• Journal of Ginseng Research
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• v.46 no.3
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• pp.426-434
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• 2022

Aim: This study investigates the effects of ginsenoside Rb1 (GsRb1) on methamphetamine (METH)-induced toxicity in SH-SY5Y neuroblastoma cells and METH-induced conditioned place preference (CPP) in adult Sprague-Dawley rats. It also examines whether GsRb1 can regulate these effects through the NR2B/ERK/CREB/BDNF signaling pathways. Methods: SH-SY5Y cells were pretreated with GsRb1 (20 mM and 40 mM) for 1 h, followed by METH treatment (2 mM) for 24 h. Rats were treated with METH (2 mg/kg) or saline on alternating days for 10 days to allow CPP to be examined. GsRb1 (5, 10, and 20 mg/kg) was injected intraperitoneally 1 h before METH or saline. Western blot was used to examine the protein expression of NR2B, ERK, P-ERK, CREB, P-CREB, and BDNF in the SH-SY5Y cells and the rats' hippocampus, nucleus accumbens (NAc), and prefrontal cortex (PFC). Results: METH dose-dependently reduced the viability of SH-SY5Y cells. Pretreatment of cells with 40 µM of GsRb1 increased cell viability and reduced the expression of METH-induced NR2B, p-ERK, p-CREB and BDNF. GsRb1 also attenuated the expression of METH CPP in a dose-dependent manner in rats. Further, GsRb1 dose-dependently reduced the expression of METH-induced NR2B, p-ERK, p-CREB, and BDNF in the PFC, hippocampus, and NAc of rats. Conclusion: GsRb1 regulated METH-induced neurotoxicity in vitro and METH-induced CPP through the NR2B/ERK/CREB/BDNF regulatory pathway. GsRb1 could be a therapeutic target for treating METH-induced neurotoxicity or METH addiction.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.199-209
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• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.81-81
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• 2020

본 연구는 새싹인삼(Panax ginseng sprout) 재배용으로 이용하기 위한 묘삼(종삼)의 장기 저온저장 시 사용되는 필름의 종류가 묘삼의 출아율이나 생육에 영향을 미치는 지 조사하기 위해 수행되었다. 포장에 사용된 필름은 다공성물질인 제올라이트와 페그마타이트가 5% 함유된 50㎛ low density polyethylene(기능성 LDPE) 필름과 nylon/polyethylene 80 ㎛(Ny/PE) 필름에 묘삼을 100g씩 포장한 후 골판지 상자에 담아 -2℃의 저장고에서 10개월 동안 저장하면서 8개월째부터 2개월마다 시료를 꺼내어 5℃에서 5일 동안 온도 순화를 시킨 후 1차 조사에서는 육안조사로 실험실에서 건전한 묘삼과 부패 묘삼을 조사하였고, 건전한 묘삼만 새싹인삼 수경재배 농가에 재식한 후 2차 조사로 묘삼의 출아율과 출아된 묘삼이 새싹인삼으로 건전하게 생육한 비율을 조사하였다. 조사결과 Ny/PE 필름에 8개월 저장된 묘삼의 경우 1차 육안검사 시 뇌두부위가 검게 변하여 묘삼이 대부분 고사된 것으로 조사되었다. 필름 개봉 전 필름 내부의 O₂ 및 CO₂ 가스농도를 측정한 결과 O₂ 농도는 1.91%, CO₂ 농도는 38.9%로 측정되었고, 필름 개봉 시 알코올 냄새의 이취가 나는 것으로 보아 Ny/PE 필름으로 포장 된 묘삼이 -2℃의 저온저장기간 동안에도 호흡을 하면서 필름 내 산소를 완전히 소모하고 혐기적인 환경으로 변화시켜 대사활동이 불가능하였기 때문에 뇌두의 싹이 고사된 것으로 조사되었다. 반면 기능성 필름으로 포장한 묘삼은 저장 8개월에 정식 후 74.3%의 출아율을 보였고, 건전한 새싹인삼의 비율은 67.2%로 조사되었다. 정식 전·후 묘삼의 개체수 대비 건전 출아율의 비율은 56.7%를 나타내어 Ny/PE 필름으로 포장한 묘삼의 결과와 큰 차이를 보였다. 기능성필름의 개봉 전 필름 내부의 O₂ 및 CO₂ 가스농도를 측정한 결과 O₂ 농도는 12.9%, CO₂ 농도는 4.6%로 측정되어 묘삼의 저온저장 시 필름을 적용할 경우 공기의 유동이 원활이 이루어져 내부 O₂ 농도를 일정 수준 이상 유지해주는 필름을 사용하는 것이 묘삼의 출아와 생육에 좋은 것으로 조사되었다.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.662-671
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• 2023

Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability (DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcription factor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayer interferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of target genes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used to analyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTS and transcription factor library. BLI analysis further showed that PPD had a higher direct interaction with PURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations in key amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showed that PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformatics analysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain, and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by binding PURA, which could provide a chemical and biological basis for the study of treating cognitive impairment by targeting PURA.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.31-42
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• 1988

The effect of Panaxadiol(PD), which is an active component of Korean Ginseng Saponins, on the secretion of catecholamines (CA) from the rabbit adrenal gland and its mode of action were investigated in the present study. $PD(400{\mu}g)$ increased significantly the secretion of CA from the isolated perfused rabbit adrenal gland. PD-induced secretion of CA was reduced markedly by treatment of atropine, CA secretion induced by Ach or PD was potentiated significantly by physostigmine-treatment. Chlorisondamine did inhibit CA secretion of PD or Ach. Perfusion of $PD(400{\mu}g)$ for 30 min enhanced the secretory activity of CA by Ach. Ouabain weakened the secretory response induced by PD but rather enhanced the response by Ach. Adenosine-treatment resulted in marked enhancement of CA secretion by PD or Ach, Pefusion with $Ca^{2+}-free$ Krebs containing EGTA (5 mM) for about 30 min totally blocked secretory effect induced by Ach and also weakened that by PD. From the above experimental results, it is suggested that PD causes secretion of catecholamines from the rabbit adrenal gland by a calcium-dependent exocytotic mechanism. The secretory effect of PD is due to the stimulation of cholinergic muscarinic and nicotinic receptors present in the adrenal gland and partly to a direct action on the chromaffin cell itself.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.1
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• pp.16-32
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• 2016

Objective : The water extract of Bojungikgi-tang (BTE) composed with Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Atractylodes Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Cimicifuga Rhizoma, and Bupleuri Radix and it has been traditionally used for chronic diseases or weakness after illness in oriental countries. However, little is known about the effects of aqueous extract of BTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS). Therefore, the aim of this study was to investigate the effects of BTE on TMA-induced CHS in BALB/c mice.Methods : In this study, the extract of BTE was prepared by extracting with distilled water at 100℃ for 2.5 h. The extract was freeze-dried following filtration through 0.45 μm filter. Mice were orally administrated with or without BTE extract of different doses (25-200 ㎎/㎏/day) for 28 days. During the challenge period, mice were externally applied with different doses of BTE extract one time per day 30 min before TMA treatment. I examined the effects of BTE on the serum levels of IgE, IgG1, IgG2a, and IgG2b, nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in isolated peritoneal macrophages, Th2 cytokine production in isolated spleen cells, ear swelling responses, and the leukocyte infiltration induced by TMA.Results : The orally and externally administration of BTE dose-dependently reduced the serum levels of hapten-specific immunoglobulin E (IgE), IgG1 titer, and PGE₂ production as well as ear swelling responses and leukocyte infiltration in TMA-induced BALB/c mice. The levels of NO and PGE₂ production from peritoneal macrophages stimulated with TMA-BSA were markedly suppressed by pretreatment with BTE in a concentration dependent manner. Furthermore, the levels of Th2 cytokines (IL-4, IL-5, IL-13) production from spleen cells stimulated with ConA were markedly suppressed by BTE treatment in a concentration dependent manner.Conclusions : These results suggest that BTE treatment suppresses chronic contact hypersensitivity, and it can be assumed that the suppression of ear swelling, serum IgE, NO and PGE₂ levels, leukocyte infiltration, and Th2 cytokines in an animal model. Therefore, these properties may contribute to the strong anti-CHS response effect of BTE.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.179-214
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• 1999

The result were as follows: 1. Yu Wan So(劉完素) regarded the cause of surgical disease as the heat(熱). He used the three method to drain(疏通), promoting pus drainage(托裏) and the balance between ying-energy(營氣) and wei-energy(衛氣). 2. Jang Jong Jeung(張從正) only refered to medicines without entire theory. 3. Lee Dong Won(李東垣) regarded the cause of surgical disease as the greasy diet(膏梁厚味), damp air(濕氣), wetness heat(濕熱). For each treatment he used the method of Yu Wan So's treatment and emphasized the balance between ying-energy(營氣) and wei-energy(衛氣), stomach energy(胃氣). 4. Ju Jin Heung(朱震亨) distinguished the cause of surgical disease from enternal(內), external(外) and channel(經). For each treatment he used the method to drain(疏通), promoting pus drainage(托裏) and the balance between ying-energy(營氣) and wei-energy(衛氣). The first stage used the clearing away heat and toxic materials(淸熱解毒) and the last stage used the invigoration and dispersion(補托). 5. Yu Wan So(劉完素) used to be very busy of Moschus(麝香), Alumen(白礬), Olibanum(乳香), Coptidis Rhizoma(黃連), Minium(黃丹) and Scutel1ariae Radix(黃芩) In classification of the medical action, great part of the medicine are activating blood circulation to dissipate blood stasis(活血祛瘀), clearing away heat and toxic materials( 淸熱解毒) and external application(外用). 6. Jang Jong Jeung(張從正) used to be very busy of Olibanum(乳香), Angelicae Gigantis Radix(當歸), Minium(黃丹), Myrrha(沒藥), Calomelas(輕粉), Rhei Radix Et Rhizoma(大黃) and Phellodendri Cortex(黃柏). In classification of the medical action, great part of the medicine arc activating blood circulation to dissipate blood stasis(活血祛瘀), clearing away heat and toxic materials(淸熱解毒) and diverged wind-cold evil(發散風寒). 7. Lee Dong Won(李東垣) used to be very busy of Forsythiae Fructus(連翹), Scuteliariae Radix(黃芩), Angelicae Gigantis Radix(當歸). Astragali Radix(황기), Glycyrrhizae Radix(炙甘草), Bupleuri Radix(紫胡), Phellodendri Cortcx(黃柏), and Coptidis Rhizoma(黃連). In classification of the medical action, great part of the medicine are activating blood circulation to dissipate blood stasis(活血祛瘀), regulating vital energy(理氣) and clearing away heat and toxic materials(淸熱解毒). 8. Ju Jin Heung(朱震亨) used to be very busy of Glycyrrhizae Radix(甘草), Astragali Radix(황기), Angelicae Gigantis Radix(當歸), Phellodendri Cortex(黃柏), Scutellariae Radix(黃芩), Ginseng Radix(人蔘), Qlibanum(乳香). In classification of the medical action, great part of the medicine are clearing away heat and toxic materiaIs(淸熱解毒), activating blood circulation to dissipate blood stasis(活血祛瘀) and diverged wind-cold evil(發散風寒).

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.1
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• pp.10-18
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• 2012

In this paper, to find out how different the treatment of special individuals named 'old people' is with that of ordinary cases, Dongeuibogam(東醫寶鑑) was chosen as the study material and some parts in it where the symptoms of old people in the same disease category were treated in different ways were excerpted to analyze the tendency of pathological symptoms and prescriptions in the physiological perspective. As the result of analysis on the parts in Dongeuibogam(東醫寶鑑) where the old people were treated in different ways, it turned out that 65 prescriptions were used in 24 pathological symptoms. The 24 symptoms are included mainly in chapters of 'inner view(內景)' and 'outer form(外形)'. They are including the pathological symptoms which had been presented as general geriatric symptoms and also seems to have added other symptoms which should be clinically reflected in the specialty of treatment for geriatric diseases. The 65 prescriptions are also recorded mainly in chapters of 'inner view(內景)' and 'outer form(外形)'. The herbs used for them were sweet and warm herbs such as Rehmannia glutinosa (Gaertner) Libosch(熟地黃), Angelica gigas Nakai(當歸), Panax ginseng C. A. Mey(人蔘) and Atractylodes macrocephala Koidz(白朮) that can support the essence blood of liver and kidney and the energy of spleen, lung and stomach. Those herbs could be added or subtracted according to the symptom. It seems to have resulted from the treatment method that old people was applied to old people in consideration of their physiological features. When the 24 symptoms and 65 prescriptions for geriatric diseases different from ordinary ones in Dongeuibogam(東醫寶鑑) were considered in the physiological view point, it could be seen that each pathological symptom was manifested as a exhaustion of kidney qi(腎氣枯渴) which was a characteristic physiologic state of old people. Through this, it could be seen that the use of prescriptions was also made to mitigate the body fluid deficiency(津液不足), the kidney yin inner heat(腎陰內熱), the heart spirit void and loss(心神虛損), the kidney yang deficiency(腎陽不足), the spleen failing in transportation(脾失健運), the spleen yang deficiency(脾陽不足), the liver fire inner movement(肝火內動) and the lung energy void and loss(肺氣虛寒).

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.93-100
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• 2013

Objectives : This study was to evaluate the anti-inflammatory and anti-pruritic effects of WSY-1075 composited with Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Ginseng Radix, Cervi parvum Cornu and Cinnamomi Cortex in rat peritoneal mast cells (RPMCs) and scratching mouse model. Methods : WSY-1075 was prepared by extracting with 30% ethanol. In the present study, we investigated the effect of WSY-1075 on the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and histamine in rat peritoneal mast cells (RPMCs) activated with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187, and on the scratching behavior in mice treated with pruriogens. Results : WSY-1075 was not cytotoxic effect in used all concentration. PMA plus A23187 treatment significantly increased TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production compared with media control in RPMCs. However, TNF-${\alpha}$, $IL1{\beta}$ and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by WSY-1075 (200 ${\mu}g/mL$ and 400 ${\mu}g/mL$). WSY-1075 also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, WSY-1075 administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin and substence P) in ICR mice. Conclusion : These results suggest that WSY-1075 administration (200 mg/kg or 400 mg/kg) has the anti-inflammatory and anti-pruritic effects on the activated rat peritoneal mast cell and mouse pruritus. WSY-1075 has a potential use as a composition of medicinal plants for treatment against inflammation- and pruritus-related disease.