• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.12
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• pp.298-305
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• 2019

Cudrania tricuspidata has been reported to have many biological activities, including anti-inflammatory, anti-cancer, and antioxidant properties. However, the effects of C. tricuspidata root extract (CTE) on human platelet aggregation induced by collagen as well as the signaling pathways involved remain unknown. In the present study, we investigated the effect of CTE on human platelets. CTE inhibited platelet aggregation via down-regulation of thromboxane A₂ (TXA₂) by blocking cyclooxygenase-1 (COX-1) activity and intracellular Ca²⁺ mobilization in collagen-induced platelets. CTE also reduced the phosphorylation of phospholipase C (PLC) γ2 and syk. CTE regulated platelet aggregation via cyclic guanosine monophosphate (cGMP)-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) Ser²³⁹. In addition, administration of CTE (50 and 100 mg/kg) significantly reduced hyper-aggregated platelet aggregation by collagen (5 ㎍/mL) without hepatotoxicity in HFD (high fat diet)-fed rats. Taken together, these results suggest that CTE has anti-platelet effects both in vitro and in vivo. Therefore, CTE may be an effective therapeutic and preventive agent for cardiovascular disease, and is a safe and natural product.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.236-243
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• 2023

Platelets act a fundamental role in primary- and secondary-hemostasis, however, platelet activation may cause thrombosis simultaneously. Therefore, control of platelet aggregation is crucial in preventing thrombosis-mediated diseases. Recently, the development of insect materials is attracting attention. Among the highly nutritious functional food sources, insects such as two-spotted cricket (Gryllus bimaculatus). Gryllus bimaculatus (G. bimaculatus) contains high protein and unsaturated fatty acids and has been registered as a food material September 2015 by the Ministry of Food and Drug Safety of Korea. In this study, we examined whether G. bimaculatus extract (GBE) inhibits platelet aggregation, intracellular calcium mobilization, thromboxane A₂ production and glycoprotein IIb/IIIa (integrin αIIb/β3) activation. We investigated whether GBE can regulate signaling molecules, such as 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A₂, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β, and SYK. Taken together, GBE is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.186-186
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• 1994

Many agonists have been known to activate the hydrolysis of membrane phospholipids through the bindings with corresponding receptors on the various cells. Diacylglycerol and inositol 1,4,5-trisphosphate(IP3) generated by the action of phosphoinositide-specific phospholipase C (PI-PLC) are well known second messengers for the activation of protein kinase C and the mobilization of Ca2+ in many cells. Three types of PI-PLC isozyme (${\alpha}$,${\gamma}$, and $\delta$) and several subtrpes for each type have been identified from mammalian sources by purification of enzymes and cloning of their cDNAs. Each type PI-PLC isozyme is coupled to different receptors and mediators, for example, ${\beta}$-types are coupled to the seven-transmembrane-receptors via Gq family of G-proteins and ${\beta}$-types directly to the receptor tyrosine kinases. Specific modulators for the signaling pathway through each type of PI-PLC should be very useful as potential potential candidates for lend substances in developing novel drugs. To establish the sensitive and convenient screening systems for searching modulators on PI-PLC mediated signaling, two kinds of approaches have been tried. (1) Establishment of in vitro assay condition for each type of PI-PLC isozyme: Overexpression by using vaccinia virus and purification of each isozyme was carried out for the preparation of large amounts of enaymes. Optimum and sensitive assay condition for the measurements of PI-ELC activities were established. (2) Development of the cell lines in which each type of PI-PLC is permanently overexpressed: A fibroblast cell line (3T3${\gamma}$1-7) in which PI-PLC-${\gamma}$1 was overexpressed by using pZip-neo expression vector was developed and used for the measurement of PDGF-induced IP3 formation. The responses for IP3 formed in 3T3${\gamma}$1-7 cells by the treatment of PDGF is 8 times more sensitive than those in control cells. 3T3${\gamma}$l-7 cell is useful for the screening of the inhibitors on the PDGF-induced cellular responses from large number of samples in a small volume(50 ${\mu}$l) and short time(5-15 min). Using these systems, we screened hundreds of herb-extracts for the inhibition of PDGF-induced IP3 formation and selected several extracts that showed the inhibition as the candidates for isolation and characterization of active substances. The determination of the acting point of selected extracts or fractions in the PDGF signaling pathway has been analyzing.

• Journal of Soil and Groundwater Environment
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• v.9 no.4
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• pp.15-23
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• 2004

Deicer operations provide traffic safety during winter driving conditions in urban areas. Using large quantities of de-icing chemicals (i.e., $CaCl_2$ and NaCl) can cause serious environmental problems and may change behaviors of heavy metals in roadside sediments, resulting in an increase in mobilization of heavy metals due to complexation of heavy metals with chloride ions. To examine effect of de-icing salt concentration on the leaching behaviors and mobility of heavy metals (cadmium, zinc, copper, lead, arsenic, nickel, chromium, cobalt, manganese, and iron), leaching experiments were conducted on roadside sediments collected from Seoul city using de-icing salt solutions having various concentrations (0.01-5.0M). Results indicate that zinc, copper, and manganese in roadside sediments were easily mobilized, whereas chromium and cobalt remain strongly fixed. The zinc, copper and manganese concentrations measured in the leaching experiments were relatively high. De-icing salts can cause a decrease in partitioning between adsorbed (or precipitated) and dissolved metals, resulting in an increase in concentrations of dissolved metals in salt laden snowmelt. As a result, run-off water quality can be degraded. The de-icing salt applied on the road surface also lead to infiltration and contamination of heavy metal to groundwater.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.63 no.4
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• pp.390-398
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• 2018

Miscanthus is a perennial energy plant that reproduces via rhizomes and has C4 metabolism. The flowering pattern of a wild type M. sacchariflorus (WTM) is affected by environmental conditions such as photoperiod and soil water status. Geodae-Uksae 1 (Geodea), which is a new M. sacchariflorus cultivar, has a lower heading rate than WMS; however the mechanism with why this happens is unknown. To confirm the effects of drought or waterlogging stresses on the growth of WTM and Geodea at the reproductive stage, we investigated variations in morphological characteristics and nutrient contents of the two Miscanthus species after four months of three water treatments. Morphological traits of the two Miscanthus species under the drought condition were similar to those under the control condition. But, the height of Geodea increased by 30% in response to the waterlogging stress. In WTM, the heading rate under the drought condition was lowest, while there was no significant difference between the waterlogging and control conditions. In the two Miscanthus species, nutrient contents, such as sucrose, total N, $P_2O_5$, K and Mg, were the highest under the drought condition, wherea Ca and Mg contents under the waterlogging condition were more than three times lower than those under the drought condition. The current study results showed that drought stress accelerated senescence and then inhibited nutrient mobilization in WTM, while waterlogging stress promoted the growth. This study is the first report to confirm that waterlogging stress promotes flowering of M. sacchariflorus.

• Journal of Ginseng Research
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• v.40 no.1
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• pp.76-85
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• 2016

Background: Binding of adhesive proteins (i.e., fibrinogen, fibronectin, vitronectin) to platelet integrin glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) by various agonists (thrombin, collagen, adenosine diphosphate) involve in strength of thrombus. This study was carried out to evaluate the antiplatelet effect of total saponin from Korean Red Ginseng (KRG-TS) by investigating whether KRG-TS inhibits thrombin-induced binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$. Methods: We investigated the effect of KRG-TS on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and dephosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, affecting binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$, and clot retraction. Results: KRG-TS had an antiplatelet effect by inhibiting the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via phosphorylation of VASP ($Ser^{157}$), and dephosphorylation of PI3K and Akt on thrombin-induced platelet aggregation. Moreover, A-kinase inhibitor Rp-8-Br-cyclic adenosine monophosphates (cAMPs) reduced KRG-TS-increased VASP ($Ser^{157}$) phosphorylation, and increased KRG-TS-inhibited fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$. These findings indicate that KRG-TS interferes with the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via cAMP-dependent phosphorylation of VASP ($Ser^{157}$). In addition, KRG-TS decreased the rate of clot retraction, reflecting inhibition of ${\alpha}IIb/{\beta}3$ activation. In this study, we clarified ginsenoside Ro (G-Ro) in KRG-TS inhibited thrombin-induced platelet aggregation via both inhibition of $[Ca^{2+}]_i$ mobilization and increase of cAMP production. Conclusion: These results strongly indicate that KRG-TS is a beneficial herbal substance inhibiting fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$, and clot retraction, and may prevent platelet ${\alpha}IIb/{\beta}3$-mediated thrombotic disease. In addition, we demonstrate that G-Ro is a novel compound with antiplatelet characteristics of KRG-TS.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Horticultural Science & Technology
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• v.31 no.6
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• pp.706-713
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• 2013

With pot-grown 4-year-old 'Fuyu' persimmon trees, this study evaluated the effect of different nitrogen (N) rates during summer on fruit characteristics, changes of leaf nutrients after harvest, reserve accumulation, and early growth the following year. A total of 0, 36 g N in June, and 72 g N in June and July was fertigated to each tree using urea solution. All the fruits were harvested on Nov. 3. Although not significant, fruits were larger for the 36 g and 72 g N than the 0 g N. Fruits for the 0 g N, having lower N concentration, were softer and had a better coloration and higher soluble solids, indicating that they matured earlier. SPAD value on Nov. 3 was 19.2 for the 0 g N and 54.9 for the 72 g N, and then the values linearly decreased in all the treatments by Nov. 14, exhibiting rapid leaf senescence. Specific leaf weight, being the lowest for the 0 g N, also gradually decreased during this period. Increasing N level significantly increased cross-sectional area of the trunk. Leaf N concentration on Nov. 3 was 0.87% for the 0 g N, whereas it was 1.18 and 1.52% for the 36 g and 72 g N, respectively. The N fertigation tended to increase leaf concentrations of soluble sugars, starch, and amino acids. Contents of N, P, K, soluble sugars, starch, and amino acids per unit leaf area gradually decreased in all the treatments during the 11 days after harvest, and the extent of the decrease was the lowest for the 0 g N. On the other hand, those of Ca, Mg, and protein did not consistently change during this period. The N fertigation resulted in higher concentrations of N in dormant shoots on Nov. 14, and although not great, it also increased soluble sugars, starch, amino acids, and protein. Clear differences were found in number of flower buds per one-year-old branch and total shoot length per tree the following year. The 72 g N trees had 5.6-fold more flower buds and 1.9-fold more shoot length, compared with those of 0 g N trees. However, it was noted that tree growth the following year was not significantly different between the 36 g and 72 g N the previous year. It was concluded that N rate during summer should be adjusted with considering the changes of fruit maturation, mobilization of leaf nutrients, and reserve accumulation.