• Journal of Ginseng Research
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• 제19권3호
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• pp.219-224
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• 1995

The modulatory effects of total ginseng saponin (TGS) on the 1, 6, and opioid receptor binding in morphine tolerance and dependence were examined in this study. The specific [$^{3}H$]DAGO ([D-$Ala^2$, N-$Mephe^4$, $Glyco^4$] enkephalin) binding was significantly increased in chronic morphine (10 mg/kg, i.p.) treated mouse striatum. The specific [$^{3}H$]DPDPE ([D-$Pen^2$, D-$Pen^5$] enkephalin) binding was ignificantly increased following morphine treatment in the mouse striatum and cortex. Also, an apparent decrease in the affinity of [$^{3}H$]DPN (diprenorphine) was observed after chronic morphine treatment in mouse striatum and cortex. 7GS produced a sleight increase of specific [$^{3}H$]DAGO, [$^{3}H$]DPDPE binding and a significant increase of specific [$^{3}H$]DPN binding in the mouse brain striatum. In cortex, TGS produced an inhibition of specific [$^{3}H$]DAGO and [$^{3}H$]DPDPE binding and increase of the specific [$^{3}H$]DPN binding. The prolonged administration of TGS (25, 50, 100, and 150 mg/kg, i.p., 3 wks) produced an inhibition of increased [$^{3}H$]DAGO specific binding following morphine without significant changes in the agonist binding to and receptors in mouse striatum and cortex. These contracted alterations in $\mu$, $\gamma$ and $\kappa$ opiate receptor binding were dependent in TGS dogs and brain sites.

• Journal of Ginseng Research
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• 제35권2호
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• pp.219-225
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• 2011

Korean red ginseng (KRG) is a valuable and important traditional medicine in East Asian countries and is currently used extensively for botanical products in the world. KRG has both stimulatory and inhibitory effects on the central nervous system (CNS) suggesting its complicated action mechanisms. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Some studies reported that KRG has antinociceptive effects, but there are few reports of the functional studies of KRG on the SG neurons of the Vc. In this study, a whole cell patch clamp study was performed to examine the action mechanism of a KRG extract on the SG neurons of the Vc from juvenile mice. KRG induced short-lived and repeatable inward currents on all the SG neurons tested in the high chloride pipette solution. The KRG-induced inward currents were concentration dependent and were maintained in the presence of tetrodotoxin, a voltage gated $Na^+$ channel blocker. The KRG-induced inward currents were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and/or picrotoxin, a gamma-aminobutyric acid $(GABA)_A$ receptor antagonist. However, the inward currents were not suppressed by d,l-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. These results show that KRG has excitatory effects on the SG neurons of the Vc via the activation of non-NMDA glutamate receptor as well as an inhibitory effect by activation of the $GABA_A$ receptor, indicating the KRG has both stimulatory and inhibitory effects on the CNS. In addition, KRG may be a potential target for modulating orofacial pain processing.

• 생약학회지
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• 제45권3호
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• Asian-Australasian Journal of Animal Sciences
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• 제32권5호
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• pp.648-656
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• 2019

Objective: An experiment was conducted to determine the effect of reduced energy density of close-up diets on metabolites, lipolysis and gluconeogenesis in cows during the transition period. Methods: Thirty-nine Holstein dry cows were blocked and assigned randomly to three groups, fed a high energy density diet (HD, 1.62 Mcal of net energy for lactation $[NE_L]/kg$ dry matter [DM]), a medium energy density diet (MD, $1.47Mcal\;NE_L/kg\;DM$), or a low energy density diet (LD, $1.30Mcal\;NE_L/kg\;DM$) prepartum; they were fed the same lactation diet to 28 days in milk (DIM). All the cows were housed in a free-stall barn and fed ad libitum. Results: The reduced energy density diets decreased the blood insulin concentration and increased nonesterified fatty acids (NEFA) concentration in the prepartum period (p<0.05). They also increased the concentrations of glucose, insulin and glucagon, and decreased the concentrations of NEFA and ${\beta}-hydroxybutyrate$ during the first 2 weeks of lactation (p<0.05). The plasma urea nitrogen concentration of both prepartum and postpartum was not affected by dietary energy density (p>0.05). The dietary energy density had no effect on mRNA abundance of insulin receptors, leptin and peroxisome proliferator-activated $receptor-{\gamma}$ in adipose tissue, and phosphoenolpyruvate carboxykinase, carnitine palmitoyltransferase-1 and peroxisome proliferator-activated $receptor-{\alpha}$ in liver during the transition period (p>0.05). The HD cows had higher mRNA abundance of hormone-sensitive lipase at 3 DIM compared with the MD cows and LD cows (p = 0.001). The mRNA abundance of hepatic pyruvate carboxy-kinase at 3 DIM tended to be increased by the reduced energy density of the close-up diets (p = 0.08). Conclusion: The reduced energy density diet prepartum was effective in controlling adipose tissue mobilization and improving the capacity of hepatic gluconeogenesis postpartum.

• 한국자기공명학회논문지
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• 제24권4호
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• pp.104-116
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• 2020

Fipronil, the phenylpyrazole insecticide, is effective and used in various fields. Especially, fipronil was reliable because it was known to be specific on invertebrate animals than vertebrate animals including mammals. However, fipronil had potential risks that affect vertebrate animals as it blocks the gamma-aminobutyric acid (GABA) receptors that also exists in vertebrates as well as invertebrates. Therefore, it was necessary that harmful effects of fipronil on vertebrates are clarified. For this purpose, the zebrafish (Danio rerio) were used on behalf of vertebrate animals in present study. The zebrafish were exposed to 5 ㎍/L, 25 ㎍/L, and 50 ㎍/L of fipronil during 12, 24 and 72 hours. To closely observe toxic process, 12 hours and 24 hours of additional time point were set in the exposure test. Nuclear magnetic resonance (NMR)-based metabolomics is an approach to detect metabolic changes in organism resulted from external stimuli. In this study, NMR-based metabolomics showed the metabolic changes in zebrafish caused by fipronil exposure. Metabolic analysis revealed that fipronil interfered with energy metabolism and decreased the antioxidant ability in zebrafish. Antioxidant ability decline was remarkable at high exposure concentration. In addition, metabolic analysis results over time suggested that reactions for alleviating the excessive nerve excitation occurred in zebrafish after fipronil exposure. Through this study, it was elucidated that the adverse effects of fipronil on vertebrate animals are evident. The risk of fipronil on vertebrates can be no longer ignored. Moreover, this study has a meaning of practically necessary research for organism by examining the effects of fipronil at low concentrations existed in real environment.

• Journal of Veterinary Science
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• 제24권3호
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• pp.37.1-37.14
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• 2023

Background: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objectives: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. Results: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1β, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. Conclusions: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

• 대한방사선기술학회지:방사선기술과학
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• 제21권1호
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• pp.79-87
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• 1998

이 실험의 목적은 4.5 및 7.5 Gy의 단일 선량으로 감마선의 전신조사에 따른 혈장 및 좌골신경 혈소판-유래성 성장인자(platelet-derived growth factor, PDGF)의 농도와 좌골신경 PDGF ${\alpha}$ -및 ${\beta}$ -수용체 밀도에 대한 시간의존성 변화를 조사 추구하는데 있다. 웅성 흰쥐(Sprague-Dawley계, 체중 $270{\pm}15.4g$)를 사용하여 $^{60}Co$ 감마선을 전신 조사(선량률 1.065 Gy/min)하고, 조사 후 1, 2, 3, 5 및 10일구에서 피폭에 따른 급성반응을 조사 추구하였다. 실험의 결과는 다음과 같다. 1) 4.5 및 7.5 Gy 선량군에서는 혈장 PDGF의 농도가 전 일구에 걸쳐 대조군($2.26{\pm}0.31\;ng/ml$)에 비해서 감소경향이 나타났으며, 한편 4.5 및 7.5 Gy 선량군 사이에서는 전 일구에 걸쳐 혈장 PDGF의 농도차에 유의적인 차이가 없었다(P>0.05). 피폭된 흰쥐의 혈장 PDGF의 농도는 4.5 및 7.5Gy 선량군에서 모두 대조군의 흰쥐에 비하여 5일구($4.5Gy:1.35{\pm}0.23\;ng/ml$; 대조군의 백분율로서 59.7%, 그리고 $7.5\;Gy:1.24{\pm}0.13\;ng/ml;54.9%$) 및 10일구($4.5Gy:1.27{\pm}0.28ng/ml;56.2%$ 그리고 $7.5Gy:1.07{\pm}0.19\;ng/ml:47.3%$)에서 각각 유의성으로 낮았다(P<0.05). 2) 4.5 및 7.5Gy 선량군에서는 좌골신경 PDGF의 농도가 전 일구간에 걸쳐 대조군($3.68{\pm}0.12\;ng/ml$)에 대하여 대체로 약간의 증가가 나타났으나, 한편 4.5 및 7.5Gy 선량군 사이에서 전 일구에 걸쳐 좌골신경 PDGF의 농도차는 무의성이었다(P>0.05). 피폭된 흰쥐의 좌골신경 PDGF의 농도는 4.5 및 7.5Gy 선량군에서 모두 대조군에 비하여 1일구($4.5Gy:4.33{\pm}0.03\;ng/m1$;대조군의 백분율로서 118% 그리고 $7.5Gy:4.81{\pm}0.36\;ng/ml$; 130%)에서 각각 증가하였으나 무의성이었다(P>0.05). 3) 방사선의 조사는 혈장 및 좌골신경 PDGF의 농도의 변화를 초래할 뿐만아니라 좌골신경 PDGF ${\alpha}$ - 및 ${\beta}$ -수용체 밀도의 변화도 초래하였다. 수용체의 밀도단위를 단백질의 상대적 함량(relative level of protein)으로 표시하고 일구-필적의 대조군을 백분율로 표시하였다. 4.5 및 7.5Gy 선량군에서의 좌골신경 PDGF ${\alpha}$ -수용체의 밀도는 대조군에 비하여 초기에 감소현상으로 나타나, 1일구에서는 40%(4.5Gy)와 50%(7.5Gy)를, 그리고 2일구에서는 33%(4.5Gy)와 50%(7.5Gy)로 가장 낮은 값을 나타낸 후 점차 대조군에 근접하는 값으로 증가하는 경향이었으며, 한편 4.5 및 7.5Gy 선량군에서 좌골신경 PDGF ${\beta}$ -수용체의 밀도는 역시 대조군에 비하여 각각 26%(4.5 Gy)와 27%(7.5Gy)의 최소 값을 나타낸 후점차 대조군에 근접하는 값으로 증가하는 경향으로 나타났다. 이러한 실험의 결과를 미루어 보아서, 혈장 및 좌골신경의 PDGF의 농도와 좌골신경 PDGF ${\alpha}$ - 및 ${\beta}$ -수용체의 밀도에 대한 방사선-유발성 변경이 골수 간세포 및 말초뉴런의 장해의 병인론에 관련되어 있는 것으로 생각된다.

• 대한약리학회지
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• 제32권1호
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• pp.13-21
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• 1996

세포내 칼슘농도는 신경세포의 다양한 기능에 매우 중요한 역할을 하고 있다. 본 연구에서는 일차배양한 마우스 소뇌과립세포에서 니코틴성 아세틸콜린 수용체가 특정 발생단계에 발현되고 세포내 칼슘의 농도조절에 관여하는 것을 관찰하였다. 니코틴에 의한 세포내 칼슘농도의 변화는 $^{45}Ca^{2+}$나 fura-2를 사용하여 형광법으로 측정하였다. 니코틴은 마우스 소뇌과립세포내 칼슘의 농도를 최대한 증가시키는 것으로 보인다. 반면에 일차배양한 Glia 세포들에서는 $^{45}Ca^{2+}$ 농도를 증가시키지 않았다. 세포내 칼슘농도에 미치는 니코틴의 효과는 NMDA 수용체에 대한 길항제에 의하여 억제되었다. 또한 Glutamate pyruvate transminase (GPT)를 사용하여 배양액의 글루타민산을 제거하면 니코틴효과가 소실되는 것이 관찰되었다. 이러한 결과는 니코틴에 의한 세포내 칼슘농도의 변화가 세포에서 유리된 글루타민산에 의한 간접적인 효과임을 암시한다. Fura-2를 사용한 형광법으로 실험한 결과 니코틴은 two phase로 세포내 칼슘농도를 증가시키는 것을 보여주었다. NMDA 수용체 길항제와 GPT는 단지 후기 plateau상만 억제하였다. 따라서 본 연구결과는 니코틴이 직접 니코틴성 아세틸콜린 수용체를 자극하여 일시적으로 세포내 칼슘농도를 증가시키고 글루타민산을 유리하여 NMDA 수용체를 활성화시킴으로써 세포내 칼슘농도를 지속적으로 증가시키는 것으로 보여진다. 이러한 결과는 니코틴성 아세틸콜린 수용체가 특정한 발생과정에 발현되어 세포내 칼슘농도 조절에 관여함으로써 신경발생과정에서 중요한 역할을 할 수 있음을 보여주고 있다. state를 나타내는 것을 알 수 있다. 또한 $[^3H]DPCPX$를 이용한 competitive binding assay에서 0.1 mM GTP는 효현제인 PIA의 apparent affinity를 감소시켰으며, DPCPX의 apparent affinity는 증가시키고, CGS-15943에는 아무런 영향을 미치지 않았다. 이것은 상기의 $[^{35}S]GTP_{\gamma}S$ binding의 결과를 뒤받침해 주는 결과라고 생각된다.요한 역할을 할 수 있으리라 사료된다.X>$Ca^{2+}$에 의하여 활성화되는 $K^+$ 통로를 개방시킴으로 세포내 $Ca^{2+}$을 감소시켜 뇌 기저동맥의 이완반응을 매개하는 것으로 사료된다. 함량을 조정하므로, 흉선세포의 apoptosis에 억제적으로 작용할 수 있음을 시사하는 것으로 사료된다. 영양액에 의하여는 회복됨을 볼 수 있었으며 $Mg^{++}$ 증가 영양액에서는 억제, TTX 동시 투여시에는 완전히 소실되었다. 이상의 실험결과로 흰쥐 해마에서 $A_1-adenosine$ 수용체를 통한 adenosine의 NE 유리 감소는 TEA 및 4AP에 예민한 $K^+$-통로가 관여하고 여기에는 세포외액의 Ca^{++}의 농도가 중요한 인자의 하나로 관여 하는 것으로 사료된다. 영상의 질을 크게 향상 시켜 줌으로 비가역 3구획모델에서의 PGA방법을 대체할 새로운 파라메터 영상구성방법으로 적합할 것이다.관계되며, YH439는 중금속으로 유도된 조직독성에 방어효과가 있음을 지지한다.총 아미노산의 순은

• 동의생리병리학회지
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• 제21권1호
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.

• Asian-Australasian Journal of Animal Sciences
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• 제25권7호
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• pp.1021-1028
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• 2012

Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and induce T-cell responses of appropriate effector phenotype accordingly. Toll-like receptors (TLRs), in part, mediate this microbial recognition and differentiation while the development of T-cell effector functions critically depends on the release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were stimulated under in vitro culture conditions by Bacillus subtilis cell wall petidoglycan, a TLR2 ligand, in a dose- and time- dependent manner. The expression of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type cytokines was measured. Stimulation was analyzed across five doses of peptidoglycan ($10{\mu}g/ml$, $20{\mu}g/ml$, $30{\mu}g/ml$, $40{\mu}g/ml$ and $50{\mu}g/ml$) for 3 h, 12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2 expression in a dose- and time-dependent manner and the peptidoglycan induced tolerance beyond $30{\mu}g/ml$ dose at all incubation periods. The correlation between peptidoglycan stimulation and TLR2 induction was found positive at all doses and for all incubation periods. Increased production of all the cytokines was observed at low doses for 3 h incubation, but the expression of IL-4 was relatively higher than IL-12 at the higher antigen doses, indicating tailoring towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4 and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating skewing to Th1 polarization. The expression of IL-12 was highest for all doses across all the incubation intervals at 24 h incubation, indicating Th1 polarization. The relative expression of TNF-${\alpha}$ and IFN-${\gamma}$ was also higher while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low doses, relative increase in the expression of IL-4 and IL-10 was observed which decreased at higher doses, as did the expression of all other cytokines. The exhaustion of cytokine production at 36 h indicated that PBMCs became refractory to further stimulation. It can be concluded from this study that the cytokine response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1 type with time till the cells become refractory to further stimulation.