of ginsenoside Rb1 on browning adipocytes specific genes and oxygen consumptions. The results demonstrate that 10 μM of ginsenoside Rb1 increases basal glucose uptake and promoted browning evidenced by significant increases in mRNA expressions of UCP-1, PGC-1α and PRDM16 in 3T3-L1 mature adipocytes. Further, ginsenoside Rb1 also increases PPARγ activity. And the browning effect is abrogated by GW9692, a PPARγ antagonist. In addition, ginsenoside Rb1 increases basal respiration rate, ATP production and uncoupling capacity in 3T3-L1 adipocytes. Those effects are also blunted by GW9692. The results suggest that ginsenoside Rb1 promote browning of 3T3-L1 adipocytes through induction of PPARγ. Our finding offer a new source to discover browning agonists and also useful to understand and extend the applications of ginseng and its constituents. Copyright © 2015 Elsevier Inc. All rights reserved.

Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis?

PubMed

Liu, Zai-Qun; Luo, Xu-Yang; Sun, Yun-Xiu; Chen, Yan-Ping; Wang, Zhi-Cai

2002-08-15

Many studies have focused on the free-radical-initiated peroxidation of membrane lipid, which is associated with a variety of pathological events. Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to deal with fatigue and physical stress. Many reports have been devoted to the effects of ginsenosides, the major active components in P. ginseng, on the lipid metabolism, immune function and cardiovascular system. The results, however, are usually contradictory since the usage of mixture of ginsenosides cannot identify the function of every individual ginsenosides on the experimental system. On the other hand, every individual ginsenosides is not compared under the same experimental condition. These facts motivate us to evaluate the antioxidant effect of various individual ginsenosides on the experimental system of free-radical-initiated peroxidation: the hemolysis of human erythrocyte induced thermally by water-soluble initiator, 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied firstly and found that the order of IC(50) is Rb3 - Rb1<Rg2Rg1 - Rc11. Rb1, Rc and Rg2, as antioxidants, can prolong the lag time of hemolysis. Contrarily, Rg3, Rd and Rh1, together with high concentration of Rb3, Rg1 and Rh2, function as prooxidants to accelerate AAPH-induced hemolysis. The addition of Re does not influence the lag time of hemolysis. The R1 with the concentration ranging from 10 to 20 microM decreases the lag time of hemolysis. These results suggest that there is a mutual interaction that existed in the molecule of ginsenosides since the difference of the structure of ginsenosides is only due to the connective position and type of sugar moieties to the ring of a triterpene dammarane. Moreover, the synergistic antioxidative properties of various individual ginsenosides with alpha-tocopherol (TOH) are also discussed

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

PubMed Central

Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

2018-01-01

Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the

Autotoxic Ginsenosides in the Rhizosphere Contribute to the Replant Failure of Panax notoginseng

PubMed Central

Yang, Min; Zhang, Xiaodan; Xu, Yanguo; Mei, Xinyue; Jiang, Bingbing; Liao, Jingjing; Yin, Zhaobo; Zheng, Jianfen; Zhao, Zhi; Fan, Liming; He, Xiahong; Zhu, Youyong; Zhu, Shusheng

2015-01-01

Background and Aims Sanqi ginseng (Panax notoginseng) growth is often hampered by replant failure. In this study, we aimed to examine the role of autotoxicity in Sanqi replant failures and assess the role of ginsenosides in autotoxicity. Methods The autotoxicities were measured using seedling emergence bioassays and root cell vigor staining. The ginsenosides in the roots, soils, and root exudates were identified with HPLC-MS. Results The seedling emergence and survival rate decreased significantly with the continuous number of planting years from one to three years. The root exudates, root extracts, and extracts from consecutively cultivated soils also showed significant autotoxicity against seedling emergence and growth. Ginsenosides, including R1, Rg1, Re, Rb1, Rb3, Rg2, and Rd, were identified in the roots and consecutively cultivated soil. The ginsenosides, Rg1, Re, Rg2, and Rd, were identified in the root exudates. Furthermore, the ginsenosides, R1, Rg1, Re, Rg2, and Rd, caused autotoxicity against seedling emergence and growth and root cell vigor at a concentration of 1.0 µg/mL. Conclusion Our results demonstrated that autotoxicity results in replant failure of Sanqi ginseng. While Sanqi ginseng consecutively cultivated, some ginsenosides can accumulate in rhizosphere soils through root exudates or root decomposition, which impedes seedling emergence and growth. PMID:25695831

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

PubMed Central

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

2013-01-01

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

Rg1 protects rat bone marrow stem cells against hydrogen peroxide-induced cell apoptosis through the PI3K/Akt pathway.

PubMed

Hu, Junzheng; Gu, Yanqing; Fan, Weimin

2016-07-01

The aim of the present study was to investigate the protective mechanism of ginsenoside Rg1 against the apoptosis of rat bone marrow stem cells (rBMSCs) under oxidative stress, and to determine the association with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. H2O2 was used to induce oxidative injury in rBMSCs. The cells in the H2O2 model group were treated with 800 µM H2O2 for 6 h to induce oxidative injury. The cells in the ginsenoside Rg1 group were treated with 10 µM ginsenoside Rg1 for 24 h, followed by H2O2 treatment. The cells in the Akt pathway blockage group were treated with 25 µM LY294002 for 1 h, followed by ginsenoside Rg1 + H2O2 treatment. The cell counting kit-8 assay was performed to determine cell viability. Cell apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The results of flow cytometry and TUNEL staining indicated that the apoptotic rate of the H2O2 model group was significantly higher compared with that of the control group. Following the ginsenoside Rg1 pretreatment, the apoptotic rate was significantly reduced. In the Akt pathway blockage group, no significant alterations in the levels of cell apoptosis were observed compared with the H2O2 model group. Western blot analysis demonstrated that the ginsenoside Rg1 group had a significant downregulation of Bax and cleaved caspase‑3 and an upregulation of Bcl‑2 and phosphorylated Akt protein expression levels compared with the H2O2 model group and the Akt pathway blockage group. In conclusion, ginsenoside Rg1 had a protective effect against the H2O2‑induced oxidative stress of rBMSCs, and the specific mechanism may be associated with the activation of the PI3K/Akt pathway by ginsenoside Rg1.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Zhong-Ze; 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; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892

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 employedmore » as in vitro probe reaction. The results showed that structure-dependent inhibition existed for the inhibition of ginsenosides towards UGT isoforms. To clarify the possibility of in vivo herb–drug interaction induced by this kind of inhibition, the ginsenoside Rg{sub 3} was selected as an example, and the inhibition kinetic type and parameters (K{sub i}) were determined. Rg{sub 3} competitively inhibited UGT1A7, 2B7 and 2B15-catalyzed 4-MU glucuronidation reaction, and exerted noncompetitive inhibition towards UGT1A8-catalyzed 4-MU glucuronidation. The inhibition parameters (K{sub i} values) were calculated to be 22.6, 7.9, 1.9, and 2.0 μM for UGT1A7, 1A8, 2B7 and 2B15. Using human maximum plasma concentration of Rg{sub 3} (400 ng/ml (0.5 μM)) after intramuscular injection of 60 mg Rg{sub 3}, the area under the plasma concentration-time curve (AUC) was extrapolated to increase by 2.2%, 6.3%, 26.3%, and 25% for the co-administered drugs completely undergoing the metabolism catalyzed by UGT1A7, 1A8, 2B7 and 2B15, respectively. All these results indicated that the ginsenosides' inhibition towards UGT isoforms might be an important reason for ginseng–drug interaction. - Highlights: ► Structure-dependent inhibition

Comparative analysis of the expression level of recombinant ginsenoside-transforming β-glucosidase in GRAS hosts and mass production of the ginsenoside Rh2-Mix

PubMed Central

Siddiqi, Muhammad Zubair; Cui, Chang-Hao; Park, Seul-Ki; Han, Nam Soo; Kim, Sun-Chang

2017-01-01

The ginsenoside Rh2, a pharmaceutically active component of ginseng, is known to have anticancer and antitumor effects. However, white ginseng and red ginseng have extremely low concentrations of Rh2 or Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3]. To enhance the production of food-grade ginsenoside Rh2, an edible enzymatic bioconversion technique was developed adopting GRAS host strains. A β-glucosidase (BglPm), which has ginsenoside conversion ability, was expressed in three GRAS host strains (Corynebacterium glutamicum, Saccharomyces cerevisiae and Lactococus lactis) by using a different vector system. Enzyme activity in these three GRAS hosts were 75.4%, 11.5%, and 9.3%, respectively, compared to that in the E. coli pGEX 4T-1 expression system. The highly expressed BglPm_C in C. glutamicum can effectively transform the ginsenoside Rg3-Mix [20(S)-Rg3, 20(R)-Rg3, Rk1, Rg5] to Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2, Rh3] using a scaled-up biotransformation reaction, which was performed in a 10-L jar fermenter at pH 6.5/7.0 and 37°C for 24 h. To our knowledge, this is the first report in which 50 g of PPD-Mix (Rb1, Rb2, Rb3, Rc, and Rd) as a starting substrate was converted to ginsenoside Rg3-Mix by acid heat treatment and then 24.5-g Rh2-Mix was obtained by enzymatic transformation of Rg3-Mix through by BglPm_C. Utilization of this enzymatic method adopting a GRAS host could be usefully exploited in the preparation of ginsenoside Rh2-Mix in cosmetics, functional food, and pharmaceutical industries, thereby replacing the E. coli expression system. PMID:28423055

Protective effects of ginsenoside Rg1 against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice through inhibiting toll-like receptor 4 signaling pathway.

PubMed

Ning, Chenqing; Gao, Xiaoguang; Wang, Changyuan; Huo, Xiaokui; Liu, Zhihao; Sun, Huijun; Yang, Xiaobo; Sun, Pengyuan; Ma, Xiaodong; Meng, Qiang; Liu, Kexin

2018-06-11

Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular mechanism in vivo and in vitro. Mice were pretreated with Rg1 for three days prior to LPS (40 μg/kg)/D-GalN (700 mg/kg) administration. The results showed that Rg1 improved the survival rate and reduced the liver to body weight ratios in mice. Rg1 also reduced the production of oxidative markers such as MDA and MPO induced by LPS/D-GalN. In addition, Rg1 significantly decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-1β, Mip-2, Mcp-1, iNOS, and increased the activity of anti-inflammatory cytokine IL-10. Moreover, Rg1 inhibited the protein expression of TLR4 and its downstream genes including NF-κB and MAPKs, which are involved in inflammatory response. Rg1 dramatically reduced oxidative stress by regulating the expression of efflux transporters Mrp2 and various enzymes including GCLC, GCLM, HO-1 and NQO1. However, the changes in these genes and protein induced by Rg1 were abrogated by TLR4 antagonist TAK-242 in vitro. In conclusion, Rg1 had hepatoprotective effect on LPS/D-GalN-induced ALI in mice. The protection may be associated with the inhibition of TLR4. These findings suggest that Rg1 may be a promising agent for prevention against ALI. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-10-01

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

Protective Effects of Processed Ginseng and Its Active Ginsenosides on Cisplatin-Induced Nephrotoxicity: In Vitro and in Vivo Studies.

PubMed

Park, Jun Yeon; Choi, Pilju; Kim, Taejung; Ko, Hyeonseok; Kim, Ho-kyong; Kang, Ki Sung; Ham, Jungyeob

2015-07-01

Although cisplatin can dramatically improve the survival rate in cancer patients, its use is limited by its nephrotoxicity. Previous investigations showed that Panax ginseng contains components that exhibit protective activity against cisplatin-induced nephropathy. The aim of the present study is to investigate the effect of microwave-assisted processing on the protective effect of ginseng and identify ginsenosides that are active against cisplatin-induced kidney damage to evaluate the potential of using ginseng in the management of nephrotoxicity. The LLC-PK1 cell damage by cisplatin was significantly decreased by treatment with microwave-processed ginseng (MG) and ginsenosides Rg3, Rg5, and Rk1. Reduced expression of p53 and c-Jun N-terminal kinase proteins by cisplatin in LLC-PK1 cells was markedly ameliorated after Rg3 and Rg5/Rk1 treatment. Additionally, elevated expression of cleaved caspase-3 was significantly reduced by ginsenosides Rg5, Rk1, and with even greater potency, Rg3. Moreover, MG and its fraction containing active ginsenosides showed protective effects against cisplatin-induced nephropathy in mice. We found that ginsenosides Rg3, Rg5, and Rk1 generated during the heat treatment of ginseng ameliorate renal damage by regulating inflammation and apoptosis. Results of current experiments provide evidence of the renoprotective effects and therapeutic potential of MG and its active ginsenosides, both in vitro and in vivo.

20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis.

PubMed

Zhou, Yan-Dan; Hou, Jin-Gang; Liu, Wei; Ren, Shen; Wang, Ying-Ping; Zhang, Rui; Chen, Chen; Wang, Zi; Li, Wei

2018-06-01

Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. Copyright © 2018 Elsevier B.V. All rights reserved.

Changes in ginsenoside compositions and antioxidant activities of hydroponic-cultured ginseng roots and leaves with heating temperature

PubMed Central

Hwang, Cho Rong; Lee, Sang Hoon; Jang, Gwi Yeong; Hwang, In Guk; Kim, Hyun Young; Woo, Koan Sik; Lee, Junsoo; Jeong, Heon Sang

2014-01-01

Background This study evaluated changes in ginsenoside compositions and antioxidant activities in hydroponic-cultured ginseng roots (HGR) and leaves (HGL) with heating temperature. Methods Heat treatment was performed at temperatures of 90°C, 110°C, 130°C, and 150°C for 2 hours. Results The ginsenoside content varied significantly with heating temperature. The levels of ginsenosides Rg1 and Re in HGR decreased with increasing heating temperature. Ginsenosides F2, F4, Rk3, Rh4, Rg3 (S form), Rg3 (R form), Rk1, and Rg5, which were absent in the raw ginseng, were formed after heat treatment. The levels of ginsenosides Rg1, Re, Rf, and Rb1 in HGL decreased with increasing heating temperature. Conversely, ginsenosides Rk3, Rh4, Rg3 (R form), Rk1, and Rg5 increased with increasing heating temperature. In addition, ginsenoside contents of heated HGL were slightly higher than those of HGR. The highest extraction yield was 14.39% at 130°C, whereas the lowest value was 10.30% at 150°C. After heating, polyphenol contents of HGR and HGL increased from 0.43 mg gallic acid equivalent/g (mg GAE eq/g) and 0.74 mg GAE eq/g to 6.16 mg GAE eq/g and 2.86 mg GAE eq/g, respectively. Conclusion Antioxidant activities of HGR and HGL, measured by 1,1-diphenyl-2-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging ability, increased with increasing heating temperature. These results may aid in improving the biological activity and quality of ginseng subjected to heat treatments. PMID:25378992

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

PubMed

Gao, Shengli; Kushida, Hirotaka; Makino, Toshiaki

2017-01-01

Recent pharmacokinetic studies have revealed that ginsenosides, the major ingredients of ginseng (the roots of Panax ginseng), are present in the plasma collected from subjects receiving ginseng, and speculated that ginsenosides might be actively transported via glucose transporters. We evaluated whether ginsenosides Rb 1 and Rg 1 , 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 IC 50 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, Rg 3 , Rh 2 , F 2 and compound K, exhibited significant inhibitory effects on SGLT1, with ginsenoside F 2 having the highest activity with an IC 50 value of 23.0 µM. Next, we measured the uptake of ginsenoside F 2 and compound K into Caco-2 cells, a cell line frequently used to evaluate the intestinal absorption of drugs. The uptake of ginsenoside F 2 and compound K into Caco-2 cells was not competitively inhibited by glucose. Furthermore, the uptake of ginsenoside F 2 and compound K into SGLT1-overexpressing HEK293 cells was not significantly higher than into mock cells. Ginsenoside F 2 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.

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

PubMed Central

Gum, Sang Il; Cho, Min Kyung

2013-01-01

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. PMID:23766864

Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.

PubMed

Ardah, Mustafa T; Paleologou, Katerina E; Lv, Guohua; Menon, Sindhu A; Abul Khair, Salema B; Lu, Jia-Hong; Safieh-Garabedian, Bared; Al-Hayani, Abdulmonem A; Eliezer, David; Li, Min; El-Agnaf, Omar M A

2015-02-01

Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

PubMed

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

2014-12-04

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.

Pivotal Roles of Ginsenoside Rg3 in Tumor Apoptosis Through Regulation of Reactive Oxygen Species.

PubMed

Sun, Hwa Yeon; Lee, Jun Hee; Han, Yong-Seok; Yoon, Yeo Min; Yun, Chul Won; Kim, Jae Heon; Song, Yun Seob; Lee, Sang Hun

2016-09-01

Elevated production of reactive oxygen species (ROS) is observed in various cancer types and pathophysiological conditions. In cancer cells, ROS induce cell proliferation, genetic instability, and a malignant phenotype. Ginsenoside Rg3 is the main pharmacologically active component in ginseng and has been reported to have an antioxidant effect. To overcome lung cancer by regulating the ROS level, we investigated the antitumor effect and mechanism of Rg3 and its antioxidative property on Lewis lung carcinoma (LLC) cells. Inhibition of ROS was suppressed in LLC cells by Rg3 treatment, and these cells were used to investigate the antioxidant, antiproliferative, and antitumor effects in LLC cells. ROS production was increased in cells grown in serum-containing media (conditioned media) compared to those grown in serum-free media. The high level of ROS induced LLC cell proliferation, but treatment with Rg3 (200 ng/ml) resulted in reduction of ROS, leading to inhibition of cell proliferation. Treatment with Rg3 significantly reduced cyclin and cyclin-dependent kinase expression in LLC cells. Additionally, Rg3 treatment significantly suppressed activation of mitogen-activated protein kinases and induced LLC cell apoptosis through activation of pro-apoptotic proteins and suppression of anti-apoptotic proteins. Taken together, these findings demonstrate the role of Rg3 in reduction of the intracellular ROS level, attenuation of proliferation via augmentation of cell cycle- and cell proliferation-associated proteins, and activation of apoptosis through regulation of apoptosis-associated proteins in LLC. These findings suggest that Rg3 could be used as a therapeutic agent in lung cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways.

PubMed

Park, Hye-Min; Kim, Shang-Jin; Kim, Jin-Shang; Kang, Hyung-Sub

2012-08-01

Panax ginseng (P. ginseng) has anti-cancer effects in several cancer models. Ginsenosides are the main bioactive components in P. ginseng. Korean red ginseng (KRG) extract can potently kill various cancer cells and ginsenosides Rg3 (GRg3) and Rh2 (GRh2) are the primary ginsenosides in KRG. This study was carried out to examine whether KRG and its primary ginsenosides (GRg3 and GRh2) affect apoptosis of human hepatocellular carcinoma cells (Hep3B). KRG, GRg3 and GRh2 have obvious cytotoxic and apoptotic effects in Hep3B cells as evidenced by a decrease in cell viability and mitochondria membrane potential, but an increase in LDH release. In the mitochondria-mediated apoptosis pathway, KRG, GRg3 and GRh2 have the ability to stimulate the release of mitochondrial cytochrome c, activation of caspase-3 and Bax protein, inhibition of Bcl-2 protein and production of intracellular reactive oxygen species in Hep3B cells. These results suggest that KRG, GRg3 and GRh2 may induce apoptosis by direct activation of the mitochondrial pathway. Copyright © 2012 Elsevier Ltd. All rights reserved.

Simultaneous Determination of Multiple Ginsenosides in Panax ginseng Herbal Medicines with One Single Reference Standard.

PubMed

Wu, Chunwei; Guan, Qingxiao; Wang, Shumei; Rong, Yueying

2017-01-01

Root of Panax ginseng C. A. Mey (Renseng in Chinese) is a famous Traditional Chinese Medicine. Ginsenosides are the major bioactive components. However, the shortage and high cost of some ginsenoside reference standards make it is difficult for quality control of P. ginseng . A method, single standard for determination of multicomponents (SSDMC), was developed for the simultaneous determination of nine ginsenosides in P. ginseng (ginsenoside Rg 1 , Re, Rf, Rg 2 , Rb 1 , Rc, Rb 2 , Rb 3 , Rd). The analytes were separated on Inertsil ODS-3 C18 (250 mm × 4.6 mm, 5 μm) with gradient elution of acetonitrile and water. The flow rate was 1 mL/min and detection wavelength was set at 203 nm. The feasibility and accuracy of SSDMC were checked by the external standard method, and various high-performance liquid chromatographic (HPLC) instruments and chromatographic conditions were investigated to verify its applicability. Using ginsenoside Rg 1 as the internal reference substance, the contents of other eight ginsenosides were calculated according to conversion factors (F) by HPLC. The method was validated with linearity ( r 2 ≥ 0.9990), precision (relative standard deviation [RSD] ≤2.9%), accuracy (97.5%-100.8%, RSD ≤ 1.6%), repeatability, and stability. There was no significant difference between the SSDMC method and the external standard method. New SSDMC method could be considered as an ideal mean to analyze the components for which reference standards are not readily available. A method, single standard for determination of multicomponents (SSDMC), was established by high-performance liquid chromatography for the simultaneous determination of nine ginsenosides in Panax ginseng (ginsenoside Rg1, Re, Rf, Rg2, Rb1, Rc, Rb2, Rb3, Rd)Various chromatographic conditions were investigated to verify applicability of FsThe feasibility and accuracy of SSDMC were checked by the external standard method. Abbreviations used: DRT: Different value of retention time; F: Conversion

Effect of ginsenoside Rg3 on tyrosine hydroxylase and related mechanisms in the forced swimming-induced fatigue rats.

PubMed

Xu, Yuxia; Zhang, Peng; Wang, Chu; Shan, Ye; Wang, Dandan; Qian, Fenglei; Sun, Mengwei; Zhu, Cuiqing

2013-10-28

Ginsenoside Rg3 has shown multiple pharmacological activities and been considered as one of the most promising approaches for fatigue treatment. However, little is known about the cellular and molecular mechanisms of Rg3 on anti-fatigue and the effect of Rg3 on dopaminergic system has not been reported yet. The major aim of this study is to investigate the effect of Rg3 on TH expression and the related biochemical parameters, such as PKAα, ERK1/2, Akt and α-synuclein in brain of fatigue rats. Weight-loaded forced swimming was performed to establish an animal model of fatigue. Rg3 (10mg/kg, 50mg/kg and 100mg/kg) was intragastrically administrated before swimming. The effect of Rg3 on the expression and phosphorylation of TH and TH-related proteins in fatigue rats or in SH-SY5Y cells was assessed with western blotting. HPLC was used to examine the level of DA and DOPAC in the fatigue rats tissues. TH and phosphorylated TH were decreased in different brain regions of which ventral midbrain were less affected in weight-loaded forced swimming rats. Pretreatment with Rg3 significantly suppressed fatigue-induced decrease expression of TH and TH phosphorylation. Also treatment with Rg3 reversed the decrease expression of PKAα as well as the phosphorylation of ERK1/2 and Akt which were induced by weight-loaded forced swimming. Moreover, weight-loaded swimming could induce the increase expression of α-synuclein in hippocampus and midbrain, while suppressed α-synuclein expression in striatum and prefrontal cortex. Furthermore, Rg3 could induce the increase of TH expression and phosphorylation which was accompanied with elevated expression and phosphorylation of related kinase proteins in vitro, while the inhibitors of kinase proteins could suppress these effects of Rg3. In addition, HPLC results showed that Rg3 could reverse the weight-loaded swimming-induced increase of DOPAC/DA ratio. Our data suggest that fatigue can induce the decrease of DA which might partially

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj

2010-08-01

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

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

PubMed

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

2013-07-01

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 < 0.05). Total ginsenosides increased by 184% while Rg1 + Rb1 increased by 273%. Application of these conditions significantly increased total ginsenosides by 49% and Rg1 + Rb1 by 103% compared to HHP treatment alone (P < 0.05). The effect of HHP on increased yield of ginsenosides is likely due in part, to acceleration of enzyme activity. Thus HHP-EH significantly improves the extraction of ginsenosides from fresh ginseng roots.

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

PubMed Central

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

2007-01-01

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

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

PubMed

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

2016-10-28

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.

Metabonomics Approach to Assessing the Metabolism Variation and Endoexogenous Metabolic Interaction of Ginsenosides in Cold Stress Rats.

PubMed

Zhang, Zhihao; Wang, Xiaoyan; Wang, Jingcheng; Jia, Zhiying; Liu, Yumin; Xie, Xie; Wang, Chongchong; Jia, Wei

2016-06-03

Metabolic profiling technology, a massive information provider, has promoted the understanding of the metabolism of multicomponent medicines and its interactions with endogenous metabolites, which was previously a challenge in clarification. In this study, an untargeted GC/MS-based approach was employed to investigate the urinary metabolite profile in rats with oral administration of ginsenosides and the control group. Significant changes of urinary metabolites contents were observed in the total ginsenosides group, revealing the impact of ginsenosides as indicated by the up- or down-regulation of several pathways involving neurotransmitter-related metabolites, tricarboxylic acid (TCA) cycle, fatty acids β-oxidation, and intestinal microflora metabolites. Meanwhile, a targeted UPLC-QQQ/MS-based metabonomic approach was developed to investigate the changes of urinary ginsenoside metabolites during the process of acute cold stress. Metabolic analysis indicated that upstream ginsenosides (rg1, re, and rf) increased significantly, whereas downstream ginsenosides (ck, ppd, and ppt) decreased correspondingly after cold exposure. Finally, the relationships between ginsenosides and significantly changed metabolites were investigated by correlation analysis.

[Study on extraction and purification process of total ginsenosides from Radix Ginseng].

PubMed

Xie, Li-Ling; Ren, Li; Lai, Xian-Sheng; Cao, Jun-Hui; Mo, Quan-Yi; Chen, Wei-Wen

2009-10-01

To optimize the technological parameters of the extraction and purification process of total ginsenosides from Radix Ginseng. With the contents of ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1, the orthogonal design was adopted to optimize the extraction process. The purification process was studied by optimizing the elutive ratio of total ginsenosides as the marker. HPLC and spectrophotometer were employed for the study. The optimum conditions were as follows:Using 8 times volume of 75% ethanol extracting for 120 minutes and 2 times, the extraction temperature was 85 degrees C. AB-8 macroporous resin was selected, and the eluant was 4 BV 70% ethanol. The optimal conditions of extracting and purifying the total ginsenosides from Radix Ginseng is feasible.

Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway.

PubMed

Xue, Li-Ping; Fu, Xiao-Lin; Hu, Min; Zhang, Li-Wei; Li, Ya-Di; Peng, Ya-Li; Ding, Peng

2018-07-02

Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes mellitus. However, the roles and mechanisms of Rg1 in proliferative diabetic retinopathy (PDR) are still unclear. In the present study, we aimed to investigate the effects of Rg1 on mesenchymal activation of high-glucose (HG) cultured müller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down-regulate TIMP-2, and promote mesenchymal activation in Müller cells. And Rg1 inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Müller cells. HG up-regulates Zeb1 and lncRNA RP11-982M15.8, and down-regulates miR-2113, and Rg1 inhibits these effects of HG. Both inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly restored the HG induced mesenchymal activasion. Taken together, our findings suggested that Rg1 inhibited HG-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway. Copyright © 2018. Published by Elsevier Inc.

Effect of white, red and black ginseng on physicochemical properties and ginsenosides.

PubMed

Jin, Yan; Kim, Yeon-Ju; Jeon, Ji-Na; Wang, Chao; Min, Jin-Woo; Noh, Hae-Yong; Yang, Deok-Chun

2015-06-01

A systematic comparison of the ginsenosides and physicochemical properties of white ginseng (WG), red ginseng (RG) and black ginseng (BG) was performed. The purpose of the present study was to identify the effects of the physicochemical properties by steaming process. During the steaming process, ginsenosides transform into specific ginsenosides by hydrolysis, dehydration and isomerization at C-3, C-6 or C-20. Steaming ginseng led to a significant increase in reducing sugar, acidic polysaccharide and phenolic compounds content. Antioxidative properties were investigated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, compared with BHA (Butylated hydroxyanisole). RG and BG exhibited higher antioxidant activity than WG. The maximum residue level for Benzo(a)pyrene was established to 5 μg/kg in food products. The levels of benzo(a)pyrene in WG and RG were not detected. Benzo(a)pyrene was detected in the BG, the content was 0.17 μg/kg. The scientific achievements of the present study could help consumers to choose different type of ginseng products available on the market.

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

PubMed

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

2014-07-01

Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. Copyright © 2013 John Wiley & Sons, Ltd.

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

PubMed

Xiao, Dan; Yue, Hao; Xiu, Yang; Sun, Xiuli; Wang, YiBo; Liu, ShuYing

2015-10-01

Ginseng (the roots of Panax ginseng Meyer) is a well-known traditional Oriental medicine and is now widely used as a health food. It contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. It has recently been reported that the qualitative and quantitative properties of ginsenosides found in ginseng may differ, depending on cultivation regions, ages, species, and so on. Therefore, it is necessary to study these variations with respect to cultivation ages and regions. In this study, 3-6-yr-old roots of P. ginseng were collected from three different cultivation regions. The contents of five ginsenosides (Rb1, Rd, Rc, Re, and Rgl) were measured by rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The Kruskal-Wallis Rank sum test and multiple t test were used for comparative analysis of the data to evaluate the dynamic changes in the accumulation of these ginsenosides affected by cultivation regions and ages. The content and composition of ginsenosides varied significantly among specimens collected from different cultivation regions and having different cultivation ages. For all samples, the content of Rg1 and Re ginsenosides increases with age and this rate of increase is different for each sample. The contents of Rb1, Rc, and Rd varied with cultivation ages in samples from different cultivation regions; especially, Rb1 from a 6-yr-old root showed approximately twofold variation among the samples from three cultivation regions. Furthermore, the content of Rb1 highly correlated with that of Rd (r = 0.89 across all locations and ages). 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.

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

PubMed

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

2015-09-01

Ginsenosides, the main pharmacologically active natural compounds in ginseng (Panax ginseng), are mostly the glycosylated products of protopanaxadiol (PPD) and protopanaxatriol (PPT). No uridine diphosphate glycosyltransferase (UGT), which catalyzes PPT to produce PPT-type ginsenosides, has yet been reported. Here, we show that UGTPg1, which has been demonstrated to regio-specifically glycosylate the C20-OH of PPD, also specifically glycosylates the C20-OH of PPT to produce bioactive ginsenoside F1. We report the characterization of four novel UGT genes isolated from P. ginseng, sharing high deduced amino acid identity (>84%) with UGTPg1. We demonstrate that UGTPg100 specifically glycosylates the C6-OH of PPT to produce bioactive ginsenoside Rh1, and UGTPg101 catalyzes PPT to produce F1, followed by the generation of ginsenoside Rg1 from F1. However, UGTPg102 and UGTPg103 were found to have no detectable activity on PPT. Through structural modeling and site-directed mutagenesis, we identified several key amino acids of these UGTs that may play important roles in determining their activities and substrate regio-specificities. Moreover, we constructed yeast recombinants to biosynthesize F1 and Rh1 by introducing the genetically engineered PPT-producing pathway and UGTPg1 or UGTPg100. Our study reveals the possible biosynthetic pathways of PPT-type ginsenosides in Panax plants, and provides a sound manufacturing approach for bioactive PPT-type ginsenosides in yeast via synthetic biology strategies. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2013-12-15

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.

Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides.

PubMed

Chen, Feng; Eckman, Elizabeth A; Eckman, Christopher B

2006-06-01

For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease.

Development of superparamagnetic iron oxide nanoparticles via direct conjugation with ginsenosides and its in-vitro study.

PubMed

Singh, Hina; Du, Juan; Singh, Priyanka; Mavlonov, Gafurjon Tom; Yi, Tae Hoo

2018-06-01

The current study focused on direct conjugation of superparamagnetic iron oxide nanoparticles (SPIONs) with ginsenosides CK and Rg3. The direct conjugation approach was low-cost, eco-friendly, simple, fast and high yield. The synthesized conjugates (SPION-CK and SPION-Rg3) were characterized by field emission transmission electron microscopy, dynamic light scattering, zeta potential, X-ray diffractometer, and magnetometer. The characterization results confirmed the formation of SPIONs conjugates. The maximum attaching percentage for ginsenosides to SPIONs was found to be 5%. In vitro cytotoxicity assay in HaCaT keratinocyte cells revealed that the conjugates were non-cytotoxic to normal cells. Moreover, the anti-inflammatory activity of SPION-CK and SPION-Rg3 were investigated. The expression of reactive oxygen species (ROS) in lipopolysaccharide-activated RAW 264.7 (murine macrophage cells) were inhibited by SPIONs conjugates in a dose-dependent manner. In addition, SPION-CK and SPION-Rg3 significantly reduced the production of nitric oxide and inducible nitric oxide synthase (iNOS) in a dose-dependent manner in the lipopolysaccharide-induced RAW 264.7 cells. Overall the results suggested that the SPIONs were conjugated with ginsenosides CK and Rg3 by using direct conjugation approach were non-cytotoxic and can be used as a carrier for intracellular release of ginsenosides in inflammatory diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-09-01

A method of ionic liquid salt aqueous two-phase extraction coupled with high-performance liquid chromatography has been developed for the analysis of seven rare ginsenosides including Rg6 , F4 , 20(S)-Rg3 , 20(R)-Rg3 , Rk3 , Rk1 , and Rg5 in Xue-Sai-Tong injection. The injection was mixed with ionic liquid 1-butyl-3-methylimidazolium bromide aqueous solution, and a mixture was obtained. With the addition of sodium dodecyl sulfate and dipotassium phosphate into the mixture, the aqueous two-phase mixture was formed after ultrasonic treatment and centrifuged. Rare ginsenosides were extracted into the upper phase. To obtain a high extraction factors, various influences were considered systematically, such as the volume of ionic liquid, the category and amount of salts, the amount of sodium dodecyl sulfate, the pH value of system, and the time of ultrasonic treatment. Under the optimal condition, rare ginsenosides in Xue-Sai-Tong injection were enriched and detected, the recoveries of seven rare ginsenosides ranged from 90.05 to 112.55%, while relative standard deviations were lower than 2.50%. The developed method was reliable, rapid and sensitive for the determination of seven rare ginsenosides in the injections. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2017-02-01

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

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

PubMed

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

2015-03-01

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

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

PubMed Central

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

2015-01-01

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

Porosity changes and retention of ginsenosides in North American ginseng root using different dehydration processes.

PubMed

Purnama, Monica; Yaghmaee, Parastoo; Durance, Tim D; Kitts, David D

2010-09-01

Air drying (AD), freeze-drying (FD), and vacuum-microwave drying (VMD) were applied to fresh North American ginseng roots to evaluate the effect of different drying techniques on pore characteristics and the subsequent recovery of ginsenoside content. FD ginseng root produced the lowest reductions in both total moisture content and water activity (P < 0.05), with no differences noted between Ontario or British Columbia ginseng. Ginseng roots from Ontario and British Columbia sources were therefore pooled to conduct the root porosity and ginsenoside measurements. Among samples, FD ginseng obtained the highest total porosity followed by VMD and AD, respectively (P < 0.05). All dehydrated samples had a porous structure with sizes that ranged from 0.002 μm to 172 μm, dominated by macropores (>1.5 μm). Pore characteristics of dried ginseng root were shown to affect recovery of ginsenosides, with the general trend being an increase in total porosity resulting in an increase in total ginsenoside recovered. High performance liquid chromatography results obtained on specific ginsenosides showed that AD of ginseng root resulted in the lowest recovery of total ginsenosides, most notably, Rg1 and Rb1, followed by VMD and FD, respectively. There was no specific difference in total ginsenoside recovery from roots dried at increasing power of VMD.

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

PubMed

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

2016-09-01

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.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-03-10

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.

Ruggedness/robustness evaluation and system suitability test on United States Pharmacopoeia XXVI assay ginsenosides in Asian and American ginseng by high-performance liquid chromatography.

PubMed

Li, Yong-Guo; Chen, Ming; Chou, Gui-Xin; Wang, Zheng-Tao; Hu, Zhi-Bi

2004-09-03

The work of the ruggedness/robustness evaluation and system suitability tests was oriented to profound understand the practicability of using assay methods issued by United States Pharmacopoeia (USP XXVI and XXVII) for ginsenosides in Asian ginseng and American ginseng. The items chosen for the method validation included quantitative related items such as recovery of Rg(1) and Rb(1), respectively, and qualitative related items such as resolution, theoretical plate number, relative retention time of two critical-band-pairs, Rg(1)/Re and Rb(1) with its neighboring peak, respectively. Totally, 16 column types were used for comparison of different vendors, different packing materials, different size, etc. and five sets of LC systems and two laboratories were involved in comparing the data of both quantitative and qualitative items. The results showed that different packing materials of columns used might significantly alters separation. The column packing material Hypersil afforded the preferable separating for the ginsenosides. No significant difference was observed from the different instrumentations and inter-laboratories. Our results suggest a modification of the system suitability test as given in USP26-NF21 and the latest version of USP27-NF22, which was not suitable for most systems. Using resolutions of Rg(1)/Re and Rb(1) with its neighboring peak as critical parameters for the ginsenosides assay and omitting the relative retention time of both Rg(1)/Re and Rb(1) with its neighboring peak is our suggestion for a more reasonable, yet practicable system suitability. Six typical chromatograms gain from different columns were figured out as well.

Influence of polymeric carrier on the disposition and retention of 20(R)-ginsenoside-rg3-loaded swellable microparticles in the lung.

PubMed

Wang, Xiuhua; Zhang, Xiao; Fan, Linlin; He, Huan; Zhang, Xiaofei; Zhang, Yuyang; Mao, Shirui

2018-02-01

The objective of this study was to investigate the influence of differently charged biocompatible polymers, including chitosan (CS), hyaluronic acid (HA), and hydroxypropyl cellulose (HPC), on the disposition and retention of 20(R)-ginsenoside-rg3 (Rg3)-loaded swellable microparticles in the lung. A high-pressure homogenization method combined with spray drying was used to prepare Rg3-loaded microparticles. In vitro aerodynamic performance of different microparticles was characterized by the Next Generation Impactor (NGI). Retention of the swellable microparticles in the rat lung was investigated using bronchoalveolar lavage fluid method. Influence of drug loading, polymer molecular weight, and polymer charge on the properties of the swellable microparticles was investigated. It was found that drug loading had no significant influence on experimental mass median aerodynamic diameter (MMAD e ) and fine particle fraction (FPF). Increasing polymer molecular weight caused no remarkable change in MMAD e value, but the FPF value decreased with the increase of polymer molecular weight. At the same molecular weight level, polymer structure and charge had no statistical influence on the in vitro aerodynamic properties of the microparticles and lung disposition, but it influenced the swelling and bioadhesion behavior and therefore lung retention profile. Desirable phagocytosis escapement and inhibition of A549 cell proliferation were achieved for the developed swellable microparticles. In conclusion, the lung retention of swellable microparticles can be adjusted by selecting polymeric carriers with different structure and charge.

The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity.

PubMed

Zhang, Bing; Zhou, Wen-Jie; Gu, Chun-Jie; Wu, Ke; Yang, Hui-Li; Mei, Jie; Yu, Jia-Jun; Hou, Xiao-Fan; Sun, Jian-Song; Xu, Feng-Yuan; Li, Da-Jin; Jin, Li-Ping; Li, Ming-Qing

2018-05-14

Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.

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

PubMed

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

2016-01-01

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

Characterization of Paenibacillus sp. MBT213 Isolated from Raw Milk and Its Ability to Convert Ginsenoside Rb1 into Ginsenoside Rd from Panax ginseng

PubMed Central

Cho, Soo Hyun; Park, Young W; Song, Gyu Yong

2017-01-01

This study was conducted to isolate and characterize Paenibacillus sp. MBT213 possessing β-glucosidase activity from raw milk, and examine the enzymatic capacity on the hydrolysis of a major ginsenoside (Rb1). Strain MBT213 was found to have a high hydrolytic ability on ginsenoside Rb1 by Esculin Iron Agar test. 16S rDNA analysis revealed that MBT213 was Paenibacillu sp. Crude enzyme of MBT213 strain exhibited high conversion capacity on ginsenoside Rb1 into ginsenoside Rd proven by TLC and HPLC analyses. The API ZYM kit confirmed that Paenibacillu sp. MBT213 exerted higher β-glucosidase and β-galactosidase activity than other strains. Optimum pH and temperature for crude enzyme were found at 7.0 and 35°C in hydrolysis of ginsenoside Rb1. After 10 d of optimal reaction conditions for the crude enzyme, ginsenoside Rb1 fully converted to ginsenoside Rd. Ginseng roots (20%) were fermented for 14 d, and analyzed by HPLC showed that amount of ginsenoside Rb1 significantly decreased, while that of ginsenoside Rd was significantly increased. The study confirmed that the β-glucosidase produced by Paenibacillus sp. MBT213 can hydrolyze the major ginsenoside Rb1 and convert to Rd during fermentation of the ginseng. The β-glucosidase activity of this novel Paenibacillus sp. MBT213 strain may be utilized in development of variety of health foods, dairy foods and pharmaceutical products. PMID:29147097

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

PubMed

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

2013-06-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-01

Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line.

PubMed

Popovich, David G; Kitts, David D

2002-10-01

Ginsenosides of the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol classifications including the aglycones, protopanaxadiol (PD), protopanaxatriol (PT), and ginsenosides Rh2 and Rh1 were shown to posses characteristic effects on the proliferation of human leukemia cells (THP-1). A similar efficacy was not apparent for ginsenoside Rg3. The concentrations to inhibit 50% of cells (LC50) for PD, Rh2, PT, and Rh1 were 13, 15, 19, and 210 microg/mL, respectively. PD and PT induced DNA fragmentation at the LC50 after 72 h of treatment, compared to Rh2, Rh1, dexamethasone, and untreated cells. Cell-cycle analysis confirmed apoptosis with PD and PT treatment of THP-1 cells resulting in a buildup of sub-G1 cells after 24, 48, and 72 h of treatment. Rh2 and dexamethasone treatments also increased apoptotic cells after 24 h, whereas Rh1 did not. After 48 and 72 h, Rh2, Rh1, and dexamethasone similarly increased apoptosis, but these effects were significantly (P<0.05) lower than those observed for both PD and PT treatments. Furthermore, treatments that produced the largest buildup of apoptotic cells were also found to have the largest release of lactate dehydrogenase. It can be concluded from these studies that the presence of sugars in PD and PT aglycone structures reduces the potency to induce apoptosis, and alternately alter membrane integrity. These cytotoxic effects were different to THP-1 cells than dexamethasone.

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

PubMed

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

2017-02-03

A hyphenated accelerated solvent extraction (ASE) technique was elaborately coupled with centrifugal partition chromatography (CPC), ultra-high-performance liquid chromatography (UHPLC), and photo-diode array detector (PDA). This approach was applied to obtain low-polar ginsenoside fractions from the leaves of Panax ginseng. The CPC fractions were isolated and analyzed using the hyphenated technique, and followed by testing and evaluation of their aromatase inhibitory effects. Subsequently, the aromatase inhibition rates of the compositions in the CPC fractions were calculated using a multivariable linear regression model. A biphasic ethyl acetate/n-butanol/ethanol/water solvent system with respective volume ratios of 10:2:2:8 was used for the ASE and CPC separation of 200g of leaves of P. ginseng raw material. The (lower) aqueous phase of the abovementioned solvent system was used as the extraction solvent. The ginsenosides were subjected to ASE, and the extraction solution was pumped into the sample loop and then directly into the CPC column. The CPC fractions were collected and monitored by an online UHPLC/PDA system at 5-min intervals. The aromatase inhibitory activities of CPC fractions were analyzed by a fluorescence method, with mathematical calculations indicating that the inhibition rates of ginsenosides Rk 1 , Rg 5 , Rs 5 , 20R-Rg 3 , and Rs 4 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.

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

PubMed

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

2015-09-25

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells.

PubMed

Zhou, Yuanyuan; Zheng, Xia; Lu, Jiaojiao; Chen, Wei; Li, Xu; Zhao, Le

2018-01-01

The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host

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

PubMed

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

2017-02-01

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

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

PubMed

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

2016-01-01

Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar-utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high-performance liquid chromatography coupled with evaporative light-scattering detection. The β-glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20-C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α-L-arabinopyranosidase and α-L-arabinofuranosidase, respectively. The fermentation product exerted dose-dependent cytotoxicity in HCT-15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana-fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use. Copyright © 2015 John Wiley & Sons, Ltd.

Intraconversion of Polar Ginsenosides, Their Transformation into Less-Polar Ginsenosides, and Ginsenoside Acetylation in Ginseng Flowers upon Baking and Steaming.

PubMed

Li, Xiang; Yao, Fan; Fan, Hang; Li, Ke; Sun, Liwei; Liu, Yujun

2018-03-26

Heating is a traditional method used in ginseng root processing, however, there aren't reports on differences resulting from baking and steaming. Moreover, ginseng flowers, with 5.06 times more total saponins than ginseng root, are not fully taken advantage of for their ginsenosides. Transformation mechanisms of ginsenosides in ginseng flowers upon baking and steaming were thus explored. HPLC using authentic standards of 20 ginsenosides and UPLC-QTOF-MS/MS were used to quantify and identify ginsenosides, respectively, in ginseng flowers baked or steamed at different temperatures and durations. Results show that baking and steaming caused a 3.2-fold increase in ginsenoside species existed in unheated ginseng flowers (20/64 ginsenosides) and transformation of a certain amount of polar ginsenosides into numerous less polar ginsenosides. Among the 20 ginsenosides with standards, polar ginsenosides were abundant in ginseng flowers baked or steamed at lower temperatures, whereas less polar ginsenosides occurred and were enriched at higher temperatures. Furthermore, the two types of heating treatments could generate mostly similar ginsenosides, but steaming was much efficient than baking in transforming polar- into less polar ginsenosides, with steaming at 120 °C being comparably equivalent to baking at 150 °C. Moreover, both the two heating methods triggered ginsenoside acetylation and thus caused formation of 16 acetylginsenosides. Finally, a new transformation mechanism concerning acetyl-ginsenosides formation was proposed.

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).

PubMed

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

2017-11-01

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.

Prevention effect of rare ginsenosides against stress-hormone induced MTOC amplification

PubMed Central

Lee, Jee-Hyun; Cheong, Kyu Jin; Jung, Youn-Sang; Woo, Tae-Gyun; Yoon, Min-Ho; Oh, Ah-Young; Kang, So-Mi; Lee, Chunghui; Sun, Hokeun; Hwang, Jihwan; Song, Gyu-Yong; Park, Bum-Joon

2016-01-01

Stress has been suggested as one of important cause of human cancer without molecular biological evidence. Thus, we test the effect of stress-related hormones on cell viability and mitotic fidelity. Similarly to estrogen, stress hormone cortisol and its relative cortisone increase microtubule organizing center (MTOC) number through elevated expression of γ-tubulin and provide the Taxol resistance to human cancer cell lines. However, these effects are achieved by glucocorticoid hormone receptor (GR) but not by estrogen receptor (ER). Since ginsenosides possess steroid-like structure, we hypothesized that it would block the stress or estrogen-induced MTOC amplification and Taxol resistance. Among tested chemicals, rare ginsenoside, CSH1 (Rg6) shows obvious effect on inhibition of MTOC amplification, γ-tubulin induction and Taxol resistance. Comparing to Fulvestant (FST), ER-α specific inhibitor, this chemical can block the cortisol/cortisone-induced MTOC deregulation as well as ER-α signaling. Our results suggest that stress hormone induced tumorigenesis would be achieved by MTOC amplification, and CSH1 would be useful for prevention of stress-hormone or steroid hormone-induced chromosomal instability. PMID:27147573

Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

PubMed Central

Zhou, Zhen; Meng, Qing-tao; Sun, Qian; Su, Wating; Xia, Zhengyuan; Xia, Zhong-yuan

2015-01-01

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway. Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R. Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α but decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-α and MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA. Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway. PMID:26161243

Ginsenoside C-Mx Isolated from Notoginseng Stem-leaf Ginsenosides Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

PubMed

Liu, Xiao-Yi; Hwang, Eunson; Park, Bom; Ngo, Hien T T; Xiao, Yong-Kun; Yi, Tae-Hoo

2018-05-20

Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create reaction the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1, and IL-6 expression while accelerating TGF-β and procollagen type I secretion. In addition, ginsenoside C-Mx reversed UVB-induced procollagen type I reduction by regulating the TGF-β/Smad signaling pathway. Moreover, ginsenoside C-Mx inhibited activation of AP-1 transcription factor, an inducer of MMPs. Ginsenoside C-Mx displayed an outstanding antioxidant capacity, increasing expression of cytoprotective antioxidants such as HO-1 and, NQO-1 expression by enhancing the nuclear accumulation of Nrf2. Interestingly, applied of ginsenoside C-Mx treatment (1, 10, 20μM) significantly diminished UVB-induced suppressed NF-κB expression, decreasing the over-released inflammatory cytokines. Taken together, our findings indicated that ginsenoside C-Mx may act as a promising natural cosmetic ingredient for prevention and treatment of UVB-induced skin damage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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

2016-07-01

The interaction of the ginsenosides (GS) including ginsenoside Rg1, Rb1 and Re with κ-casein and the effects of GS inhibiting amyloid fibril formation by κ-casein have been investigated in vitro by fluorescence and ultraviolet spectra. Results showed that Rg1 and Rb1 had dose-dependent inhibitory effects on reduced and carboxymethylated κ-casein (RCMκ-CN) fibril formation, while Re resulted in an increase in the rate of fibril formation. The enhancement in RLS intensity was attributed to the formation of new complex between GS and RCMκ-CN, and the corresponding thermodynamic parameters (ΔH, ΔS and ΔG) were assayed. The steady-state ultraviolet-visible absorption spectra had also been tested to observe if the ground-state complex formed, and it showed the same result as RLS spectra. The binding constants and the number of binding sites between GS and RCMκ-CN at different temperatures had been evaluated from relevant fluorescence data. According to the Förster non-radiation energy transfer theory, the binding distance between RCMκ-CN and GS was calculated. The fluorescence lifetime of RCMκ-CN was longer in the presence of GS than in absence of GS, which was evident that the hydrophobic interaction plays a major role in the binding of GS to RCMκ-CN. From the results of synchronous fluorescence, it could be deduced that the polarity around RCMκ-CN Trp97 residue decreased and the hydrophobicity increased after addition of Rg1 or Rb1. Based on all the above results, it is explained that Rg1 and Rb1 inhibited amyloid fibril formation by κ-casein because the molecular spatial conformation and physical property of κ-casein changed causing by the complex formation between GS and κ-casein. Copyright © 2016 Elsevier B.V. All rights reserved.

Teledyne H1RG, H2RG, and H4RG Noise Generator

NASA Technical Reports Server (NTRS)

Rauscher, Bernard J.

2015-01-01

This paper describes the near-infrared detector system noise generator (NG) that we wrote for the James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec). NG simulates many important noise components including; (1) white "read noise", (2) residual bias drifts, (3) pink 1/f noise, (4) alternating column noise, and (5) picture frame noise. By adjusting the input parameters, NG can simulate noise for Teledyne's H1RG, H2RG, and H4RG detectors with and without Teledyne's SIDECAR ASIC IR array controller. NG can be used as a starting point for simulating astronomical scenes by adding dark current, scattered light, and astronomical sources into the results from NG. NG is written in Python-3.4.

Quantitative LC-MS/MS analysis of seven ginsenosides and three aconitum alkaloids in Shen-Fu decoction

PubMed Central

2013-01-01

Background Shen-Fu decoction is a traditional Chinese medicine prescription with a 3:2 ratio of Radix Ginseng and Fuzi (Radix Aconiti lateralis praeparata). Ginsenosides and alkaloids are considered to be the main active components of Shen-Fu decoction. However, no analytical methods have been used to quantitatively analyse both components in Shen-Fu decoction simultaneously. Results We successfully developed a rapid resolution liquid chromatography coupled with tandem mass spectrometry (RRLC-MS/MS) method for the simultaneous analysis of seven ginsenosides and three aconitum alkaloids in Shen-Fu decoction, the decoction of Radix ginseng and Fuzi (Radix Aconiti lateralis praeparata). Chromatogrpahic separation by RPLC was achieved using a reversed-phase column and a water/acetonitrile mobile phase, containing 0.05% formic acid and using a gradient system. The method was optimized to allow for simultaneous analysis of all analytes in 11minutes without the need for baseline resolution of the components. Furthermore, the separation demonstrated good linearity (r > 0.9882), repeatability (RSD < 7.01%), intra- and inter-day precisions (RSD < 5.06%) and high yields of recovery (91.13-111.97%) for ten major constituents, namely ginsenoside-Re, Rg1, Rb1, Rc, Rb2, Rd, Rf, aconitine, hypacoitine and mesaconitine. Conclusions The developed method could be used as a rapid and reliable approach for assessment of the quantity of the major constituents in Shen-Fu decoction. PMID:24107599

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

PubMed

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

2012-12-01

White ginseng was reported to be sulphur-fumigated during post-harvest handling. In the present study, the influence of sulphur-fumigation on the quality of white ginseng and its decoction were quantitatively evaluated through simultaneous quantification of 14 major ginsenosides by a validated high performance liquid chromatography. Poroshell 120 EC-C18 (100mm×3.0mm, 2.7μm) column was chosen for the separation of the major ginsenosides, which were eluted with gradient water and acetonitrile as mobile phase. The analytes were monitored by UV at 203nm. The method was validated in terms of linearity, sensitivity, precision, accuracy and stability. The sulphur-fumigated and non-fumigated white ginseng samples, as well as their respective decoctions, were comparatively analysed with the newly-validated method. It was found that the contents of nine ginsenosides detected in raw materials decreased by about 3-85%, respectively, and the total content of the nine ginsenosides detected in raw materials, decreased by almost 54% after sulphur-fumigation. On the other hand, the contents of 10 ginsenosides detected in decoctions of sulphur-fumigated white ginseng were decreased by about 33-83%, respectively, and the total content of ginsenosides was decreased by up to 64% when compared with that of non-fumigated white ginseng. In addition, ginsenoside Rh(2) and Rg(5) could be detected in the decoctions of sulphur-fumigated white ginseng but not in that of non-fumigated white ginseng. It is suggested that sulphur-fumigation can significantly influence not only the contents of original ginsenosides, but also the decocting-induced chemical transformation of ginsenosides in white ginseng. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Contents of total anthocyanins and total saponins as well as composition of saponin monomers of Purple and Green Notoginseng Radix et Rhizoma].

PubMed

Zhao, Chang-ling; Yang, Sheng-chao; Chen, Zhong-jian; Shen, Yong; Wei, Fu-gang; Wang, Wu; Long, Ting-ju

2014-10-01

The contents of total anthocyanins and total saponins as well as the composition of saponin monomers of Purple and Green Notoginseng Radix et Rhizoma were studied to compare the medicinal quality and commercial values. Three-year-old Notoginseng Radix et Rhizoma was selected as the research materials. The contents of total anthocyanins and total saponins were determined by spectrophotometry. The compositions of saponin monomers were monitored by HPLC. The significance of content differences was determined by variance analysis. The contents of total anthocyanins and total saponins of Purple Notoginseng Radix et Rhizomawere about 204.85% and 33.86% higher than those of Green Notoginseng Radix et Rhizoma respectively. The Purple and Green Notoginseng Radix et Rhizoma both contained five saponin monomers whose contents were as follows: ginsenoside Rg1 > ginsenoside Rb1 > notoginsenoside R1 > ginsenoside Rd > ginsenoside Re. The contents of notoginsenoside R1, ginsenoside Rd and ginsenoside Re of Purple Notoginseng Radix et Rhizoma were about 16.03%, 10.83% and 5.39% higher than those of Green Notoginseng Radix et Rhizoma respectively. However, the contents of ginsenoside Rg1 and ginsenoside Rb1 of Green Notoginseng Radix et Rhizoma were about 0.93% and 3.33% higher than those of Purple Notoginseng Radix et Rhizoma respectively. With respect to Green Notoginseng Radix et Rhizoma, the increase of the total anthocyanins in Purple Notoginseng Radix et Rhizoma reached a significant level, but the increases of total saponins, notoginsenoside R1, ginsenoside Rd and ginsenoside Re and the decreases of ginsenoside Rg1 and ginsenoside Rb1 did not. The total anthocyanins accumulation in Notoginseng Radix et Rhizoma implies the content increases of the total saponins, notoginsenoside R1, ginsenoside Rd and ginsenoside Re, and the slight decreases of ginsenoside Rg1 and ginsenoside Rb1 contents; but the type and relative contents of saponin monomers remain unchanged. The medicinal

[Active constituents reducing side-effects of prednisone acetate in leaves of Panax ginseng C.A.Mey].

PubMed

Dou, D; Wen, Y; Pei, Y; Chen, Y; Ma, Z

1997-03-01

The rise of total lipid, triglyceride and total cholesterol, and the drop of cortisol in serum induced by PA can be significantly inhibited by total ginsenosides in the leaves of Panax ginseng [GSL, 60 mg/(kg.d)]. From GSL ten compounds have been isolated and identified as ginsenoside-Rb2, -Rc, -Rd, -Re, -Rg1 -F3, F2, -Rg2, 20(R)-Rg2 and -Rh1, respectively. Pharmacological study has proved ginsenoside-Re to be the chief active constituent of GSL.

Simultaneous determination of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Weifuchun tablet.

PubMed

Jin, Yiran; Tian, Tingting; Ma, Yinghua; Xu, Huijun; Du, Yingfeng

2015-09-01

A sensitive, specific and rapid liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for analysis of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma using sulfamethoxazole as an internal standard (IS). Separation was conducted out on an Agilent Eclipse XDB C18 column with liner gradient elution using acetonitrile (A) and 0.1% aqueous acetic acid (B). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi-determination-periods program was executed to achieve a higher sensitivity by setting three scanning periods. All analytes exhibited good linearity within the concentration range (r>0.9973). The lower limits of quantitation (LLOQ) of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin were 2.64, 4.32, 2.32 and 1.56ng/mL, respectively. Intra-day and inter-day precisions of the investigated components exhibited an RSD within 8.3%, and the accuracy (RE) ranged from -8.6% to 6.0% at all quality control levels. The developed method was successfully applied to a pharmacokinetic study of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rats after oral administration of a Weifuchun tablet. Copyright © 2015 Elsevier B.V. All rights reserved.

Burst noise in the HAWAII-1RG multiplexer

NASA Astrophysics Data System (ADS)

Bacon, Candice M.; McMurtry, Craig W.; Pipher, Judith L.; Forrest, William J.; Garnett, James D.

2005-08-01

Burst noise (also known as popcorn noise and random telegraph signal/noise) is a phenomenon that is understood to be a result of defects in the vicinity of a p-n junction. It is characterized by rapid level shifts in both positive and negative directions and can have varying magnitudes. This noise has been seen in both HAWAII-1RG and HAWAII-2RG multiplexers and is under investigation. We have done extensive burst noise testing on a HAWAII-1RG multiplexer, where we have determined a significant percentage of pixels exhibit the phenomenon. In addition, the prevalence of small magnitude transitions make sensitivity of detection the main limiting factor. Since this is a noise source for the HAWAII-1RG multiplexer, its elimination would make the HAWAII-1RG and the HAWAII-2RG even lower noise multiplexers.

Semisynthesis and bioactive evaluation of oxidized products from 20(S)-ginsenoside Rg3, Rh2, protopanaxadiol (PPD) and their 20(R)-epimers as cytotoxic agents.

PubMed

Yang, Jie; Li, Xuwen; Sun, Ting; Gao, Yan; Chen, Yanxin; Jin, Yongri; Li, Yang

2016-02-01

A series of oxidized products have been systematically semisynthesized from 20(S)-ginsenoside Rg3, Rh2, 20(S)-protopanaxadiol (PPD) and their 20(R)-epimers and the majority of these products were evaluated for their cytotoxic activity against HeLa cells and HepG2 cells by MTT assay for the first time. Twenty-two products were obtained and elucidated based on comprehensive (1)H NMR, (13)C NMR, two-dimensional (2D) NMR, and mass spectral data and the results reported in previous literature. All the four ocotillol type saponins (20S,24R(δ86, δ85); 20S,24S(δ87, δ88); 20R,24R(δ86, δ86); 20R,24S(δ86, δ87) were obtained. In addition, eight compounds (3, 8, 9, 10, 15, 16, 19 and 22) with the cyclized side chain were firstly identified. Most of the tested compounds possessed cytotoxicity to a certain degree against the two types of cells which implied these oxidized products could play a certain role on anti-cancer functions of the raw materials in vivo. Meanwhile, the results proved that the configurations at C-20 or C-24 and the number of glycosyl at C-3 have important influence on the cytotoxicity. The products 1, 2, 11-17, 20 and 22 should possess great activities and deserved further investigation as potential cytotoxic agents. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-02-19

Ginsenosides, the major bio-active ingredients included in Panax ginseng, have been known for the hair growth activity and used to treat patients who suffer from hair loss; however, the detailed mechanisms of this action are still largely unknown. This study was conducted to investigate the molecular and cellular mechanisms responsible for hair growth promoting effect of ginsenoside Re (GRe) in vitro and in vivo. Different doses of minoxidil and GRe were administered topically to the back regions of nude mice for up to 45 days, and hair shaft length and hair cycles were determined for hair promoting activities. Topical treatment of GRe significantly increased the hair shaft length and hair existent time, which was comparable to the action of minoxidil. We also demonstrated that GRe stimulated hair shaft elongation in the ex vivo cultures of vibrissa hair follicles isolated from C57BL/6 mouse. Systemic transcriptome analysis by next generation sequencing demonstrated that TGF-β-pathway related genes were selectively down-regulated by treatment of GRe in vivo, and the same treatment suppressed TGF-β-induced phosphorylation of ERK in HeLa cells. The results clearly indicated that GRe is the effective constituent in the ginseng on hair promotion via selective inhibition of the hair growth phase transition related signaling pathways, TGF-β signaling cascades. Copyright © 2016. Published by Elsevier Inc.

Preparation of minor ginsenosides C-Mc, C-Y, F2, and C-K from American ginseng PPD-ginsenoside using special ginsenosidase type-I from Aspergillus niger g.848.

PubMed

Liu, Chun-Ying; Zhou, Rui-Xin; Sun, Chang-Kai; Jin, Ying-Hua; Yu, Hong-Shan; Zhang, Tian-Yang; Xu, Long-Quan; Jin, Feng-Xie

2015-07-01

Minor ginsenosides, those having low content in ginseng, have higher pharmacological activities. To obtain minor ginsenosides, the biotransformation of American ginseng protopanaxadiol (PPD)-ginsenoside was studied using special ginsenosidase type-I from Aspergillus niger g.848. DEAE (diethylaminoethyl)-cellulose and polyacrylamide gel electrophoresis were used in enzyme purification, thin-layer chromatography and high performance liquid chromatography (HPLC) were used in enzyme hydrolysis and kinetics; crude enzyme was used in minor ginsenoside preparation from PPD-ginsenoside; the products were separated with silica-gel-column, and recognized by HPLC and NMR (Nuclear Magnetic Resonance). The enzyme molecular weight was 75 kDa; the enzyme firstly hydrolyzed the C-20 position 20-O-β-D-Glc of ginsenoside Rb1, then the C-3 position 3-O-β-D-Glc with the pathway Rb1→Rd→F2→C-K. However, the enzyme firstly hydrolyzed C-3 position 3-O-β-D-Glc of ginsenoside Rb2 and Rc, finally hydrolyzed 20-O-L-Ara with the pathway Rb2→C-O→C-Y→C-K, and Rc→C-Mc1→C-Mc→C-K. According to enzyme kinetics, K m and V max of Michaelis-Menten equation, the enzyme reaction velocities on ginsenosides were Rb1 > Rb2 > Rc > Rd. However, the pure enzyme yield was only 3.1%, so crude enzyme was used for minor ginsenoside preparation. When the crude enzyme was reacted in 3% American ginseng PPD-ginsenoside (containing Rb1, Rb2, Rc, and Rd) at 45°C and pH 5.0 for 18 h, the main products were minor ginsenosides C-Mc, C-Y, F2, and C-K; average molar yields were 43.7% for C-Mc from Rc, 42.4% for C-Y from Rb2, and 69.5% for F2 and C-K from Rb1 and Rd. Four monomer minor ginsenosides were successfully produced (at low-cost) from the PPD-ginsenosides using crude enzyme.

Chemical Diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng

PubMed Central

Kim, Dong-Hyun

2012-01-01

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

[Correlation of insulin-like growth factor-1 (IGF-1) to angiogenesis of breast cancer in IGF-1-deficient mice].

PubMed

Tang, Hong-Bo; Ren, Yu-Ping; Zhang, Jun; Ma, Shi-Hui; Gao, Feng; Wu, Yi-Ping

2007-11-01

Insulin-like growth factors (IGFs) play important roles in the development and progression of tumors. But the mechanism of tumorigenesis in relation to IGF-1 is unclear yet. This study was to explore the correlation of circulating IGF-1 level to the angiogenesis of breast cancer in IGF-1-deficient mice. The liver-specific IGF-1-deficient (LID) mice and control mice were injected with 7,12-dimethybenz(a)anthracene (DMBA) to develop breast cancer. Ginsenoside Rg3 was used to intervene tumor growth. The occurrence rates of breast cancer were compared. The expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) was detected by immunohistochemistry. The occurrence rate of breast cancer was 66.67% in untreated control mice, 33.33% in untreated LID mice, 36.00% in Rg3-treated control mice, and 12.00% in Rg3-treated LID mice. The tumor size was (0.79+/-0.20) cm in untreated control mice, (0.37+/-0.08) cm in untreated LID mice, (0.32+/-0.08) cm in Rg3-treated control mice, and (0.15+/-0.05) cm in Rg3-treated LID mice. The average light density and positive rate of VEGF were the highest in untreated control mice (0.34+/-0.10 and 0.04+/-0.02, P<0.05), and the lowest in Rg3-treated LID mice (0.13+/-0.03 and 0.01+/-0.00, P<0.05). The MVD was 31.9+/-5.3 in untreated control mice, 26.8+/-4.9 in untreated LID mice, 20.1+/-4.9 in Rg3-treated control mice, and 14.4+/-4.9 in Rg3-treated LID mice. Circulating IGF-1 plays a role in the onset and development of breast cancer. Degrading serum IGF-1 level could inhibit angiogenesis and growth of breast cancer. Rg3 could promote this effect.

Study on Transformation of Ginsenosides in Different Methods

PubMed Central

Zheng, Meng-meng; Xu, Fang-xue; Li, Yu-juan; Xi, Xiao-zhi; Cui, Xiao-wei

2017-01-01

Ginseng is a traditional Chinese medicine and has the extensive pharmacological activity. Ginsenosides are the major constituent in ginseng and have the unique biological activity and medicinal value. Ginsenosides have the good effects on antitumor, anti-inflammatory, antioxidative and inhibition of the cell apoptosis. Studies have showed that the major ginsenosides could be converted into rare ginsenosides, which played a significant role in exerting pharmacological activity. However, the contents of some rare ginsenosides are very little. So it is very important to find the effective way to translate the main ginsenosides to rare ginsenosides. In order to provide the theoretical foundation for the transformation of ginsenoside in vitro, in this paper, many methods of the transformation of ginsenoside were summarized, mainly including physical methods, chemical methods, and biotransformation methods. PMID:29387726

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

PubMed

Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

2013-12-01

To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively

[Urine metabonomic study on long-term use of total ginsenosides in rats].

PubMed

Xie, Xie; Chen, Shao-Qiu; Lv, Ying-Fang; Wang, Xiao-Yan; Jia, Wei

2014-12-01

Due to its effect of systems regulation and promotion on body, Ginseng is always referred to be long-term used as a dietary supplement. But it was still unclear about its target of the tonic effects and also the side-effects long-term use may bring. Urine metabolomic method is suitable for long-term studies of pharmaco-dynamics, pharmacology and toxicology of traditional Chinese medicine because of its characteristics of non-invasive and monitoring the whole-body metabolism. This study was designed to detect the dynamic variation of rat urine metabolome along with a long-term administration of total ginsenosides using GC-TOF based metabolomic technology. Our result showed that either short-term or chronic administration of ginsenosides did not impact the rat urine metabolome significantly (as the PCA subgroup was not successful). By comparison, the short-term (1-3 w) dose of ginsenosides had the biggest metabolic influence including TCA cycle, catecholamines and neurotransmitter amino acids. Medium-term (6-10 w) dose had a gradually lower effect and long-term (27 w) dose almost had no effect. Our study indicates that both short and long-term administration of ginsenosides showed almost no obvious side-effect on the experimental animals.

Cloning and characterization of ginsenoside Ra1-hydrolyzing beta-D-xylosidase from Bifidobacterium breve K-110.

PubMed

Hyun, Yang-Jin; Kim, Bomi; Kim, Dong-Hyun

2012-04-01

beta-D-Xylosidase (E.C. 3.2.1.37) from Bifidobacterium breve K-110, which hydrolyzes ginsenoside Ra1 to ginsenoside Rb2, was cloned and expressed in Escherichia coli. The (His6)-tagged recombinant enzyme, designated as XlyBK- 110, was efficiently purified using Ni²⁺-affinity chromatography (109.9-fold, 84% yield). The molecular mass of XylBK- 100 was found to be 55.7 kDa by SDS-PAGE. Its sequence revealed a 1,347 bp open reading frame (ORF) encoding a protein containing 448 amino acids, which showed 82% identity (DNA) to the previously reported glycosyl hydrolase family 30 of Bifidobacterium adolescentis ATCC 15703. The Km and Vmax values toward p-nitrophenyl-beta-D-xylopyranoside (pNPX) were 1.45mM and 10.75 micromol/min/mg, respectively. This enzyme had pH and temperature optima at 6.0 and 45 degrees C, respectively. XylBK-110 acted to the greatest extent on xyloglucosyl kakkalide, followed by pNPX and ginsenoside Ra1, but did not act on p-nitrophenyl-alpha-Larabinofuranoside, p-nitrophenyl-beta-D-glucopyranoside, or p-nitrophenyl-beta-D-fucopyranoside. In conclusion, this is the first report on the cloning and expression of beta-Dxylosidase- hydrolyzing ginsenoside Ra1 and kakkalide from human intestinal microflora.

Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement.

PubMed

Guo, Jinhui; Chang, Li; Zhang, Xin; Pei, Sujuan; Yu, Meishuang; Gao, Jianlian

2014-10-01

The aim of the present study was to investigate the effect of ginsenoside compound K on β-amyloid (Aβ) peptide clearance in primary astrocytes. Aβ degradation in primary astrocytes was determined using an intracellular Aβ clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme-linked immunosorbent assay was used for Aβ detection. The results demonstrated that compound K promoted the clearance of Aβ and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Aβ clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes.

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

PubMed

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

2016-03-23

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

Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng.

PubMed

Xiong, Jing; Guo, Jianxin; Huang, Luosheng; Meng, Boyu; Ping, Qineng

2008-08-06

The purpose of this research is to evaluate the effect of self-micelle formation and incorporation of lipid in the formulation on absorption of ginsenosides Rg1 and Rb1 from intestinal tract in rats. Ginsenosides Rg1 and Rb1 were extracted from Panax notoginseng saponins (PNS). The critical micellar concentration (CMC) of PNS in deionzied water was determined to be 0.339 mg/ml. At normal physiological ionic strengths, PNS was salted out from the solution above the CMC. The particle size of the micelle grows as PNS concentration increases. By in situ injection to a closed loop of the rat jejunum, AUC0-6h obtained after administration of low concentration solution (12 mg/ml) was 3.61 times for ginsenoside Rg1 and 3.84-folds for ginsenoside Rb1 compared with high concentration solution (120 mg/ml). The release rate of ginsenosides in aqueous medium was too slow to complete in 24h, especially for Rb1. The data suggested that the self-micelle formation tendency in ginsenosides might prevent them from permeation or absorption through the cell membrane of gastrointestinal (GI) tract. To inhibit the formation of micelles, lipid was incorporated in the PNS formulation. The intraduodenal bioavailability in rats showed that the bioavailability was enhanced remarkably relative to the aqueous solution. AUC 0-infinity of ginsenoside Rg1 and Rb1 in the lipid-based formulation were 207.52+/-53.95 and 1961.72+/-686.60 microg ml(-1) h, compared with 7.87+/-2.85 and 148.58+/-36.73 microg ml(-1) h, respectively from its aqueous solution. These findings suggested a new strategy to increase the absorption of amphiphilic saponins.

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

PubMed

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

2015-01-01

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

Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus.

PubMed

Tan, Joanne Sh; Yeo, Chia-Rou; Popovich, David G

2017-07-01

Ginsenosides are believed to be the principal components behind the pharmacological actions of ginseng, and their bioactive properties are closely related to the type, position, and number of sugar moieties attached to the aglycone; thus, modification of the sugar chains may markedly change their biological activities. In this study, major protopanaxadiol type ginsenosides (PD) Rb1, Rc, and Rb2 were isolated from Panax ginseng and were transformed using two probiotic strains namely Bifidobacterium lactis Bi-07 and Lactobacillus rhamnosus HN001 to obtain specific deglycosylated ginsenosides. It was demonstrated that B. lactis transformed ginsenosides Rb1, Rc, and Rb2 to Rd within 1 h of fermentation and rare ginsenoside F2 by the conversion of Rd after 12-h fermentation. The maximum Rd concentration was 147.52 ± 1.45 μg/mL after 48-h fermentation as compared to 45.85 ± 0.71 μg/mL before fermentation. In contrast, L. rhamnosus transformed Rb1, Rc, and Rb2 into Rd as the final metabolite after 72-h fermentation. B. lactis displayed significantly (p < 0.05) higher β-glucosidase activity against p-nitrophenyl-β-glucopyranoside than L. rhamnosus and higher bioconversion efficiency during fermentation. The present study suggests that the fermentation of major PD type ginsenosides with B. lactis Bi-07 may serve as an effective means to afford bioactive deglycosylated ginsenosides and to create novel ginsenoside extracts.

Producing aglycons of ginsenosides in bakers' yeast

PubMed Central

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

2014-01-01

Ginsenosides are the primary bioactive components of ginseng, which is a popular medicinal plant that exhibits diverse pharmacological activities. Protopanaxadiol, protopanaxatriol and oleanolic acid are three basic aglycons of ginsenosides. Producing aglycons of ginsenosides in Saccharomyces cerevisiae was realized in this work and provides an alternative route compared to traditional extraction methods. Synthetic pathways of these three aglycons were constructed in S. cerevisiae by introducing β-amyrin synthase, oleanolic acid synthase, dammarenediol-II synthase, protopanaxadiol synthase, protopanaxatriol synthase and NADPH-cytochrome P450 reductase from different plants. In addition, a truncated 3-hydroxy-3-methylglutaryl-CoA reductase, squalene synthase and 2,3-oxidosqualene synthase genes were overexpressed to increase the precursor supply for improving aglycon production. Strain GY-1 was obtained, which produced 17.2 mg/L protopanaxadiol, 15.9 mg/L protopanaxatriol and 21.4 mg/L oleanolic acid. The yeast strains engineered in this work can serve as the basis for creating an alternative way for producing ginsenosides in place of extractions from plant sources. PMID:24424342

Ginsenoside Rg3 Inhibits Melanoma Cell Proliferation through Down-Regulation of Histone Deacetylase 3 (HDAC3) and Increase of p53 Acetylation

PubMed Central

Shan, Xiu; Fu, Yuan-Shan; Aziz, Faisal; Wang, Xiao-Qi; Yan, Qiu; Liu, Ji-Wei

2014-01-01

Malignant melanoma is an aggressive and deadly form of skin cancer, and despite recent advances in available therapies, is still lacking in completely effective treatments. Rg3, a monomer extracted from ginseng roots, has been attempted for the treatment of many cancers. It is reported that the expressions of histone deacetylase 3 (HDAC3) and p53 acetylation correlate with tumor cell growth. However, the antitumor effect of Rg3 on melanoma and the mechanism by which it regulates HDAC3 expression and p53 acetylation remain unknown. We found high expression of HDAC3 in human melanoma tissues to be significantly correlated to lymph node metastasis and clinical stage of disease (p<0.05). In melanoma cells, Rg3 inhibited cell proliferation and induced G0/G1 cell cycle arrest. Rg3 also decreased the expression of HDAC3 and increased the acetylation of p53 on lysine (k373/k382). Moreover, suppression of HDAC3 by either siRNA or a potent HDAC3 inhibitor (MS-275) inhibited cell proliferation, increased p53 acetylation and transcription activity. In A375 melanoma xenograft studies, we demonstrated that Rg3 and HDAC3 short hairpin RNA (shHDAC3) inhibited the growth of xenograft tumors with down-regulation of HDAC3 expression and up-regulation of p53 acetylation. In conclusion, Rg3 has antiproliferative activity against melanoma by decreasing HDAC3 and increasing acetylation of p53 both in vitro and in vivo. Thus, Rg3 serves as a potential therapeutic agent for the treatment of melanoma. PMID:25521755

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

PubMed

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

2016-07-28

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.

The effects of ginsenoside Rb1 on endothelial damage and ghrelin expression induced by hyperhomocysteine.

PubMed

Xu, Zhiwei; Lan, Taohua; Wu, Weikang; Wu, Yiling

2011-01-01

Studies have indicated that ginsenoside Rb1 and ghrelin could both prevent homocysteine (Hcy)-induced endothelial dysfunction through the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) mechanism. This study investigated whether endogenous ghrelin mediates the endothelial protection of ginsenosidee Rb1 through in vitro and in vivo experiments. Rats were randomized into a control group, a hyperhomocysteine (HHcy) model group with a high methionine diet, a ginsenosides (GS) group, and HHcy plus GS group. Plasma ghrelin was detected by enzyme-linked immunosorbent assay. Aortic rings for control and HHcy groups were treated with ghrelin or not. Endothelium-dependent vasodilatation function was evaluated by the aortic ring assay, and the structural changes were visualized by hematoxylin and eosin staining. Human umbilical vein endothelial cells (HUVECs) were cultured, and the experimental conditions were optimized according to NO production. After treatment, the NO, ghrelin, and von Willebrand factor (vWF) levels in the media were detected and analyzed with linear regression. Ghrelin and eNOS expression were observed by cell immunohistochemical staining. Ghrelin receptor antagonist was used to detect the mechanism of ginsenoside Rb1 on NO production, which was reflected by diacetylated 4,5-diaminofluorescein-2 diacetate fluorescence. In vivo experiments demonstrated that plasma ghrelin levels in the HHcy group were significantly elevated vs controls (P < .05) and were significantly increased in the HHcy plus GS group (P < .01). Compared with control, endothelium-dependent vasodilatation function was greatly reduced in the HHcy group (P < .01), which was significantly increased in HHcy plus ghrelin group compared with HHcy group (P < .01). The arterial walls of HHcy group exhibited characteristic pathologic changes, which were repaired in HHcy plus ghrelin group. In vivo, compared with Hcy (200 μM) group, HUVECs pretreated with ginsenoside Rb1 (10 μM) for 30

Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice.

PubMed

Sun, Jianhua; Hu, Songhua; Song, Xiaoming

2007-01-22

Protopanaxadiol saponins (Rg3, Rd, Rc, Rb1 and Rb2) and protopanaxatriol saponins (Rg1, Re and Rg2) isolated from the root of Panax ginseng C.A. Meyer were evaluated for their adjuvant effects on the immune responses to ovalbumin (OVA) in mice. BALB/c mice were subcutaneously injected twice at a 3-week interval with 10 microg of ovalbumin or 10 microg of OVA plus 50 microg of ginsenosides Rg3, Rd, Rc, Rb1, Rb2, Rg1, Re or Rg2 or Quil A (n=5). Blood samples were collected for measuring specific total-IgG, IgG1 and IgG2a, and splenocytes were harvested for determining lymphocyte proliferation as well as IFN-gamma and IL-5 production 2 weeks after the boosting. The results indicated that OVA-specific antibody responses were significantly higher in mice immunized with OVA co-administered with Rg1, Re, Rg2, Rg3 and Rb1 but not with Rd, Rc and Rb2 when compared with the control (immunized with OVA only). Significantly enhanced splenocyte proliferative responses to Con A, LPS and OVA as well as the production of both IL-5 and IFN-gamma stimulated by OVA were also detected in mice immunized with OVA co-administered with Rg1 but not with Rb1, Re and Rg3. Of the ginsenosides studied, Rg1, Re, Rg2, Rg3 and Rb1 have more potent adjuvant properties than the others, indicating that they are the major constituents contributing to the adjuvant activities of total ginseng saponins. Varieties of ginsenosides in adjuvant activity might be attributed to the varieties of molecular conformations determined by the side sugar chains attaching to their dammarane skeleton.

Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

PubMed Central

Peña, Ike dela; Yoon, Seo Young; Kim, Hee Jin; Park, Sejin; Hong, Eun Young; Ryu, Jong Hoon; Park, Il Ho; Cheong, Jae Hoon

2013-01-01

Background Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results Ginseol k-g3 (25–200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. 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. PMID:24558303

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

PubMed

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

2013-04-01

A novel, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantitation of eight main active ingredients (evodiamine, rutaecarpine, dehydroevodiamine, limonin, ginsenoside Rb1, Rd, Re and Rg1) in rat plasma after oral administration of Wu-Zhu-Yu (WZY) decoction, which is a celebrated and widely used Traditional Chinese Medicine formula for the treatment of headache. The analytes and internal standard (IS) were separated on a SHIM-PACK XR-ODS II column, and the detection was performed on a UFLC-MS/MS system with turbo ion spray source. The lower limits of quantification were 1.5, 0.5, 1.0, 2.0, 2.0, 1.0, 0.5 and 0.2 ng ml(-1) for evodiamine, rutaecarpine, dehydroevodiamine, limonin, gensenoside Rb1, Rd, Re and Rg1, respectively. Linearity, accuracy, precision and absolute recoveries of the eight analytes were all within satisfaction. The IS-normalized matrix factor was adopted for assessing the matrix effect and accompanied with a satisfactory result. The validated method has been successfully applied to compare pharmacokinetic profiles of the eight active ingredients in rat plasma between normal and headache rats after administration. Exact pharmaceutical effect of WZY decoction on headache was demonstrated by the ethological response of headache rats induced by nitric oxide donor after administration. The results indicated that the absorption of evodiamine, rutaecarpine, gensenoside Rb1, Re and Rg1 in headache group were significantly higher than those in normal group with similar concentration-time curves while no significant differences existed in limonin and ginsenoside Rd between the two groups. Copyright © 2013 John Wiley & Sons, Ltd.

Ginsenoside Ameliorates Cognitive Dysfunction in Type 2 Diabetic Goto-Kakizaki Rats.

PubMed

Tian, Zhiyan; Ren, Ning; Wang, Jinghua; Zhang, Danhong; Zhou, Yuying

2018-06-10

BACKGROUND Ginsenoside is the major bioactive component of ginseng, which has been proven to be a neuroprotective drug. The aim of this study was to evaluate the therapeutic effect of ginsenoside in a diabetic Goto-Kakizaki (GK) rat model. MATERIAL AND METHODS Twenty GK rats were randomly divided into a diabetic model (DM) group (n=10) and a ginsenoside + DM group (n=10); Wistar rats with the same age and body weight were used as the control (CON) group (n=10). Food and water intake, body weight, and blood fasting plasma glucose were measured. The Morris water maze test was used to detect learning and memory functions of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the hippocampus were analyzed after ginsenoside treatment. RESULTS The blood glucose, body weight, Morris correlation index, SOD, MDA, and other test results were increased in the diabetic rats. Ginsenoside ameliorated diabetic cognitive decline. CONCLUSIONS The possible mechanism was related to inhibiting brain oxidative/nitrosative damage and affecting the expression of the cytokines IL-1β, IL-6, and TNF-α.

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

PubMed Central

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

2010-01-01

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

Protective properties of ginsenoside Rb1 against UV-B radiation-induced oxidative stress in human dermal keratinocytes.

PubMed

Oh, Sun-Joo; Kim, Kyunghoon; Lim, Chang-Jin

2015-06-01

Ginsenosides, also known as ginseng saponins, are responsible for most pharmacological effect of ginseng. Ginsenoside Rb1 (Rb1) exerts a variety of pharmacological properties, including anti-inflammatory, antistress, anti-aging and anti-neurodegenerative activities. The aim of the present work was to assess the skin anti-photoaging properties of Rb1 in human dermal keratinocyte HaCaT cells. The anti-photoaging activity was evaluated by analyzing the levels of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) as well as cell viability for HaCaT cells under UV-B irradiation. Rb1 was able to suppress the ROS levels which were elevated under UV-B irradiation, and unable to influence cellular survival in UV-B-irradiated HaCaT cells. Rb1 diminished the enhancement of MMP-2 gelatinolytic activity in conditioned medium, which corresponded with the decreased MMP-2 protein levels in both conditioned medium and cellular lysate prepared from UV-B-irradiated HaCaT cultures. Rb1 could restore the total glutathione (GSH) and superoxide dismutase (SOD) activity diminished in UV-B-irradiated HaCaT cells. Ginsenoside Rb1 possesses skin anti-photoaging properties through scavenging ROS and decreasing MMP-2 levels possibly by enhancing antioxidant activity in keratinocytes under UV-B irradiation.

Changes in Intestinal Microbiota Affect Metabolism of Ginsenoside Re.

PubMed

Zhang, Lei; Li, Fei; Qin, Wang-Jun; Fu, Chao; Zhang, Xiang-Lin

2018-05-10

Ginsenoside Re, an active ingredient in Panax ginseng, is widely used as a therapeutic and nutriment. Intestinal microbiota plays crucial roles in modulating the pharmacokinetics and pharmacological actions of ginsenoside Re. The aim of this study was to explore the relationship between bacterial community variety and the metabolic profiles of ginsenoside Re. We developed two models with intestinal dysbacteriosis: a pseudo-germ-free model induced by a non-absorbable antimicrobial mixture (ATM), and Qi-deficiency model established via over-fatigue and acute cold stress (OACS). First, the bacterial community structures in control, ATM, and OACS rats were compared via 16S rRNA amplicon sequencing. Then, gut microbial metabolism of ginsenoside Re was assessed qualitatively and quantitatively in the three groups by UPLC-Q-TOF/MS and HPLC-TQ-MS, respectively. Ten metabolites of ginsenoside Re were detected and tentatively identified, three of which were novel. Moreover, due to significant differences in bacterial communities, deglycosylated products, as the main metabolites of ginsenoside Re, were produced at lower levels in ATM and OACS models. Importantly, the levels of these deglycosylated metabolites correlated with alterations in Prevotella, Lactobacillus, and Bacteroides populations, as well as glycosidase activities. Collectively, biotransformation of ginsenoside Re is potentially influenced by regulating the composition of intestinal microbiota and glycosidase activities. This article is protected by copyright. All rights reserved.

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

PubMed

Song, Xiaolin; Wu, Hao; Yin, Zhenhao; Lian, Meilan; Yin, Chengri

2017-05-23

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 IC 50 value was 0.94 mg mL -1 .

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

PubMed

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

2015-03-25

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.

Mass Spectrometry Based Profiling and Imaging of Various Ginsenosides from Panax ginseng Roots at Different Ages

PubMed Central

Lee, Jae Won; Ji, Seung-Heon; Lee, Young-Seob; Choi, Doo Jin; Choi, Bo-Ram; Kim, Geum-Soog; Baek, Nam-In; Lee, Dae Young

2017-01-01

(1) Background: Panax ginseng root is one of the most important herbal products, and the profiling of ginsenosides is critical for the quality control of ginseng roots at different ages in the herbal markets. Furthermore, interest in assessing the contents as well as the localization of biological compounds has been growing. The objective of this study is to carry out the mass spectrometry (MS)-based profiling and imaging of ginsenosides to assess ginseng roots at different ages; (2) Methods: Optimal ultra performance liquid chromatography coupled to quadrupole time of flight/MS (UPLC-QTOF/MS) was used to profile various ginsenosides from P. ginseng roots. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/MS-based imaging was also optimized to visualize ginsenosides in ginseng roots; (3) Results: UPLC-QTOF/MS was used to profile 30 ginsenosides with high mass accuracy, with an in-house library constructed for the fast and exact identification of ginsenosides. Using this method, the levels of 14 ginsenosides were assessed in P. ginseng roots cultivated for 4, 5, and 6 years. The optimal MALDI-imaging MS (IMS) was also applied to visualize the 14 ginsenosides in ginseng roots. As a result, the MSI cross sections showed the localization of 4 ginsenoside ions ([M + K]+) in P. ginseng roots at different ages; (4) Conclusions: The contents and localization of various ginsenosides differ depending on the cultivation years of P. ginseng roots. Furthermore, this study demonstrated the utility of MS-based profiling and imaging of ginsenosides for the quality control of ginseng roots. PMID:28538661

Mass Spectrometry Based Profiling and Imaging of Various Ginsenosides from Panax ginseng Roots at Different Ages.

PubMed

Lee, Jae Won; Ji, Seung-Heon; Lee, Young-Seob; Choi, Doo Jin; Choi, Bo-Ram; Kim, Geum-Soog; Baek, Nam-In; Lee, Dae Young

2017-05-24

(1) Background: Panax ginseng root is one of the most important herbal products, and the profiling of ginsenosides is critical for the quality control of ginseng roots at different ages in the herbal markets. Furthermore, interest in assessing the contents as well as the localization of biological compounds has been growing. The objective of this study is to carry out the mass spectrometry (MS)-based profiling and imaging of ginsenosides to assess ginseng roots at different ages; (2) Methods: Optimal ultra performance liquid chromatography coupled to quadrupole time of flight/MS (UPLC-QTOF/MS) was used to profile various ginsenosides from P. ginseng roots. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/MS-based imaging was also optimized to visualize ginsenosides in ginseng roots; (3) Results: UPLC-QTOF/MS was used to profile 30 ginsenosides with high mass accuracy, with an in-house library constructed for the fast and exact identification of ginsenosides. Using this method, the levels of 14 ginsenosides were assessed in P. ginseng roots cultivated for 4, 5, and 6 years. The optimal MALDI-imaging MS (IMS) was also applied to visualize the 14 ginsenosides in ginseng roots. As a result, the MSI cross sections showed the localization of 4 ginsenoside ions ([M + K]⁺) in P. ginseng roots at different ages; (4) Conclusions: The contents and localization of various ginsenosides differ depending on the cultivation years of P. ginseng roots. Furthermore, this study demonstrated the utility of MS-based profiling and imaging of ginsenosides for the quality control of ginseng roots.

Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats.

PubMed

Zhuang, Cheng-Le; Mao, Xiang-Yu; Liu, Shu; Chen, Wei-Zhe; Huang, Dong-Dong; Zhang, Chang-Jing; Chen, Bi-Cheng; Shen, Xian; Yu, Zhen

2014-10-05

Ginsenoside Rb1 is reported to possess anti-fatigue activity, but the mechanisms remain unknown. The aim of this study was to investigate the molecular mechanisms responsible for the anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection (MSIR) in aged rat. Aged rats with MSIR were administrated with ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Rats without MSIR but going through the same surgery procedure were administrated with saline as blank controls. Anti-fatigue effect was assessed by an open field test; superoxide dismutase, reactive oxygen species and malondialdehyde in skeletal muscle were determined. The mRNA levels of Akt2 and Nrf2 in skeletal muscle were measured by real-time quantitative PCR. The activation of Akt and Nrf2 was examined by western blot and immunohistofluorescence. Our results revealed that ginsenoside Rb1 significantly increased the journey and the rearing frequency, decreased the time of rest in aged rats with MSIR. In addition, ginsenoside Rb1 significantly reduced reactive oxygen species and malondialdehyde release and increased the superoxide dismutase activity of skeletal muscle in aged rats with MSIR. Ginsenoside Rb1 also increased the expression of Akt2 and Nrf2 mRNA, up-regulated Akt phosphorylation and Nrf2 nuclear translocation. These findings indicate that ginsenoside Rb1 has an anti-fatigue effect on postoperative fatigue syndrome in aged rat, and the mechanism possibly involves activation of the PI3K/Akt pathway with subsequent Nrf2 nuclear translocation and induction of antioxidant enzymes. Copyright © 2014 Elsevier B.V. All rights reserved.

Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide

PubMed Central

Scott, Glenda I; Colligan, Peter B; Ren, Bonnie H; Ren, Jun

2001-01-01

Panax ginseng is used to enhance stamina and relieve fatigue as well as physical stress. Ginsenoside, the effective component of ginseng, regulates cardiovascular function. This study was to examine the effect of ginsenosides Rb1 and Re on cardiac contractile function at the cellular level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz. Contractile properties analysed included: peak shortening (PS), time-to-90%PS (TPS), time-to-90% relengthening (TR90), and fluorescence intensity change (ΔFFI). Nitric oxide synthase (NOS) activity was determined by the 3H-arginine to 3H-citrulline conversion assay. Both Rb1 and Re exhibited dose-dependent (1 – 1000 nM) inhibition in PS and ΔFFI, with maximal inhibitions between 20 – 25%. Concurrent application Rb1 and Re did not produce any additive inhibition on peak shortening amplitude (with a maximal inhibition of 24.9±6.1%), compared to Rb1 or Re alone. Pretreatment with the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM) abolished the effect of Rb1 and Re. Both Rb1 and Re significantly (P<0.05) stimulated NOS activity concentration-dependently. This study demonstrated a direct depressant action of ginsenosides on cardiomyocyte contraction, which may be mediated in part through increased NO production. PMID:11704635

[Anti-feeding activity of total ginsenoside from Panax ginseng to 4th-instar Mythimna separata larvae].

PubMed

Tan, Shi-qiang; Ma, Lin; Xu, Yong-hua; Lei, Feng-jie; Zhang, Ai-hua; Zhang, Lian-xue

2015-07-01

This paper is in order to study the anti-feeding and growth inhibition activity of toatal ginsenoside of ginseng stems and leaves against 4th-instar Mythimna separata larvae. Simulating natural growing condition indoors, on the base, To study the anti-feeding and growth inhibition activity of toatal ginsenoside against 4th-instar M. separata larvae by leaf disc test. The toatal ginsenoside appeared to be of significant antifeeding activity against 4th-instar M. separata larvae. The 4th-instar M. separata larvae fed on the leaves of Sorghum bicolor treated with 20, 10, 5 g · L(-1) toatal ginsenoside. At 8 h, non-selective anti-feeding rate were 88.67%, 64.40% and 47.36%, and selective anti-feeding rate were 62.49% , 44.29% and 34.19%; Compared with the photographic, The toatal ginsenoside conld make the development period had prolonged 13h in treated group. The toatal ginsenoside had significant inhibition effect on feeding and growth and development against 4th-instar M. separata larvae, and inhibition effect increases as the increase of concentration ginsenoside.

Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars

PubMed Central

Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

2017-01-01

Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape (Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L-tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N-acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N-acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N-acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro. Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant–rhizobacterium interactions that affect

Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

PubMed

Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

2016-01-01

Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape ( Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L -tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N -acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N -acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N -acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro . Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant-rhizobacterium interactions that affect

A comparison between high hydrostatic pressure extraction and heat extraction of ginsenosides from ginseng (Panax ginseng CA Meyer).

PubMed

Lee, Hyun-Sun; Lee, Hyun Jung; Yu, Hyung Jo; Ju, Do Weon; Kim, Yoonsook; Kim, Chong-Tai; Kim, Chul-Jin; Cho, Yong-Jin; Kim, Namsoo; Choi, Sin-Yang; Suh, Hyung Joo

2011-06-01

To determine biomaterial components, the components must first be transferred into solution; thus extraction is the first step in biomaterial analysis. High hydrostatic pressure technology was used for ginsenoside extraction from ginseng roots. In the extraction of fresh and red ginseng, high hydrostatic pressure extraction (HHPE) was found to be more effective than heat extraction (HE). In fresh ginseng extraction under HHPE, total ginsenosides (1602.2 µg mL⁻¹) and ginsenoside metabolite (132.6 µg mL⁻¹) levels were slightly higher than those under HE (1259.0 and 78.7 µg mL⁻¹), respectively. In red ginseng, similar results indicated total ginsenoside and ginsenoside metabolite amounts according to the extraction methods. Most volatile compounds by HHPE were higher than by HE treatment. HHPE of red ginseng was conducted under four pressures: 0.1 MPa (1 atm), 30, 50, and 80 MPa. Total sugar, uronic acid, and polyphenol amounts increased until 30 MPa of pressure and then showed decreasing tendencies. Total ginsenoside and ginsenoside metabolite contents linearly increased with increasing pressure, and a maximum was reached at 80 MPa for the metabolites. HHPE used for red ginseng processing contributes to enhanced extraction efficiencies of functional materials such as ginsenosides through cell structure modification. Copyright © 2011 Society of Chemical Industry.

Synthesis and Biological Evaluation of Ginsenoside Compound K Derivatives as a Novel Class of LXRα Activator.

PubMed

Huang, Yan; Liu, Hongmei; Zhang, Yingxian; Li, Jin; Wang, Chenping; Zhou, Li; Jia, Yi; Li, Xiaohui

2017-07-24

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41.51%; expression of ABCA1 mRNA: 319%) and low cytotoxicity.

Production of rare ginsenosides (compound Mc, compound Y and aglycon protopanaxadiol) by β-glucosidase from Dictyoglomus turgidum that hydrolyzes β-linked, but not α-linked, sugars in ginsenosides.

PubMed

Lee, Gi-Woong; Kim, Kyoung-Rok; Oh, Deok-Kun

2012-09-01

Optimal hydrolytic activity of β-glucosidase from Dictyoglomus turgidum for the ginsenoside Rd was at pH 5.5 and 80 °C, with a half-life of ~11 h. The enzyme hydrolysed β-linked, but not α-linked, sugar moieties of ginsenosides. It produced the rare ginsenosides, aglycon protopanaxadiol (APPD), compounds Y, and Mc, via three unique transformation pathways: Rb(1) → Rd → F(2) → compound K → APPD, Rb(2) → compound Y, and Rc → compound Mc. The enzyme converted 0.5 mM Rb(2) and 0.5 mM Rc to 0.5 mM compound Y and 0.5 mM compound Mc after 3 h, respectively, with molar conversion yields of 100 %.

Optimization of lipase-catalyzed synthesis of ginsenoside Rb1 esters using response surface methodology.

PubMed

Hu, Jiang-Ning; Lee, Jeung-Hee; Zhu, Xue-Mei; Shin, Jung-Ah; Adhikari, Prakash; Kim, Jae-Kyung; Lee, Ki-Teak

2008-11-26

In the lipase (Novozyme 435)-catalyzed synthesis of ginsenoside Rb1 esters, different acyl donors were found to affect not only the degree of conversion but also the regioselectivity. The reaction of acyl donors with short carbon chain was more effective, showing higher conversion than those with long carbon chain. Among the three solvent systems, the reaction in tert-amyl alcohol showed the highest conversion rate, while the reaction in the mixed solvent of t-BuOH and pyridine (1:1) had the lowest conversion rate. To allow the increase of GRb1 lipophilicity, we decided to further study the optimal condition of synthesis of GRb1 with vinyl decanoate with 10 carbon chain fatty acids in tert-amyl alcohol. Response surface methodology (RSM) was employed to optimize the synthesis condition. From the ridge analysis with maximum responses, the maximum GRb1 conversion was predicted to be 61.51% in a combination of factors (40.2 h, 52.95 degrees C, substrate mole ratio 275.57, and enzyme amount 39.81 mg/mL). Further, the adequacy of the predicted model was examined by additional independent experiments at the predicted maximum synthesis conditions. Results showed that the RSM was effective to optimize a combination of factors for lipase-catalyzed synthesis of ginsenoside Rb1 with vinyl decanoate.

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

PubMed Central

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

2014-01-01

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3+/CD69+, CD4+/CD25+, CD8+ T-cell, CD19+, B220/CD23+ B-cell, MHCII+/CD11c+, and Gr-1+/CD11b+ cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1β, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice. PMID:24833816

Protective effects of panax notoginseng saponins on cardiovascular diseases: a comprehensive overview of experimental studies.

PubMed

Yang, Xiaochen; Xiong, Xingjiang; Wang, Heran; Wang, Jie

2014-01-01

Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.

Local Explosion Monitoring using Rg

NASA Astrophysics Data System (ADS)

O'Rourke, C. T.; Baker, G. E.

2016-12-01

Rg is the high-frequency fundamental-mode Rayleigh wave, which is only excited by near-surface events. As such, an Rg detection indicates that a seismic source is shallow, generally less than a few km depending on the velocity structure, and so likely man-made. Conversely, the absence of Rg can indicate that the source is deeper and so likely naturally occurring. We have developed a new automated method of detecting Rg arrivals from various explosion sources at local distances, and a process for estimating the likelihood that a source is not shallow when no Rg is detected. Our Rg detection method scans the spectrogram of a seismic signal for a characteristic frequency peak. We test this on the Bighorn Arch Seismic Experiment data, which includes earthquakes, active source explosions in boreholes, and mining explosions recorded on a dense network that spans the Bighorn Mountains and Powder River Basin. The Rg passbands used were 0.4-0.8 Hz for mining blasts and 0.8-1.2 Hz for borehole shots. We successfully detect Rg across the full network for most mining blasts. The lower-yield shots are detectable out to 50 km. We achieve <1% false-positive rate for the small-magnitude earthquakes in the region. Rg detections on known non-shallow earthquake seismograms indicates they are largely due to windowing leakage at very close distances or occasionally to cultural noise. We compare our results to existing methods that use cross-correlation to detect retrograde motion of the surface waves. Our method shows more complete detection across the network, especially in the Powder River Basin where Rg exhibits prograde motion that does not trigger the existing detector. We also estimate the likelihood that Rg would have been detected from a surface source, based on the measured P amplitude. For example, an event with a large P wave and no detectable Rg would have a high probability of being a deeper event, whereas we cannot confidently determine whether an event with a small P

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

PubMed Central

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

2016-01-01

Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care. PMID:26932472

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

PubMed

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

2014-07-01

Ethanol metabolism produces harmful compounds that contribute to liver damage and cause an alcohol hangover. The intermediate metabolite acetaldehyde is responsible for alcohol hangover and CYP2E1-induced reactive oxygen species damage liver tissues. In this study, we examined whether ginsenoside-free molecules (GFMs) from steam-dried ginseng berries promote ethanol metabolism and scavenge free radicals by stimulating primary enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, CYP2E1, and catalase) and antioxidant effects using in vitro and in vivo models. The results revealed that GFM effectively scavenged 2,2-diphenyl-1-picrylhydrazyl hydrate radicals and hydroxyl radicals. Notably, GFM significantly enhanced the expression of primary enzymes within 2 h in HepG2 cells. GFM clearly removed the consumed ethanol and significantly reduced the level of acetaldehyde as well as enhancement of primary gene expression in BALB/c mice. Moreover, GFM successfully protected HepG2 cells from ethanol attack. Of the major components identified in GFM, it was believed that linoleic acid was the most active ingredient. Based on these findings, we conclude that GFM holds promise for use as a new candidate for ethanol metabolism and as an antihangover agent. © 2014 Institute of Food Technologists®

Induction of apoptosis and reversal of permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM by ginsenoside Rh2.

PubMed

Zhang, Hui; Gong, Jian; Zhang, Huilai; Kong, Di

2015-01-01

Multidrug resistance is a phenomenon that cancer cells develop a cross-resistant phenotype against several unrelated drugs, and permeability glycoprotein derived from the overexpression of multidrug resistance gene 1 has been taken as the most significant cause of multidrug resistance. In the present study, ginsenoside Rh2 was used to reverse permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM cell line. Effects of ginsenoside Rh2 on the apoptotic process and caspase-3 activity of MCF-7 and MCF-7/ADM cell lines were determined using flow cytometry and microplate reader. Methyl thiazolyl tetrazolium test was conducted to assess the IC50 values of ginsenoside Rh2 and adriamycin on MCF-7 and MCF-7/ADM cultures; Rhodamin 123 assay was used to assess the retention of permeability glycoprotein after ginsenoside Rh2 treatment; flow cytometry and real time polymerase chain reaction were used to determine the expression levels of permeability glycoprotein and multidrug resistance gene 1 in drug-resistant cells and their parental cells after exposure to ginsenoside Rh2. The results showed that ginsenoside Rh2, except for inducing apoptosis, had the ability to reverse multidrug resistance in MCF-7/ADM cell line without changing the expression levels of permeability glycoprotein and multidrug resistance gene 1. Our findings provided some valuable information for the application of ginsenoside Rh2 in cancer therapy, especially for multidrug resistance reversal in clinic.

Stimulation of Innate Immune Function by Panax ginseng after Heat Processing.

PubMed

Shin, Myoung-Sook; Song, Ji Hoon; Choi, Pilju; Lee, Jong Hun; Kim, Song-Yi; Shin, Kwang-Soon; Ham, Jungyeob; Kang, Ki Sung

2018-05-09

Panax ginseng Meyer has been used for the treatment of immune diseases and for strengthening the immune function. In this study, we evaluated the innate immune-stimulating functions and action mechanisms of white ginseng (WG) and heat-processed ginseng (HPG) in RAW264.7 cells. According to LC-MS analysis results, WG contained typical ginsenosides, such as Rb1, Rc, Rb2, Rd, and Rg1, whereas HPG contained Rg3, Rk1, and Rg5 as well as typical ginsenosides. HPG, not WG, enhanced NF-κB transcriptional activity, cytokine production (IL-6 and TNF-α), and MHC class I and II expression in RAW264.7 cells. In addition, HPG phosphorylated MAPKs and NF-kB pathways. In experiments with inhibitors, the ERK inhibitor completely suppressed the effect of HPG on IL-6 and TNF-α production. HPG-induced c-Jun activation was suppressed by an ERK inhibitor and partially suppressed by JNK, p38, and IκBα inhibitors. Collectively, these results suggested that HPG containing Rg3, Rg5, and Rk1 increased macrophage activation which was regulated by the ERK/c-Jun pathway in RAW264.7 cells.

Monoclonal Antibodies against Small Molecule Natural Products and Their Applications, Eastern Blotting and Knockout Extract

PubMed Central

Shoyama, Yukihiro

2011-01-01

To determine the hapten number in hapten-carrier protein conjugate matrix-assisted laser desorption/ionization (MALDI) tof mass spectrometry was applied. Highly specific anti-ginsenoside Rb1 and Rg1 monoclonal antibodies (MAbs) were prepared. Ginsenosides were developed on thin layer chromatography (TLC) plates which were covered by a polyvinylidene difluoride (PVDF) membrane resulting in blotting. The membrane was treated with NaIO4 solution to release the aldehyde group on the sugar moiety of the ginsenosides. By treatment of the membrane with a protein solution the ginsenoside-protein conjugation as a Schiff-base occurred, which can function to fix it to the PVDF membrane. A part of the ginsenoside aglycone was reacted with anti-ginsenoside Rb1 MAb, secondary MAb conjugated with enzyme and finally a substrate was added, resulting in a specific and highly sensitive staining that we named Eastern blotting. Furthermore, it makes one-step isolation of ginsenoside Rb1 possible using an immuno-affinity column conjugated with anti-ginsenoside Rb1 MAb. Furthermore, immunoaffinity concentration was carried out allowing high sensitivity analysis of lower concentrations of ginsenoside Rb1 so that several unknown bands could be structurally determined.

Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion injury via Akt/endothelial nitric oxide synthase signaling and the B‑cell lymphoma/B‑cell lymphoma‑associated X protein pathway.

PubMed

Wang, Yiping; Hu, Zhaohui; Sun, Bing; Xu, Jiahong; Jiang, Jinfa; Luo, Ming

2015-06-01

Previous studies have suggested that ginsenoside Rg3 (GSRg3) extract from the medicinal plant Panax ginseng, may increase nitric oxide production via increases in the phosphorylation and expression of endothelial nitric oxide synthase (eNOS). The present study used an in vitro neonatal rat cardiomyocyte (NRC) model of anoxia‑reoxygenation injury and an in vivo rat model of myocardial ischemia/reperfusion (MI/R) injury. Hemodynamic, histopathological and biochemical assessment of the myocardial injury was performed and the expression levels of lactate dehydrogenase (LDH), superoxide dismutase and creatine kinase (CK) were measured in serum from the animal model, which may reflect myocardial injury. NRC injury was determined using a Cell Counting kit‑8. The GSRg3 anti‑apoptotic effects were assessed using flow cytometry to investigate the number of early‑late apoptotic cells and western blot analysis was performed to analyze the protein expression levels of caspase‑3, caspase‑9, B‑cell lymphoma‑2 (Bcl‑2), phosphorylated (p‑)Akt and eNOS. The results suggested that pretreatment with GSRg3 (60 mg/kg) significantly improved rat cardiac function, as demonstrated by increased left ventricular systolic pressure, heart rate and first derivative of left ventricular pressure. GSRg3 also reduced the size of the myocardial infarct and LDH/CK levels in the blood following MI/R. In vitro investigations revealed that GSRg3 (10 mM) decreased NRC apoptosis through inhibiting the activation of caspase‑3 and caspase‑9, and increasing the expression levels of p‑Akt, eNOS and the ratio of Bcl‑2/Bcl‑2‑associated X protein (Bax). Overall, the present study revealed that GSRg3 mediated a cardioprotective effect against MI/R‑induced apoptosis via Akt/eNOS signaling and the Bcl‑2/Bax pathway.

Ginsenosides from stems and leaves of ginseng prevent ethanol-induced lipid accumulation in human L02 hepatocytes.

PubMed

Hu, Chao-Feng; Sun, Li-Ping; Yang, Qin-He; Lu, Da-Xiang; Luo, Sen

2017-06-01

To investigate the effect of ginsenosides from stems and leaves of ginseng on ethanol-induced lipid deposition in human L02 hepatocytes. L02 cells were exposed to ethanol for 36 h and treated with or without ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyl-tetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid droplets were determined by oil red O staining. Intracellular reactive oxygen species (ROS) production and the mitochondrial membrane potential were tested by flow cytometry. The ATP level was measured by reverse phase high performance liquid chromatography. The expression of cytochrome p450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) was detected by reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Ethanol exposure resulted in the increase of TG level, lipid accumulation and ROS generation, and the decrease of mitochondrial membrane potential and ATP production in the cells. However, ginsenosides significantly reduced TG content (9.69±0.22 μg/mg protein vs. 4.93±0.49 μg/mg protein, P<0.01), and ROS formation (7254.8±385.7 vs. 5825.2±375.9, P<0.01). Meanwhile, improvements in mitochondrial membrane potential (10655.33±331.34 vs. 11129.52±262.35, P<0.05) and ATP level (1.20±0.18 nmol/mg protein vs. 2.53±0.25 nmol/mg protein, P<0.01) were observed by treatment with ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression (P<0.01) and upregulate PPARα expression (P<0.01) in ethanol-treated cells. Ginsenosides could prevent ethanol-induced hepatocyte steatosis in vitro related to the inhibition of oxidative stress and the improvement of mitochondrial function. In addition, the modulation of CYP2E1 and PPARα expression may also play an important role in the protective effect of ginsenosides against lipid accumulation.

Antitumoral Activity of (20R)- and (20S)-Ginsenoside Rh2 on Transplanted Hepatocellular Carcinoma in Mice.

PubMed

Lv, Qun; Rong, Na; Liu, Li-Jia; Xu, Xiao-Lin; Liu, Jian-Ting; Jin, Feng-Xie; Wang, Chun-Mei

2016-05-01

Hepatocellular carcinoma is one of the leading causes of malignancy-related death in China. Its therapy in clinics is a big challenge. Ginsenoside Rh2 is one of the most notable cancer-preventing components from red ginseng and it has been reported that ginsenoside Rh2 exhibited potent cytotoxicity against human hepatoma cells. Rh2 exists as two different stereoisomeric forms, (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2. Previous reports showed that the Rh2 epimers demonstrated different pharmacological activities and only (20S)-ginsenoside Rh2 showed potent proliferation inhibition on cancer cells in vitro. However, the in vivo anti-hepatoma activity of (20R)-ginsenoside Rh2 and (20S)-ginsenoside Rh2 has not been reported yet. This work assessed and compared the anti-hepatoma activities of (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2 using H22 a hepatoma-bearing mouse model in vivo. In addition, hematoxylin and eosin staining, the deoxynucleotidyl transferase dUTP nick-end labeling assay, and the semiquantitative reverse transcriptase polymerase chain reaction method were used to further study the apoptosis of the tumors. The results showed that both (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2 suppressed the growth of H22 transplanted tumors in vivo, and the highest inhibition rate could be up to 42.2 and 46.8 %, respectively (p < 0.05). Further, hematoxylin/eosin staining and the deoxynucleotidyl transferase dUTP nick-end labeling assay indicated that both (20R)-ginsenoside Rh2 and (20S)-ginsenoside Rh2 could induce H22 hepatoma tumor cell apoptosis, with apoptosis indexes of 3.87 %, and 3.80 %, respectively (p < 0.05). Moreover, this effect was accompanied by downregulating the level of Bcl-2 mRNA. In conclusion, both (20S)-ginsenoside Rh2 and (20R)-ginsenoside Rh2 can suppress the growth of H22 hepatomas without causing severe side effects, and this effect is associated with the induction of apoptosis. Georg Thieme Verlag KG Stuttgart �

Ginsenoside improves physicochemical properties and bioavailability of curcumin-loaded nanostructured lipid carrier.

PubMed

Vijayakumar, Ajay; Baskaran, Rengarajan; Maeng, Han-Joo; Yoo, Bong Kyu

2017-07-01

The aim of this study was to develop a ginsenoside-modified nanostructured lipid carrier (G-NLC) dispersion containing curcumin. The NLC was prepared by melt emulsification with slight modification process. Different G-NLC dispersion systems were prepared using lipid carrier matrix composed of ginsenoside, phosphatidylcholine, lysophosphatidylcholine, and hydrogenated bean oil. TEM image of the nanoparticles in the NLC dispersion showed core/shell structure, and there was corona-like layer surrounding the particles in the G-NLC. The mean particle size of G-NLC dispersion was in the range of about 300-500 nm and stayed submicron size up to 12 months. The in vitro release of curcumin was faster in pH 1.2 compared to pH 6.8 and it showed linear release pattern after lag time of 1 h. When the G-NLC dispersion was orally administered to rats, C max of the free curcumin was 15.2 and 32.3 ng/mL at doses of 50 and 100 mg/kg, respectively, while it was below quantification limit when curcumin was administered as of dispersion in distilled water. Based on these results, it is certain that ginsenoside modulated the NLC dispersion, leading to enduring shelf-life of the dispersion system and enhanced bioavailability. These results strongly suggest that ginsenoside holds a promising potential as a pharmaceutical excipient in the pharmaceutical industries to increase the utility of various bioactives.

Red Ginseng (Panax ginseng) Decreases Isoproterenol-Induced Cardiac Injury via Antioxidant Properties in Porcine

PubMed Central

Lim, Kyu Hee; Cho, Jae Youl; Kim, Bumseok; Bae, Bong-Seuk

2014-01-01

Abstract Red ginseng (RG, Panax ginseng) has been shown to possess various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The present study was designed to evaluate the cardioprotective potential of RG against isoproterenol (ISO)-induced myocardial infarction (MI), by assessing electrocardiographic, hemodynamic, and biochemical parameters. Male porcines were orally administered with RG (250 and 500 mg/kg) or with vehicle for 9 days, with concurrent intraperitoneal injections of ISO (20 mg/kg) on the 8th and 9th day. RG significantly attenuated ISO-induced cardiac dysfunctions as evidenced by improved ventricular hemodynamic functions and reduced ST segment and QRS complex intervals. Also, RG significantly ameliorated myocardial injury parameters such as antioxidants. Malonaldialdehyde formation was also inhibited by RG. Based on the results, it is concluded that RG possesses significant cardioprotective potential through the inhibition of oxidative stress and may serve as an adjunct in the treatment and prophylaxis of MI. PMID:24456361

Ginsenoside Re: pharmacological effects on cardiovascular system.

PubMed

Peng, Lu; Sun, Shi; Xie, Lai-Hua; Wicks, Sheila M; Xie, Jing-Tian

2012-08-01

Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs to the panaxatriol group. Many reports demonstrated that G-Re possesses the multifaceted beneficial pharmacological effects on cardiovascular system. G-Re has negative effect on cardiac contractility and autorhythmicity. It causes alternations in cardiac electrophysiological properties, which may account for its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and induces angiogenic regeneration. In this review, we first outline the chemistry and the pharmacological effects of G-Re on the cardiovascular system. © 2011 Blackwell Publishing Ltd.

Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.

PubMed

Li, Li B; Ma, Chao; Awong, Geneve; Kennedy, Marion; Gornalusse, German; Keller, Gordon; Kaufman, Dan S; Russell, David W

2016-03-01

Many applications of pluripotent stem cells (PSCs) require efficient editing of silent chromosomal genes. Here, we show that a major limitation in isolating edited clones is silencing of the selectable marker cassette after homologous recombination and that this can be overcome by using a ubiquitous chromatin opening element (UCOE) promoter-driven transgene. We use this strategy to edit the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus (rAAV)-targeting vector in the absence of potentially genotoxic, site-specific nucleases and show that IL2RG is required for natural killer and T-cell differentiation of human PSCs. Insertion of an active UCOE promoter into a silent locus altered the histone modification and cytosine methylation pattern of surrounding chromatin, but these changes resolved when the UCOE promoter was removed. This same approach could be used to correct IL2RG mutations in X-linked severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent graft versus host disease in regenerative medicine applications, or to edit other silent genes.

Preparation and evaluation of self-microemulsions for improved bioavailability of ginsenoside-Rh1 and Rh2.

PubMed

Yang, Feifei; Zhou, Jing; Hu, Xiao; Yu, Stephanie Kyoungchun; Liu, Chunyu; Pan, Ruile; Chang, Qi; Liu, Xinmin; Liao, Yonghong

2017-10-01

Due to intestinal cytochrome P450 (CYP450)-mediated metabolism and P-glycoprotein (P-gp) efflux, poor oral bioavailability hinders ginsenoside-Rh1 (Rh1) and ginsenoside-Rh2 (Rh2) from clinical application. In this study, Rh1 and Rh2 were incorporated into two self-microemulsions (SME-1 and SME-2) to improve oral bioavailability. SME-1 contained both CYP450 and P-gp inhibitory excipients while SME-2 only consisted of P-gp inhibitory excipients. Results for release, cellular uptake, transport, and lymph node distribution demonstrated no significant difference between either self-microemulsions in vivo, but were elevated significantly in comparison to the free drug. The pharmaceutical profiles in vivo showed that the bioavailability of Rh1 in SME-1 (33.25%) was significantly higher than that in either SME-2 (21.28%) or free drug (12.92%). There was no significant difference in bioavailability for Rh2 between SME-1 (48.69%) or SME-2 (41.73%), although they both had remarkable increase in comparison to free drug (15.02%). We confirmed that SME containing CYP450 and P-gp inhibitory excipient could distinctively improve the oral availabilities of Rh1 compared to free drug or SME containing P-gp inhibitory excipient. No notable increase was observed between either SME for Rh2, suggesting that Rh2 undergoes P-gp-mediated efflux, but may not undergo distinct CYP450-mediated metabolism.

Counting RG flows

DOE PAGES

Gukov, Sergei

2016-01-05

Here, interpreting renormalization group flows as solitons interpolating between different fixed points, we ask various questions that are normally asked in soliton physics but not in renormalization theory. Can one count RG flows? Are there different "topological sectors" for RG flows? What is the moduli space of an RG flow, and how does it compare to familiar moduli spaces of (supersymmetric) dowain walls? Analyzing these questions in a wide variety of contexts -- from counting RG walls to AdS/CFT correspondence -- will not only provide favorable answers, but will also lead us to a unified general framework that is powerfulmore » enough to account for peculiar RG flows and predict new physical phenomena. Namely, using Bott's version of Morse theory we relate the topology of conformal manifolds to certain properties of RG flows that can be used as precise diagnostics and "topological obstructions" for the strong form of the C-theorem in any dimension. Moreover, this framework suggests a precise mechanism for how the violation of the strong C-theorem happens and predicts "phase transitions" along the RG flow when the topological obstruction is non-trivial. Along the way, we also find new conformal manifolds in well-known 4d CFT's and point out connections with the superconformal index and classifying spaces of global symmetry groups.« less

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

PubMed

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

2014-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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.

Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration.

PubMed

Chen, Yin Bin; Wang, Yu Fang; Hou, Wei; Wang, Ying Ping; Xiao, Sheng Yuan; Fu, Yang Yang; Wang, Jia; Zheng, Si Wen; Zheng, Pei He

2017-04-01

Both ginsenoside Re and B-complex vitamins are widely used as nutritional supplements. They are often taken together so as to fully utilize their antifatigue and refreshing effects, respectively. Whether actually a drug-nutrient interaction exists between ginsenoside Re and B-complex vitamins is still unknown. The objective of this study was to simultaneously investigate the effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after their oral administration. The study results will provide valuable theoretical guidance for the combined utilization of ginseng and B-complex vitamins. Ginsenoside Re with or without B-complex vitamins was orally administered to mice to evaluate its antifatigue effects and to rats to evaluate its bioavailability. The antifatigue activity was evaluated by the weight-loaded swimming test and biochemical parameters, including hepatic glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of ginsenoside Re in plasma was determined by liquid chromatography-tandem mass spectrometry. No antifatigue effect of ginsenoside Re was noted when ginsenoside Re in combination with B-complex vitamins was orally administered to mice. B-complex vitamins caused to a reduction in the bioavailability of ginsenoside Re with the area under the concentration-time curve from zero to infinity markedly decreasing from 11,830.85 ± 2,366.47 h·ng/mL to 890.55 ± 372.94 h·ng/mL. The results suggested that there were pharmacokinetic and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B-complex vitamins. B-complex vitamins can significantly weaken the antifatigue effect and decrease the bioavailability of ginsenoside Re when simultaneously administered orally.

Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin

PubMed Central

Im, Dong-soon; Nah, Seung-yeol

2013-01-01

Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine as a tonic herb that provides many beneficial effects. Pharmacologic studies in the last decades have shown that ginsenosides (ginseng saponins) are primarily responsible for the actions of ginseng. However, the effects of ginseng are not fully explained by ginsenosides. Recently, another class of active ingredients called gintonin was identified. Gintonin is a complex of glycosylated ginseng proteins containing lysophosphatidic acids (LPAs) that are the intracellular lipid mitogenic mediator. Gintonin specifically and potently activates the G protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics. In the present review, we evaluate the pharmacology of ginseng with the traditional viewpoint of Yin and Yang components. Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs. PMID:24122014

Comprehensive Profiling and Quantification of Ginsenosides in the Root, Stem, Leaf, and Berry of Panax ginseng by UPLC-QTOF/MS.

PubMed

Lee, Jae Won; Choi, Bo-Ram; Kim, Young-Chang; Choi, Doo Jin; Lee, Young-Seob; Kim, Geum-Soog; Baek, Nam-In; Kim, Seung-Yu; Lee, Dae Young

2017-12-04

The effective production and usage of ginsenosides, given their distinct pharmacological effects, are receiving increasing amounts of attention. As the ginsenosides content differs in different parts of Panax ginseng, we wanted to assess and compare the ginsenosides content in the ginseng roots, leave, stems, and berries. To extract the ginsenosides, 70% (v/v) methanol was used. The optimal ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) method was used to profile various ginsenosides from the different parts of P. ginseng. The datasets were then subjected to multivariate analysis including principal component analysis (PCA) and hierarchical clustering analysis (HCA). A UPLC-QTOF/MS method with an in-house library was constructed to profile 58 ginsenosides. With this method, a total of 39 ginsenosides were successfully identified and quantified in the ginseng roots, leave, stem, and berries. PCA and HCA characterized the different ginsenosides compositions from the different parts. The quantitative ginsenoside contents were also characterized from each plant part. The results of this study indicate that the UPLC-QTOF/MS method can be an effective tool to characterize various ginsenosides from the different parts of P. ginseng.

The DcpS inhibitor RG3039 improves motor function in SMA mice

PubMed Central

Van Meerbeke, James P.; Gibbs, Rebecca M.; Plasterer, Heather L.; Miao, Wenyan; Feng, Zhihua; Lin, Ming-Yi; Rucki, Agnieszka A.; Wee, Claribel D.; Xia, Bing; Sharma, Shefali; Jacques, Vincent; Li, Darrick K.; Pellizzoni, Livio; Rusche, James R.; Ko, Chien-Ping; Sumner, Charlotte J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene, retention of the survival motor neuron 2 (SMN2) gene and insufficient expression of full-length survival motor neuron (SMN) protein. Quinazolines increase SMN2 promoter activity and inhibit the ribonucleic acid scavenger enzyme DcpS. The quinazoline derivative RG3039 has advanced to early phase clinical trials. In preparation for efficacy studies in SMA patients, we investigated the effects of RG3039 in severe SMA mice. Here, we show that RG3039 distributed to central nervous system tissues where it robustly inhibited DcpS enzyme activity, but minimally activated SMN expression or the assembly of small nuclear ribonucleoproteins. Nonetheless, treated SMA mice showed a dose-dependent increase in survival, weight and motor function. This was associated with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size. RG3039 also enhanced survival of conditional SMA mice in which SMN had been genetically restored to motor neurons. As this systemically delivered drug may have therapeutic benefits that extend beyond motor neurons, it could act additively with SMN-restoring therapies delivered directly to the central nervous system such as antisense oligonucleotides or gene therapy. PMID:23727836

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

PubMed Central

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

2015-01-01

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

Improved inflammatory balance of human skeletal muscle during exercise after supplementations of the ginseng-based steroid Rg1.

PubMed

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

2015-01-01

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

Effect of ginseng saponins on the recombinant serotonin type 3A receptor expressed in xenopus oocytes: implication of possible application as an antiemetic.

PubMed

Min, Kyeong T; Koo, Bon N; Kang, Jeong W; Bai, Sun Joon; Ko, Sung R; Cho, Zang-Hee

2003-08-01

Nausea and vomiting are the most frequently reported side-effects by patients who are given general anesthesia perioperatively and patients with cancer who undergo chemotherapy or radiotherapy. Serotonin (5-hydroxytryptamine, 5HT) type 3A receptor (5HT(3A) receptor) is known to mediate nausea and vomiting and its antagonists have been used effectively to prevent and/or reduce the incidence and severity of nausea and vomiting. However, the adverse effects on cardiac function, such as QT interval prolongation, limit their routine use by these patients. This study was designed to elucidate the effect of ginseng saponins on the recombinant 5HT(3A) receptor expressed in the xenopus oocyte. After in vitro transcription of the recombinant human 5HT(3A) receptor in the Xenopus laevis oocyte, we examined Panax ginseng saponins (total saponin [TS], panaxadiol saponin [PD] fraction, panaxatriol saponin [PT] fraction, and ginsenoside-Rb1 and -Rg1) for their ability to inhibit current flow through the 5HT(3A) receptor using the voltage-clamp technique. All saponin fractions (TS, PD, PT fraction, as well as ginsenoside-Rb1 and -Rg1) inhibited the peak current induced by the agonist 5HT on the 5HT(3A) receptor in a concentration-dependent, reversible, and voltage-independent manner. The PT fraction inhibited 5HT-induced currents in 5HT(3A) receptor more than the PD fraction; meanwhile, there was a similar degree of inhibition between ginsenoside-Rg1 and -Rb1, the main substitutes of PT fraction and PD saponin fractions, respectively. These results indicate that ginseng saponins, especially PT fraction, have substantial inhibitory effects on the recombinant 5HT(3A) receptor, suggesting that some of the specific types of ginsenoside might have an antagonistic action against 5HT(3A) receptor related to nausea and vomiting.

Rare ginsenoside Ia synthesized from F1 by cloning and overexpression of the UDP-glycosyltransferase gene from Bacillus subtilis: synthesis, characterization, and in vitro melanogenesis inhibition activity in BL6B16 cells.

PubMed

Wang, Dan-Dan; Jin, Yan; Wang, Chao; Kim, Yeon-Ju; Perez, Zuly Elizabeth Jimenez; Baek, Nam In; Mathiyalagan, Ramya; Markus, Josua; Yang, Deok-Chun

2018-01-01

Ginsenoside F1 has been described to possess skin-whitening effects on humans. We aimed to synthesize a new ginsenoside derivative from F1 and investigate its cytotoxicity and melanogenesis inhibitory activity in B16BL6 cells using recombinant glycosyltransferase enzyme. Glycosylation has the advantage of synthesizing rare chemical compounds from common compounds with great ease. UDP-glycosyltransferase (BSGT1) gene from Bacillus subtilis was selected for cloning. The recombinant glycosyltransferase enzyme was purified, characterized, and utilized to enzymatically transform F1 into its derivative. The new product was characterized by NMR techniques and evaluated by MTT, melanin count, and tyrosinase inhibition assay. The new derivative was identified as (20 S )-3 β ,6 α ,12 β ,20-tetrahydroxydammar-24-ene-20- O - β -D-glucopyranosyl-3- O - β -D-glucopyranoside (ginsenoside Ia), which possesses an additional glucose linked into the C-3 position of substrate F1. Ia had been previously reported; however, no in vitro biological activity was further examined. This study focused on the mass production of arduous ginsenoside Ia from accessible F1 and its inhibitory effect of melanogenesis in B16BL6 cells. Ia showed greater inhibition of melanin and tyrosinase at 100 μmol/L than F1 and arbutin. These results suggested that Ia decreased cellular melanin synthesis in B16BL6 cells through downregulation of tyrosinase activity. To our knowledge, this is the first study to report on the mass production of rare ginsenoside Ia from F1 using recombinant UDP-glycosyltransferase isolated from B. subtillis and its superior melanogenesis inhibitory activity in B16BL6 cells as compared to its precursor. In brief, ginsenoside Ia can be applied for further study in cosmetics.

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

PubMed

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

2015-10-23

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

Large Scale Culture of Ginseng Adventitious Roots for Production of Ginsenosides

NASA Astrophysics Data System (ADS)

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

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

Infrared Spectroscopy of C_6D_6-Rg_n(n=1,2)

NASA Astrophysics Data System (ADS)

George, Jobin; Yousefi, Mahdi; Rezaei, Mojtaba; McKellar, Bob; Moazzen-Ahmadi, Nasser

2014-06-01

Benzene-noble gas complexes were one of the earliest topics of interest in spectroscopic investigation of van der Waals (vdW) complexes. Smalley et al. observed C_6H_6-(He)1,2 vdW complexes in the late 1970s by means of electronic spectroscopy. A recent study on the same species was done by M. Hayashi et al. Here, we present the infrared observation of C_6D_6-Rg_n (n=1,2) with the rare gas being He, Ne, or Ar, in the regions of νb{12} fundamental band of C_6D_6 (˜2289 wn) and the νb{2} + νb{13} combination band (˜2275 wn) which are coupled by a Fermi resonance. The spectra were observed at a resolution of 60 MHz using a tunable optical parametric oscillator to probe a pulsed supersonic-jet expansion from a slit nozzle. In the case of C_6D_6-Rg dimers, the spectra were assigned to a symmetric top with C6v symmetry with the rare gas atom being located on the C6 symmetry axis. To observe C_6D_6-Rg_2 trimers, the nozzle was cooled using a closed-cycle methanol refrigerator and the spectra were simulated with a rotational temperature of 1.3K. The spectra of the C_6D_6-Rg_2 trimers were in agreement with a D6h symmetry structure, where the rare gas atoms are positioned above and below the C_6D_6 plane. Data analysis and observation are presently ongoing. S. M. Beck, M. G. Liverman, D. L. Monts and R. E. Smalley, J. Chem. Phys. 70, 232 (1979). M. Hayashi, Y. Ohshima, Chem. Phys. 419, 131 (2013).

Ginsenoside 25-OCH3-PPD promotes activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome in the development of hepatic fibrosis.

PubMed

Han, Xin; Song, Jian; Lian, Li-Hua; Yao, You-Li; Shao, Dan-Yang; Fan, Ying; Hou, Li-Shuang; Wang, Ge; Zheng, Shuang; Wu, Yan-Ling; Nan, Ji-Xing

2018-06-22

Ginseng is widely used in energy drinks, dietary supplements and herbal medicines, and its pharmacological actions are related with energy metabolism. As an important modulating energy metabolism pathway, liver X receptors (LXRs) can promote the resolving of hepatic fibrosis and inflammation. The present study aims to evaluate the regulation of 25-OCH3-PPD, a ginsenoside isolated from Panax ginseng, against hepatic fibrosis and inflammation in thioacetamide (TAA)-stimulated mice by activating LXRs pathway. 25-OCH3-PPD decreases serum ALT/AST levels and improves the histological pathology of liver in TAA-induced mice; attenuates transcripts of pro-fibrogenic markers associated with hepatic stellate cell activation; attenuates the levels of pro-Inflammatory cytokines and blocks apoptosis happened in liver; inhibits NLRP3 inflammasome by affecting P2X7R activation; regulates PI3K/Akt and LKB1/AMPK-SIRT1. 25-OCH3-PPD also facilitates LX25Rs and FXR activities decreased by TAA stimulation. 25-OCH3-PPD also decreases α-SMA via regulation of LXRs and P2X7R-NLRP3 in vitro. Our data suggest the possibility that 25-OCH3-PPD promotes activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome in the development of hepatic fibrosis.

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

PubMed

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

2016-02-01

Ginseng flower bud as a part of Panax ginseng has received much attention as a valuable functional food with medicinal potential. A few studies focused on systematic and comprehensive studies on its major ingredients. This study aims to rapidly characterize ginsenosides in ginseng flower buds and provide scientific basis for developing functional food, exploiting pharmaceutical effects and making full use of ginseng resources. A rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method was developed for rapid qualitative and quantitative analysis of ginsenosides in ginseng flower buds. The compounds were identified by comparing retention time of the reference standards, accurate mass measurement and the fragment ions obtained from RRLC-Q-TOF-MS/MS analyses. A total of 14 kinds of ginsenosides were identified and 5 kinds of malonyl-ginsenosides were first tentatively identified in ginseng flower buds. Ten kinds of main ginsenosides were quantitatively analyzed. The developed RRLC-Q-TOF-MS method was demonstrated as an effective analytical means for rapid characterization of the ginsenosides in flower buds of P. ginseng. The research result is valuable for quality control, assessment of authenticity and stability evaluation of ginseng flower buds. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Isolation and Quantification of Ginsenoside Rh23, a New Anti-Melanogenic Compound from the Leaves of Panax ginseng.

PubMed

Lee, Dae Young; Kim, Hyoung-Geun; Lee, Yeong-Geun; Kim, Jin Hee; Lee, Jae Won; Choi, Bo-Ram; Jang, In-Bae; Kim, Geum-Soog; Baek, Nam-In

2018-01-29

A new ginsenoside, named ginsenoside Rh23 ( 1 ), and 20- O -β-d-glucopyranosyl-3β,6α,12β,20β,25-pentahydroxydammar-23-ene ( 2 ) were isolated from the leaves of hydroponic Panax ginseng . Compounds were isolated by various column chromatography and their structures were determined based on spectroscopic methods, including high resolution quadrupole/time of flight mass spectrometry (HR-QTOF/MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy. To determine anti-melanogenic activity, the change in the melanin content in melan-a cells treated with identified compounds was tested. Additionally, we investigated the melanin inhibitory effects of ginsenoside Rh23 on pigmentation in a zebrafish in vivo model. Compound 1 inhibited potent melanogenesis in melan-a cells with 37.0% melanogenesis inhibition at 80 µM and also presented inhibition on the body pigmentation in zebrafish model. Although compound 2 showed slightly lower inhibitory activity than compound 1 , it also showed significantly decreased melanogenesis in melan-a cell and in zebrafish model. These results indicated that compounds isolated from hydroponic P. ginseng may be used as new skin whitening compound through the in vitro and in vivo systems. Furthermore, this study demonstrated the utility of MS-based compound 1 for the quantitative analysis. Ginsenoside Rh23 ( 1 ) was found at a level of 0.31 mg/g in leaves of hydroponic P. ginseng .

In situ analysis of chemical components induced by steaming between fresh ginseng, steamed ginseng, and red ginseng.

PubMed

In, Gyo; Ahn, Nam-Geun; Bae, Bong-Seok; Lee, Myoung-Woo; Park, Hee-Won; Jang, Kyoung Hwa; Cho, Byung-Goo; Han, Chang Kyun; Park, Chae Kyu; Kwak, Yi-Seong

2017-07-01

The chemical constituents of Panax ginseng are changed by processing methods such as steaming or sun drying. In the present study, the chemical change of Panax ginseng induced by steaming was monitored in situ . Samples were separated from the same ginseng root by incision during the steaming process, for in situ monitoring. Sampling was sequentially performed in three stages; FG (fresh ginseng) → SG (steamed ginseng) → RG (red ginseng) and 60 samples were prepared and freeze dried. The samples were then analyzed to determine 43 constituents among three stages of P. ginseng . The results showed that six malonyl-ginsenoside (Rg1, Rb1, Rb3, Rc, Rd, Rb2) and 15 amino acids were decreased in concentration during the steaming process. In contrast, ginsenoside-Rh1, 20( S )-Rg2, 20( S, R )-Rg3 and Maillard reaction product such as AF (arginine-fructose), AFG (arginine-fructose-glucose), and maltol were newly generated or their concentrations were increased. This study elucidates the dynamic changes in the chemical components of P. ginseng when the steaming process was induced. These results are thought to be helpful for quality control and standardization of herbal drugs using P. ginseng and they also provide a scientific basis for pharmacological research of processed ginseng (Red ginseng).

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

NASA Astrophysics Data System (ADS)

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

2006-01-01

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

Neuroprotective effects of ginsenoside Rb1 on high glucose-induced neurotoxicity in primary cultured rat hippocampal neurons.

PubMed

Liu, Di; Zhang, Hong; Gu, Wenjuan; Liu, Yuqin; Zhang, Mengren

2013-01-01

Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, so the present study aimed to observe the effects of ginsenoside Rb1 on ER stress signaling pathways in high glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high glucose for 72 h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 μM Rb1 for 72 h protected the neurons against high glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated proteins including protein kinase RNA (PKR)-like ER kinase (PERK) and C/EBP homology protein (CHOP) and downregulation of Bcl-2 induced by high glucose. Moreover, Rb1 inhibited both the elevation of intracellular reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high glucose. In addition, the high glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress 4-phenylbutyric acid (4-PBA) and anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and mitochondrial dysfunction.

Possible role of ginsenoside Rb1 in skin wound healing via regulating senescent skin dermal fibroblast.

PubMed

Hou, Jingang; Kim, Sunchang

2018-05-05

Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H 2 O 2 exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP). The induction of SASP was regulated by p38MAPK/MSK2/NF-κB pathway. Interestingly, inhibition of p38MAPK activation only partially suppressed SASP. However, SASP was significantly inhibited by SB747651A, a specific MSK inhibitor. Additionally, we demonstrate that SASP stimulates migration of keratinocytes and myofibroblast transition of fibroblast, through fold-increased secretion of growth factors, platelet-derived growth factor AA (PDGF-AA) and AB (PDGF-AB), transforming growth factor beta 1 (TGF-β1) and beta 2 (TGF-β2), vascular endothelial growth factor A (VEGF-A) and D (VEGF-D), vascular endothelial growth factor receptor 2 (VEGFR2) and 3 (VEGFR3). Importantly, we also confirmed ginsenoside Rb1 promoted SASP-mediated healing process via p38MAPK/MSK2/NF-κB pathway. The results pointed to senescent fibroblast as a potential mechanism of wound healing control in human skin. Further, it provided a candidate targeted for wound therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of the removal of ethanethiol in twin-biotrickling filters inoculated with strain RG-1 and B350 mixed microorganisms.

PubMed

An, Taicheng; Wan, Shungang; Li, Guiying; Sun, Lei; Guo, Bin

2010-11-15

This study aims to compare the biological degradation performance of ethanethiol using strain RG-1 and B350 commercial mixed microorganisms, which were inoculated and immobilized on ceramic particles in twin-biotrickling filter columns. The parameters affecting the removal efficiency, such as empty bed residence time (EBRT) and inlet concentration, were investigated in detail. When EBRT ranged from 332 to 66 s at a fixed inlet concentration of 1.05 mg L(-1), the total removal efficiencies for RG-1 and B350 both decreased from 100% to 70.90% and 47.20%, respectively. The maximum elimination capacities for RG-1 and B350 were 38.36 (removal efficiency=89.20%) and 25.82 g m(-3) h(-1) (removal efficiency=57.10%), respectively, at an EBRT of 83 s. The variation of the inlet concentration at a fixed EBRT of 110 s did not change the removal efficiencies which remained at 100% for RG-1 and B350 at concentrations of less than 1.05 and 0.64 mg L(-1), respectively. The maximum elimination capacities were 39.93 (removal efficiency=60.30%) and 30.34 g m(-3) h(-1) (removal efficiency=46.20%) for RG-1 and B350, respectively, at an inlet concentration of 2.03 mg L(-1). Sulfate was the main metabolic product of sulfur in ethanethiol. Based the results, strain RG-1 would be a better choice than strain B350 for the biodegradation of ethanethiol. Copyright © 2010 Elsevier B.V. All rights reserved.

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

PubMed

Huang, Qi; Wang, Ting; Yang, Liu; Wang, He-Yao

2017-05-19

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.

Triterpene saponins from Vietnamese ginseng (Panax vietnamensis) and their hepatocytoprotective activity.

PubMed

Tran, Q L; Adnyana, I K; Tezuka, Y; Nagaoka, T; Tran, Q K; Kadota, S

2001-04-01

The methanol extract of Vietnamese ginseng (Panax vietnamensis) was found to possess hepatocytoprotective effects on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Further chemical investigation of the extract afforded two new dammarane-type triterpene saponins, ginsenoside Rh(5) (1) and vina-ginsenoside R(25) (2), as well as eight known dammarane-type triterpene saponins, majonoside R(2) (3), pseudo-ginsenoside RT(4) (4), vina-ginsenosides R(1) (5), R(2) (6), and R(10) (7), ginsenosides Rg(1) (8), Rh(1) (9), and Rh(4) (10), and a known sapogenin protopanaxatriol oxide II (11). Their structures were elucidated on the basis of spectral analysis. In addition, by the using LC-electrospray ionization (ESI)-MS method, five known saponins, ginsenosides Rb(1), Rb(2), Rc, Rd, and Re (12--16), were also identified in the extract. Among the compounds isolated, majonoside R(2) (3), the main saponin in Vietnamese ginseng, showed strong protective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. This demonstrates that the hepatocytoprotective effect of Vietnamese ginseng is due to dammarane-type triterpene saponins that have an ocotillol-type side chain, a characteristic constituent of Vietnamese ginseng.

N = 1 Deformations and RG flows of N = 2 SCFTs, part II: non-principal deformations

DOE PAGES

Agarwal, Prarit; Maruyoshi, Kazunobu; Song, Jaewon

2016-12-20

We continue to investigate the N = 1 deformations of four-dimensional N = 2 superconformal field theories (SCFTs) labeled by a nilpotent element of the flavor symmetry [1]. This triggers a renormalization group (RG) flow to an N = 1 SCFT. We systematically analyze all possible deformations of this type for certain classes of N = 2 SCFTs: conformal SQCDs, generalized Argyres-Douglas theories and the E 6 SCFT. We find a number of examples where the amount of supersymmetry gets enhanced to N = 2 at the end point of the RG flow. Most notably, we find that the SU(N)more » and Sp(N) conformal SQCDs can be deformed to flow to the Argyres-Douglas (AD) theories of type (A 1,D 2 N-1) and (A 1,D 2 N) respectively. This RG flow therefore allows us to compute the full superconformal index of the (A 1,D N) class of AD theories. Moreover, we find an infrared duality between N = 1 theories where the fixed point is described by an N = 2 AD theory. We observe that the classes of examples that exhibit supersymmetry enhancement saturate certain bounds for the central charges implied by the associated two-dimensional chiral algebra.« less

N = 1 Deformations and RG flows of N = 2 SCFTs, part II: non-principal deformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Prarit; Maruyoshi, Kazunobu; Song, Jaewon

We continue to investigate the N = 1 deformations of four-dimensional N = 2 superconformal field theories (SCFTs) labeled by a nilpotent element of the flavor symmetry [1]. This triggers a renormalization group (RG) flow to an N = 1 SCFT. We systematically analyze all possible deformations of this type for certain classes of N = 2 SCFTs: conformal SQCDs, generalized Argyres-Douglas theories and the E 6 SCFT. We find a number of examples where the amount of supersymmetry gets enhanced to N = 2 at the end point of the RG flow. Most notably, we find that the SU(N)more » and Sp(N) conformal SQCDs can be deformed to flow to the Argyres-Douglas (AD) theories of type (A 1,D 2 N-1) and (A 1,D 2 N) respectively. This RG flow therefore allows us to compute the full superconformal index of the (A 1,D N) class of AD theories. Moreover, we find an infrared duality between N = 1 theories where the fixed point is described by an N = 2 AD theory. We observe that the classes of examples that exhibit supersymmetry enhancement saturate certain bounds for the central charges implied by the associated two-dimensional chiral algebra.« less

Involvement of GSK3 and PP2A in ginsenoside Rb1's attenuation of aluminum-induced tau hyperphosphorylation.

PubMed

Zhao, Hai-hua; Di, Jing; Liu, Wen-su; Liu, Hui-li; Lai, Hong; Lü, Yong-li

2013-03-15

Environmental agent aluminum, a well-known neurotoxin, has been proposed to play a role in the development of Alzheimer's disease (AD), and produced clinical and pathological features which were strikingly similar to those seen in AD brain, such as neurofibrillary tangles. Ginsenoside Rb1, highly abundant active component of ginseng, has been demonstrated to be neuroprotective against various neurotoxins. In this study we investigated the effect of Rb1 on aluminum-induced tau hyperphosphorylation in ICR mice. Mice were exposed to aluminum chloride (200 mg/kg/day) for 6 months followed by a post treatment of Rb1 (20 mg/kg/day) for another 4 months. Aluminum exposure induced the cognitive ability by Morris water maze, and upregulated the tau phosphorylation level at Ser396 accompanied by increasing p-GSK and decreasing PP2A level in motor, sensory cortex and hippocampal formation. Post treatment of Rb1 significantly improved the learning and memory and reduced the tau phosphorylation by reversing the p-GSK3 and PP2A level. Our results indicate that ginsenoside Rb1 protected mice against Al-induced toxicity. The possible mechanism may be its role in preventing tau hyperphosphorylation by regulating p-GSK3 and PP2A level, which implicate Rb1 as the potential preventive drug candidate for AD and other tau pathology-related neuronal degenerative diseases. Copyright © 2013. Published by Elsevier B.V.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wayne Moe

2012-08-01

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

Ginsenoside extraction from Panax quinquefolium L. (American ginseng) root by using ultrahigh pressure.

PubMed

Zhang, Shouqin; Chen, Ruizhan; Wu, Hua; Wang, Changzheng

2006-04-11

A new method of ultrahigh pressure extraction (UPE) was used to extract the ginsenosides from Panax quinquefolium L. (American ginseng) root at room temperature. Several solvents, including water, ethanol, methanol, and n-butanol were used in the UPE. The ginsenosides were quantified by a HPLC equipped with UV-vis detector. The results showed that ethanol is the most efficient solvent among the used ones. Compared with other methods, i.e., Soxhlet extraction, heat reflux extraction, ultrasound-assisted extraction, microwave-assisted extraction, and supercritical CO2 extraction, the UPE has the highest extraction yield in the shortest time. The extraction yield of 0.861% ginsenoside-Rc in 2 min was achieved by the UPE, while the yields of 0.284% and 0.661% were obtained in several hours by supercritical CO2 extraction and the heat reflux extraction, respectively.

Ginsenosides from American ginseng: Chemical and pharmacological diversity

PubMed Central

Qi, Lian-Wen; Wang, Chong-Zhi; Yuan, Chun-Su

2011-01-01

Ginseng occupies a prominent position in the list of best-selling natural products in the world. Compared to the long history of use and widespread research on Asian ginseng, the study of American ginseng is relatively limited. In the past decade, some promising advances have been achieved in understanding the chemistry, pharmacology and structure-function relationship of American ginseng. To date, there is no systematic review of American ginseng. In this review, we present the different structures of the ginsenosides in American ginseng, including naturally occurring compounds and those resulting from steaming or biotransformation. Preclinical and clinical studies published in the past decade will also be discussed. We highlight the chemical and pharmacological diversity and potential structural-activity relationship of ginsenosides. Our hope is that this article is a useful reference to chemists and biologists researching American ginseng, and will open the door to novel agents in drug discovery. PMID:21396670

Studies on target tissue distribution of ginsenosides and epimedium flavonoids in rats after intravenous administration of Jiweiling freeze-dried powder.

PubMed

Liu, Minyan; Wang, Hongtao; Zhao, Shaohua; Shi, Xiaowei; Zhang, Yongfeng; Xu, Honghui; Wang, Yufeng; Li, Xiangjun; Zhang, Lantong

2011-11-01

A simple and rapid liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for analysis of ginsenoside Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, icariin and epimedin A, B, C in rat target tissues (spinal cord, brain, muscle and sciatic nerve) after intravenous administration of Jiweiling freeze-dried powder using genistein as an internal standard (IS). The tissue samples were treated by protein precipitation with methanol prior to HPLC and chromatographic separation was performed on a C18 column utilizing a gradient elution program with acetonitrile and 0.1% formic acid aqueous. Electrospray ionization (ESI) source was employed and the 11 analytes and IS were detected by multiple reaction monitoring (MRM) scanning under the negative ionization mode. Higher sensitivity was achieved and the optimized mass transition ion-pairs (m/z) for quantitation were selected. The calibration curves were linear over the investigated concentration ranges with correlation coefficients higher than 0.995. The intra- and inter-day RSDs were all less than 10% with the relative error (RE) within ± 9.3%. The mean extraction recoveries for all compounds were between 93.3 and 106%. The proposed method was successfully applied to investigate the target tissue distribution of the 11 compounds in rat after intravenous administration of Jiweiling freeze-dried powder. Copyright © 2011 John Wiley & Sons, Ltd.

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

PubMed

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

2015-05-10

A dry purified extract of Panax ginseng (PEG) was prepared using a manufacturing process that includes column chromatography, acid hydrolysis, and an enzyme reaction. During the manufacturing process, the more polar ginsenosides were altered into less polar forms via cleavage of their sugar chains and structural modifications of the aglycones, such as hydroxylation and dehydroxylation. The structural changes of ginsenosides during the intermediate steps from dried ginseng extract (DGE) to PEG were monitored by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectroscopy (UPLC-QTOF/MS). 22 ginsenosides isolated from PEG were used as the reference standards for determining of unknown ginsenosides and further suggesting of the metabolic markers. The elution order of 22 ginsenosides based on the type of aglycones, and the location and number of sugar chains can be used for the structural elucidation of unknown ginsenosides. This information could be used in a dereplication process for quick and efficient identification of ginsenoside derivatives in ginseng preparations. A dereplication approach helped the identification of the metabolic markers in the UPLC-QTOF/MS chromatograms during the conversion process with multivariate analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) plots. These metabolic markers were identified by comparing with the dereplication information of the reference standards of 22 ginsenosides, or they were assigned using the pattern of the MS/MS fragmented ions. Consequently, the developed metabolic profiling approach using UPLC-QTOF/MS and multivariate analysis represents a new method for providing quality control as well as useful criteria for a similarity evaluation of the manufacturing process of ginseng preparations. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-07-15

The root of Panax ginseng C.A. Mey. (P. ginseng) is one of the most popular traditional Chinese medicines, with ginsenosides as its main bioactive components. Because different ginsenosides have varied pharmacological effects, extraction and separation of ginsenosides are usually required for the investigation of pharmacological effects of different ginsenosides. However, the contents of ginsenosides vary with the ages and tissues of P. ginseng root. In this research, an efficient method to explore the distribution of ginsenosides and differentiate P. ginseng roots with different ages was developed based on matrix assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI). After a simple sample preparation, there were 18 peaks corresponding to 31 ginsenosides with distinct localization in the mass range of m/z 700-1400 identified by MALDI-TOF-MSI and MALDI-TOF-MS/MS. All the three types of ginsenosides were successfully detected and visualized in images, which could be correlated with anatomical features. The P. ginseng at the ages of 2, 4 and 6 could be differentiated finely through the principal component analysis of data collected from the cork based on the ion images but not data from the whole tissue. The experimental result implies that the established method for the direct analysis of metabolites in plant tissues has high potential for the rapid identification of metabolites and analysis of their localizations in medicinal herbs. Furthermore, this technique also provides valuable information for the component-specific extraction and pharmacological research of herbs. Copyright © 2015 Elsevier B.V. All rights reserved.

[Effects of culture conditions on biomass and active components of adventitious roots culture in Panax ginseng].

PubMed

Huang, Tao; Gao, Wenyuan; Wang, Juan; Cao, Yu

2010-01-01

To optimize the culture condition of adventitious roots of Panax ginseng. The adventitious roots were obtained through tissue culture by manipulation of inoculum, various sucrose concentrations and salt strength. The contents of ginsenosides Re, Rb1 and Rg1 were determined by HPLC while the contents of polysaccharides were determined by ultraviolet spectrophotometry. The multiplication of adventitious roots reached the peak when the inoculum was 20 g x L(-1). The effects of sucrose concentration and salt strength on adventitious roots were observed. The contents of polysaccharides were higher when the medium contained more sucrose. 40 g x L(-1) sucrose was favorable for roots growth and biosynthesis of Re, while 30 g x L(-1) was favorable for the biosynthesis of Rb1 and Rg1. 3/4MS medium was benefit for the growth of adventitious roots and the biosynthesis of ginsenosides. The contents of polysaccharides were decreased with the increase of salt strength. The results showed that inoculum, various sucrose concentrations and salt strength have significant influences on adventitious roots growth, secondary metabolite and polysaccharide synthesis in P. ginseng.

Rg-Lg coupling as a Lg-wave excitation mechanism

NASA Astrophysics Data System (ADS)

Ge, Z.; Xie, X.

2003-12-01

Regional phase Lg is predominantly comprised of shear wave energy trapped in the crust. Explosion sources are expected to be less efficient for excitation of Lg phases than earthquakes to the extent that the source can be approximated as isotropic. Shallow explosions generate relatively large surface wave Rg compared to deeper earthquakes, and Rg is readily disrupted by crustal heterogeneity. Rg energy may thus scatter into trapped crustal S-waves near the source region and contribute to low-frequency Lg wave. In this study, a finite-difference modeling plus the slowness analysis are used for investigating the above mentioned Lg-wave excitation mechanism. The method allows us to investigate near source energy partitioning in multiple domains including frequency, slowness and time. The main advantage of this method is that it can be applied at close range, before Lg is actually formed, which allows us to use very fine near source velocity model to simulate the energy partitioning process. We use a layered velocity structure as the background model and add small near source random velocity patches to the model to generate the Rg to Lg coupling. Two types of simulations are conducted, (1) a fixed shallow explosion source vs. randomness at different depths and (2) a fixed shallow randomness vs. explosion sources at different depths. The results show apparent couplings between the Rg and Lg waves at lower frequencies (0.3-1.5 Hz). A shallow source combined with shallow randomness generates the maximum Lg-wave, which is consistent with the Rg energy distribution of a shallow explosion source. The Rg energy and excited Lg energy show a near linear relationship. The numerical simulation and slowness analysis suggest that the Rg to Lg coupling is an effective excitation mechanism for low frequency Lg-waves from a shallow explosion source.

RG flows and instantons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gava, Edi

2012-09-24

In these two lectures I discuss RG flow solutions in (1,0) six dimensional supergravity involving SU(2) Yang-Mills instantons. in the conformally flat part of the 6D metric. The solutions interpolate between two (4,0) supersymmetric AdS{sub 3} Multiplication-Sign S{sup 3} backgrounds with different values of AdS{sub 3} and S{sup 3} radii and describe RG flows in the dual 2D SCFT. The flows described are of v.e.v. type, driven by a vacuum expectation value of a (not exactly) marginal operator of dimension 2 in the UV. We give an interpretation of the supergravity solution in terms of the D1/D5 system in typemore » I string theory on K3, whose effective field theory is expected to flow to a (4,0) SCFT in the infrared.« less

RG flows and bifurcations

DOE PAGES

Gukov, Sergei

2017-03-29

Interpreting RG flows as dynamical systems in the space of couplings we produce a variety of constraints, global (topological) as well as local. These constraints, in turn, rule out some of the proposed RG flows and also predict new phases and fixed points, surprisingly, even in familiar theories such as model, QED3, or QCD4.

The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models

PubMed Central

Gogliotti, Rocky G.; Cardona, Herminio; Singh, Jasbir; Bail, Sophie; Emery, Carina; Kuntz, Nancy; Jorgensen, Michael; Durens, Madel; Xia, Bing; Barlow, Courtenay; Heier, Christopher R.; Plasterer, Heather L.; Jacques, Vincent; Kiledjian, Megerditch; Jarecki, Jill; Rusche, James; DiDonato, Christine J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/− SMA mice), and positively impacts neuromuscular pathologies. In 2B/− SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/− SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects. PMID:23736298

[The bonding characteristic of titanium and RG experiment porcelain].

PubMed

Ren, Wei-hong; Guo, Tian-wen; Tian, Jie-mo; Zhang, Yun-long

2003-07-01

To study the bonding characteristic of Titanium and RG experiment porcelain. 5 specimens with a size of 10 mm x 5 mm x 1.4 mm were cast from pure titanium. Then 1 mm of RG experiment opaque and body porcelain were fused on the surface of the titanium specimens. The interface of titanium and porcelain was analyzed with a scanning electron microscope with energy-despersive spectrometry; 6 metal specimens with the size of 25 mm x 3 mm x 0.5 mm were cast from Ni-Cr alloy and a uniform thickness of 1 mm of VMK 99 porcelain was veneered on the central area of 8 mm x 3 mm 18 metal specimens as the same size were cast from pure titanium. The uniform thickness of 1 mm of VITA TITANKERAMIK porcelain, of Noritake super porcelain Ti-22 and of RG experiment porcelain were veneered on every 6 specimens respectively in the central area of 8 mm x 3 mm. The specimens were subjected to a three-point bending test on a load-test machine with a span of 20 mm, then the failure loads were recorded and statistically analysised. The RG porcelain/titanium crown was fabricated by fusing RG opaque porcelain and body porcelain to cast titanium substrate crown. The SEM results show no porosity and crackle were found in the interface. The energy-dispersive spectrometry show that there are Si, Ti and O in the 1 micro m layer between porcelain and titanium, which suggesting titanium and experiment porcelain bonding well. The three point test showed the fracture force for the combinations of titanium/VITA TITANKERAMIK porcelain, titanium/Noritake super porcelain Ti-22 and titanium/RG experiment porcelain were (7.233 +/- 2.539) N, (5.533 +/- 1.199) N and (6.316 +/- 1.433) N respectively. There were not statistically significant differences among them (t test, P < 0.01). The fracture force for the Ni-Cr alloy/VMK99 porcelain combination (12.733 +/- 3.297) N was significantly greater than those of the cast titanium/porcelain (t test, P > 0.05). The crown was translucent with no crack. RG porcelain is

Detection and quantification of ginsenoside Re in ginseng samples by a chromatographic immunostaining method using monoclonal antibody against ginsenoside Re.

PubMed

Morinaga, Osamu; Tanaka, Hiroyuki; Shoyama, Yukihiro

2006-01-02

A chromatographic immunostaining method has been developed for the determination of ginsenoside Re (G-Re) in ginseng samples on a polyethersulphone (PES) membrane. G-Re standard and the extracts of ginseng roots were applied to a PES membrane and developed by methanol-water-acetic acid (45:55:1, by volume). G-Re was clearly detected by an immunostaining method using a monoclonal antibody against G-Re. The coloring spots of G-Re were analyzed quantitatively using NIH Image software indicating at least 0.125 microg of G-Re was detectable. G-Re can be analyzed quantitatively between 0.25 and 4.0 microg.

Effect of azoxystrobin fungicide on the physiological and biochemical indices and ginsenoside contents of ginseng leaves.

PubMed

Liang, Shuang; Xu, Xuanwei; Lu, Zhongbin

2018-04-01

The impact of fungicide azoxystrobin, applied as foliar spray, on the physiological and biochemical indices and ginsenoside contents of ginseng was studied in ginseng ( Panax ginseng Mey. cv. "Ermaya") under natural environmental conditions. Different concentrations of 25% azoxystrobin SC (150 g a.i./ha and 225 g a.i./ha) on ginseng plants were sprayed three times, and the changes in physiological and biochemical indices and ginsenoside contents of ginseng leaves were tested. Physiological and biochemical indices were measured using a spectrophotometer (Shimadzu UV-2450). Every index was determined three times per replication. Extracts of ginsenosides were analyzed by HPLC (Shimadzu LC20-AB) utilizing a GL-Wondasil C 18 column. Chlorophyll and soluble protein contents were significantly ( p  = 0.05) increased compared with the control by the application of azoxystrobin. Additionally, activities of superoxide dismutase, catalase, ascorbate peroxidase, peroxidase, and ginsenoside contents in azoxystrobin-treated plants were improved, and malondialdehyde content and O 2 - contents were reduced effectively. Azoxystrobin treatments to ginseng plants at all growth stages suggested that the azoxystrobin-induced delay of senescence was due to an enhanced antioxidant enzyme activity protecting the plants from harmful active oxygen species. When the dose of azoxystrobin was 225 g a.i./ha, the effect was more significant. This work suggested that azoxystrobin played a role in delaying senescence by changing physiological and biochemical indices and improving ginsenoside contents in ginseng leaves.

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

PubMed

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

2015-11-10

A metabonomic method was established to find potential biomarkers and study the metabolism disturbance in Alzheimer disease animal model. Total ginsenosides, as potential agent in neuroprotection and anti-inflammation, was also studied to learn the regulation mechanism to plasma metabolites in model animals. In experiment, amyloid beta 1-42 was occupied to form Alzheimer disease animal model. After drug administration, animals were evaluated by Morris water maze behavior test and sacrificed. Plasma samples were then analyzed using UHPLC-TOF/MS method to determine the endogenous metabolites. Behavior test results revealed that the spatial learning and memory abilities were deficit in model mice, and total ginsenosides could improve cognition abilities in dose-dependent manners. Principal component analysis showed that model and sham were divided into two groups, which means the metabolic network of mice was disturbed after modeling. Accordingly, 19 biomarkers were found and identified. In model group, the levels of proline, valine, tryptophan, LPC (14:0), LPC (15:0), LPC (15:1), LPC (17:0), LPC (18:2), LPC (18:3) and LPC (20:4) were up-regulated, while the levels of acetylcarnitine, palmitoylcarnitine, vaccenylcarnitine, phytosphingosine, N-eicosanoylethanolamine, hexadecenoic acid, docosahexaenoic acid, docosapentaenoic acid and octadecadienoic acid were down-regulated. The levels of these metabolites were recovered in different degrees after total ginsenosides administration. Combining with behavior study results, total ginsenosides could ameliorate both cognition symptoms and metabolic changes in model animals. This metabonomic approach provided a feasible way to understand the endogenous alterations of AD and to study the pharmacodynamic activity of novel agents. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-08-20

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

[Analysis of parameters of serum concentration and pharmacokinetic of liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats].

PubMed

Zha, Lin; Zhao, Yan; Zhu, Hong-Yan; Cai, En-Bo; Liu, Shuang-Li; Yang, He; Zhao, Ying; Gao, Yu-Gang; Zhang, Lian-Xue

2017-05-01

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total

[Effect of ginseng rare ginsenoside components combined with paclitaxel on A549 lung cancer].

PubMed

Yang, Lei; Zhang, Zhen-Hai; Jia, Xiao-Bin

2018-04-01

Traditional Chinese medicine combined with anticancer drugs is a new direction of clinical cancer therapy in recent years. In this study, the optimal ratio of ginseng rare ginsenoside components and paclitaxel was optimized by MTT method, and the proliferative, apoptotic and anti-tumor effects of lung cancer A549 cells were investigated. It was found that the inhibitory effect on the proliferation of lung cancer A549 cells was the same as that on paclitaxel when the ratio of rare ginseng rare ginsenoside components to paclitaxel was 4∶6. Further studies showed that the combined therapy significantly increased the inductive effect of apoptosis in A549 cells, and up-regulated the expression of caspase-3 protein and down-regulated the ratio of Bcl-2/Bax. The tumor-bearing mice model showed that the combination therapy of ginseng rare ginsenoside components and paclitaxel could significantly inhibit the growth of tumor and alleviate the toxic and side effects of paclitaxel on liver. A multi-component system of ginseng rare ginsenoside components-paclitaxel was established in this paper. The proliferation and growth of lung cancer A549 cells were inhibited by paclitaxel-induced apoptosis, the dosage of paclitaxel and the toxicity of paclitaxel were reduced, and the effect of anti-lung cancer was enhanced, which provided a theoretical basis for later studies and clinical application. Copyright© by the Chinese Pharmaceutical Association.

HM{sup +}–RG complexes (M = group 2 metal; RG = rare gas): Physical vs. chemical interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Joe P.; Dodson, Hannah; Wright, Timothy G., E-mail: Tim.Wright@nottingham.ac.uk

2015-04-21

Previous work on the HM{sup +}–He complexes (M = Be–Ra) has been extended to the cases of the heavier rare gas atoms, HM{sup +}–RG (RG = Ne–Rn). Optimized geometries and harmonic vibrational frequencies have been calculated using MP2 theory and quadruple-ζ quality basis sets. Dissociation energies for the loss of the rare gas atom have been calculated at these optimized geometries using coupled cluster with single and double excitations and perturbative triples, CCSD(T)theory, extrapolating interaction energies to the basis set limit. Comparisons are made between the present data and the previously obtained helium results, as well as to those ofmore » the bare HM{sup +} molecules; furthermore, comparisons are made to the related M{sup +}–RG and M{sup 2+}–RG complexes. Partial atomic charge analyses have also been undertaken, and these used to test a simple charge-induced dipole model. Molecular orbital diagrams are presented together with contour plots of the natural orbitals from the quadratic configuration with single and double excitations (QCISD) density. The conclusion is that the majority of these complexes are physically bound, with very little sharing of electron density; however, for M = Be, and to a lesser extent M = Mg, some evidence for chemical effects is seen in HM{sup +}–RG complexes involving RG atoms with the higher atomic numbers.« less

Chemical characteristics for different parts of Panax notoginseng using pressurized liquid extraction and HPLC-ELSD.

PubMed

Wan, J B; Yang, F Q; Li, S P; Wang, Y T; Cui, X M

2006-08-28

The chemical characteristics for different parts of Panax notoginseng, including root, fibre root, rhizome, stem, leaf, flower and seed, were determined using high performance liquid chromatography-evaporative light scattering detection (HPLC-ELSD) and pressurized liquid extraction (PLE). Eight major saponins, namely notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd were also quantitatively compared among the different parts of P. notoginseng. The chromatograms showed that there was significant difference between underground (root, fibre root, rhizome) and aerial (leaf and flower) parts from P. notoginseng, though the similarities of entire chromatographic patterns among tested samples from underground (0.965+/-0.029, n=12) and aerial parts (0.987+/-0.014, n=5) were similar, respectively. Especially, no saponin was detected in the seed of P. notoginseng. Hierarchical clustering analysis based on eight investigated saponins or the ratios of contents for ginsenoside Rg1/Rb1 and ginsenoside Rb3/Rb1 showed that the samples from different parts of P. notoginseng were divided into three main clusters. One cluster was underground parts, which contained rich protopanaxatriol and protopanaxadiol types saponins. The leaf and flower were in the same cluster, which contained protopanaxadiol type saponins only. Especially, ginsenoside Rc, Rb2 and Rb3, rare in the underground parts, were rich in aerial parts of P. notoginseng. The stem of P. notoginseng was another cluster. Based on the cluster analysis, the chemical characteristics for different parts of P. notoginseng were revealed. They are composite cluster (underground parts), protopanaxadiol cluster (aerial parts) and interim (stem) cluster, which was the one between the two typical clusters, respectively. The result shows that chemical characteristics of underground parts and aerial parts from P. notoginseng are obviously different, which is helpful for pharmacological evaluation and quality control of P

MicroRNA Responses to the Genotoxic Carcinogens Aflatoxin B1 and Benzo[a]pyrene in Human HepaRG Cells.

PubMed

Marrone, April K; Tryndyak, Volodymyr; Beland, Frederick A; Pogribny, Igor P

2016-02-01

Recent advances in toxicogenomics present an opportunity to develop new in vitro testing methodologies to identify human carcinogens. We have investigated microRNA expression responses to the treatment of human liver HepaRG cells with the human genotoxic carcinogens aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P), and the structurally similar compounds aflatoxin B2 (AFB2) and benzo[e]pyrene (B[e]P) that exhibit minimal carcinogenic potential. We demonstrate that treatment of HepaRG cells with AFB1 or B[a]P resulted in specific changes in the expression of miRNAs as compared with their non-carcinogenic analogues, particularly in a marked over-expression of miR-410. An additional novel finding is the dose- and time-dependent inhibition of miR-122 in AFB1-treated HepaRG cells. Mechanistically, the AFB1-induced down-regulation of miR-122 was attributed to inhibition of the HNF4A/miR-122 regulatory pathway. These results demonstrate that HepaRG cells can be used to investigate miRNA responses to xenobiotic exposure, and illustrate the existence of early non-genotoxic events, in addition to a well-established genotoxic mode of action changes, in the mechanism of AFB1 and B[a]P carcinogenicity. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

Panax ginseng genome examination for ginsenoside biosynthesis.

PubMed

Xu, Jiang; Chu, Yang; Liao, Baosheng; Xiao, Shuiming; Yin, Qinggang; Bai, Rui; Su, He; Dong, Linlin; Li, Xiwen; Qian, Jun; Zhang, Jingjing; Zhang, Yujun; Zhang, Xiaoyan; Wu, Mingli; Zhang, Jie; Li, Guozheng; Zhang, Lei; Chang, Zhenzhan; Zhang, Yuebin; Jia, Zhengwei; Liu, Zhixiang; Afreh, Daniel; Nahurira, Ruth; Zhang, Lianjuan; Cheng, Ruiyang; Zhu, Yingjie; Zhu, Guangwei; Rao, Wei; Zhou, Chao; Qiao, Lirui; Huang, Zhihai; Cheng, Yung-Chi; Chen, Shilin

2017-11-01

Ginseng, which contains ginsenosides as bioactive compounds, has been regarded as an important traditional medicine for several millennia. However, the genetic background of ginseng remains poorly understood, partly because of the plant's large and complex genome composition. We report the entire genome sequence of Panax ginseng using next-generation sequencing. The 3.5-Gb nucleotide sequence contains more than 60% repeats and encodes 42 006 predicted genes. Twenty-two transcriptome datasets and mass spectrometry images of ginseng roots were adopted to precisely quantify the functional genes. Thirty-one genes were identified to be involved in the mevalonic acid pathway. Eight of these genes were annotated as 3-hydroxy-3-methylglutaryl-CoA reductases, which displayed diverse structures and expression characteristics. A total of 225 UDP-glycosyltransferases (UGTs) were identified, and these UGTs accounted for one of the largest gene families of ginseng. Tandem repeats contributed to the duplication and divergence of UGTs. Molecular modeling of UGTs in the 71st, 74th, and 94th families revealed a regiospecific conserved motif located at the N-terminus. Molecular docking predicted that this motif captures ginsenoside precursors. The ginseng genome represents a valuable resource for understanding and improving the breeding, cultivation, and synthesis biology of this key herb. © The Author 2017. Published by Oxford University Press.

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

PubMed

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

2015-01-01

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

Engineering of mesoporous silica nanoparticles for release of ginsenoside CK and Rh2 to enhance their anticancer and anti-inflammatory efficacy: in vitro studies

NASA Astrophysics Data System (ADS)

Singh, Priyanka; Singh, Hina; Castro-Aceituno, Verónica; Ahn, Sungeun; Kim, Yeon Ju; Farh, Mohamed El-Agamy; Yang, Deok Chun

2017-07-01

The current study highlights the fabrication of drug delivery system by utilizing 200 nm mesoporous silica nanoparticles (MSNPs) with 4-nm pore size, as a carrier system for delivery ginsenoside compound K (CK) and Rh2 to enhance their efficacy. The two pharmacologically imperative ginsenosides, CK and Rh2, were loaded to the MSNPs to prepare MSNPs-CK and MSNPs-Rh2, respectively. A fluorescein isothiocyanate (FITC) fluorescent dye was combined in the MSNPs carrier system, in order to trace the cellular uptake of ginsenoside-loaded nanoparticles for in vitro studies. Following purification, the so-prepared MSNPs-CK-FITC and MSNPs-Rh2-FITC were characterized by several analytical techniques, which includes, high-pressure liquid chromatography (HPLC), 1H NMR, field emission transmission electron microscopy (FE-TEM), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), thermogravimetric analysis (TGA), and dynamic light scattering (DLS). In vitro cytotoxicity assay in HaCaT skin cells, A549 lung cancer cells, HepG2 liver carcinoma cells, and HT-29 colon cancer cell lines were tested for MSNPs-CK-FITC and MSNPs-Rh2-FITC. The results demonstrate the excellent biocompatibility of nanoparticles in normal cell lines (HaCaT skin cells) and anticancer efficacy in all the tested cancer cell lines at 10-μM concentration. Additionally, the in vitro anti-inflammatory behavior of MSNPs-CK-FITC and MSNPs-Rh2-FITC were checked in RAW264.7 (murine macrophage) cell lines. The outcomes showed higher anti-inflammatory efficacy of MSNPs-CK-FITC and MSNPs-Rh2-FITC as compared to standard ginsenosides CK and Rh2 in RAW264.7 cell lines. Thus, with 200 nm MSNPs carrier system for the delivery ginsenosides CK and Rh2, a high amount of loading and increasing in vitro pharmacological efficacies of ginsenosides were realized. This study may provide useful insights for designing and improving the applicability of MSNPs for ginsenoside delivery.

Rg to Lg Scattering Observations and Modeling

NASA Astrophysics Data System (ADS)

Baker, G. E.; Stevens, J. L.; Xu, H.

2005-12-01

Lg is important to explosion yield estimation and earthquake/explosion discrimination, but the source of explosion generated Lg is still an area of active investigation. We investigate the contribution of Rg scattering to Lg. Common spectral nulls in vertical component Rg and Lg have been interpreted as evidence that scattered Rg is the dominant source of Lg in some areas. The nulls are assumed to result from non-spherical components of the explosion source, modeled as a CLVD located above the explosion. We compare Rg with 3-component Sg and Lg spectra in different source areas. Wavenumber synthetics and nonlinear source calculations constrain the predicted source spectra of Rg and directly generated Lg. Modal scattering calculations place bounds on the contribution of Rg to Lg relative to pS, S*, and directly generated S-waves. Rg recorded east and west of the Quartz 3 Deep Seismic Sounding explosion have persistent spectral nulls, but at different frequencies. The azimuthal dependence of the source spectra suggests that it may not be simply related to a CLVD source. The spectral nulls of Sg, Lg, and Lg coda do not correspond to the Rg spectral nulls, so for this overburied source, the spectral observations do not indicate that Rg scattering is a dominant contributor to Lg. Preliminary comparisons of Rg with Lg spectra for events from the Semipalatinsk Test Site yield a similar result. We compare Rg at 20-100 km with Lg at 650 km for Balapan and Degelen explosions with known yield and source depth. The events range from 130 to 50 percent of theoretical containment depth, so relative contributions from a CLVD are expected to vary significantly. For studied previously NTS and Kazakh depth of burial data, the use of 3-components provides further insight into scattering between components. In a complementary analysis, to assess whether S-wave generation is affected by source depth or scaled depth, we have examined regional phase amplitudes of 13 Degelen explosions

Metabolite profiling of ginsenosides in rat plasma, urine and feces by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Panax ginseng extract.

PubMed

Dong, Wei-Wei; Han, Xiong-Zhe; Zhao, Jinhua; Zhong, Fei-Liang; Ma, Rui; Wu, Songquan; Li, Donghao; Quan, Lin-Hu; Jiang, Jun

2018-03-01

Panax ginseng is widely consumed as a functional food in the form of tea, powder, capsules, among others, and possesses a range of pharmacological activities including adaptogenic, immune-modulatory, anti-tumor, anti-aging and anti-inflammatory effects. The aim of this study was to identify and quantify the major ginsenosides and their metabolites in rat plasma, urine and feces after administration of P. ginseng extract using LC-MS/MS. We collected rat plasma samples at 0.5, 1, 2, 4, 8, 12, 24 and 48 h, and the amounts of urine and fecal samples accumulated in 24 h. Fourteen major ginsenosides and their metabolites were observed in fecal samples at high levels; however, low levels of 11 ginsenosides were detected in urine samples. The pharmacokinetics of the major ginsenosides and their metabolites was investigated in plasma. The results indicated that the maximum plasma concentration, time to maximum concentration and area under the curve of compound K were significantly greater than those of other ginsenosides. This study thus provides valuable information for drug development and clinical application of P. ginseng. Copyright © 2017 John Wiley & Sons, Ltd.

Photosynthesis rates, growth, and ginsenoside contents of 2-yr-old Panax ginseng grown at different light transmission rates in a greenhouse.

PubMed

Jang, In-Bae; Lee, Dae-Young; Yu, Jin; Park, Hong-Woo; Mo, Hwang-Sung; Park, Kee-Choon; Hyun, Dong-Yun; Lee, Eung-Ho; Kim, Kee-Hong; Oh, Chang-Sik

2015-10-01

Ginseng is a semishade perennial plant cultivated in sloping, sun-shaded areas in Korea. Recently, owing to air-environmental stress and various fungal diseases, greenhouse cultivation has been suggested as an alternative. However, the optimal light transmission rate (LTR) in the greenhouse has not been established. The effect of LTR on photosynthesis rate, growth, and ginsenoside content of ginseng was examined by growing ginseng at the greenhouse under 6%, 9%, 13%, and 17% of LTR. The light-saturated net photosynthesis rate (A sat) and stomatal conductance (g s) of ginseng increased until the LTR reached 17% in the early stage of growth, whereas they dropped sharply owing to excessive leaf chlorosis at 17% LTR during the hottest summer period in August. Overall, 6-17% of LTR had no effect on the aerial part of plant length or diameter, whereas 17% and 13% of LRT induced the largest leaf area and the highest root weight, respectively. The total ginsenoside content of the ginseng leaves increased as the LTR increased, and the overall content of protopanaxatriol line ginsenosides was higher than that of protopanaxadiol line ginsenosides. The ginsenoside content of the ginseng roots also increased as the LTR increased, and the total ginsenoside content of ginseng grown at 17% LTR increased by 49.7% and 68.3% more than the ginseng grown at 6% LTR in August and final harvest, respectively. These results indicate that 13-17% of LTR should be recommended for greenhouse cultivation of ginseng.

Pharmacology of RG W-2938: a cardiotonic agent with vasodilator activity.

PubMed

Barrett, J A; Woltmann, R F; Swillo, R S; Kasiewski, C; Faith, W C; Campbell, H F; Perrone, M H

1990-10-01

The cardiovascular effects of RG W-2938, 6-[6-(3,4-dihydro-3-methyl-2(1H)-2-oxoquinazolinyl)]-4,5-dihydro-3 (2H-pyridazinone, a new nonglycoside, noncatecholamine cardiotonic/vasodilator agent were examined in vivo in anesthetized and conscious dogs and in vitro in isolated guinea pig hearts; in the latter, RG W-2938 5 nmol-5 mumol increased contractility in a dose-related fashion. RG W-2938 30-300 micrograms/kg administered intravenously (i.v.) to anesthetized dogs increased contractile force while decreasing arterial pressure and total peripheral resistance (TPR) in a dose-related manner. Heart rate (HR) was only slightly increased, and aortic flow was not appreciably altered. A single oral dose of RG W-2938 0.3 mg/kg administered to conscious chronically instrumented dogs produced a marked and sustained increase in contractility 15-240 min after treatment while only slightly increasing HR. The effects of RG W-2938 30-300 micrograms/kg, i.v. were studied in a mecamylamine-propranolol-induced model of heart failure. RG W-2938 effectively reversed the drug-induced heart failure by increasing myocardial contractility and decreasing arterial pressure while only slightly affecting HR. These studies show that RG W-2938 is an orally effective positive inotropic/vasodilator agent.

Alternative reverse genetics system for influenza viruses based on a synthesized swine 45S rRNA promoter.

PubMed

Wang, Kai; Huang, Qi; Yang, Zhiwei; Qi, Kezong; Liu, Hongmei; Chen, Hongjun

2017-08-01

We generated an alternative reverse genetics (RG) system based on a synthesized swine 45S rRNA promoter to rescue the H3N2 subtype swine influenza virus. All eight flanking segment cassettes of A/swine/Henan/7/2010 (H3N2) were amplified with ambisense expression elements from RG plasmids. All segments were then recombined with the pHC2014 vector, which contained the synthesized swine 45S rRNA promoter (spol1) and its terminal sequence (t1) in a pcDNA3 backbone. As a result, we obtained a set of RG plasmids carrying the corresponding eight-segment cassettes. We efficiently generated the H3N2 virus after transfection into 293T/PK15, PK15, and 293T cells. The efficiency of spol1-driven influenza virus rescue in PK15 cells was similar to that in 293T cells by titration using the human pol1 RG system. Our approach suggests that an alternative spol1-based RG system can produce influenza viruses.

Sulfur fumigation reducing systemic exposure of ginsenosides and weakening immunomodulatory activity of ginseng.

PubMed

Ma, Bin; Kan, Winnie Lai Ting; Zhu, He; Li, Song-Lin; Lin, Ge

2017-01-04

Ginseng (Ginseng Radix et Rhizoma) is used worldwide for its miracle tonic effects, especially for its immunomodulatory activities. Sulfur fumigation, a fast and convenient method to prevent pesticidal and bacterial contamination in the food industry, has been recently employed during post-harvest processing of ginseng. Our previous studies demonstrated that sulfur fumigation significantly altered the chemical profile of the bioactive ingredients in ginseng. However, the effects of sulfur fumigation on the pharmacokinetics and bioactivities of ginseng remain unknown. To examine the effects of sulfur fumigation on the pharmacokinetics and immunomodulatory activities of ginseng. For pharmacokinetic studies, male Sprague-Dawley rats exposed to single/multiple dosages of non-fumigated ginseng (NFG) and sulfur fumigated ginseng (SFG) were investigated using HPLC-MS/MS analysis. For bioactivity studies, male ICR mice were used to compare the immunomodulatory effects of NFG or SFG under both normal and cyclophosphamide (CY)-induced immunocompromised conditions using white blood cell counts, serum cytokine levels, and spleen and thymus weight indices. Sulfur fumigation significantly reduced the contents of the bioactive ginsenosides in ginseng, which resulted in drastically low systemic exposure of ginsenosides in SFG-treatment group compared to NFG-treatment group. This observation was consistent with the bioactivities obtained in NFG- and SFG-treatment groups. The bioactivity studies also demonstrated the immunomodulatory effects of NFG but not SFG in the CY-induced immunosuppressed mice. Sulfur fumigation significantly reduced contents of bioactive ginsenosides in ginseng, leading to dramatic decrease in the systemic exposure of these ginsenosides in the body and detrimental reduction of immunomodulatory effects of ginseng. Our results provided scientific evidences and laid a solid foundation for the needs of thorough evaluation of the significant impact of sulfur

Protective effect of ginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney injury in vitro and in vivo.

PubMed

Baek, Seung-Hoon; Shin, Byong-Kyu; Kim, Nam Jae; Chang, Sun-Young; Park, Jeong Hill

2017-07-01

Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed Panax ginseng ). Cytotoxicity was induced by treatment of 20μM cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination. The in vitro assay demonstrated that KG-KH (50 μg/mL) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, per os ) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold). Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses.

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

PubMed

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

2014-10-01

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.

Ginsenoside Re and notoginsenoside R1: Immunologic adjuvants with low haemolytic effect.

PubMed

Sun, Hong-Xiang; Chen, Yuehua; Ye, Yiping

2006-07-01

The further purification of the total saponins from the roots of Panax notoginseng (Burk.) F. H. Chen by ordinary and reversed-phase silica-gel, as well as Sephadex LH-20 chromatography afforded two adjuvant active dammarane-type saponins, ginsenoside Re (1) and notoginsenoside R1 (2). These two saponins were evaluated for haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The concentrations inducing 50% of the maximum haemolysis (HD50), using 0.5% red blood cell suspensions, were 469.6+/-16.9 and 420.4+/-22.9 microg/ml for 1 and 2, respectively. Compounds 1 and 2 significantly increased the concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in the OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA-specific IgG, IgG1, and IgG2b antibody titres in serum were also significantly enhanced by 1 and 2 compared with OVA control group (P<0.05, P<0.01, or P<0.001). The results indicate that 1 and 2 showed a slight haemolytic activity and significant adjuvant effect on specific antibody and cellular immune response against OVA in mice, and that the type of the terminal sugar of the sugar chain at C(6) of protopanaxatriol could not only affect their haemolytic activities and adjuvant potentials, but have significant effects on the nature of the immune responses. The information about this structure-function relationship might be useful for developing semisynthetic dammarane-type saponin derivatives with immunological adjuvant activity.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Hye Gwang; Pokharel, Yuba Raj; Han, Eun Hee

2007-07-20

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung

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

Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal model of postoperative fatigue syndrome.

PubMed

Tan, Shan-Jun; Li, Ning; Zhou, Feng; Dong, Qian-Tong; Zhang, Xiao-Dong; Chen, Bi-Cheng; Yu, Zhen

2014-10-01

Postoperative fatigue syndrome (POFS) is a common clinical complication followed by almost every major abdominal surgery. Ginsenoside Rb1 (GRb1), a principle ginsenoside in ginseng, could exert a potent anti-fatigue effect on POFS. However, the mechanism is still unknown. Previous studies revealed that alterations in the energy metabolism in the skeletal muscle may play a vital role in the development and progression of fatigue. In the present study, we investigate the effect of GRb1 on energy metabolism in the skeletal muscle of a rat model of POFS induced by major small intestinal resection. GRb1 (10 mg/kg) was intraperitoneally administrated once daily for 1, 3, 7, and 10 d from the operation day, respectively. The locomotor activity was recorded every day, and total food intake was calculated starting from 24 h after surgery. After GRb1 treatment was completed, blood and skeletal muscle were sampled. The level of blood glucose was determined by an automatic biochemical analyzer. The content of adenosine triphosphate (ATP) in skeletal muscle was determined by high-performance liquid chromatography. The activity of energy metabolic enzymes Na(+)-K(+)-ATPase, pyruvate kinase, and succinate dehydrogenase (SDH) was assessed by commercially available kits. The results revealed that GRb1 could increase locomotor activity of POFS rats and significantly increase their total food intake postoperatively (P < 0.05). Furthermore, GRb1 also significantly increased ATP content in the skeletal muscle of POFS rats (P < 0.05). Meanwhile, the activity of Na(+)-K(+)-ATPase and SDH in the skeletal muscle of POFS rats was enhanced by GRb1 (P < 0.05). However, no significant differences in blood glucose and pyruvate kinase were found between the POFS and GRb1 treatment rats (P > 0.05). These results suggest that GRb1 may improve skeletal muscle energy metabolism in POFS, and the underlying mechanism may be associated with an increase in the content of ATP and an enhancement in the

Contextualizing Hepatocyte Functionality of Cryopreserved HepaRG Cell Cultures

PubMed Central

Jackson, Jonathan P.; Li, Linhou; Chamberlain, Erica D.; Wang, Hongbing

2016-01-01

Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (∼28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format of HepaRG cells (termed here “cryo-HepaRG”) has emerged as a new model that improves global availability and experimental flexibility; however, it is largely unknown whether HepaRG cells in this format fully retain their hepatic characteristics. Therefore, we systematically investigated the hepatocyte functionality of cryo-HepaRG cultures in context with the range of interindividual variation observed with PHH in both sandwich-culture and suspension formats. These evaluations uncovered a novel adaptation period for the cryo-HepaRG format and demonstrated the impact of extracellular matrix on cryo-HepaRG functionality. Pharmacologically important drug-metabolizing alleles were genotyped in HepaRG cells and poor metabolizer alleles for CYP2D6, CYP2C9, and CYP3A5 were identified and consistent with higher frequency alleles found in individuals of Caucasian decent. We observed liver enzyme inducibility with aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor activators comparable to that of sandwich-cultured PHH. Finally, we show for the first time that cryo-HepaRG supports proper CAR cytosolic sequestration and translocation to hepatocyte nuclei in response to phenobarbital treatment. Taken together, these data reveal important considerations for the use of this cell model and demonstrate that cryo-HepaRG are suitable for metabolism and toxicology screening. PMID:27338863

Functional Analysis of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Encoding Genes in Triterpene Saponin-Producing Ginseng1[C][W

PubMed Central

Kim, Yu-Jin; Lee, Ok Ran; Oh, Ji Yeon; Jang, Moon-Gi; Yang, Deok-Chun

2014-01-01

Ginsenosides are glycosylated triterpenes that are considered to be important pharmaceutically active components of the ginseng (Panax ginseng ‘Meyer’) plant, which is known as an adaptogenic herb. However, the regulatory mechanism underlying the biosynthesis of triterpene saponin through the mevalonate pathway in ginseng remains unclear. In this study, we characterized the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) concerning ginsenoside biosynthesis. Through analysis of full-length complementary DNA, two forms of ginseng HMGR (PgHMGR1 and PgHMGR2) were identified as showing high sequence identity. The steady-state mRNA expression patterns of PgHMGR1 and PgHMGR2 are relatively low in seed, leaf, stem, and flower, but stronger in the petiole of seedling and root. The transcripts of PgHMGR1 were relatively constant in 3- and 6-year-old ginseng roots. However, PgHMGR2 was increased five times in the 6-year-old ginseng roots compared with the 3-year-old ginseng roots, which indicates that HMGRs have constant and specific roles in the accumulation of ginsenosides in roots. Competitive inhibition of HMGR by mevinolin caused a significant reduction of total ginsenoside in ginseng adventitious roots. Moreover, continuous dark exposure for 2 to 3 d increased the total ginsenosides content in 3-year-old ginseng after the dark-induced activity of PgHMGR1. These results suggest that PgHMGR1 is associated with the dark-dependent promotion of ginsenoside biosynthesis. We also observed that the PgHMGR1 can complement Arabidopsis (Arabidopsis thaliana) hmgr1-1 and that the overexpression of PgHMGR1 enhanced the production of sterols and triterpenes in Arabidopsis and ginseng. Overall, this finding suggests that ginseng HMGRs play a regulatory role in triterpene ginsenoside biosynthesis. PMID:24569845

The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

PubMed Central

Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

2016-01-01

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805

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

PubMed

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

2015-04-01

Our previous study indicated that sulphur-fumigation of ginseng in post-harvest handling processes could induce chemical transformation of ginsenosides to generate multiple ginsenoside sulphur derivatives. In this study, the influence of sulphur-fumigation on intestinal metabolism and absorption in vivo of ginsenosides in ginseng was sequentially studied. The intestinal metabolic and absorbed profiles of ginsenosides in rats after intra-gastric (i.g.) administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG) were comparatively characterized by a newly established ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with electrospray ionization negative (ESI-) mode. A novel strategy based on the characteristic product ions and fragmentation pathways of different types of aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully applied to rapid structural identification of ginsenoside sulphur derivatives and relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26 ginsenoside sulphur derivative metabolites in the faeces together with six ginsenoside sulphur derivatives in the plasma were identified in the SFG-administrated group but not in the NFG-administrated group. The results clearly demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides in sulphur-fumigated and non-fumigated ginseng were quite different, which inspired that sulphur-fumigation of ginseng should not be recommended before the bioactivity and toxicity of the ginsenoside sulphur derivatives were systematically evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

Generation of immunodeficient rats with Rag1 and Il2rg gene deletions and human tissue grafting models.

PubMed

Ménoret, Séverine; Ouisse, Laure-Hélène; Tesson, Laurent; Delbos, Frédéric; Garnier, Delphine; Remy, Séverine; Usal, Claire; Concordet, Jean-Paul; Giovannangeli, Carine; Chenouard, Vanessa; Brusselle, Lucas; Merieau, Emmanuel; Nerrière-Daguin, Véronique; Duteille, Franck; Bellier-Waast, Frédérique; Fraichard, Alexandre; Nguyen, Tuan H; Anegon, Ignacio

2018-04-24

Immunodeficient mice are invaluable tools to analyze the long-term effects of potentially immunogenic molecules in the absence of adaptive immune responses. Nevertheless, there are models and experimental situations that would beneficiate of larger immunodeficient recipients. Rats are ideally suited to perform experiments in which larger size is needed and are still a small animal model suitable for rodent facilities. Additionally, rats reproduce certain human diseases better than mice, such as ankylosing spondylitis and Duchenne disease and these disease models would greatly benefit of immunodeficient rats to test different immunogenic treatments. We describe the generation of Il2rg-deficient rats and their crossing with previously described Rag1-deficient rats to generate double-mutant RRG animals. As compared to Rag1-deficient rats, Il2rg-deficient rats were more immunodeficient since partially lacked not only T and B cells but also NK cells. RRG animals showed a more profound immunossuppressed phenotype since they displayed undetectable levels of T, B and NK cells. Similarly, all immunoglobulin isotypes in sera were decreased in Rag1 or Il2rg-deficient rats and undetectable in RRG animals. Rag1 or Il2rg-deficient rats rejected allogeneic skin transplants and human tumors whereas RRG animals not only accepted allogeneic rat skin but also xenogeneic human tumors, skin and hepatocytes. Immune humanization of RRG animals was unsuccessful. Thus, immunodeficient RRG animals are useful recipients for long term studies in which immune responses could be an obstacle, including tissue humanization of different tissues.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Chemical differentiation and quality evaluation of commercial Asian and American ginsengs based on a UHPLC-QTOF/MS/MS metabolomics approach.

PubMed

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

2015-01-01

Asian and American ginsengs are widely used medicinal materials and are being used more and more in health products. The two materials look alike but function differently. Various forms of both types of ginseng are found in the market, causing confusion for consumers in their choice. To evaluate the overall quality of commercial Asian and American ginsengs and investigate the characteristic chemical markers for differentiating between them. This article investigated 17 Asian and 21 American ginseng samples using an ultra-HPLC combined with quadrupole time-of-flight MS/MS technique. The data were processed by principal component analysis and orthogonal partial least squared discriminant analysis. In the chromatograms, a total of 40 peaks were detected. Among them, six were positively identified, and all of the remainder were tentatively identified. According to statistical results, ginsenosides Rf, Rb2 and Rc together with their isomers and derivatives were more likely to be present in Asian ginsengs, whereas ginsenoside Rb1 , pseudoginsenoside F11 and ginsenoside Rd together with their isomers and derivatives tended to be present in American ginsengs. For Asian ginsengs, ginsenoside Ra3 and 20-β-D-glucopyranosyl-ginsenoside-Rf were more likely to be present in forest samples, whereas contents of floralquinquenoside B, ginsenosides Ro and Rc, and zingibroside R1 were higher in sun-dried ginsengs. For American ginseng, wild samples often had more of the notoginsenosides R1 and Rw2 and less of the ginsenosides Rd, Rd isomer and 20 (S)-Rg3 than cultivated samples. The method provided important fingerprint information for authentication and evaluation of Asian and American ginsengs from various commercial products. Copyright © 2014 John Wiley & Sons, Ltd.

Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure–Activity Relationships, and Molecular Mechanisms of Action

PubMed Central

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

2012-01-01

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 vascular endothelial growth factor), 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 COX-2), and protein kinases (JNK, Akt, and AMP-activated protein kinase). We also discuss the structure–activity relationship of various ginsenosides and their potentials in the treatment of various human cancers. In summary, recent advances in the discovery and evaluation of ginsenosides as cancer therapeutic agents support further pre-clinical and clinical development of these agents for the treatment of primary and metastatic tumors. PMID:22403544

Rare Gases Inserted into Biological Building Blocks: A Theoretical Study of Glycine - Rg Compounds (Rg-Xe, Kr, Ar)

NASA Technical Reports Server (NTRS)

Chaban, Galina M.

2005-01-01

Compounds formed by insertion of rare-gas atoms (Xe, Kr, and Ar) into glycine molecule are investigated using accurate ab initio computational methods. Identification of such insertion compounds may open new frontiers in the field of rare-gas chemistry, such as possible existence of biological molecules that include chemically bound rare gas atoms. The most stable glycine-Rg configuration is found to correspond to insertion of Rg atoms into the 0-H bond of glycine. These NH2CH2COORgH compounds are metastable , but separated by sizable potential barriers from the Rg + glycine dissociation products. Preliminary calculations show that NH2CH2COOXeH compound is energetically stable with respect to another (3-body) dissociation channel (NH2CH2COO + Rg + H), while the corresponding Ar species is not stable in this respect. The compound with the inserted Kr is a borderline case, with the 3-body dissociation products being close in energy to the NH2CH2COOKrH minimum.

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

PubMed Central

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

2016-01-01

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

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

PubMed

Cui, Chang-Hao; Kim, Da Jung; Jung, Suk-Chae; Kim, Sun-Chang; Im, Wan-Taek

2017-05-19

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.

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

PubMed Central

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

2012-01-01

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

Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.

PubMed

Hiramoto, Takafumi; Li, Li B; Funk, Sarah E; Hirata, Roli K; Russell, David W

2018-05-02

X-linked severe combined immunodeficiency (X-SCID) has been successfully treated by hematopoietic stem cell (HSC) transduction with retroviral vectors expressing the interleukin-2 receptor subunit gamma gene (IL2RG), but several patients developed malignancies due to vector integration near cellular oncogenes. This adverse side effect could in principle be avoided by accurate IL2RG gene editing with a vector that does not contain a functional promoter or IL2RG gene. Here, we show that adeno-associated virus (AAV) gene editing vectors can insert a partial Il2rg cDNA at the endogenous Il2rg locus in X-SCID murine bone marrow cells and that these ex vivo-edited cells repopulate transplant recipients and produce CD4 + and CD8 + T cells. Circulating, edited lymphocytes increased over time and appeared in secondary transplant recipients, demonstrating successful editing in long-term repopulating cells. Random vector integration events were nearly undetectable, and malignant transformation of the transplanted cells was not observed. Similar editing frequencies were observed in human hematopoietic cells. Our results demonstrate that therapeutically relevant HSC gene editing can be achieved by AAV vectors in the absence of site-specific nucleases and suggest that this may be a safe and effective therapy for hematopoietic diseases where in vivo selection can increase edited cell numbers. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of esophageal cancer

PubMed Central

Ou, Yao; Zhang, Quan; Tang, Yiting; Lu, Zhonghua; Lu, Xujing; Zhou, Xifa; Liu, Changmin

2018-01-01

Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca-109 and TE-1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca-109 cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect changes to microvessels and tumor growth by immunohistochemistry (IHC). RNA-seq was used to identify differentially expressed genes. We found that RG108 increased the radiosensitivity of EC cells. Apoptosis and G2/M-phase arrest were induced by X-ray irradiation and were significantly enhanced by RG108. In addition, growth of tumor xenografts from the Eca-109 cells was significantly inhibited by irradiation in combination with RG108. The RNA-seq analysis revealed that, compared with radiation alone, X-ray irradiation in combination with RG108 altered the expression of 121 genes in multiple pathways, including the TGF-β signaling pathway and the Epstein-Barr virus infection pathway. In conclusion, RG108 induced radiosensitivity in EC cells both in vitro and in vivo. PMID:29328411

Study on the Correlation between Gene Expression and Enzyme Activity of Seven Key Enzymes and Ginsenoside Content in Ginseng in Over Time in Ji'an, China.

PubMed

Yin, Juxin; Zhang, Daihui; Zhuang, Jianjian; Huang, Yi; Mu, Ying; Lv, Shaowu

2017-12-11

Panax ginseng is a traditional medicine. Fresh ginseng is one of the most important industries related to ginseng development, and fresh ginseng of varying ages has different medicinal properties. Previous research has not systematically reported the correlation between changes in key enzyme activity with changes in ginsenoside content in fresh ginseng over time. In this study, for the first time, we use ginseng samples of varying ages in Ji'an and systematically reported the changes in the activity of seven key enzymes (HMGR, FPS, SS, SE, DS, CYP450, and GT). We investigated the content of ginsenoside and gene expression of these key enzymes. Ginsenoside content was measured using HPLC. HPLC, GC-MS, and LC-MS were combined to measure the enzyme activity of the key enzymes. Quantitative PCR was used in the investigation of gene expression. By analyzing the correlation between the enzyme activity and the transcription level of the key enzymes with ginsenoside content, we found that DS and GT enzyme activities are significantly correlated with the ginsenoside content in different ages of ginseng. Our findings might provide a new strategy to discriminate between ginseng of different years. Meanwhile, this research provides important information for the in-depth study of ginsenoside biosynthesis.

Optimization of dynamic-microwave assisted enzymatic hydrolysis extraction of total ginsenosides from stems and leaves of panax ginseng by response surface methodology.

PubMed

Wang, Xiao-Yan; Ren, Hui

2018-03-21

Ginseng stems and leaves (GSAL) are abundant in ginsenosides compounds. For efficient utilization of GSAL and the enhancement of total ginsenosides (TG) compound yields in GSAL, TG from GSAL were extracted, using dynamic-microwave assisted extraction coupled with enzymatic hydrolysis (DMAE-EH) method. The extraction process has been simulated and its main influencing factors such as ethanol concentration, microwave temperature, microwave time and pump flow rate have been optimized by response surface methodology coupled with a Box-Behnken design(BBD). The experimental results indicated that optimal extraction conditions of TG from GSAL were as follows: ethanol concentration of 75%, microwave temperature of 60°C, microwave time of 20 min and pump flow rate of 38 r/min. After experimental verification, the experimental yields of TG was 60.62 ± 0.85 mg g -1 , which were well agreement with the predicted by the model. In general, the present results demonstrated that DMAE-EH method was successfully used to extract total ginsenosides in GSAL.

77 FR 47670 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,919] RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG Steel LLC, Including All On-Site Leased Workers, Sparrows Point, MD; Amended Certification Regarding Eligibility To Apply for...

Performance of the first HAWAII 4RG-15 arrays in the laboratory and at the telescope

NASA Astrophysics Data System (ADS)

Hall, Donald N. B.; Atkinson, Dani; Beletic, James W.; Blank, Richard; Farris, Mark; Hodapp, Klaus W.; Jacobson, Shane M.; Loose, Markus; Luppino, Gerard

2012-07-01

The primary goal of the HAWAII 4RG-15 (H4RG-15) development is to provide a 16 megapixel 4096x4096 format at significantly reduced price per pixel while maintaining the superb low background performance of the HAWAII 2RG (H2RG). The H4RG-15 design incorporates several new features, notably clocked reference output and interleaved reference pixel readout, that promise to significantly improve noise performance while the reduction in pixel pitch from 18 to 15 microns should improve transimpedance gain although at the expense of some degradation in full well and crosstalk. During the Phase-1 development, Teledyne has produced and screen tested six hybrid arrays. In preparation for Phase-2, the most promising of these are being extensively characterized in the University of Hawaii’s (UH) ULBCam test facility originally developed for the JWST H2RG program. The end-to-end performance of the most promising array has been directly established through astronomical imaging observations at the UH 88-inch telescope on Mauna Kea. We report the performance of these Phase-1 H4RG-15s within the context of established H2RG performance for key parameters (primarily CDS read noise), also highlighting the improvements from the new readout modes.

Evaluation of organic anion-transporting polypeptide 1B1 and CYP3A4 activities in primary human hepatocytes and HepaRG cells cultured in a dynamic three-dimensional bioreactor system.

PubMed

Ulvestad, Maria; Darnell, Malin; Molden, Espen; Ellis, Ewa; Åsberg, Anders; Andersson, Tommy B

2012-10-01

The long-term stability of liver cell functions is a major challenge when studying hepatic drug transport, metabolism, and toxicity in vitro. The aim of the present study was to investigate organic anion-transporting polypeptide (OATP) 1B1 and CYP3A4 activities in fresh primary human hepatocytes and differentiated cryopreserved HepaRG cells when cultured in a three-dimensional (3D) bioreactor system. OATP1B1 activity was determined by loss from media experiments of [(3)H]estradiol-17β-D-glucuronide and atorvastatin acid (ATA) for up to 7 days in culture. ATA metabolite formation was determined at days 3 to 4 to evaluate CYP3A4 activity. Overall, the results showed that freshly isolated human hepatocytes inoculated in the bioreactor retained OATP1B1 activity for at least 7 days, whereas in HepaRG cells no OATP1B1 activity was observed beyond day 2. The activity data were in agreement with immunohistochemical stainings, which showed that OATP1B1 protein expression was preserved for at least 9 days in fresh human hepatocytes, whereas OATP1B1 was expressed markedly lower in HepaRG cells after 9 days in culture. Fresh human hepatocytes and HepaRG cells exhibited similar CYP3A4 activity in bioreactor culture, and immunohistochemical stainings supported these findings. Activity and mRNA expression of OATP1B1 and CYP3A4 in primary human hepatocytes compared with HepaRG cells in fresh suspensions were in agreement with data obtained in bioreactor culture. In conclusion, freshly isolated human hepatocytes cultured in a 3D bioreactor system preserve both OATP1B1 and CYP3A4 activities, allowing long-term in vitro studies on drug disposition and toxicity.

[Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

PubMed

Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

2015-08-01

This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract.

77 FR 70478 - RG Steel Wheeling, LLC, Wheeling Office, A Division Of RG Steel, LLC, Including On-Site Leased...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,880: TA-A-81,880A] RG Steel Wheeling, LLC, Wheeling Office, A Division Of RG Steel, LLC, Including On-Site Leased Workers From Pro Unlimited and Green Energy Initiatives LLC, Including Workers Whose Wages Were Reported Through Severstal Wheeling, Wheeling, WV: Mountain State...

Stable Overexpression of the Constitutive Androstane Receptor Reduces the Requirement for Culture with Dimethyl Sulfoxide for High Drug Metabolism in HepaRG Cells.

PubMed

van der Mark, Vincent A; Rudi de Waart, D; Shevchenko, Valery; Elferink, Ronald P J Oude; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

2017-01-01

Dimethylsulfoxide (DMSO) induces cellular differentiation and expression of drug metabolic enzymes in the human liver cell line HepaRG; however, DMSO also induces cell death and interferes with cellular activities. The aim of this study was to examine whether overexpression of the constitutive androstane receptor (CAR, NR1I3), the nuclear receptor controlling various drug metabolism genes, would sufficiently promote differentiation and drug metabolism in HepaRG cells, optionally without using DMSO. By stable lentiviral overexpression of CAR, HepaRG cultures were less affected by DMSO in total protein content and obtained increased resistance to acetaminophen- and amiodarone-induced cell death. Transcript levels of CAR target genes were significantly increased in HepaRG-CAR cultures without DMSO, resulting in increased activities of cytochrome P450 (P450) enzymes and bilirubin conjugation to levels equal or surpassing those of HepaRG cells cultured with DMSO. Unexpectedly, CAR overexpression also increased the activities of non-CAR target P450s, as well as albumin production. In combination with DMSO treatment, CAR overexpression further increased transcript levels and activities of CAR targets. Induction of CYP1A2 and CYP2B6 remained unchanged, whereas CYP3A4 was reduced. Moreover, the metabolism of low-clearance compounds warfarin and prednisolone was increased. In conclusion, CAR overexpression creates a more physiologically relevant environment for studies on hepatic (drug) metabolism and differentiation in HepaRG cells without the utilization of DMSO. DMSO still may be applied to accomplish higher drug metabolism, required for sensitive assays, such as low-clearance studies and identification of (rare) metabolites, whereas reduced total protein content after DMSO culture is diminished by CAR overexpression. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

The effect of recycled Natural Rubber Glove (rRG) Plasticizers to Deflection and Flexural Strength Properties of PP/MMt/rRG Smart Composites and Its Inflammability

NASA Astrophysics Data System (ADS)

Suharty, N. S.; Ismail, H.; Diharjo, K.; Handayani, D. S.; Saputri, L. N. M. Z.; Ariesta, N.

2018-03-01

Had been synthesized PP/rRG/MMt+ZB smart material composite in solution reactive processes with various rRG concentration. The addition of rRG plasticizers will improve the deflection properties and increase the filler capacity MMt loading to reach the optimum concentration. The addition of 3% rRG is capable of loading filler capacity MMt to 23% as the optimum condition. At the optimum conditions it can increase the deflection (Defl) and flexural strength (FS) up to 16% and 15% respectively compared to that of the composites without rRG. The rRG plasticizer serves as a bio-compatibilizer that can reduce surface tension of the mixture and leads to decrease the Defl., follow by the increase of loading filler capacity and well interaction finally can increase the FS properties. The increase of loading filler MMt up to 23% can also improve the inflammability of the composites. Time to Ignition (TTI) increase by 5% and Burning Rate (BR) decrease by 4.5% compared to that of the composites which is containing MMt 20% without rRG.

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.

PubMed

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

2017-02-20

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

Static electric polarizabilities and first hyperpolarizabilities of molecular ions RgH + (Rg = He, Ne, Ar, Kr, Xe): ab initio study

NASA Astrophysics Data System (ADS)

Cukras, Janusz; Antušek, Andrej; Holka, Filip; Sadlej, Joanna

2009-06-01

Extensive ab initio calculations of static electric properties of molecular ions of general formula RgH + (Rg = He, Ne, Ar, Kr, Xe) involving the finite field method and coupled cluster CCSD(T) approach have been done. The relativistic effects were taken into account by Douglas-Kroll-Hess approximation. The numerical stability and reliability of calculated values have been tested using the systematic sequence of Dunning's cc-pVXZ-DK and ANO-RCC-VQZP basis sets. The influence of ZPE and pure vibrational contribution has been discussed. The component αzz has increasing trend in RgH + while the relativistic effect on αzz leads to a small increase of this molecular parameter.

WFIRST: Principal Components Analysis of H4RG-10 Near-IR Detector Data Cubes

NASA Astrophysics Data System (ADS)

Rauscher, Bernard

2018-01-01

The Wide Field Infrared Survey Telescope’s (WFIRST) Wide Field Instrument (WFI) incorporates an array of eighteen Teledyne H4RG-10 near-IR detector arrays. Because WFIRST’s science investigations require controlling systematic uncertainties to state-of-the-art levels, we conducted principal components analysis (PCA) of some H4RG-10 test data obtained in the NASA Goddard Space Flight Center Detector Characterization Laboratory (DCL). The PCA indicates that the Legendre polynomials provide a nearly orthogonal representation of up-the-ramp sampled illuminated data cubes, and suggests other representations that may provide an even more compact representation of the data in some circumstances. We hypothesize that by using orthogonal representations, such as those described here, it may be possible to control systematic errors better than has been achieved before for NASA missions. We believe that these findings are probably applicable to other H4RG, H2RG, and H1RG based systems.

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

PubMed

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

2016-01-19

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

Boomerang RG flows in M-theory with intermediate scaling

NASA Astrophysics Data System (ADS)

Donos, Aristomenis; Gauntlett, Jerome P.; Rosen, Christopher; Sosa-Rodriguez, Omar

2017-07-01

We construct novel RG flows of D=11 supergravity that asymptotically approach AdS 4 × S 7 in the UV with deformations that break spatial translations in the dual field theory. In the IR the solutions return to exactly the same AdS 4 × S 7 vacuum, with a renormalisation of relative length scales, and hence we refer to the flows as `boomerang RG flows'. For sufficiently large deformations, on the way to the IR the solutions also approach two distinct intermediate scaling regimes, each with hyperscaling violation. The first regime is Lorentz invariant with dynamical exponent z = 1 while the second has z = 5/2. Neither ofthe two intermediatescaling regimesare associatedwith exact hyperscaling violation solutions of D = 11 supergravity. The RG flow solutions are constructed using the four dimensional N = 2 STU gauged supergravity theory with vanishing gauge fields, but non-vanishing scalar and pseudoscalar fields. In the ABJM dual field theory the flows are driven by spatially modulated deformation parameters for scalar and fermion bilinear operators.

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

PubMed

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

2014-01-01

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

Dynamic Changes in Neutral and Acidic Ginsenosides with Different Cultivation Ages and Harvest Seasons: Identification of Chemical Characteristics for Panax ginseng Quality Control.

PubMed

Liu, Zhi; Wang, Chong-Zhi; Zhu, Xing-You; Wan, Jin-Yi; Zhang, Jing; Li, Wei; Ruan, Chang-Chun; Yuan, Chun-Su

2017-05-04

In this study, dynamic changes in ginsenoside content and ratios in the Panax ginseng root were investigated with different cultivation ages and different collection months, using high-performance liquid chromatography (HPLC). Our data indicate that changes in ginsenoside Ro and malonyl ginsenosides content were dependent on the ginseng cultivation age ( p < 0.05); especially, the Ro content varied from 0.16 to 4.91 mg/g, with a difference about 30-fold. Further, we found that the samples of 5 and 6-year-old P. ginseng had high Ro/Re ratio, whereas two and three-year-old P. ginseng possessed low Ro/Re ratio. Thus, the Ro/Re ratio can be used as a characteristic marker for differentiating the age of the root. The relative content of ginsenosides Rg₁ and Re were affected by the ginseng's harvest season. The Re content was higher than the Rg₁ content in May and June, but lower than the Rg₁ content from August to October. Thus, the Rg₁/Re ratio can be used as a characteristic marker for differentiating the ginseng's harvest seasons. These results indicate that the chemical characteristics of P. ginseng at different cultivation ages and harvest seasons are clearly different, which may cause differences in pharmacological activities and therapeutic effects. In addition, we developed HPLC coupled with hierarchical cluster analysis and principal component analysis methods to identify the cultivation age and harvest season of P. ginseng using characteristic ginsenosides. Our results showed that this method can be used to discriminate the cultivation age and harvest season of P. ginseng.

Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding

PubMed Central

Ozdilek, Bagdeser A.; Thompson, Valery F.; Ahmed, Nasiha S.; White, Connor I.

2017-01-01

Abstract RGG/RG domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties remain poorly understood. Here, we report a detailed analysis of the RNA binding characteristics of intrinsically disordered RGG/RG domains from Fused in Sarcoma (FUS), FMRP and hnRNPU. For FUS, previous studies defined RNA binding as mediated by its well-folded domains; however, we show that RGG/RG domains are the primary mediators of binding. RGG/RG domains coupled to adjacent folded domains can achieve affinities approaching that of full-length FUS. Analysis of RGG/RG domains from FUS, FMRP and hnRNPU against a spectrum of contrasting RNAs reveals that each display degenerate binding specificity, while still displaying different degrees of preference for RNA. PMID:28575444

α -decay chains of the superheavy nuclei Rg-350255

NASA Astrophysics Data System (ADS)

Santhosh, K. P.; Nithya, C.

2017-05-01

The decay modes and half-lives of 96 isotopes of the superheavy element roentgenium (Rg) within the range of 255 ≤A ≤350 come under investigation in the present paper. The isotopes which lie beyond the proton drip line are identified by calculating the one-proton and two-proton separation energies. The α -decay half-lives are calculated using the Coulomb and proximity potential model for deformed nuclei (CPPMDN). For a theoretical comparison the α half-lives are also evaluated using the Viola-Seaborg semiempirical relation, the universal curve of Poenaru et al., the analytical formula of Royer, and the universal decay law of Qi et al. Spontaneous fission half-lives are computed with the shell-effect-dependent formula of Santhosh and Nithya and the semiempirical formula of Xu et al. The decay modes are predicted by comparing the α -decay half-lives within the CPPMDN with the corresponding spontaneous fission half-lives computed by the shell-effect-dependent formula of Santhosh and Nithya. In our paper it is seen that the isotopes 255-271,273Rg lie beyond the proton drip line and hence decay through proton emission. The isotopes 272,274-277Rg exhibit long α chains. Three α chains are predicted from the isotopes Rg-282278. The isotopes Rg-345283 decay through spontaneous fission. The isotopes Rg-350346 are found to be stable against α decay. The theoretical results are compared with the available experimental results and are seen to be matching well. We hope that our predictions will be useful in future experimental investigations.

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

PubMed Central

Peres, Lázaro Eustáquio Pereira

2012-01-01

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

The tomato (Solanum lycopersicum cv. Micro-Tom) natural genetic variation Rg1 and the DELLA mutant procera control the competence necessary to form adventitious roots and shoots.

PubMed

Lombardi-Crestana, Simone; da Silva Azevedo, Mariana; e Silva, Geraldo Felipe Ferreira; Pino, Lílian Ellen; Appezzato-da-Glória, Beatriz; Figueira, Antonio; Nogueira, Fabio Tebaldi Silveira; Peres, Lázaro Eustáquio Pereira

2012-09-01

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

RG-inspired machine learning for lattice field theory

NASA Astrophysics Data System (ADS)

Foreman, Sam; Giedt, Joel; Meurice, Yannick; Unmuth-Yockey, Judah

2018-03-01

Machine learning has been a fast growing field of research in several areas dealing with large datasets. We report recent attempts to use renormalization group (RG) ideas in the context of machine learning. We examine coarse graining procedures for perceptron models designed to identify the digits of the MNIST data. We discuss the correspondence between principal components analysis (PCA) and RG flows across the transition for worm configurations of the 2D Ising model. Preliminary results regarding the logarithmic divergence of the leading PCA eigenvalue were presented at the conference. More generally, we discuss the relationship between PCA and observables in Monte Carlo simulations and the possibility of reducing the number of learning parameters in supervised learning based on RG inspired hierarchical ansatzes.

Apparent Explosion Moments from Rg Waves Recorded on SPE

DOE PAGES

Larmat, Carene; Rougier, Esteban; Patton, Howard John

2016-11-29

Seismic moments for the first four chemical tests making up phase I of the Source Physics Experiments (SPE) are estimated from 6-Hz Rg waves recorded along a single radial line of geophones under the assumption that the tests are pure explosions. These apparent explosion moments are compared with moments determined from the reduced displacement potential method applied to free-field data. Light detection and ranging (lidar) observations, strong ground motions on the free surface in the vicinity of ground zero, and moment tensor inversion results are evidence that the fourth test SPE-4P is a pure explosion, and the moments show goodmore » agreement, 8×10 10 N·m for free-field data versus 9×10 10 N·m for Rg waves. In stark contrast, apparent moments for the first three tests are smaller than near-field moments by factors of 3–4. Relative amplitudes for the three tests determined from Rg interferometry using SPE-4P as an empirical Green’s function indicate that radiation patterns are cylindrically symmetric within a factor of 1.25 (25%). This fact assures that the apparent moments are reliable even though they were measured on just one azimuth. Spallation occurred on the first three tests, and ground-based lidar detected permanent deformations. As such, the source medium suffered late-time damage. In conclusion, destructive interference between Rg waves radiated by explosion and damage sources will reduce amplitudes and explain why apparent moments are smaller than near-field moments based on compressional energy emitted directly from the source.« less

Apparent Explosion Moments from Rg Waves Recorded on SPE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larmat, Carene; Rougier, Esteban; Patton, Howard John

Seismic moments for the first four chemical tests making up phase I of the Source Physics Experiments (SPE) are estimated from 6-Hz Rg waves recorded along a single radial line of geophones under the assumption that the tests are pure explosions. These apparent explosion moments are compared with moments determined from the reduced displacement potential method applied to free-field data. Light detection and ranging (lidar) observations, strong ground motions on the free surface in the vicinity of ground zero, and moment tensor inversion results are evidence that the fourth test SPE-4P is a pure explosion, and the moments show goodmore » agreement, 8×10 10 N·m for free-field data versus 9×10 10 N·m for Rg waves. In stark contrast, apparent moments for the first three tests are smaller than near-field moments by factors of 3–4. Relative amplitudes for the three tests determined from Rg interferometry using SPE-4P as an empirical Green’s function indicate that radiation patterns are cylindrically symmetric within a factor of 1.25 (25%). This fact assures that the apparent moments are reliable even though they were measured on just one azimuth. Spallation occurred on the first three tests, and ground-based lidar detected permanent deformations. As such, the source medium suffered late-time damage. In conclusion, destructive interference between Rg waves radiated by explosion and damage sources will reduce amplitudes and explain why apparent moments are smaller than near-field moments based on compressional energy emitted directly from the source.« less

[Correlation of gene expression related to amount of ginseng saponin in 15 tissues and 6 kinds of ginseng saponin biosynthesis].

PubMed

Wang, Kang-yu; Zhang, Mei-ping; Li, Chuang; Jiang, Shi-cui; Yin, Rui; Sun, Chun-yu; Wang, Yi

2015-08-01

Fifteen tissues of 4-year-old fruit repining stage Jilin ginseng were chosen as materials, six kinds of monomer saponins (ginsenosides Rg1, Re, Rb1, Rc, Rb2 and Rd) content in 15 tissues was measured by HPLC and vanillin-sulfuric acid method. The relative expression of FPS, SQS, SQE, OSC, β-AS and P450 genes in 15 tissues was analyzed by real-time PCR. The correlations between ginseng saponin content in 15 tissues of Jilin ginseng and biosynthetic pathway -related genes were obtained. The results showed that was a synergistic increase and decrease trend of positive linear correlation among six kinds of monomer saponin content, and there was a significantly (P < 0.01) positive correlation between monomer saponin content and total saponins content. Monomer saponin content and 6 kinds of enzyme gene correlation were different. Biosynthesis of ginseng total saponins and monomer saponin were regulated by six kinds of participation ginsenoside biosynthesis enzyme genes, the expression of these six kinds of genes in different tissues of ginseng showed collaborative increase and decrease trend, and regulated biosynthesis of ginseng ginsenoside by group coordinative manner.

Active compounds in Chinese herbs and medicinal animal products which promote blood circulation via inhibition of Na+, K+-ATPase.

PubMed

Tzen, Jason Tc; Chen, Ronald Jy; Chung, Tse-Yu; Chen, Yi-Ching; Lin, Nan-Hei

2010-01-01

The therapeutic effect of cardiac glycosides for congestive heart failure lies in their reversible inhibition on Na+, K+-ATPase located in human myocardium. Several steroid-like compounds containing a core structure similar to cardiac glycosides have been found in many Chinese herbs and medicinal animal products conventionally used to promote blood circulation. They are putatively responsible for the therapeutic effect of those medicinal products via the same mechanism of inhibiting Na+, K+-ATPase. Inhibitory potency on Na+, K+-ATPase by ginsenosides, one of the identified steroid-like compounds, is significantly affected by sugar attachment that might cause steric hindrance of their binding to Na+, K+-ATPase. Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, substantially inhibit Na+, K+-ATPase. However, their inhibitory potency is abolished when sugar moieties are linked to the C-6 or C-20 position of the steroid-like structure. In contrast, no appreciable contents of steroid-like compounds are found in danshen, a well-known Chinese herb traditionally regarded as an effective medicine promoting blood circulation. Instead, magnesium lithospermate B (MLB), the major soluble ingredient in danshen, is assumed to be responsible for the therapeutic effect by inhibiting Na+, K+-ATPase in a manner comparable to cardiac glycosides. Neuroprotective effects of cardiac glycosides, ginsenosides and MLB against ischemic stroke were accordingly observed in a cortical brain slice-based assay model. Whether the neuroprotection is also triggered by inhibition of Na+, K+-ATPase remains to be investigated. Molecular modeling suggests that cardiac glycosides, ginsenosides and MLB presumably bind to the same extracellular pocket of the Na+, K+-ATPase alpha subunit.

[Expression of saponin biosynthesis related genes in different tissues of Panax quinquefolius].

PubMed

Wang, Kang-Yu; Liu, Wei-Can; Zhang, Mei-Ping; Zhao, Ming-Zhu; Wang, Yan-Fang; Li, Li; Sun, Chun-Yu; Hu, Ke-Xin; Cong, Yue-Yi; Wang, Yi

2018-01-01

The relationship between saponin content of Panax quinquefolius in different parts of the organization and expression of ginsenoside biosynthesis related gene was obtained by the correlation analysis between saponin content and gene expression. The 14 tissue parts of P. quinquefolius were studied, six saponins in P. quinquefolius. Samples (ginsenoside Rg₁, Re, Rb₁, Rc, Rb₂ and Rd), group saponins and total saponins were determined by high performance liquid chromatography and vanillin-sulfuric acid colorimetric method. Simultaneously, the expression levels of 7 ginsenoside biosynthesis related genes ( SQS, OSC, DS, β-AS, SQE, P450 and FPS ) in different tissues of P. quinquefolius were determined by Real-time fluorescence quantitative PCR. Although 7 kinds of ginsenoside biosynthesis related enzyme gene in the P. quinquefolius involved in ginsenoside synthesis, the expression of β-AS and P450 genes had no significant effect on the content of monosodium saponins, grouping saponins and total saponins, FPS, SQS, OSC, DS and SQE had significant or extremely significant on the contents of single saponins Re, Rg1, Rb1, Rd, group saponin PPD and PPT, total saponin TMS and total saponin TS ( P <0.05 or P <0.01). The biosynthesis of partial saponins, grouping saponins and total saponins in P. quinquefolius was affected by the interaction of multiple enzyme genes in the saponin synthesis pathway, the content of saponins in different tissues of P. quinquefolius was determined by the differences in the expression of key enzymes in the biosynthetic pathway. Therefore, this study further clarified that FPS, SQS, OSC, DS and SQE was the key enzyme to control the synthesis of saponins in P. quinquefolius by correlation analysis, the biosynthesis of ginsenosides in P. quinquefolius was regulated by these five kind of enzymes in cluster co-expression of interaction mode. Copyright© by the Chinese Pharmaceutical Association.

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

PubMed

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

2016-01-01

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

Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal cancer cells.

PubMed

Han, Songhee; Jeong, Ae Jin; Yang, Heejung; Bin Kang, Kyo; Lee, Haeri; Yi, Eun Hee; Kim, Byung-Hak; Cho, Chung-Hyun; Chung, Jin Woong; Sung, Sang Hyun; Ye, Sang-Kyu

2016-12-24

Panax ginseng is one of the most well-known medicinal herbs in Korea and China, which has been used for treatment and prevention of cancer, obesity, diabetes, and cardiovascular diseases. Ginsenosides are the major components of P. ginseng, having a wide range of pharmacological activities. Among the ginsenosides, protopanaxadiol (PPD)-types reportedly have potent anti-cancer effects. Rh2 is PPD-type ginsenoside, and two stereoisomeric forms of Rh2 as 20(S)- and 20(R)-Rh2 were selectively isolated recently. The biological activities of Rh2 ginsenosides are known to depend on their differences in stereochemistry. Colorectal cancer (CRC) is one of the most lethal neoplasm, and cancer-related death is usually associated with metastasis to other organs. We aimed this study to investigate whether 20(S)- and 20(R)-Rh2 can suppress tumor invasion in human CRC cells. 20(S)- and 20(R)-Rh2 were isolated from the roots of ginseng. Human CRC cells were incubated with 20(S)- or 20(R)-Rh2 in the presence or absence of interleukin-6. An MTT assay was used to measure cell viability. Western blot and quantitative real-time PCR analyses were performed to determine levels of expression and phosphorylation. An invasion assay was performed using a Boyden chamber system with the Matrigel-coated membrane to measure cancer cell invasion. 20(S)- and 20(R)-Rh2 showed differential cytotoxic activity. Only 20(S)-Rh2 decreased cancer cell viability. Additionally, 20(S)-Rh2 effectively inhibited IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of matrix metalloproteinases (MMPs), including MMP-1, -2, and -9, resulting in inhibition of cancer cell invasion. Interestingly, these pharmacological activities of 20(S)-Rh2 were more potent than those of 20(R)-Rh2. Furthermore, combination treatment showed that 20(S)-Rh2 enhanced the sensitization of doxorubicin-treated anti-cancer activities in CRC cells. Our results demonstrated that

Rapid estimation of the electron correlation energy for van der Waals complexes RgX (Rg = Kr, Xe, X = Br, I)

NASA Astrophysics Data System (ADS)

Xinying, Li; Yongfang, Zhao; Xiaogong, Jing; Fengli, Liu; Fengyou, Hao

2006-01-01

We present the rules of electron correlation energies for RgX (Rg = Kr, Xe, X = Br, I) van der Waals (vdW) complex systems at CCSD(T) theoretical level with SDB-cc-pVQZ basis set by the Gaussian 98 program. A new method to derive the dispersion coefficient C6 by fitting the intermonomer electron correlation energies to C6R-6 function is introduced. The present C6 values are compared with the corresponding theoretical ones.

RG-I regions from elderflower pectins substituted on GalA are strong immunomodulators.

PubMed

Ho, Giang Thanh Thi; Zou, Yuan-Feng; Wangensteen, Helle; Barsett, Hilde

2016-11-01

Sambuci flos, also known as elderflower, has traditionally been used and is still in use for treatment of various types of illnesses related to the immune system such as cold, flu, fever and inflammation. Pectic polysaccharides from 50% EtOH, 50°C water and 100°C water extracts from elderflowers were treated with endo-α-d-(1-4)-polygalacturonase after previous de-esterification with the intention of isolating hairy regions and relate variation in structure to immunomodulating activity. High molecular weight sub-fractions (25-29kDa) and medium molecular weight sub-fractions (6-17kDa) were isolated after enzymatic treatment in addition to oligogalacturonides. Structural elucidation indicated that RG-I regions with AG-I and AG-II sidechains were the predominant structures in the high molecular weight sub-fractions, and two of three 1,4-linked GalA units in the rhamnogalacturonan backbone were branched in either position 2 or 3. The medium molecular weight sub-fractions had monomers and linkages typical for both RG-I and RG-II. The results showed that the high molecular RG-I containing polymers exhibit the highest dose-dependent complement fixing and macrophage stimulating activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Two new fatty acids esters were detected in ginseng stems by the application of azoxystrobin and the increasing of antioxidant enzyme activity and ginsenosides content.

PubMed

Liang, Shuang; Xu, Xuan-Wei; Zhao, Xiao-Feng; Hou, Zhi-Guang; Wang, Xin-Hong; Lu, Zhong-Bin

2016-11-01

Panax ginseng C.A. Meyer is a valuable herb in China that has also gained popularity in the West because of its pharmacological properties. The constituents isolated and characterized in ginseng stems include ginsenosides, fatty acids, amino acids, volatile oils, and polysaccharides. In this study, the effects of fungicide azoxystrobin applied on antioxidant enzyme activity and ginsenosides content in ginseng stems was studied by using Panax ginseng C. A. Mey. cv. (the cultivar of Ermaya) under natural environmental conditions. The azoxystrobin formulation (25% SC) was sprayed three times on ginseng plants at different doses (150ga.i./ha and 225ga.i./ha), respectively. Two new fatty acids esters (ethyl linoleate and methyl linolenate) were firstly detected in ginseng stems by the application of azoxystrobin as foliar spray. The results indicated that activities of enzymatic antioxidants, the content of ginsenosides and two new fatty acids esters in ginseng stems in azoxystrobin-treated plants were increased. Azoxystrobin treatments to ginseng plants at all growth stages suggest that the azoxystrobin-induced delay of senescence is due to an enhanced antioxidant enzyme activity protecting the plants from harmful active oxygen species (AOS). The activity of superoxide dismutase (SOD) in azoxystrobin-treated plants was about 1-3 times higher than that in untreated plants. And the effects was more significant (P=0.05) when azoxystrobin was applied at dose of 225ga.i./ha. This work suggests that azoxystrobin plays an important role in delaying of senescence by changing physiological and biochemical indicators and increasing ginsenosides content in ginseng stems. Copyright © 2016 Elsevier B.V. All rights reserved.

The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng.

PubMed

Kim, Eunji; Kim, Donghyun; Yoo, Sulgi; Hong, Yo Han; Han, Sang Yun; Jeong, Seonggu; Jeong, Deok; Kim, Jong-Hoon; Cho, Jae Youl; Park, Junseong

2018-04-01

Compound K (CK) is a ginsenoside, a metabolite of Panax ginseng . There is interest both in increasing skin health and antiaging using natural skin care products. In this study, we explored the possibility of using CK as a cosmetic ingredient. To assess the antiaging effect of CK, RT-PCR was performed, and expression levels of matrix metalloproteinase-1, cyclooxygenase-2, and type I collagen were measured under UVB irradiation conditions. The skin hydrating effect of CK was tested by RT-PCR, and its regulation was explored through immunoblotting. Melanin content, melanin secretion, and tyrosinase activity assays were performed. CK treatment reduced the production of matrix metalloproteinase-1 and cyclooxygenase-2 in UVB irradiated NIH3T3 cells and recovered type I collagen expression level. Expression of skin hydrating factors-filaggrin, transglutaminase, and hyaluronic acid synthases-1 and -2-were augmented by CK and were modulated through the inhibitor of κBα, c-Jun N-terminal kinase, or extracellular signal-regulated kinases pathway. In the melanogenic response, CK did not regulate tyrosinase activity and melanin secretion, but increased melanin content in B16F10 cells was observed. Our data showed that CK has antiaging and hydrating effects. We suggest that CK could be used in cosmetic products to protect the skin from UVB rays and increase skin moisture level.

Bouncing and emergent cosmologies from Arnowitt–Deser–Misner RG flows

NASA Astrophysics Data System (ADS)

Bonanno, Alfio; Gionti, S. J. Gabriele; Platania, Alessia

2018-03-01

Asymptotically safe gravity provides a framework for the description of gravity from the trans-Planckian regime to cosmological scales. According to this scenario, the cosmological constant and Newton’s coupling are functions of the energy scale whose evolution is dictated by the renormalization group (RG) equations. The formulation of the RG equations on foliated spacetimes, based on the Arnowitt–Deser–Misner (ADM) formalism, furnishes a natural way to construct the RG energy scale from the spectrum of the Laplacian operator on the spatial slices. Combining this idea with an RG improvement procedure, in this work we study quantum gravitational corrections to the Einstein–Hilbert action on Friedmann–Lemaître–Robertson–Walker backgrounds. The resulting quantum-corrected Friedmann equations can give rise to both bouncing cosmologies and emergent Universe solutions. Our bouncing models do not require the presence of exotic matter and emergent Universe solutions can be constructed for any allowed topology of the spatial slices.

Comparative studies of saponins in 1-3-year-old main roots, fibrous roots, and rhizomes of Panax notoginseng, and identification of different parts and growth-year samples.

PubMed

Jia, Xiu-Hong; Wang, Chao-Qun; Liu, Jin-Huai; Li, Xiao-Wei; Wang, Xuan; Shang, Ming-Ying; Cai, Shao-Qing; Zhu, Shu; Komatsu, Katsuko

2013-04-01

Notoginsenosides R1, R4, Fa, and K (N-R1, N-R4, N-Fa, and N-K), as well as ginsenosides Rg1, Rb1, Rd, Re, Rf, Rg2 and Rh1 (G-Rg1, G-Rb1, G-Rd, G-Re, G-Rf, G-Rg2 and G-Rh1) in 47 Notoginseng samples including 1-, 2- and 3-year-old main roots, rhizomes and fibrous roots of Panax notoginseng were determined by high-performance liquid chromatography-diode array detection method. Total contents (%) of the 11 saponins were 9.82-14.57 for 2-year old and 14.20-16.00 for 3-year-old rhizomes; 2.72-4.50 for 2-year-old and 1.98-4.92 for 3-year-old fibrous roots; 1.75-3.05 for 1-year-old whole roots; and 3.71-8.98 for 2-year-old and 7.03-11.23 for 3-year-old main roots. Contents of most saponins and total content of 11 saponins were in the order 3- >2- >1-year-old main root samples. G-Rf content, sum of G-Rf and G-Rh1 were, respectively, 0.08-0.18 and 0.14-0.32 for 2- or 3-year-old rhizomes, and 0.01-0.07 and 0.03-0.10 for 2- or 3-year-old main roots. Combined contents of N-R1, G-Rg1 and G-Rb1 were 5.78-9.37 in 3-year-old main roots, and 2.99-7.13 in 2-year-old main roots, of which nearly one-third of samples were lower than the limit (5 %) in the Chinese Pharmacopoeia. Those of 2- or 3-year-old fibrous roots (1.47-3.83) and 1-year-old whole roots (1.41-2.44) were much lower than the limit, and were considered not suitable for use as Notoginseng. Two-year-old main roots are not appropriate for collection as Notoginseng. Different parts and growth years of P. notoginseng can be identified from each another according to differences in saponin content.

Predicted NMR properties of noble gas hydride cations RgH +

NASA Astrophysics Data System (ADS)

Cukras, Janusz; Sadlej, Joanna

2008-12-01

The NMR shielding constants and, for the first time, the spin-spin coupling constants of Rg and H in RgH + compounds for Rg = Ne, Ar, Kr, Xe have been investigated by non-relativistic Hartree-Fock (HF) and relativistic Dirac-Hartree-Fock (DHF) methods. Electron-correlation effects have been furthermore calculated using SOPPA and CCSD at the non-relativistic level. The correlation effects are large on both parameters and opposite to the relativistic effects. The results indicate that both the relativistic and correlation effects need to be taken into account in a quantitative computations, especially in the case of the spin-spin coupling constants.

Dissociation energies of Ag–RG (RG = Ar, Kr, Xe) and AgO molecules from velocity map imaging studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, Graham A.; Gentleman, Alexander S.; Iskra, Andreas

2015-09-28

The near ultraviolet photodissociation dynamics of silver atom—rare gas dimers have been studied by velocity map imaging. Ag–RG (RG = Ar, Kr, Xe) species generated by laser ablation are excited in the region of the C ({sup 2}Σ{sup +})←X ({sup 2}Σ{sup +}) continuum leading to direct, near-threshold dissociation generating Ag* ({sup 2}P{sub 3/2}) + RG ({sup 1}S{sub 0}) products. Images recorded at excitation wavelengths throughout the C ({sup 2}Σ{sup +})←X ({sup 2}Σ{sup +}) continuum, coupled with known atomic energy levels, permit determination of the ground X ({sup 2}Σ{sup +}) state dissociation energies of 85.9 ± 23.4 cm{sup −1} (Ag–Ar), 149.3 ±more » 22.4 cm{sup −1} (Ag–Kr), and 256.3 ± 16.0 cm{sup −1} (Ag–Xe). Three additional photolysis processes, each yielding Ag atom photoproducts, are observed in the same spectral region. Two of these are markedly enhanced in intensity upon seeding the molecular beam with nitrous oxide, and are assigned to photodissociation of AgO at the two-photon level. These features yield an improved ground state dissociation energy for AgO of 15 965 ± 81 cm{sup −1}, which is in good agreement with high level calculations. The third process results in Ag atom fragments whose kinetic energy shows anomalously weak photon energy dependence and is assigned tentatively to dissociative ionization of the silver dimer Ag{sub 2}.« less

ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import.

PubMed

Howard, Kellie; Cherezova, Lidia; DeMaster, Laura K; Rose, Timothy M

2017-11-01

The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype. Copyright © 2017. Published by Elsevier Inc.

Ab initio studies of the Rg–NO{sup +}(X{sup 1}Σ{sup +}) van der Waals complexes (Rg = He, Ne, Ar, Kr, and Xe)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orek, Cahit; Bulut, Niyazi, E-mail: jklos@umd.edu, E-mail: francois.lique@univ-lehavre.fr, E-mail: bulut-niyazi@yahoo.com; Kłos, Jacek, E-mail: jklos@umd.edu, E-mail: francois.lique@univ-lehavre.fr, E-mail: bulut-niyazi@yahoo.com

2016-05-28

We used the explicitly correlated variant of the coupled clusters method with single, double, and noniterative triple excitations [CCSD(T)-F12] to compute two-dimensional potential energy surfaces of van der Waals complexes formed by rare gas atoms (Rg) and NO{sup +}(X{sup 1}Σ{sup +}) cations. We used the correlation-consistent, triple-zeta (cc-pVTZ-F12) atomic basis sets, and for Kr and Xe rare gases, we employed corresponding pseudopotential cc-pVTZ-PP-F12 atomic basis sets. These basis sets were additionally augmented with mid-bond functions. The complexes are all of skewed T-shape type with Rg atom being closer to the N-side. Using analytical representation of the potentials, we have estimatedmore » zero-point energy corrected dissociation energies from anharmonic calculations with BOUND program and also from the harmonic approximation. The binding energies increase with the polarization of the Rg atom in series from He to Xe and are 196 cm{sup −1}, 360 cm{sup −1}, 1024 cm{sup −1}, 1434 cm{sup −1}, and 2141 cm{sup −1}, respectively. Their corresponding dissociation energies are 132 cm{sup −1}, 300 cm{sup −1}, 927 cm{sup −1}, 1320 cm{sup −1}, and 1994 cm{sup −1} for the complexes with He to Xe, respectively. We find good agreement with previous theoretical and experimental results. The harmonic vibrational frequencies were calculated for the bending and stretching modes of the Rg–NO{sup +} complexes.« less

Holographic RG flows on curved manifolds and quantum phase transitions

NASA Astrophysics Data System (ADS)

Ghosh, J. K.; Kiritsis, E.; Nitti, F.; Witkowski, L. T.

2018-05-01

Holographic RG flows dual to QFTs on maximally symmetric curved manifolds (dS d , AdS d , and S d ) are considered in the framework of Einstein-dilaton gravity in d + 1 dimensions. A general dilaton potential is used and the flows are driven by a scalar relevant operator. The general properties of such flows are analyzed and the UV and IR asymptotics computed. New RG flows can appear at finite curvature which do not have a zero curvature counterpart. The so-called `bouncing' flows, where the β-function has a branch cut at which it changes sign, are found to persist at finite curvature. Novel quantum first-order phase transitions are found, triggered by a variation in the d-dimensional curvature in theories allowing multiple ground states.

Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respir atory distress syndrome

PubMed Central

Sun, Rongju; Li, Yana; Chen, Wei; Zhang, Fei; Li, Tanshi

2015-01-01

Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

Panax ginseng Adventitious Root Suspension Culture: Protocol for Biomass Production and Analysis of Ginsenosides by High Pressure Liquid Chromatography.

PubMed

Murthy, Hosakatte Niranjana; Paek, Kee Yoeup

2016-01-01

Panax ginseng C.A. Meyer (Korean ginseng) is a popular herbal medicine. It has been used in Chinese and Oriental medicines since thousands of years. Ginseng products are generally used as a tonic and an adaptogen to resist the adverse influence of a wide range of physical, chemical and biological factors, and to restore homeostasis. Ginsenosides or ginseng saponins are the principal active ingredients of ginseng. Since ginseng cultivation process is very slow and needs specific environment for field cultivation, cell and tissue cultures are sought as alternatives for the production of ginseng biomass and bioactive compounds. In this chapter, we focus on methods of induction of adventitious roots from ginseng roots, establishment of adventitious root suspension cultures using bioreactors, procedures for processing of adventitious roots, and analysis of ginsenosides by high pressure liquid chromatography.

Combined Therapy against Recurrent Hemangiopericytoma: A Case Report

PubMed Central

Li, Xiao-dong; Jiang, Jing-ting; Wu, Chang-ping

2012-01-01

Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China A patient with a seven-year history of recurrent metastatic hemangiopericytoma (HPC) was admitted. During his treatment, he received surgical resection, radiotherapy, radiofrequency hyperthermia and chemotherapy using combined doxorubicin, dacarbazin, vincristine, ginsenoside Rg3, and recombinant human endostatin. This synergistic method provides an encouraging model for treating HPC. PMID:23691471

Coupling of ultrasound-assisted extraction and expanded bed adsorption for simplified medicinal plant processing and its theoretical model: extraction and enrichment of ginsenosides from Radix Ginseng as a case study.

PubMed

Mi, Jianing; Zhang, Min; Zhang, Hongyang; Wang, Yuerong; Wu, Shikun; Hu, Ping

2013-02-01

A high-efficient and environmental-friendly method for the preparation of ginsenosides from Radix Ginseng using the method of coupling of ultrasound-assisted extraction with expanded bed adsorption is described. Based on the optimal extraction conditions screened by surface response methodology, ginsenosides were extracted and adsorbed, then eluted by the two-step elution protocol. The comparison results between the coupling of ultrasound-assisted extraction with expanded bed adsorption method and conventional method showed that the former was better than the latter in both process efficiency and greenness. The process efficiency and energy efficiency of the coupling of ultrasound-assisted extraction with expanded bed adsorption method rapidly increased by 1.4-fold and 18.5-fold of the conventional method, while the environmental cost and CO(2) emission of the conventional method were 12.9-fold and 17.0-fold of the new method. Furthermore, the theoretical model for the extraction of targets was derived. The results revealed that the theoretical model suitably described the process of preparing ginsenosides by the coupling of ultrasound-assisted extraction with expanded bed adsorption system. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

PubMed

Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Basha, Mona; Salama, Abeer

2017-03-01

To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG. Copyright © 2016 Elsevier B.V. All rights reserved.

Heterologous production of a ginsenoside saponin (compound K) and its precursors in transgenic tobacco impairs the vegetative and reproductive growth.

PubMed

Gwak, Yu Shin; Han, Jung Yeon; Adhikari, Prakash Babu; Ahn, Chang Ho; Choi, Yong Eui

2017-06-01

Production of compound K (a ginsenoside saponin) and its precursors in transgenic tobacco resulted in stunted growth and seed set failure, which may be caused by strong autotoxicity of heterologously produced phytochemicals against the tobacco itself. Panax ginseng roots contain various saponins (ginsenosides), which are major bioactive compounds. A monoglucosylated saponin, compound K (20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol), has high medicinal and cosmetic values but is present in undetectable amounts in naturally grown ginseng roots. The production of compound K (CK) requires complicated deglycosylation of ginsenosides using physicochemical and/or enzymatic degradation. In this work, we report the production of CK in transgenic tobacco by co-overexpressing three genes (PgDDS, CYP716A47 and UGT71A28) isolated from P. ginseng. Introduction and expression of the transgenes in tobacco lines were confirmed by genomic PCR and RT-PCR. All the lines of transgenic tobacco produced CK including its precursors, protopanaxadiol and dammarenediol-II (DD). The concentrations of CK in the leaves ranged from 1.55 to 2.64 µg/g dry weight, depending on the transgenic line. Interestingly, production of CK in tobacco brought stunted plant growth and gave rise to seed set failure. This seed set failure was caused by both long-styled flowers and abnormal pollen development in transgenic tobacco. Both CK and DD treatments highly suppressed in vitro germination and tube growth in wild-type pollens. Based on these results, metabolic engineering for CK production in transgenic tobacco was successfully achieved, but the production of CK and its precursors in tobacco severely affects vegetative and reproductive growth due to the cytotoxicity of phytochemicals that are heterologously produced in transgenic tobacco.

Prediction of metastable metal-rare gas fluorides: FMRgF (M=Be and Mg; Rg=Ar, Kr and Xe).

PubMed

Jayasekharan, T; Ghanty, T K

2008-04-14

The structure, stability, charge redistribution, bonding, and harmonic vibrational frequencies of rare gas containing group II-A fluorides with the general formula FMRgF (where M=Be and Mg; Rg=Ar, Kr, and Xe) have been investigated using second order Møller-Plesset perturbation theory, density functional theory, and coupled cluster theory [CCSD(T)] methods. The species, FMRgF show a quasilinear structure at the minima and a bent structure at the transition state. The predicted species are unstable with respect to the two-body dissociation channel, leading to the global minima (MF2+Rg) on the singlet potential energy surface. However, with respect to other two-body dissociation channel (FM+RgF), they are found to be stable and have high positive energies on the same surface. The computed binding energy for the two-body dissociation channels are 94.0, 164.7, and 199.7 kJ mol(-1) for FBeArF, FBeKrF, FBeXeF, respectively, at CCSD(T) method. The corresponding energy values are 83.4, 130.7, and 180.1 kJ mol(-1) for FMgArF, FMgKrF, and FMgXeF, respectively, at the same level of theory. With respect to the three-body dissociation (FM+Rg+F) channel as well as dissociation into atomic constituent, they are also found to be stable and have high positive energies. The dissociation of the predicted species typically proceeds via MRgF bending mode at the transition state. The computed barrier heights for the transition states are 11.4, 32.2, and 57.6 kJ mol(-1) for FBeArF, FBeKrF, and FBeXeF, respectively, at the CCSD(T) method. The corresponding barrier heights for the Mg containing species are 2.1, 9.2, and 32.1 kJ mol(-1) along the series Ar--Kr--Xe, respectively. The M--Rg bond energies of the FMRgF species is significantly higher than the corresponding bond energies of the M+--Rg species ( approximately 53 and approximately 15 kJ mol(-1) for Be+--Ar and Mg+--Ar, respectively). The computed energy diagram as well as the geometrical parameters along with the AIM results

Prediction of metastable metal-rare gas fluorides: FMRgF (M =Be and Mg; Rg =Ar, Kr and Xe)

NASA Astrophysics Data System (ADS)

Jayasekharan, T.; Ghanty, T. K.

2008-04-01

The structure, stability, charge redistribution, bonding, and harmonic vibrational frequencies of rare gas containing group II-A fluorides with the general formula FMRgF (where M =Be and Mg; Rg =Ar, Kr, and Xe) have been investigated using second order Møller-Plesset perturbation theory, density functional theory, and coupled cluster theory [CCSD(T)] methods. The species, FMRgF show a quasilinear structure at the minima and a bent structure at the transition state. The predicted species are unstable with respect to the two-body dissociation channel, leading to the global minima (MF2+Rg) on the singlet potential energy surface. However, with respect to other two-body dissociation channel (FM+RgF), they are found to be stable and have high positive energies on the same surface. The computed binding energy for the two-body dissociation channels are 94.0, 164.7, and 199.7kJmol-1 for FBeArF, FBeKrF, FBeXeF, respectively, at CCSD(T) method. The corresponding energy values are 83.4, 130.7, and 180.1kJmol-1 for FMgArF, FMgKrF, and FMgXeF, respectively, at the same level of theory. With respect to the three-body dissociation (FM+Rg+F) channel as well as dissociation into atomic constituent, they are also found to be stable and have high positive energies. The dissociation of the predicted species typically proceeds via MRgF bending mode at the transition state. The computed barrier heights for the transition states are 11.4, 32.2, and 57.6kJmol-1 for FBeArF, FBeKrF, and FBeXeF, respectively, at the CCSD(T) method. The corresponding barrier heights for the Mg containing species are 2.1, 9.2, and 32.1kJmol-1 along the series Ar KrXe, respectively. The M Rg bond energies of the FMRgF species is significantly higher than the corresponding bond energies of the M+Rg species (˜53 and ˜15kJmol-1 for Be+Ar and Mg+Ar, respectively). The computed energy diagram as well as the geometrical parameters along with the AIM results suggest that the species are metastable

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

PubMed

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

2015-03-01

Ginseng is any one of the eleven species belonging to the genus Panax of the family Araliaceae and is found in North America and in eastern Asia. Ginseng is characterized by the presence of ginsenosides. Principally Panax ginseng and Panax quinquefolius are the adaptogenic herbs and are commonly distributed as health food markets. In the present study high performance liquid chromatography has been used to identify and quantify ginsenosides in the two subject species and the different parts of the plant (roots, neck, leaves, flowers, fruits). The power of this chromatographic technique to evaluate the identity of botanical material and to distinguishing different part of the plants has been investigated with metabolomic technique such as principal component analysis. Metabolomics provide a good opportunity for mining useful chemical information from the chromatographic data set resulting an important tool for quality evaluation of medicinal plants in the authenticity, consistency and efficacy. Copyright © 2015 Elsevier B.V. All rights reserved.

Depth Discrimination Using Rg-to-Sg Spectral Amplitude Ratios for Seismic Events in Utah Recorded at Local Distances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tibi, Rigobert; Koper, Keith D.; Pankow, Kristine L.

Short-period fundamental-mode Rayleigh waves (Rg) are commonly observed on seismograms of anthropogenic seismic events and shallow, naturally occurring tectonic earthquakes (TEs) recorded at local distances. In the Utah region, strong Rg waves traveling with an average group velocity of about 1.8 km/s are observed at ~1 Hz on waveforms from shallow events ( depth<10 km ) recorded at distances up to about 150 km. At these distances, Sg waves, which are direct shear waves traveling in the upper crust, are generally the dominant signals for TEs. Here in this study, we leverage the well-known notion that Rg amplitude decreases dramaticallymore » with increasing event depth to propose a new depth discriminant based on Rg-to-Sg spectral amplitude ratios. The approach is successfully used to discriminate shallow events (both earthquakes and anthropogenic events) from deeper TEs in the Utah region recorded at local distances ( <150 km ) by the University of Utah Seismographic Stations (UUSS) regional seismic network. Using Mood’s median test, we obtained probabilities of nearly zero that the median Rg-to-Sg spectral amplitude ratios are the same between shallow events on the one hand (including both shallow TEs and anthropogenic events), and deeper earthquakes on the other, suggesting that there is a statistically significant difference in the estimated Rg-to-Sg ratios between the two populations. We also observed consistent disparities between the different types of shallow events (e.g., mining blasts vs. mining-induced earthquakes), implying that it may be possible to separate the subpopulations that make up this group. Lastly, this suggests that using local distance Rg-to-Sg spectral amplitude ratios one can not only discriminate shallow events from deeper events but may also be able to discriminate among different populations of shallow events.« less

Ginsenoside-Rp3 inhibits platelet activation and thrombus formation by regulating MAPK and cyclic nucleotide signaling.

PubMed

Irfan, Muhammad; Jeong, Da Hye; Kwon, Hyuk-Woo; Shin, Jung-Hae; Park, Sang-Joon; Kwak, Dongmi; Kim, Tae-Hwan; Lee, Dong-Ha; Park, Hwa-Jin; Rhee, Man Hee

2018-06-08

Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. The in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca 2+ ] i mobilization, granule secretion, integrin α IIb β 3 activation, and clot retraction were assessed in rat platelets. Its effects on vasodilator-stimulated phosphoprotein (VASP) expression, phosphorylation of MAPK signaling molecules, and PI3K/Akt activation were also studied. Moreover, the tyrosine phosphorylation of components of the P 2 Y 12 receptor downstream signaling pathway was also examined. The in vivo effects of G-Rp3 were studied using an acute pulmonary thromboembolism model and lung histopathology. G-Rp3 significantly inhibited collagen, ADP, and thrombin-induced platelet aggregation. G-Rp3 elevated cAMP levels and VASP phosphorylation and suppressed agonist-induced [Ca 2+ ] i mobilization, ATP release, and P-selectin expression along with fibrinogen binding to integrin α IIb β 3 , fibronectin adhesion, and clot retraction. G-Rp3 also attenuated the phosphorylation of MAPK, Src, and PLCγ2 as well as PI3K/Akt activation. Furthermore, it inhibited tyrosine phosphorylation of the Src family kinases (Src, Fyn, and Lyn) and PLCγ2 and protected mice from thrombosis. G-Rp3 modulates agonist-induced platelet activation and thrombus formation by inhibiting granule secretion, integrin α IIb β 3 activation, MAPK signaling, and Src, PLCγ2, and PI3K/Akt activation, and VASP stimulation. Our data suggest that G-Rp3 has therapeutic potential as a treatment for platelet-related cardiovascular disorders. Copyright © 2017. Published by Elsevier Inc.

Yang Baxter and anisotropic sigma and lambda models, cyclic RG and exact S-matrices

NASA Astrophysics Data System (ADS)

Appadu, Calan; Hollowood, Timothy J.; Price, Dafydd; Thompson, Daniel C.

2017-09-01

Integrable deformation of SU(2) sigma and lambda models are considered at the classical and quantum levels. These are the Yang-Baxter and XXZ-type anisotropic deformations. The XXZ type deformations are UV safe in one regime, while in another regime, like the Yang-Baxter deformations, they exhibit cyclic RG behaviour. The associ-ated affine quantum group symmetry, realized classically at the Poisson bracket level, has q a complex phase in the UV safe regime and q real in the cyclic RG regime, where q is an RG invariant. Based on the symmetries and RG flow we propose exact factorizable S-matrices to describe the scattering of states in the lambda models, from which the sigma models follow by taking a limit and non-abelian T-duality. In the cyclic RG regimes, the S-matrices are periodic functions of rapidity, at large rapidity, and in the Yang-Baxter case violate parity.

[Research on quality changes in ginseng stems and leaves before and after frost].

PubMed

Zhao, Yan; Ma, Shuang; Cai, En-Bo; Liu, Shuang-Li; Yang, He; Zhang, Lian-Xue; Wang, Shi-Jie

2014-08-01

The present study is to investigate the quality changes of ginseng stems and leaves before and after frost. The contents changes of ginsenoside, free amino acid, and total phenolic compounds, as well as DPPH radical scavenging effect before and after frost were measured. The content of 9 ginsenoside monomer in ginseng stems was decreased except for Rg, and Re after frost, but in ginseng leaves was all decreased. The total content of amino acids was decreased in ginseng stems after frost, while increased in ginseng leaves. The content of phenolic compounds in ginseng stems and leaves were both decreased after frost while the ability of DPPH radical scavenging was improved. The factor of frost has great impact on the quality of ginseng stems and leaves.

HPLC-based metabolic profiling and quality control of leaves of different Panax species

PubMed Central

Yang, Seung-Ok; Lee, Sang Won; Kim, Young Ock; Sohn, Sang-Hyun; Kim, Young Chang; Hyun, Dong Yoon; Hong, Yoon Pyo; Shin, Yu Su

2013-01-01

Leaves from Panax ginseng Meyer (Korean origin and Chinese origin of Korean ginseng) and P. quinquefolius (American ginseng) were harvested in Haenam province, Korea, and were analyzed to investigate patterns in major metabolites using HPLC-based metabolic profiling. Partial least squares discriminant analysis (PLS-DA) was used to analyze the HPLC chromatogram data. There was a clear separation between Panax species and/or origins from different countries in the PLS-DA score plots. The ginsenoside compounds of Rg1, Re, Rg2, Rb2, Rb3, and Rd in Korean leaves were higher than in Chinese and American ginseng leaves, and the Rb1 level in P. quinquefolius leaves was higher than in P. ginseng (Korean origin or Chinese origin). HPLC chromatogram data coupled with multivariate statistical analysis can be used to profile the metabolite content and undertake quality control of Panax products. PMID:23717177

Near-Source Scattering of Explosion-Generated Rg: Insight From Difference Spectrograms of NTS Explosions

NASA Astrophysics Data System (ADS)

Gupta, I.; Chan, W.; Wagner, R.

2005-12-01

Several recent studies of the generation of low-frequency Lg from explosions indicate that the Lg wavetrain from explosions contains significant contributions from (1) the scattering of explosion-generated Rg into S and (2) direct S waves from the non-spherical spall source associated with a buried explosion. The pronounced spectral nulls observed in Lg spectra of Yucca Flats (NTS) and Semipalatinsk explosions (Patton and Taylor, 1995; Gupta et al., 1997) are related to Rg excitation caused by spall-related block motions in a conical volume over the shot point, which may be approximately represented by a compensated linear vector dipole (CLVD) source (Patton et al., 2005). Frequency-dependent excitation of Rg waves should be imprinted on all scattered P, S and Lg waves. A spectrogram may be considered as a three-dimensional matrix of numbers providing amplitude and frequency information for each point in the time series. We found difference spectrograms, derived from a normal explosion and a closely located over-buried shot recorded at the same common station, to be remarkably useful for an understanding of the origin and spectral contents of various regional phases. This technique allows isolation of source characteristics, essentially free from path and recording site effects, since the overburied shot acts as the empirical Green's function. Application of this methodology to several pairs of closely located explosions shows that the scattering of explosion-generated Rg makes significant contribution to not only Lg and its coda but also to the two other regional phases Pg (presumably by the scattering of Rg into P) and Sn. The scattered energy, identified by the presence of a spectral null at the appropriate frequency, generally appears to be more prominent in the somewhat later-arriving sections of Pg, Sn, and Lg than in the initial part. Difference spectrograms appear to provide a powerful new technique for understanding the mechanism of near-source scattering

Boron-bridged RG-II and calcium are required to maintain the pectin network of the Arabidopsis seed mucilage ultrastructure.

PubMed

Shi, Da-Chuan; Wang, Juan; Hu, Rui-Bo; Zhou, Gong-Ke; O'Neill, Malcolm A; Kong, Ying-Zhen

2017-06-01

The structure of a pectin network requires both calcium (Ca 2+ ) and boron (B). Ca 2+ is involved in crosslinking pectic polysaccharides and arbitrarily induces the formation of an "egg-box" structure among pectin molecules, while B crosslinks rhamnogalacturonan II (RG-II) side chain A apiosyl residues in primary cell walls to generate a borate-dimeric-rhamnogalacturonan II (dRG-II-B) complex through a boron-bridge bond, leading to the formation of a pectin network. Based on recent studies of dRG-II-B structures, a hypothesis has been proposed suggesting that Ca 2+ is a common component of the dRG-II-B complex. However, no in vivo evidence has addressed whether B affects the stability of Ca 2+ crosslinks. Here, we investigated the L-fucose-deficient dwarf mutant mur1, which was previously shown to require exogenous B treatment for phenotypic reversion. Imbibed Arabidopsis thaliana seeds release hydrated polysaccharides to form a halo of seed mucilage covering the seed surface, which consists of a water-soluble outer layer and an adherent inner layer. Our study of mur1 seed mucilage has revealed that the pectin in the outer layer of mucilage was relocated to the inner layer. Nevertheless, the mur1 inner mucilage was more vulnerable to rough shaking or ethylene diamine tetraacetic acid (EDTA) extraction than that of the wild type. Immunolabeling analysis suggested that dRG-II-B was severely decreased in mur1 inner mucilage. Moreover, non-methylesterified homogalacturonan (HG) exhibited obvious reassembly in the mur1 inner layer compared with the wild type, which may imply a possible connection between dRG-II-B deficiency and pectin network transformation in the seed mucilage. As expected, the concentration of B in the mur1 inner mucilage was reduced, whereas the distribution and concentration of Ca 2+ in the inner mucilage increased significantly, which could be the reason why pectin relocates from the outer mucilage to the inner mucilage. Consequently, the

Diversity of cultivable β-glycosidase-producing micro-organisms isolated from the soil of a ginseng field and their ginsenosides-hydrolysing activity.

PubMed

Fu, Y; Yin, Z; Wu, L; Yin, C

2014-02-01

This research aimed to explore the diversity of cultivable β-glycosidase-producing micro-organisms in ginseng field soil. Fifty-three strains showing β-glucosidase activity were isolated from a ginseng field, using a newly designed Esculin-R2A agar. All the isolated strains belonged to the genus Agrobacterium, Arthrobacter, Burkholderia, Dyella, Edaphobacter, Luteibacter, Mucilaginibacter, Paenibacillus, Phenylobacterium, Pseudomonas, Sphingomonas and Streptomyces. The main β-glucosidase-producing micro-organisms in the ginseng field soil were Sphingomonas, Burkholderia, Luteibacter and Streptomyces, while concentrations of Agrobacterium, Arthrobacter, Paenibacillus and Pseudomonas were relatively low. Of these micro-organisms, the strain GS 09 could hydrolyse major ginsenosides Rb1, Rb2 and Rc to the active metabolite compound K. The strain GS 09 belonged to the genus Sphingomonas, and its 16S rRNA gene sequence showed 100% similarities with that of Sphingomonas asaccharolytica. This is the first study to provide information of cultivable β-glycosidase-producing micro-organisms in ginseng field soil. The strain GS 09 has potential to be applied on the preparation for minor ginsenoside C-K in pharmaceutical industry. © 2013 The Society for Applied Microbiology.

[Effect of salicylic acid on photosynthesis, physio-biochemistry and quality of Panax ginseng under full sun shine in spring].

PubMed

Cao, Wu-lin; Meng, Xiang-cai; Ma, Wei

2015-09-01

In order to search for a new pathway to improve the yield of ginseng through growing at the full sun shine accompanied by salicylic acid (SA), the net photosynthetic rate (P(n)), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), malondialdehyde (MDA) in Panax ginseng leaves, and the content of ginsenosides in roots were compared under various concentrations of SA and full sun shine with the traditional shade shed. Under the full sun shine, 0.05, 0.2 mmol x L(-1) SA increased net photosynthetic rate to a great extent. Under the cloudy day, the average net photosynthetic rate increased by 127.8% and 155.0% over the traditional shade shed, 13.9% and 27.5% over the treatment without SA respectively; under the clear day, 23.5% and 30.4% over the traditional shade shed, 8.6% and 14.6% over the treatment without SA, particularly obvious in the morning and late afternoon. With such concentration, SA increased activities of SOD, CAT, POD, and decreased the contents of the MDA. This difference resulted from different light intensity, rise of light saturation point, and fall of compensation point. Full sun shine decreased ginsenosides contents, but with SA, the ginsenosides regained, the content of Rg1 and Re, Rb1, total six types of ginsenosides in SA 0.2 mmol x L(-1) group were higher than those in the control group (P < 0.05) and other groups. The application of 0.2 mmol x L(-1) SA under full sun shine during a short time has little threat to the P. ginseng in spring, and could enhance the resistance to the adversity, which would improve the yield of ginseng heavily.

Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats.

PubMed

Liu, Lei; Hoang-Gia, Trinh; Wu, Hui; Lee, Mi-Ra; Gu, Lijuan; Wang, Chunyan; Yun, Beom-Sik; Wang, Qijun; Ye, Shengquan; Sung, Chang-Keun

2011-03-25

Ginsenoside Rb1 (Rb1) is known to improve learning and memory in hippocampus-dependent tasks. However, the cellular mechanism remains unknown. Cell genesis in hippocampus is involved in spatial learning and memory. In the present study, Rb1 was orally administrated to adult rats for 30days. The behavioral training tests indicated that Rb1 improved spatial cognitive performance of rats in Morris water maze (MWM). Furthermore, we investigated the effects of Rb1 on cell genesis in adult rats' hippocampus, using thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. It has been shown that hippocampal cell genesis can be influenced by several factors such as learning and exercise. In order to avoid the effects of the interfering factors, only the rats treated with Rb1 without training in MWM were used to investigate cell genesis in hippocampus. When BrdU was given to the rats 30days prior to being killed, it was shown that oral administration of Rb1 significantly increased cell survival in dentate gyrus and hippocampal subregion CA3. However, when BrdU was injected 2h prior to sacrifice, the results indicated that Rb1 had no significant influence on cell proliferation in the hippocampal subregions. Thus, an increase of cell survival in hippocampus stimulated by Rb1 may be one of the mechanisms by which ginseng facilitates spatial learning and memory. Our study also indicates that Rb1 may be developed as a therapeutic agent for patients with memory impairment. Copyright © 2011 Elsevier B.V. All rights reserved.

Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats.

PubMed

Shen, Ling; Wang, David Q-H; Lo, Chunmin C; Arnold, Myrtha; Tso, Patrick; Woods, Stephen C; Liu, Min

2015-12-01

Ginsenoside Rb1 (Rb1) reduces food intake in both lean and high-fat diet induced-obese rats; however, the sites and/or mediation of the eating-suppressive effect of Rb1 have not previously been identified. We hypothesized that intraperitoneally (ip) administered Rb1 exerts its anorectic action by enhancing sensitivity to satiation signals, such as cholecystokinin (CCK), and/or that it acts through vagal afferent nerves that relay the satiating signaling to the hindbrain. To test these hypotheses, we gave ip bolus doses of Rb1 (2.5-10.0mg/kg) and CCK-8 (0.125-4.0μg/kg) alone or in combination and assessed food intake in rats. Low doses of Rb1 (2.5mg/kg) or CCK-8 (0.125μg/kg) alone had no effect on food intake whereas higher doses did. When these subthreshold doses of Rb1 and CCK-8 were co-administered, the combination significantly reduced food intake relative to saline controls, and this effect was attenuated by lorglumide, a selective CCK1-receptor antagonist. Interestingly, lorglumide blocked food intake induced by an effective dose of CCK-8 alone, but not by Rb1 alone, suggesting that Rb1's anorectic effect is independent of the CCK1 receptor. To determine whether peripherally administered Rb1 suppresses feeding via abdominal vagal nerves, we evaluated the effect of ip Rb1 injection in subdiaphragmatic vagal deafferentation (SDA) and control rats. Rb1's effect on food intake was significantly attenuated in SDA rats, compared with that in SHAM controls. These data indicate that the vagal afferent system is the major pathway conveying peripherally administered Rb1's satiation signal. Copyright © 2015 Elsevier Inc. All rights reserved.

Time-dependent real space RG on the spin-1/2 XXZ chain

NASA Astrophysics Data System (ADS)

Mason, Peter; Zagoskin, Alexandre; Betouras, Joseph

In order to measure the spread of information in a system of interacting fermions with nearest-neighbour couplings and strong bond disorder, one could utilise a dynamical real space renormalisation group (RG) approach on the spin-1/2 XXZ chain. Under such a procedure, a many-body localised state is established as an infinite randomness fixed point and the entropy scales with time as log(log(t)). One interesting further question that results from such a study is the case when the Hamiltonian explicitly depends on time. Here we answer this question by considering a dynamical renormalisation group treatment on the strongly disordered random spin-1/2 XXZ chain where the couplings are time-dependent and chosen to reflect a (slow) evolution of the governing Hamiltonian. Under the condition that the renormalisation process occurs at fixed time, a set of coupled second order, nonlinear PDE's can be written down in terms of the random distributions of the bonds and fields. Solution of these flow equations at the relevant critical fixed points leads us to establish the dynamics of the flow as we sweep through the quantum critical point of the Hamiltonian. We will present these critical flows as well as discussing the issues of duality, entropy and many-body localisation.

A validated high performance liquid chromatograph-photodiode array method for simultaneous determination of 10 bioactive components in compound hongdoushan capsule

PubMed Central

Zhu, Liancai; Yang, Xian; Tan, Jun; Wang, Bochu; Zhang, Xue

2014-01-01

Background: The compound Hongdoushan capsule (CHC) is widely known as compound herbal preparation and is often used to treat ovarian cancer and breast cancer, and to enhance the body immunity, etc., in clinical practice. Objective: To determine simultaneously 10 bioactive components from CHC, namely glycyrrhetinic acid, liquiritin, glycyrrhizin, baccatin III, 10-deacetylbaccatin III, cephalomannine, taxol, ginsenoside Rg1, ginsenoside Re, and ginsenoside Rb1. Materials and Methods: A high performance liquid chromatograph method coupled with photodiode array detector was developed and validated for the 1st time. Chromatographic analysis was performed on a SHIMADZU C18 by utilizing a gradient elution program. The mobile phase was acetonitrile (A)-water (B) at a flow rate of 0.8 mL/min. Results: The calibration curve was linear over the investigated concentration ranges with the values of r2 higher than 0.9993 for all the 10 bioactive components. The average recovery rates range from 98.4% to 100.5% with relative standard deviations ≤2.9%. The developed method was successfully applied to analyze 10 compounds in six CHC samples from different batches. In addition, the herbal sources of 32 chromatographic peaks were identified through comparative studying on chromatograms of standard, the respective extracts of Hongdoushan, RenShen, GanCao, and CHC. Conclusion: All the results imply that the accurate and reproducible method developed has high separation rate and enables the determination of 10 bioactive components in a single run for the quality control of CHC. PMID:24696551

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

PubMed

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

2015-09-17

Exploration of new natural compounds is of vital significance for drug discovery and development. The conventional approaches by systematic phytochemical isolation are low-efficiency and consume masses of organic solvent. This study presents an integrated strategy that combines offline comprehensive two-dimensional liquid chromatography, hybrid linear ion-trap/Orbitrap mass spectrometry, and NMR analysis (2D LC/LTQ-Orbitrap-MS/NMR), aimed to establish a green protocol for the efficient discovery of new natural molecules. A comprehensive chemical analysis of the total ginsenosides of stems and leaves of Panax ginseng (SLP), a cardiovascular disease medicine, was performed following this strategy. An offline 2D LC system was constructed with an orthogonality of 0.79 and a practical peak capacity of 11,000. The much greener UHPLC separation and LTQ-Orbitrap-MS detection by data-dependent high-energy C-trap dissociation (HCD)/dynamic exclusion were employed for separation and characterization of ginsenosides from thirteen fractionated SLP samples. Consequently, a total of 646 ginsenosides were characterized, and 427 have not been isolated from the genus of Panax L. The ginsenosides identified from SLP exhibited distinct sapogenin diversity and molecular isomerism. NMR analysis was finally employed to verify and offer complementary structural information to MS-oriented characterization. The established 2D LC/LTQ-Orbitrap-MS/NMR approach outperforms the conventional approaches in respect of significantly improved efficiency, much less use of drug materials and organic solvent. The integrated strategy enables a deep investigation on the therapeutic basis of an herbal medicine, and facilitates new compounds discovery in an efficient and environmentally friendly manner as well. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-04-01

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.

Dexamethasone effects on (/sup 125/I)albumin distribution in experimental RG-2 gliomas and adjacent brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakagawa, H.; Groothuis, D.R.; Owens, E.S.

1987-12-01

A total of 72 RG-2 transplanted gliomas were studied in 58 rats at three time points (1, 30, 240 min) after intravenous injection of (/sup 125/I)radioiodinated serum albumin ((/sup 125/I)RISA). The animals were divided into two groups: a control group that received no treatment and a second group that was treated with five doses of 1.5 mg/kg of dexamethasone over 2.5 days. Local tissue concentrations of (/sup 125/I)RISA were measured with quantitative autoradiography based on morphological features of the tumors and used to calculate the tissue distribution space. Two models were used to analyze the data. A two compartment modelmore » yielded estimates of local blood-to-tissue influx constants (K1), lower limit extracellular volumes (Ve), and plasma vascular volumes (Vp) in different tumor regions. Treatment with dexamethasone consistently reduced the RISA distribution space in the RG-2 tumors; the reduction in Ve was statistically significant in almost all tumor regions: whole tumor Ve (mean +/- SE) was reduced from 0.14 +/- 0.02 ml g-1 in control animals to 0.08 +/- 0.01 ml g-1 in dexamethasone treated animals. K1 and Vp were also decreased in all tumor regions after treatment with dexamethasone (whole tumor K1 decreased from 2.36 +/- 0.89 to 0.83 +/- 0.29 microliter g-1 min-1 and Vp decreased slightly from 0.016 +/- 0.013 to 0.010 +/- 0.005 ml g-1 after dexamethasone treatment), but these changes were not statistically significant. A comparison of the tumor influx constants in control animals and the aqueous diffusion constants of two different size molecules (RISA and aminoisobutyric acid) suggests that the ''pores'' across RG-2 capillaries are large and may not restrict the free diffusion of RISA (estimated minimum pore diameter greater than 36 nm) and that the total pore area is approximately 6.2 X 10(-5) cm2 g-1 in RG-2 tumor tissue.« less

Holographic RG flows from Quasi-Topological Gravity

NASA Astrophysics Data System (ADS)

Camara da Silva, U.; Sotkov, G. M.

2013-09-01

We investigate the holographic Renormalization Group (RG) flows and the critical phenomena that take place in the QFT's dual to the d-dimensional cubic Quasi-Topological Gravity coupled to scalar matter. The knowledge of the corresponding flat Domain Walls (DW's) solutions allows us to derive the explicit form of the QFT's β-functions, as well as of the trace anomalies a(l) and c(l), in terms of the matter superpotential. As a consequence we are able to determine the complete set of CFT data characterizing the universality classes of the UV and IR critical points and to follow the particular RG evolution of this data. We further analyse the dependence of the critical properties of such dual QFT's on the values of the Lovelock couplings and on the shape of the superpotential. For odd values of d, the explicit form of the "a and c-central charges" as functions of the running coupling constant, enable us to establish the conditions under which the a&c-Theorems for their decreasing are valid. The restrictions imposed on the massless holographic RG flows by the requirements of the positivity of the energy fluxes are derived. The particular case of quartic Higgs-like superpotential is studied in detail. It provides an example of unitary dual QFT's having few c≠a-critical points representing second or infinite order phase transitions. Depending on the range of the values of the coupling constant they exhibit massive and massless phases, described by a chain of distinct DW's solutions sharing common boundaries. Remember that the definition of the new maximal "h-scale" in the case of negative h<0 is given by fh=L2/(.

Investigation of structural heterogeneity at the SPE site using combined P–wave travel times and Rg phase velocities

DOE PAGES

Rowe, Charlotte A.; Patton, Howard J.

2015-10-01

Here, we present analyses of the 2D seismic structure beneath Source Physics Experiments (SPE) geophone lines that extended radially at 100 m spacing from 100 to 2000 m from the source borehole. With seismic sources at only one end of the geophone lines, standard refraction profiling methods cannot resolve seismic velocity structures unambiguously. In previous work, we demonstrated overall agreement between body-wave refraction modeling and Rg dispersion curves for the least complex of the five lines. A more detailed inspection supports a 2D reinterpretation of the structure. We obtained Rg phase velocity measurements in both the time and frequency domains,more » then used iterative adjustment of the initial 1D body-wave model to predict Rg dispersion curves to fit the observed values. Our method applied to the most topographically severe of the geophone lines is supplemented with a 2D ray-tracing approach, whose application to P-wave arrivals supports the Rg analysis. In addition, midline sources will allow us to refine our characterization in future work.« less

Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng saponins.

PubMed

Tian, Zhihao; Pang, Huanhuan; Zhang, Qiang; Du, Shouying; Lu, Yang; Zhang, Lin; Bai, Jie; Li, Pengyue; Li, Danqi; Zhao, Mengdi; Chen, Xiaonan

2018-02-01

Panax notoginseng saponins, a traditional Chinese medicine extraction, and aspirin are both widely used to treat cerebral infarction in China. Good results in clinical practice have been achieved, when Panax notoginseng saponins was taken together with aspirin. To investigate the interaction of the two drugs in vivo, the concentration of notoginsenoside R 1 , ginsenoside Rg 1 , Rb 1 , Re and Rd. in blood were simultaneously measured by UPLC/MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal standard saikosaponin A standard. The separation of six components was achieved by using an ACQUITY UPLC ®BEH C18 column (1.7μm 2.1×100mm) by gradient elution using water (containing 0.2% formic acid) and acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of 0.2mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. The transport of notoginsenoside R 1 , ginsenoside Rg 1 , Rb 1 , Re and Rd. in MDCK -MDR1 cell monolayer was also used to verify the conclusion of pharmacokinetic drug-drug interaction and study the mechanism of drug interaction. The concentrations of the five components increased in a certain extent when the two drugs administered together in rats. The values of apparent permeability coefficients were significantly increased when the two drugs were used together. Aspirin and salicylic acid could destroy the tight junction protein and open the intercellular space to increase the absorption of Panax notoginseng saponins. Pharmacokinetic drug-drug interaction in vivo existed between Panax notoginseng saponins and aspirin. The drug-drug interaction mainly occurred in the process of absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis

PubMed Central

Liu, Xiu Fen; Xiang, Laiman; Zhou, Qi; Carralot, Jean-Philippe; Prunotto, Marco; Niederfellner, Gerhard; Pastan, Ira

2016-01-01

RG7787 is a mesothelin-targeted immunotoxin designed to have low-immunogenicity, high-cytotoxic activity and fewer side effects. RG7787 kills many types of mesothelin-expressing cancer cells lines and causes tumor regressions in mice. Safety and immunogenicity of RG7787 is now being assessed in a phase I trial. To enhance the antitumor activity of RG7787, we screened for clinically used drugs that can synergize with RG7787. Actinomycin D is a potent transcription inhibitor that is used for treating several cancers. We report here that actinomycin D and RG7787 act synergistically to kill many mesothelin-positive cancer cell lines and produce major regressions of pancreatic and stomach cancer xenografts. Analyses of RNA expression show that RG7787 or actinomycin D alone and together increase levels of TNF/TNFR family members and NF-κB–regulated genes. Western blots revealed the combination changed apoptotic protein levels and enhanced cleavage of Caspases and PARP. PMID:27601652

HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro.

PubMed

Lübberstedt, Marc; Müller-Vieira, Ursula; Mayer, Manuela; Biemel, Klaus M; Knöspel, Fanny; Knobeloch, Daniel; Nüssler, Andreas K; Gerlach, Jörg C; Zeilinger, Katrin

2011-01-01

Primary human hepatocytes are considered as a highly predictive in vitro model for preclinical drug metabolism studies. Due to the limited availability of human liver tissue for cell isolation, there is a need of alternative cell sources for pharmaceutical research. In this study, the metabolic activity and long-term stability of the human hepatoma cell line HepaRG were investigated in comparison to primary human hepatocytes (pHH). Hepatocyte-specific parameters (albumin and urea synthesis, galactose and sorbitol elimination) and the activity of human-relevant cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) were assayed in both groups over a period of 14 days subsequently to a two week culture period in differentiated state in case of the HepaRG cells, and compared with those of cryopreserved hepatocytes in suspension. In addition, the inducibility of CYP enzymes and the intrinsic clearances of eleven reference drugs were determined. The results show overall stable metabolic activity of HepaRG cells over the monitored time period. Higher albumin production and galactose/sorbitol elimination rates were observed compared with pHH, while urea production was not detected. CYP enzyme-dependent drug metabolic capacities were shown to be stable over the cultivation time in HepaRG cells and were comparable or even higher (CYP2C9, CYP2D6, CYP3A4) than in pHH, whereas commercially available hepatocytes showed a different pattern The intrinsic clearance rates of reference drugs and enzyme induction of most CYP enzymes were similar in HepaRG cells and pHH. CYP1A2 activity was highly inducible in HepaRG by β-naphthoflavone. In conclusion, the results from this study indicate that HepaRG cells could provide a suitable alternative to pHH in pharmaceutical research and development for metabolism studies such as CYP induction or sub-chronic to chronic hepatotoxicity studies. Copyright © 2010 Elsevier Inc. All rights reserved.

Further analysis of the structure and immunological activity of an RG-I type pectin from Panax ginseng.

PubMed

Zhang, Xu; Li, Shanshan; Sun, Lin; Ji, Li; Zhu, Jingjing; Fan, Yuying; Tai, Guihua; Zhou, Yifa

2012-06-20

In this paper, we further analysed the structure of a type I rhamnogalacturonan (RG-I) pectin (WGPA-2-RG) fractionated from ginseng polysaccharides. Methylation and periodate oxidation analyses showed that WGPA-2-RG has a backbone consisting of alternating rhamnose (Rha) and galacturonic acid (GalA) residues and side chains consisting of type II arabinogalactan (AG-II). Partial acidic hydrolysis for 6h completely removed arabinose (Ara), partial galactose (Gal), but little GalA and Rha. During partial hydrolysis, the molecular weight of WGPA-2-RG decreased smoothly, suggesting that the Ara and cleavable Gal residues exist on the surface of the molecule, while GalA and Rha residues exist in the core of the molecule. The bioactivity assay showed that the arabinogalactan side chains of WGPA-2-RG are essential structures for stimulating NO secretion and lymphocyte proliferation. However, removal of the Ara and Gal residues through hydrolysis did not appreciably affect the ability of WGPA-2-RG to enhance macrophage phagocytosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antimicrobial activity of saponins produced by two novel endophytic fungi from Panax notoginseng.

PubMed

Jin, Zhaoxia; Gao, Lin; Zhang, Lin; Liu, Tianyi; Yu, Fang; Zhang, Zongshen; Guo, Qiong; Wang, Biying

2017-11-01

Endophytes in plants may be co-producer of the bioactive compounds of their hosts. We conducted a study to bioprospect for saponin-producing endophytic fungi from Panax notoginseng and evaluate the antimicrobial activity of saponins. Two novel fungal endophytes, Fusarium sp. PN8 and Aspergillus sp. PN17, were isolated from traditional Chinese medicinal herb P. notoginseng. After eight days of fermentation, the total saponins produced in the culture broth of PN8 and PN17 were 1.061 and 0.583 mg mL -1 , respectively. The saponin extracts exhibited moderate to high (inhibition zone diameter 15.7-28.4 mm, MIC 1.6-12.5 mg mL -1 ) antimicrobial activity against pathogens tested. Further analysis showed that triterpenoid saponins produced by Fusarium PN8 were Rb 1 , Rd and 20(S)-Rg 3 , while Aspergillus PN17 had the ability to synthesise ginsenoside Re, Rd and 20(S)-Rg 3 . The isolated endophytes may be used as potential sources for microbial production of plant secondary metabolites and for antimicrobial agents.

[Everted intestinal sac method for quick finding absorption ingredients of Wuzhuyu decoction].

PubMed

Gong, Muxin; Wang, Yaxun; Song, Yafang; Wang, Zhimin; Zhang, Qiwei; Wang, Weihao; Zhu, Jingjing

2010-06-01

To establish a method for quick finding the absorption ingredients of Wuzhuyu decoction in order to select the index to control its quality. The absorption of three concentration of Wuzhuyu decotion was investigated with the in vitro-everted intestinal sac model. The intestinal bag fluid of jejunum and ileum were collected in different time and the eight ingredients, which were evodiamine (Ev), rutaecarpine (Ru), limonin (Li), ginsenoside-Rb1, -Rg1, -Re (Rb1, Rg1, Re), isorhamnetin-3-O-beta-D-glucosyl(6''-->1'")-alpha-L-rhamnoside (Irs)and 6-gingerol (6-Gi), were detected by HPLC as the represent constituents in samples. Eight ingredients except Ru in samples could be detected, but Ev could not be detected in high concentration samples. The ratios between absorption ingredients were different from in Wuzhuyu decotion. The in vitro-everted intestinal sac canc absorb the ingredients of Wuzhuyu decotion selectivity. Compare with the ileum, the jejunum can provide the more absorption information and faster, the best test time is 60-90 min.

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

PubMed Central

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

2014-01-01

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

Interferon-γ-Mediated Natural Killer Cell Activation by an Aqueous Panax ginseng Extract

PubMed Central

Takeda, Kazuyoshi; Okumura, Ko

2015-01-01

Panax ginseng extracts are used in traditional herbal medicines, particularly in eastern Asia, but their effect on natural killer (NK) cell activity is not completely understood. This study aimed to examine the effects of P. ginseng extracts on the cytotoxic activity of NK cells. We orally administered P. ginseng extracts or ginsenosides to wild-type (WT) C57BL/6 (B6) and BALB/c mice and to B6 mice deficient in either recombination activating gene 2 (RAG-2) or interferon-γ (IFN-γ). We then tested the cytotoxic activity of NK cells (of spleen and liver mononuclear cells) against NK-sensitive YAC-1 cells. Oral administration of P. ginseng aqueous extract augmented the cytotoxicity of NK cells in WT B6 and BALB/c mice and in RAG-2-deficient B6 mice, but not in IFN-γ-deficient B6 mice. This effect was only observed with the aqueous extract of P. ginseng. Interestingly, the ginsenosides Rb1 and Rg1 did not augment NK cell cytotoxicity. These results demonstrated that the aqueous P. ginseng extract augmented NK cell activation in vivo via an IFN-γ-dependent pathway. PMID:26649061

[Effects of Total Ginsenosides and Volatile Oil of Acorus tatarinowii Co-Administration on Ability of Learning and Memory and Apoptosis in Alzheimer's Disease Mice Model Induced By D-Galactose and Aluminium Chloride].

PubMed

Deng, Min-zhen; Huang, Li-ping; Fang, Yong-qi

2015-05-01

To observe the effects of the co-administration of total ginsenosides and volatile oil of Acorus tatarinowii on the ability of learning and memory and apoptosis in Alzheimer's disease (AD) mice model induced by D-galactose and aluminium chloride. 50 Kunming (KM) mice were randomly divided into normal group, model group, Aricept group (1 mg/kg), Ding Zhi Wan group (10 g/kg) and co-administration of total ginsenosides and volatile oil of Acorus tatarinowii group (co-administered group, the doses of volatile oil of Acorus tatarinowii and total ginsenosides were 30 mg/kg and 150 mg/kg, respectively). In addition to normal group, mice in other groups were given D-galactose 150 mg/ (kg x d), ip, and aluminium chloride 5 mg/kg, ig, once daily for 40 days. At the same time, mice in the treated groups were administrated with the corresponding drug from the 20th day after the modeling, once daily for 40 days. Water maze and avoiding darkness experiments were used to test learning and memory abilities; Aβ1-42 and BCL-2 content in cortex and hippocampus were detected by ELISA; the vitalities of acetyl cholinesterase ( AChE) and acetylcholine transferase (ChAT) were detected by ultraviolet spectrophotometry. Superoxide dismutase (SOD) vitalities were detected by a water-soluble tetrazolium salt (WST-1) method; the content of malondialdehyde ( MDA) in cortex and hippocampus were detected by the thiobarbituric acid (TBA) method; senile plaque on Aβ1-42 precipitation were observed by immunohistochemistry; brain tissues were observed by hematoxylin-eosin staining (HE). As compared with model group, in the co-administered group, the time of AD mice swimming, the numbers of blind area and electric shock reduced significantly (P < 0.05), and the latent period was prolonged (P < 0.05); AChE activity and levels of Aβ1-42 and MDA in cortex and hippocampus were decreased significantly (P < 0.05 or P < 0.01); ChAT and SOD activities as well as BCL-2 content were increased significantly

Effects of American Ginseng on Preimplantation Development and Pregnancy in Mice.

PubMed

Belanger, Danyka; Calder, Michele D; Gianetto-Berruti, Alessandra; Lui, Edmund M; Watson, Andrew J; Feyles, Valter

2016-01-01

In North America, a high proportion of pregnant women use herbal medications including North American ginseng. This medicinal plant contains high amounts of triterpene saponins (ginsenosides), which are the main bioactive compounds. It is important to assess ginseng's impact on all reproductive functions to ensure the safety of pregnant women and fetuses. In this study, we defined the concentration-responsive effects of North American alcoholic and aqueous ginseng extracts on preimplantation development in vitro and on pregnancy and post-partum development in the mouse. Two-cell mouse embryos were cultured with 5 different concentrations of whole ginseng root extracts, or ginsenosides Rb1, Rg1 and Re alone, a combinatorial ginsenoside solution and a crude polysaccharide fraction solution. Embryonic development and recovery from each treatment was assessed. To investigate the in vivo effects of ginseng extracts, female mice were gavaged with 50[Formula: see text]mg/kg/day, 500[Formula: see text]mg/kg/day or 2000[Formula: see text]mg/kg/day of either extract (treatment) or water (sham) for 2 weeks prior to mating and throughout gestation. Gestation period, litter size, pup growth and pup sex ratio were evaluated. Oral ginseng consumption did not significantly affect fertility or pregnancy in the mouse. High doses of ginseng (2000[Formula: see text]mg/kg/day) decreased maternal weight gain. Direct treatment of preimplantation embryos in vitro demonstrated that ALC and AQ extract treatment reduced development in a concentration responsive manner, while only ALC extract effects were largely reversible. Treatments with individual or combinatorial ginsenosides, or the polysaccharide fraction solution alone did not impair preimplantation development, in vitro. In conclusion, maternal oral consumption of ginseng has little negative impact on pregnancy in the mouse, however, direct exposure to ginseng extract during mouse preimplantation development in vitro is detrimental.

The relationship between genetic and chemotypic diversity in American ginseng (Panax quinquefolius L.).

PubMed

Schlag, Erin M; McIntosh, Marla S

2013-09-01

Ginseng is one of the world's most important herbals used as an adaptogen and a cure for an impressively large range of ailments. Differences in the medicinal properties of ginseng roots have been attributed to variation in ginsenoside composition. In this study, the association between genetic and chemotypic profiles of wild and cultivated American ginseng (Panax quinquefolius L.) roots grown in Maryland was investigated. Ginseng roots were classified into chemotypes based on their relative composition of Re and Rg1. Genetic profiles of these roots were determined from the analysis of 38 polymorphic RAPD markers and used for a cluster analysis of genetic similarities. The close correspondence between chemotype and genetic cluster provides the first DNA-based evidence for the genetic basis of ginsenoside composition. Results of this research are significant for plant breeding and conservation, phytochemical research, and clinical and pharmacological studies. Also, the correlation between RAPD markers and chemotype indicates the potential to use RAPD markers as a reliable and practical method for identification and certification of ginseng roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice*

PubMed Central

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D.; Kelley, David E.; Myers, Robert W.; Li, Cai

2016-01-01

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2NI) and R531G (AMPKγ2RG), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2NI or AMPKγ2RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2NI or AMPKγ2RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2NI and AMPKγ2RG, respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2NI or AMPKγ2RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2WT mice, AMPKγ2NI and AMPKγ2RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2RG but not AMPKγ2NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2NI and AMPKγ2RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. PMID:27621313

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice.

PubMed

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D; Kelley, David E; Myers, Robert W; Li, Cai; Guan, Hong-Ping

2016-11-04

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2 NI ) and R531G (AMPKγ2 RG ), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2 NI or AMPKγ2 RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2 NI or AMPKγ2 RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2 NI and AMPKγ2 RG , respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2 NI or AMPKγ2 RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2 WT mice, AMPKγ2 NI and AMPKγ2 RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2 RG but not AMPKγ2 NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2 NI and AMPKγ2 RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2 RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Bioconversion Using Lactic Acid Bacteria: Ginsenosides, GABA, and Phenolic Compounds.

PubMed

Lee, Na-Kyoung; Paik, Hyun-Dong

2017-05-28

Lactic acid bacteria (LAB) are used as fermentation starters in vegetable and dairy products and influence the pH and flavors of foods. For many centuries, LAB have been used to manufacture fermented foods; therefore, they are generally regarded as safe. LAB produce various substances, such as lactic acid, β-glucosidase, and β-galactosidase, making them useful as fermentation starters. Existing functional substances have been assessed as fermentation substrates for better component bioavailability or other functions. Representative materials that were bioconverted using LAB have been reported and include minor ginsenosides, γ-aminobutyric acid, equol, aglycones, bioactive isoflavones, genistein, and daidzein, among others. Fermentation mainly involves polyphenol and polysaccharide substrates and is conducted using bacterial strains such as Streptococcus thermophilus, Lactobacillus plantarum, and Bifidobacterium sp. In this review, we summarize recent studies of bioconversion using LAB and discuss future directions for this field.

Building an Experimental Setup to Characterize an H4RG-15

NASA Astrophysics Data System (ADS)

Hirata, Mickie; Hodapp, K.; Hall, Donald N. B.; Goebel, Sean B.; Jacobson, Shane M.

2018-01-01

The Teledyne Imaging Sensors H4RG-15 infrared detector is designed for the next era of extremely large telescopes. Characterization of individual H4RG-15 detectors are critical for future astronomical use. ULBcam, a former UH88 IR camera and remnant test dewar for H2RG characterization, was previously modified for H4RG-15 characterization. During the summer, this system was further upgraded with a baffle tube to a blackbody illumination source to allow controlled field illumination. This baffle tube, designed in OpenSCAD, was constructed in the IfA machine shop. Specific placements of the 50-micron aperture and scatter restrictive baffling was designed in Zemax. Four separate data sets were acquired to look into detector persistence, dark current, read noise, and charge gain. With the illumination source set at 450 K, ten ramps of 90/90 read frames were taken to pass saturation values. These tests were repeated at 500K to show results at over saturated conditions. Five ramps of 136/136 read frames were taken with a blank shutter applied. The persistence results showed expected results with signals settling from the third ramp. Dark current results showed higher than Teledyne stated values at 0.06 electrons/second, a factor of 6 higher than expected, which exposes systematic ULBcam dark testing capabilities. The read noise resulted with an expected value of 0.014 electrons. The charge gain showed 0.02 electrons/ADU where the expected value is 2 electrons/ADU. Data analysis using reference frame subtraction will be done for future work.

RgIA4 Potently Blocks Mouse α9α10 nAChRs and Provides Long Lasting Protection against Oxaliplatin-Induced Cold Allodynia.

PubMed

Christensen, Sean B; Hone, Arik J; Roux, Isabelle; Kniazeff, Julie; Pin, Jean-Philippe; Upert, Grégory; Servent, Denis; Glowatzki, Elisabeth; McIntosh, J Michael

2017-01-01

Transcripts for α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are found in diverse tissues. The function of α9α10 nAChRs is best known in mechanosensory cochlear hair cells, but elsewhere their roles are less well-understood. α9α10 nAChRs have been implicated as analgesic targets and α-conotoxins that block α9α10 nAChRs produce analgesia. However, some of these peptides show large potency differences between species. Additionally several studies have indicated that these conotoxins may also activate GABA B receptors (GABA B Rs). To further address these issues, we cloned the cDNAs of mouse α9 and α10 nAChR subunits. When heterologously expressed in Xenopus oocytes, the resulting α9α10 nAChRs had the expected pharmacology of being activated by acetylcholine and choline but not by nicotine. A conotoxin analog, RgIA4, potently, and selectively blocked mouse α9α10 nAChRs with low nanomolar affinity indicating that RgIA4 may be effectively used to study murine α9α10 nAChR function. Previous reports indicated that RgIA4 attenuates chemotherapy-induced cold allodynia. Here we demonstrate that RgIA4 analgesic effects following oxaliplatin treatment are sustained for 21 days after last RgIA4 administration indicating that RgIA4 may provide enduring protection against nerve damage. RgIA4 lacks activity at GABA B receptors; a bioluminescence resonance energy transfer assay was used to demonstrate that two other analgesic α-conotoxins, Vc1.1 and AuIB, also do not activate GABA B Rs expressed in HEK cells. Together these findings further support the targeting of α9α10 nAChRs in the treatment of pain.

Ginseng (Panax quinquefolius) Reduces Cell Growth, Lipid Acquisition and Increases Adiponectin Expression in 3T3-L1 Cells

PubMed Central

Yeo, Chia-Rou; Lee, Sea-Ming; Popovich, David G.

2011-01-01

An American ginseng (Panax quinquefolius) extract (GE) that contained a quantifiable amount of ginsenosides was investigated for the potential to inhibit proliferation, affect the cell cycle, influence lipid acquisition and adiponectin expression in 3T3-L1 cells. Six fingerprint ginsenosides were quantified by high performance liquid chromatography and the respective molecular weights were confirmed by LC-ESI-MS analysis. The extract contained Rg1 (347.3 ± 99.7 μg g−1, dry weight), Re (8280.4 ± 792.3 μg g−1), Rb1 (1585.8 ± 86.8 μg g−1), Rc (32.9 ± 8 μg g−1), Rb2 (62.6 ± 10.6 μg g−1) and Rd (90.4 ± 3.2 μg g−1). The GE had a dose-dependent effect on 3T3-L1 cell growth, the LC50 value was determined to be 40.3 ± 5 μg ml−1. Cell cycle analysis showed modest changes in the cell cycle. No significant changes observed in both G1 and G2/M phases, however there was a significant decrease (P < .05) in the S phase after 24 and 48 h treatment. Apoptotic cells were modest but significantly (P < .05) increased after 48 h (3.2 ± 1.0%) compared to untreated control cells (1.5 ± 0.1%). Lipid acquisition was significantly reduced (P < .05) by 13 and 22% when treated at concentrations of 20.2 and 40.3 μg ml−1 compared to untreated control cells. In relation to adiponectin activation, western blot analysis showed that the protein expression was significantly (P < .05) increased at concentrations tested. A quantified GE reduced the growth of 3T3-L1 cells, down-regulated the accumulation of lipid and up-regulated the expression of adiponectin in the 3T3-L1 adipocyte cell model. PMID:21799682

Ginsenoside-Rb1 targets chemotherapy-resistant ovarian cancer stem cells via simultaneous inhibition of Wnt/β-catenin signaling and epithelial-to-mesenchymal transition

PubMed Central

Deng, Shan; Wong, Chris Kong Chu; Lai, Hung-Cheng; Wong, Alice Sze Tsai

2017-01-01

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth. Rb1 and compound K treatment also sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These effects were associated with the Wnt/β-catenin signaling pathway by downregulating β-catenin/T-cell factor-dependent transcription and expression of its target genes ATP-binding cassette G2 and P-glycoprotein. We also identified reversal of epithelial-to-mesenchymal transition as a new player in the Rb1 and compound K-mediated inhibition of CSCs. Rb1 and compound K treatment also inhibited the self-renewal of CSCs derived from ovarian carcinoma patients as well as in xenograft tumor model. Moreover, we did not observe toxicity in response to doses of Rb1 and compound K that produced an anti-CSC effect. Therefore, Rb1 should be explored further as a promising nutraceutical prototype of treating refractory tumors. PMID:27825116

Simultaneous analysis of nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry.

PubMed

Huang, Yang; Zhang, Tingting; Zhao, Yumei; Zhou, Haibo; Tang, Guangyun; Fillet, Marianne; Crommen, Jacques; Jiang, Zhengjin

2017-09-10

Nucleobases, nucleosides and ginsenosides, which have a significant impact on the physiological activity of organisms, are reported to be the active components of ginseng, while they are less present in ginseng extracts. Few analytical methods have been developed so far to simultaneously analyze these three classes of compounds with different polarities present in ginseng extracts. In the present study, a simple and efficient analytical method was successfully developed for the simultaneous separation of 17 nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry (SFC-MS). The effect of various experimental factors on the separation performance, such as the column type, temperature and backpressure, the type of modifier and additive, and the concentration of make-up solvent were systematically investigated. Under the selected conditions, the developed method was successfully applied to the quality evaluation of 14 batches of ginseng extracts from different origins. The results obtained for the different batches indicate that this method could be employed for the quality assessment of ginseng extracts. Copyright © 2017 Elsevier B.V. All rights reserved.

Subacute Oral Toxicity Study of Korean Red Ginseng Extract in Sprague-Dawley Rats

PubMed Central

Park, Sang-Jin; Lim, Kwang-Hyun; Noh, Jeong-Ho; Jeong, Eun Ju; Kim, Yong-Soon; Han, Byung-Cheol; Lee, Seung-Ho

2013-01-01

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day. PMID:24578799

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolosa, Laia

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrialmore » membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.« less

Three-dimensional HepaRG model as an attractive tool for toxicity testing.

PubMed

Leite, Sofia B; Wilk-Zasadna, Iwona; Zaldivar, Jose M; Airola, Elodie; Reis-Fernandes, Marcos A; Mennecozzi, Milena; Guguen-Guillouzo, Christiane; Chesne, Christopher; Guillou, Claude; Alves, Paula M; Coecke, Sandra

2012-11-01

The culture of HepaRG cells as three dimensional (3D) structures in the spinner-bioreactor may represent added value as a hepatic system for toxicological purposes. The use of a cost-effective commercially available bioreactor, which is compatible with high-throughput cell analysis, constitutes an attractive approach for routine use in the drug testing industry. In order to assess specific aspects of the biotransformation capacity of the bioreactor-based HepaRG system, the induction of CYP450 enzymes (i.e., CYP1A2, 2B6, 2C9, and 3A4) and the activity of the phase II enzyme, uridine diphosphate glucuronoltransferase (UGT), were tested. The long-term functionality of the system was demonstrated by 7-week stable profiles of albumin secretion, CYP3A4 induction, and UGT activities. Immunofluorescence-based staining showed formation of tissue-like arrangements including bile canaliculi-like structures and polar distribution of transporters. The use of in silico models to analyze the in vitro data related to hepatotoxic activity of acetaminophen (APAP) demonstrated the advantage of the integration of kinetic and dynamic aspects for a better understanding of the in vitro cell behavior. The bioactivation of APAP and its related cytotoxicity was assessed in a system compatible to high-throughput screening. The approach also proved to be a good strategy to reduce the time necessary to obtain fully differentiated cell cultures. In conclusion, HepaRG cells cultured in 3D spinner-bioreactors are an attractive tool for toxicological studies, showing a liver-like performance and demonstrating a practical applicability for toxicodynamic approaches.

Comparative Proteomics Reveals Novel Components at the Plasma Membrane of Differentiated HepaRG Cells and Different Distribution in Hepatocyte- and Biliary-Like Cells

PubMed Central

Woods, Alisa G.; Lazar, Catalin; Radu, Gabriel L.; Darie, Costel C.; Branza-Nichita, Norica

2013-01-01

Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and eventually death. Despite important progress in deciphering HBV internalization, the early virus-cell interactions leading to infection are not known. HepaRG is a human bipotent liver cell line bearing the unique ability to differentiate towards a mixture of hepatocyte- and biliary-like cells. In addition to expressing metabolic functions normally found in liver, differentiated HepaRG cells support HBV infection in vitro, thus resembling cultured primary hepatocytes more than other hepatoma cells. Therefore, extensive characterization of the plasma membrane proteome from HepaRG cells would allow the identification of new cellular factors potentially involved in infection. Here we analyzed the plasma membranes of non-differentiated and differentiated HepaRG cells using nanoliquid chromatography-tandem mass spectrometry to identify the differences between the proteomes and the changes that lead to differentiation of these cells. We followed up on differentially-regulated proteins in hepatocytes- and biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1, PDI and PDI A4/ERp72. Major differences between the two proteomes were found, including differentially regulated proteins, protein-protein interactions and intracellular localizations following differentiation. The results advance our current understanding of HepaRG differentiation and the unique properties of these cells. PMID:23977166

Comparative proteomics reveals novel components at the plasma membrane of differentiated HepaRG cells and different distribution in hepatocyte- and biliary-like cells.

PubMed

Petrareanu, Catalina; Macovei, Alina; Sokolowska, Izabela; Woods, Alisa G; Lazar, Catalin; Radu, Gabriel L; Darie, Costel C; Branza-Nichita, Norica

2013-01-01

Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and eventually death. Despite important progress in deciphering HBV internalization, the early virus-cell interactions leading to infection are not known. HepaRG is a human bipotent liver cell line bearing the unique ability to differentiate towards a mixture of hepatocyte- and biliary-like cells. In addition to expressing metabolic functions normally found in liver, differentiated HepaRG cells support HBV infection in vitro, thus resembling cultured primary hepatocytes more than other hepatoma cells. Therefore, extensive characterization of the plasma membrane proteome from HepaRG cells would allow the identification of new cellular factors potentially involved in infection. Here we analyzed the plasma membranes of non-differentiated and differentiated HepaRG cells using nanoliquid chromatography-tandem mass spectrometry to identify the differences between the proteomes and the changes that lead to differentiation of these cells. We followed up on differentially-regulated proteins in hepatocytes- and biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1, PDI and PDI A4/ERp72. Major differences between the two proteomes were found, including differentially regulated proteins, protein-protein interactions and intracellular localizations following differentiation. The results advance our current understanding of HepaRG differentiation and the unique properties of these cells.

Chemical constituents of Panax ginseng exposed to. gamma. irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Joongho; Belanger, J.M.R.; Sigouin, M.

1990-03-01

Chemical constituents were monitored to assess the biochemical and nutritional safety of Panax ginseng powders that were irradiated at doses of 1-10 kGy. Quantitative analysis has shown that the main effective components - saponins - are not altered by {sup 60}Co {gamma} irradiation. Ginsenoside-Rg{sub 1} was not affected by the treatment. Negligible changes were observed in the free carbohydrate contents. Doses of more than 5 kGy caused significant decreases in sulfur-containing amino acids and in tyrosine. At doses of 10 kGy, free amino acids, such as proline and lysine, showed an appreciable increase. The composition in minerals was not alteredmore » irrespective of the applied doses.« less

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

PubMed

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

2013-03-01

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

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

PubMed Central

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

2013-01-01

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

Shallow Refraction and Rg Analysis at the Source Physics Experiment Site

NASA Astrophysics Data System (ADS)

Rowe, C. A.; Carmichael, J. D.; Patton, H. J.; Snelson, C. M.; Coblentz, D. D.; Larmat, C. S.; Yang, X.

2014-12-01

We present analyses of the two-dimensional (2D) seismic structure beneath Source Physics Experiments (SPE) geophone lines that extended 100 to 2000 m from the source borehole with 100 m spacing. With seismic sources provided only at one end of the geophone lines, standard refraction profiling methods are unable to resolve the seismic velocity structures unambiguously. In previous work we have shown overall agreement between body-wave refraction modeling and Rg dispersion curves for the least complex of the five lines, Line 2, leading us to offer a simplified1D model for this line. A more detailed inspection of Line 2 supports a 2D re-interpretation of the structure on this line. We observe variation along the length of the line, as evidenced by abrupt and consistent changes in the behavior of surface waves at higher frequencies. We interpret this as a manifestation of significant material or structural heterogeneity in the shallowest strata. This interpretation is consistent with P-wave and Rg attenuation observations. Planned additional sources, both at the distal ends of the profiles and intermittently within their lengths, will provide significant enhancement to our ability to resolve this complicated shallow structure.

Reliability Generalization (RG) Analysis: The Test Is Not Reliable

ERIC Educational Resources Information Center

Warne, Russell

2008-01-01

Literature shows that most researchers are unaware of some of the characteristics of reliability. This paper clarifies some misconceptions by describing the procedures, benefits, and limitations of reliability generalization while using it to illustrate the nature of score reliability. Reliability generalization (RG) is a meta-analytic method…

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

PubMed

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

2014-10-05

The aim of this study is to explore the potential enhancing effect of ginsenoside 20(S)-Rh2 (Rh2) towards ciprofloxacin (CIP) against Staphylococcus aureus (S. aureus) infection in vitro and in vivo, and analyze the possible mechanisms through NorA inhibition from a target cellular pharmacokinetic view. In combination with non-toxic dosage of Rh2, the susceptibilities of S. aureus strains to CIP were significantly augmented, and the antibacterial kinetics of CIP in the S. aureus strains were markedly promoted. This enhancing effect of Rh2 towards CIP was also observed in S. aureus infected peritonitis mice, with elevated survival rate and reduced bacteria counts in blood. However, Rh2 did not influence the plasma concentrations of CIP. Further analysis indicated that Rh2 significantly promoted the accumulations of CIP in S. aureus, and inhibited the NorA mediated efflux of pyronin Y. The expressions of NorA gene on S. aureus were positively correlated with the enhancing effect of Rh2 with CIP. This is the first report of the enhancing effect of Rh2 with CIP for S. aureus infection in vitro and in vivo, of which it is probably that Rh2 inhibited NorA-mediated efflux and promoted the accumulation of CIP in the bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of a new eastern blotting technique for the analysis of ginsenoside Re in American ginseng berry pulp extracts.

PubMed

Morinaga, Osamu; Uto, Takuhiro; Yuan, Chun-Su; Tanaka, Hiroyuki; Shoyama, Yukihiro

2010-06-01

A new eastern blotting technique has been established for ginsenoside Re (G-Re) contained in American ginseng berry pulp extracts. G-Re in American ginseng berry pulp was extracted using 100% methanol, 100% ethanol, 50% aqueous methanol, and 50% aqueous ethanol. The combined crude extracts were applied onto a polyethersulfone membrane and developed using the methanol-water-acetic acid solvent system (45:55:1 v/v). Separated components were immunostained using anti-G-Re monoclonal antibody. G-Re was first specifically detected and then quantitatively analyzed using NIH Imaging software. We also confirmed that the most suitable solvent was 50% aqueous methanol for extracting G-Re from American ginseng berry pulp. (c) 2009 Elsevier B.V. All rights reserved.

HPLC determination of four active saponins from Panax notoginseng in rat serum and its application to pharmacokinetic studies.

PubMed

Li, Lie; Sheng, Yuxin; Zhang, Jinlan; Wang, Chuanshe; Guo, Dean

2004-12-01

Four main active saponins (ginsenosides Rg1, Rb1, Rd and notoginsenoside R1) in Panax notoginseng in rat serum after oral and intravenous administration of total saponins of P. notoginseng (PNS) to rats were determined using a simple and sensitive high-performance chromatographic method. The serum samples were pretreated with solid-phase extraction before analysis. The calibration curves for the four saponins were linear in the given concentration ranges. The intra-day and inter-day assay coefficients in serum were less than 10.0% and the recoveries of the method were higher than 80.0% in the high, middle and low concentrations. This method was applied to study the pharmacokinetics following oral and intravenous administration of PNS. Copyright 2004 John Wiley & Sons, Ltd.

Rigorous RG Algorithms and Area Laws for Low Energy Eigenstates in 1D

NASA Astrophysics Data System (ADS)

Arad, Itai; Landau, Zeph; Vazirani, Umesh; Vidick, Thomas

2017-11-01

One of the central challenges in the study of quantum many-body systems is the complexity of simulating them on a classical computer. A recent advance (Landau et al. in Nat Phys, 2015) gave a polynomial time algorithm to compute a succinct classical description for unique ground states of gapped 1D quantum systems. Despite this progress many questions remained unsolved, including whether there exist efficient algorithms when the ground space is degenerate (and of polynomial dimension in the system size), or for the polynomially many lowest energy states, or even whether such states admit succinct classical descriptions or area laws. In this paper we give a new algorithm, based on a rigorously justified RG type transformation, for finding low energy states for 1D Hamiltonians acting on a chain of n particles. In the process we resolve some of the aforementioned open questions, including giving a polynomial time algorithm for poly( n) degenerate ground spaces and an n O(log n) algorithm for the poly( n) lowest energy states (under a mild density condition). For these classes of systems the existence of a succinct classical description and area laws were not rigorously proved before this work. The algorithms are natural and efficient, and for the case of finding unique ground states for frustration-free Hamiltonians the running time is {\\tilde{O}(nM(n))} , where M( n) is the time required to multiply two n × n matrices.

Investigations of the Rg-BrCl (Rg = He, Ne, Ar, Kr, Xe) binary van der Waals complexes: ab initio intermolecular potential energy surfaces, vibrational states and predicted pure rotational transition frequencies

NASA Astrophysics Data System (ADS)

Li, Song; Zheng, Rui; Chen, Shan-Jun; Chen, Yan; Chen, Peng

2017-03-01

The intermolecular potential energy surfaces (PESs) of the ground electronic state for the Rg-BrCl (Rg = He, Ne, Ar, Kr, Xe) van der Waals complexes have been constructed by using the coupled-cluster method in combination with the augmented quadruple-zeta correlation-consistent basis sets supplemented with an additional set of bond functions. The features of the anisotropic PESs for these complexes are remarkably similar, which are characterized by three minima and two saddle points between them. The global minimum corresponds to a collinear Rg-Br-Cl configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry and a nearly T-shaped structure, can also be located on each PES. The quantum bound state calculations enable us to investigate intermolecular vibrational states and rotational energy levels of the complexes. The transition frequencies are predicted and are fitted to obtain their corresponding spectroscopic constants. In general, the periodic trends are observed for this complex family. Comparisons with available experimental data for the collinear isomer of Ar-BrCl demonstrate reliability of our theoretical predictions, and our results for the other two isomers of Ar-BrCl as well as for other members of the complex family are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl, the data presented in this paper would be beneficial to improve our knowledge for these experimentally unknown species.

Investigations of the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) binary van der Waals complexes: ab initio intermolecular potential energy surfaces, vibrational states and predicted pure rotational transition frequencies.

PubMed

Li, Song; Zheng, Rui; Chen, Shan-Jun; Chen, Yan; Chen, Peng

2017-03-05

The intermolecular potential energy surfaces (PESs) of the ground electronic state for the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) van der Waals complexes have been constructed by using the coupled-cluster method in combination with the augmented quadruple-zeta correlation-consistent basis sets supplemented with an additional set of bond functions. The features of the anisotropic PESs for these complexes are remarkably similar, which are characterized by three minima and two saddle points between them. The global minimum corresponds to a collinear Rg-Br-Cl configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry and a nearly T-shaped structure, can also be located on each PES. The quantum bound state calculations enable us to investigate intermolecular vibrational states and rotational energy levels of the complexes. The transition frequencies are predicted and are fitted to obtain their corresponding spectroscopic constants. In general, the periodic trends are observed for this complex family. Comparisons with available experimental data for the collinear isomer of Ar-BrCl demonstrate reliability of our theoretical predictions, and our results for the other two isomers of Ar-BrCl as well as for other members of the complex family are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl, the data presented in this paper would be beneficial to improve our knowledge for these experimentally unknown species. Copyright © 2016 Elsevier B.V. All rights reserved.

Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients

PubMed Central

Ishida, Julie H.; Patel, Anita; Mehta, Aneesh K.; Gatault, Philippe; McBride, Jacqueline M.; Burgess, Tracy; Derby, Michael A.; Snydman, David R.; Emu, Brinda; Feierbach, Becket; Fouts, Ashley E.; Maia, Mauricio; Deng, Rong; Rosenberger, Carrie M.; Gennaro, Lynn A.; Striano, Natalee S.; Liao, X. Charlene

2016-01-01

ABSTRACT Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, a combination of two monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant recipients in a randomized, double-blind, placebo-controlled trial. CMV-seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R−) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had seroconverted (D+R+) or withdrawn before dosing were excluded from the analysis (n = 4). CMV viremia occurred in 27 of 59 (45.8%) patients receiving RG7667 and 35 of 57 (61.4%) patients receiving placebo (stratum-adjusted difference, 15.3%; P = 0.100) within 12 weeks posttransplant and in 30 of 59 (50.8%) patients receiving RG7667 and 40 of 57 (70.2%) patients receiving placebo (stratum-adjusted difference, 19.3%; P = 0.040) within 24 weeks posttransplant. Median time to CMV viremia was 139 days in patients receiving RG7667 compared to 46 days in patients receiving placebo (hazard ratio, 0.53; P = 0.009). CMV disease was less common in the RG7667 than placebo group (3.4% versus 15.8%; P = 0.030). Adverse events were generally balanced between treatment groups. In high-risk kidney transplant recipients, RG7667 was well tolerated, numerically reduced the incidence of CMV infection within 12 and 24 weeks posttransplant, delayed time to CMV viremia, and was associated with less CMV disease than the placebo. (This study has been registered at ClinicalTrials.gov under registration no. NCT01753167.) PMID:27872061

Successful rotational atherectomy over RG3 guidewire after failure of various techniques to deliver RotaWire.

PubMed

Kaneko, Umihiko; Kashima, Yoshifumi; Kanno, Daitaro; Sugie, Takuro; Kobayashi, Ken; Fujita, Tsutomu

2017-10-01

Although performing rotational atherectomy (RA) requires guidewire exchange for the dedicated guidewire, RotaWire guidewire (Boston Scientific) exhibits much lower performance than conventional guidewire. Consequently, there are times when RotaWire cannot be advanced past the lesion independently or using a microcatheter exchange technique, rendering RA impossible. We present a case of a heavily calcified, device-uncrossable, and non-expansible chronic total occlusion lesion successfully revascularized with RA over RG3 guidewire (Asahi Intecc), which has a length of 330 cm, hydrophilic coating, and a 0.010-inch-long shaft. RG3 provided excellent cross-ability and RA could also be performed over RG3 without guidewire exchange for the RotaWire.

Characterization of Korean Red Ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition

PubMed Central

Lee, Sang Myung; Bae, Bong-Seok; Park, Hee-Weon; Ahn, Nam-Geun; Cho, Byung-Gu; Cho, Yong-Lae; Kwak, Yi-Seong

2015-01-01

It has been reported that Korean Red Ginseng has been manufactured for 1,123 y as described in the GoRyeoDoGyeong record. The Korean Red Ginseng manufactured by the traditional preparation method has its own chemical component characteristics. The ginsenoside content of the red ginseng is shown as Rg1: 3.3 mg/g, Re: 2.0 mg/g, Rb1: 5.8 mg/g, Rc:1.7 mg/g, Rb2: 2.3 mg/g, and Rd: 0.4 mg/g, respectively. It is known that Korean ginseng generally consists of the main root and the lateral or fine roots at a ratio of about 75:25. Therefore, the red ginseng extract is prepared by using this same ratio of the main root and lateral or fine roots and processed by the historical traditional medicine prescription. The red ginseng extract is prepared through a water extraction (90°C for 14–16 h) and concentration process (until its final concentration is 70–73 Brix at 50–60°C). The ginsenoside contents of the red ginseng extract are shown as Rg1: 1.3 mg/g, Re: 1.3 mg/g, Rb1: 6.4 mg/g, Rc:2.5 mg/g, Rb2: 2.3 mg/g, and Rd: 0.9 mg/g, respectively. Arginine-fructose-glucose (AFG) is a specific amino-sugar that can be produced by chemical reaction of the process when the fresh ginseng is converted to red ginseng. The content of AFG is 1.0–1.5% in red ginseng. Acidic polysaccharide, which has been known as an immune activator, is at levels of 4.5–7.5% in red ginseng. Therefore, we recommended that the chemical profiles of Korean Red Ginseng made through the defined traditional method should be well preserved and it has had its own chemical characteristics since its traditional development. PMID:26869832