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뇌 및 신경계

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뇌 및 신경세포에 대한 작용
 1.뇌 허혈을 개선하고 뇌 혈류를 증가시킨다.
 2.신경세포 보호 및 재생 작용이 있다.

1.Extracts from the leaves of Ginkgo biloba (EGb) and ginsenosides (GS) have been reported to be effective at increasing vascular relaxationThe actions of EGb and GS on the vascular functions of porcine basilar arteries were investigated in vitro our data support the potential of these compounds as therapeutic strategies in cerebral ischaemia and other related vascular dysfunctions."
은행 엽 추출물(EGb)와 진세노사이드(GS)는 혈관이완에 효과적이라고 보고 되었다. 돼지의 두개 저 동맥의 혈관 기능에 대한 EGb와 GS의 작용을 실험관내로 실험하였다. 우리는 이들 물질이 뇌 허혈과 다른 혈관관련 기능부전에 치료 전략으로 충분하다는 데이터를 얻었다.
2.뇌 허혈 환자를 대상으로 한 115와(100mg*2/day) Hydergin(1.5mg)의 대조실험에서 34.36%의 개선 율을 보였다(Hydergin에서는 58.43%) (Quiroga 1982)
                                문헌집 
1. Zhongguo Zhong Yao Za Zhi. 2003 Sep;28(9):851-3.
[The relationship between the protection of ginsenoside for spinal cell and nitric oxide]
Pan SY, Pan XW, Wang SP.Center of Army Hyperbaric Oxygen, General Navy Hospital, Beijing 100037, China.OBJECTIVE:

 To study the relationship between the protection of Ginsenoside(GS) for spinal cells and nitric oxide (NO). METHOD: Spinal cells were cultured in vitro, the model of peripheral nerve was established by scarifying the cells, and NO was measured by Griess method. RESULT: NO in injury group was high than that in noninjury group and NO in group cultured by GS was less than that in group cultured by common medium. CONCLUSION: NO increases when peripheral nerve is injuried, and the protective effect of GS on spinal cells may be through inhibiting NO release. 
PMID: 15015381 [PubMed - indexed for MEDLINE Mol Cells. 2003 Dec 31;16(3):402-6.
진세노사이드의 척추세포 보호 작용과 NO
목적: 진세노사이드(GS)의 척추세포 보호 작용과 NO의 관계를 연구
방법: 척추세포를 실험관 내에서 배양하고 세포를 죽여서 말초 신경 모델를 만들고 NO는 Griess 방법으로 측정하였다.
결과: 상처를 입은 군에서 NO는 비 상처 군에 비해 높았으며 GS로 배양된 군에서는 대조군에 비해 낮았다.
결론: 말초 신경이 손상되면 NO는 증가하는데 GS의 척추 세포 보호효과는  NO의 방출을 억제해서 일어나는 것 같다.

2. Zhongguo Zhong Yao Za Zhi. 2002 May;27(5):371-3.
[Protective effects and its mechanism of panaxatriol saponins isolated from Panax notoginseng on cerebral ischemia 
ao XH, Li XJ.Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.

OBJECTIVE: To study the protective effects and its mechanism of Panaxatriol Saponins isolated from Panax notoginseng (PTS) on focal cerebral ischemia in rat brain.
METHOD: The influences of PTS on cerebral water content and threespecific proteins (VEGF, HSP70 and transferrin) related with cerebral ischemia were studied with unilateral(편) occlusion of the middle cerebral artery (MCAO) and Western Blot. RESULT: PTS 12.5 mg.kg-1 i.p. x 7 d (5 d before MCAO and 2 d after MCAO) inhibited the increase of cerebral water content caused by MCAO and influenced contents of HSP70 and transferrin, but had no influence on VEGF protein level. CONCLUSION: PTS shows a protective effect on focal cerebral ischemia in rat brain by alleviating cerebral edema, up-regulating the expression of HSP70, down-regulating transferrin and maintaining blood-brain barrier.
뇌 허혈에 있어 전칠 삼으로부터 분리한 PPT계 사포닌의 방어효과와 그 기전
목적: 전칠 삼으로부터 분리한 PPT계 사포닌(PTS)의 쥐의 뇌의 뇌 허혈에 대한 방어효과와 그 기전 을 연구하기 위함 
방법:  중뇌 동맥(MCAO )의 한쪽을 막고 Western Blot로  PTS가 뇌수와 뇌 허혈에 관련 있는 3개의 특별한 단백질(VEGF, HSP70 and transferrin)에 대한 영향을 연구하였다.
결과: PTS 12.5mg/kg i.p7일(5일은 MCAO전 2일은 후)투여는 MCAO로 야기된 뇌 수의 증가를 막고 HSP70의 양에 영향을 주었으나 VEGF 단백질에는 영향이 없었다.
결론:PTS는 쥐의 뇌에서 뇌 허혈에 방어적 효과를 보여줘 뇌부종을 감소시켰고 HSP70의 발현을 올려서 조절하였으며 을transferrin  낮춰서 조절하고 뇌 혈액 울타리를 유지시켰다.
PMID: 12774330 [PubMed - indexed for MEDLINE]

3. Jpn J Pharmacol. 2002 Nov;90(3):254-62
Axonal and dendritic extension by protopanaxadiol-type saponins from ginseng drugs in SK-N-SH cells
.Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K.Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical andPharmaceutical University, Toyama, Japan.

Extension of axons(축삭돌기) and dendrites(신경세포의 수상돌기) in neurons may compensate for and repair damaged neuronal networks in the dementia brain. To find out drugs capable of regenerating the neuronal network, we focused on several herbal drugs belonging to the genus Panax, kinds of Ginseng, and investigated neurite outgrowth activity of their extracts and compounds. 
We found that the methanol extracts of Ginseng (root of P. ginseng), Notoginseng (root of P. notoginseng) and Ye-Sanchi in Chinese (rhizome of a relative to P. vietnamensis) increased neurite outgrowth in SK-N-SH cells. The protopanaxadiol-type saponins, ginsenosides Rb(1) and Rb(3), and notoginsenosides R(4) and Fa isolated from Ye-Sanchi extract extended neurites, while protopanaxatriol-, ocotillol- and oleanane-type saponins had no effect on the neurite outgrowth.
The percentage of cells with multipolar neurites and number of varicosities were intensely high in cells treated with the methanol extract of Ye-Sanchi as well as ginsenosides Rb(1) and Rb(3), and notoginsenosides R(4) and Fa. Both phosphorylated NF-H-expressing neurites and MAP2-expressing ones were extended by treatment with those saponins and the extract. Especially, longer neurites were mainly positive for phosphorylated NF-H. These results suggest that protopanaxadiol-type saponins enhance axonal and dendritic formation activity.
 SKN-SH세포에서 인삼제제의 PPD 계 사포닌에 의한 축삭 돌기와 수상돌기의 확장
축삭돌기와 수상돌기의 확장은 치매 뇌에서 손상된 신경계에 재생 및 보충을 해줄 것이다. 신경계의 재생 듂쩜 지닌 약을 찾기위해 인삼의 종인 순수 인삼에 속하는 몇 가지 생약에 촛점을 맞추고  이들 추출물과 복합물의 신경돌기 성장을 연구하였다. 고려인삼, 전칠 삼, 베트남 인삼의 메탄올 추출물이SK-SH세포에서 신경돌기의 성장을 증가시키는 것이 밝혀졌다. PPD계의 사포닌인 Rb1,Rb3,R4(notoginsenosides)와  베트남 삼에서 분리된 Fa는 신경돌기를 확장한 반면 PPT -, ocotillol- and oleanane 계 사포닌은 효과가 없었다. 다 극성 신경돌기와 많은 정맥류를 지닌 세포의 백분율은 베트남 삼의 메탄올 추출물이나 Rb1,Rb3,R4와 Fa로 처리한 세포에서 매우 높았다 인산화된 NF-H발현 신경돌기와 MAP2발현은 확장되었다. 특히 긴 신경돌기는 인산화된 NF-H에 중요한 긍정적 효과이다. 이결과는 PPD계 사포닌은 축삭 및 수상돌기 형성 작용을 촉진한다고  추측된다.PMID: 12499580 [PubMed - indexed for MEDLINE]
 
4. Acta Pharmacol Sin. 2002 Dec;23(12):1152-6.
Effect of Korea red ginseng on cerebralblood flow and superoxide production.
Kim CS, Park JB, Kim KJ, Chang SJ, Ryoo SW, Jeon BH.Department of Physiology, College of Medicine, Chungnam National University, Taejon, KOREA. bhjeon@cnu.ac.kr

AIM: To investigate the effects of Korea red ginseng (KRG) on the cerebral perfusion rate in the rats and the generation of superoxide anion in the endothelial cells. METHODS: The cerebral perfusion rate was measured using laser-doppler flowmetry before and after the administration of crude saponin (CS) and saponin-free fraction (SFF) of KRG in the anesthetized rats. The superoxide generation was measured by the method based on lucigenin-enhanced chemiluminescence in the cultured endothelial cells. RESULTS: The relative cerebral perfusion rate (rCBF) was significantly increased by the intraperitoneal injection of CS (100 mg/kg) in the rats, but SFF had no effect on the rCBF. Chronic treatment with CS for 7 d significantly inhibited the decrease of forebrain cerebral blood flow induced by clamping both carotid arteries in the rats. Furthermore, CS (0.1 g/L) significantly suppressed NADPH-induced superoxide generation in the human umbilical vein endothelial cells (P <0.01). CONCLUSION: The present study demonstrated that crude saponin fraction of KRG enhanced cerebral blood flow in rats. Furthermore, crude saponin fraction of KRG abrogated(파기하다) the NADPH-driven superoxide generation in endothelial cells.
고려인삼이 뇌혈류와 과산화 생성에 미치는 영향
목적:쥐의 뇌 관류와  상피세포에서 과산화 양이온의 생성에 고려인삼의 미치는 영향을 연구하기 위함 방법:뇌 관류는 고려인삼의 조 사포닌과 사포닌 분획을 투여 전 후 레이저 doppler flowmetry를 이용하여  마취된 쥐를 대상으로 측정하였다. 과산화 생성은 배양된 상피세포에서 lucigenin-enhanced hemiluminescence를 기초로 한 방법으로 측정하였다. 결과: 뇌 관류 속도는 조 사포닌을 복강 내로 투여 한 군에서 의미 있게 증가한 반면 사포닌 분획은 아니었다. 조 사포닌을 7일간 투여한 경우 쥐의 경동맥을 조여서 유도된 전 뇌의 감소된 혈액 흐름을 억제하였다. 나아가 조 사포닌은 인간 배꼽 정맥 상피세포에서 NADPH로 유도된 과산화 산소 생성을 의미 있게 억제하였다. 결론: 고려인삼의 조 사포닌은 쥐에서 뇌 혈류흐름을 강화하는 것을 이 연구는 보여주며 나아가 상피세포에서 NADPH로 유도된 과산화 생성 을 없앤다.PMID: 12466053 [PubMed - indexed for MEDLINE]
 
5. Neurosci Lett. 2002 Jun 7;325(2):129-33.
Protective effect of ginsenosides, active ingredients of Panax ginseng, on kainic acid-induced neurotoxicity in rat hippocampus.
Lee JH, Kim SR, Bae CS, Kim D, Hong H, Nah S.Department of Anatomy, College of Veterinary Medicine, Chonnam National University, Kwangju 500-757, South Korea.
Ginsenosides are known to attenuate glutamate-induced cell injuries in vitro. We investigated the in vivo effect of ginsenosides on kainic acid (KA)-induced neurotoxicity in rat hippocampus using the methods of acid fuchsin (AF) staining and heat-shock protein-70 (HSP-70) immunoreactivity to detect neuronal death and stress, respectively. Pretreatment of ginsenosides (50 or 100 mg/kg for 7 days) via intraperitoneal (i.p.) administration significantly attenuated KA (10 mg/kg i.p.)-induced cell death by decreasing AF-positive neurons in both CA1 and CA3 regions of rat hippocampus compared with KA treatment alone. Pretreatment of ginsenosides (50 or 100 mg/kg for 7 days) via i.p. administration also significantly suppressed KA-induced induction of HSP-70 in both regions of rat hippocampus. These results show that ginsenosides are effective in protecting hippocampal CA1 and CA3 cells against KA-induced neurotoxicity.
쥐의 해마조직에 kainic산으로 유도된 신경독성에 대한 인삼 활성 성분인 진세노사이드의 방어 효과
실험관내 실험에서 진세노사이드는 glutamate로 유도된 세포 손상을 감소시킨다고 알려져 있다. 우리는 쥐의 해마조직에서 kainic산으로 유도된 신경독성에 대한 인삼의 효과를 acid fuchsin (AF) 염색과 신경의 죽음과 충격을 감지하는 열 충격 충격단백질 70의  면역 작용 을 이용하여 생체 내 실험으로 연구하였다 진세노사이드를 복강내로 50-100mg/kg으로 7일간 전 처리하면 KA(10mg/kg i.p)로 유도된 세포 사멸을 줄이는데 KA단독 처리와 비교하여 쥐의 해마조직 부위CA1과 CA3 양 영역에서 AF 양성 신경을 감소시켰고 KA로 유도된 HSP-70의 유도를 의미 있게 억제하였다. 이 결과는 진세노사이드가 KA로 유도된 신경독성으로부터 해마조직의 CA1과 CA3세포를 보호하는데 효과적인 것을 보여준다.
PMID: 12044638 [PubMed - indexed for MEDLINE]
6. Brain Res. 2004 Sep 17;1021(1):41-53.

Ginsenosides Rb1 and Rg1 effects on mesencephalic (중뇌)dopaminergic cells stressed with glutamate.
Radad K, Gille G, Moldzio R, Saito H, Rausch WD.Institute for Medical Chemistry, Veterinary Medical University, Veterinaerplatz 1, A-1210 Vienna, Austria.
Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a well known and popular herbal medicine used worldwide. Among more than 30 ginsenosides, the active ingredients of ginseng, ginsenosides Rb1 and Rg1 are regarded as the main compounds responsible for many pharmaceutical actions of ginseng. In our study, primary cultures from embryonic mouse mesencephala were exposed to neurotoxic glutamate concentration and potential protective effects of these two ginsenosides on survival and neuritic growth of dopaminergic cells were tested.
Treatment of primary mesencephalic culture with 500 microM glutamate for 15 min on the 10th day in vitro (DIV) increased the release of lactate dehydrogenase (LDH) into the culture medium, the propidium iodide (PI) uptake by cultured cells and the total number of nuclei withcondensed and fragmented chromatin (apoptotic features) as evaluated with Hoechst 33342. Moreover, it extensively decreased the number of tyrosine hydroxylase immunopositive (TH+) cells and adversely affected the length and number of their neuronal processes. The toxic effect of glutamate was primarily mediated by over-activation of N-methyl-D-aspartate receptor (NMDA) as treatment of cultured cells with (+)-MK 801, an NMDA receptor antagonist, nearly abolished dopaminergic cells loss and LDH release induced by glutamate. When either ginsenoside was added alone for six consecutive days (at final concentrations 0.1, 1, 10, 20 microM), ginsenoside Rb1 (at 10 microM) significantly enhanced the survival of dopaminergic neurons compared to untreated controls. Inthese cultures, neurite lengths and numbers were not affected by both ginsenosides. Against glutamate exposure, ginsenosides Rb1 and Rg1 could not prevent cell death. However when pre-treating for 4 days or post-treating for 2 days following glutamate exposure, they significantly increased the numbers and lengths of neurites of surviving dopaminergic cells. Thus our study indicates that ginsenosides Rb1 and Rg1 have a partial neurotrophic and neuroprotective role in dopaminergic cell culture. 

진세노사이드 Rb1과 Rg1이 glutamate로 압박했을 때 중뇌 dopamine생성 세포에 미치는 영향
고려인삼은 세계적으로 잘 알려지고 대중화된 약초이다.  인삼의 활성 성분인 30개가 넘은 진세노사이드 중 Rb1과 Rg1은 인삼의 많은 약리작용을 대표하는 중요 물질로 여겨졌다. 우리연구에서는 쥐의 태아 중뇌로부터 배양된 물질을 신경독성이 있는 glutamate에 노출시켜 이 두 물질이 도파민 생성 세포의 신경돌기 성장과 생존에 대한 방어효과를 실험하였다. 실험실 내에서  먼저 중뇌 배양 물에  500microM glutamate를 15분씩 10일간 처리하면lactate dehydrogenase(LDH)의 유출 및  배양된 세포에 의한 propidium iodide(PI) 흡수 , Hoechst 33342로 평가 시 조각난chromatin(세포 자가 소멸된 모습)과 농축된 총 핵이 증가하며 tyrosine hydroxylase immunopositive (TH+) 세포의 수는 현저히 감소하고 신경단위의 과정의 수와 길이에는 역 영향을 미친다.Glutamate의 독성 효과는 배양된 세포에 NMDA수용체 길항제인 (+)-MK 80로 처치하면N-methyl-D-aspartate receptor (NMDA) 의 과 작용에 의해 먼저 중개된다. 각 진세노사이드를 6일동안 연속적으로 첨가했을 때( 마지막 농도는0.1,1,10,10micro M) 진세노사이드 Rb1(10microM)에서 대조 군에 비해 의미 있게 도파민 생성 신경세포의 생존을 높였다. 이 배양에서 신경세포 길이와 숫자는 진세노사이드의 영향이 없었다. Glutamate에 노출 시 진세노사이드 Rb1과 Rg1은 세포 사멸을 억제하지 못하였으나 4일간의 전 처리나 glutamate 노출 후 2일간의 후 처리에서 진세노사이드는 생존 도파민 생성세포의 신경돌기의 길이와 숫자를 의미 있게 증가 시켰다. 연구는 도파민 생성 세포 배양액에서 Rb1과 Rg1은 부분적인 신경강장 및 신경보호 역할을 한다.
PMID: 15328030 [PubMed - in process] 

7. Brain Res Bull. 1998 Jun;46(3):245-51
Effects of ginsenosides on Ca2+ channels and membrane capacitance in rat adrenal chromaffin cells.
Kim HS, Lee JH, Goo YS, Nah SY.Department of Pharmacology, College of Pharmacy, Chungbuk National University, Cheongju, Korea. hskim@trut.chungbuk.ac.kr
We investigated the effects of ginseng total saponins (GTS) and five ginsenosides on voltage-dependent Ca2+ channels and membrane capacitance using rat adrenal chromaffin cells. In this study, cells were voltage-clamped in a whole-cell recording mode and a perforated patch-clamp technique was used. The inward Ca2+ currents (I(Ca)) was elicited by depolarization and the change in cell membrane capacitance (deltaCm) was monitored. The application of GTS (100 microg/ml) induced rapid and reversible inhibition of the Ca2+ current by 38.8 +/- 3.6% (n = 16). To identify the particular single component that seems to be responsible for Ca2+ current inhibition, the effects of five ginsenosides (ginsenoside Rb1, Rc, Re, Rf, and Rg1) on the Ca2+ current were examined. 
The inhibitions to the Ca2+ current by Rb1, Rc, Re, Rf, and Rg1 were 15.3 +/- 2.2% (n = 5); 36.9 +/- 2.4% (n = 7); 28.1 +/- 1.9% (n = 12); 19.0 +/- 2.5% (n = 10); and 16.3 +/- 1.6% (n = 15), respectively. The order of inhibitory potency (100 microM) was Rc > Re > Rf > Rg1 > Rb1. A software based phase detector technique was used to monitor membrane capacitance change (deltaCm). The application of GTS (100 microg/ml) induced inhibitory effects on deltaCm by 60.8 +/- 9.7% (n = 10). The inhibitions of membrane capacitance by Rb1, Rc, Re, Rf, and Rg1 were 35.3 +/- 5.5% (n = 7); 41.8 +/- 7.0% (n = 8); 40.5 +/- 5.9% (n = 9); 51.2 +/- 7.6% (n = 9); and 35.9 +/- 5.1% (n =10), respectively. The inhibitory potencies of the ginsenosides on deltaCm were Rf > Rc > Re > Rg1 > Rb1. Therefore, we found that GTS and ginsenosides exerted inhibitory effects on both Ca2+ currents and deltaCm in rat adrenal chromaffin cells. These results suggest that ginseng saponins regulate catecholamine secretion from adrenal chromaffin cells and this regulation could be the cellular basis of antistress effects induced by ginseng.

쥐의 부신 chromaffin 세포에있어  진세노사이드의 Ca++통로와 세포막 용량에 미치는 영향
우리는 쥐의 부신 chromaffin세포를 이용하여 인삼 총사포닌(GTS)와 5개의 진세노사이드가 전압 의존성 Ca++통로와 세포막 용량에 미치는 영향을 연구하였다. 이 연구에서 세포는 모든 세포 기록 방식으로 전압이 고정되었고 구멍 뚫린 헝겊 고정기술이 사용되었다. 내부 Ca++전류(I(Ca)) 는 감극에 의해 유도되었고 세포막 용량(deltaCm)의 변화를 추적하였다. GTS(100micro g/ml)의 적용은 빠르고 가역적인 Ca++전류의 억제(38.8 +/- 3.6% (n = 16)가 유도되었다. 어떤 특별한 단일 물질이 Ca++전류 억제를 하나를 증명하기위해 5개의 진세노사이드(Rb1, Rc, Re, Rf, and Rg1)를 Ca++전류에 대한 효과를 실험하였다.Ca++에 대한 억제 율은Rb1:15.3+/-2.2%(n=5),Rc: ); 36.9 +/- 2.4% (n = 7),Re: 28.1 +/- 1.9% (n = 12),Rf: ); 19.0 +/- 2.5% (n = 10,Rg1: 16.3 +/- 1.6% (n = 15),이었고 억제력 순서는 (100microM) Rc > Re > Rf > Rg1 > Rb1이었다. 상태 감지 기술에 기초로 한 software가 세포막 용량변화를 추적하는데 사용되었다. GTS의 적용의 (100 microg/ml) deltaCm억제효과는 60.8 +/- 9.7% (n = 10이었다. Rb1, Rc, Re, Rf, and Rg1의 억제 율은 각각 35.3 +/- 5.5% (n = 7); 41.8 +/- 7.0% (n = 8); 40.5 +/- 5.9% (n = 9); 51.2 +/- 7.6% (n = 9); and 35.9 +/- 5.1% (n = 10)이었고 억제력 순서는 Rf > Rc > Re > Rg1 > Rb1이었다. 따라서 우리는  쥐의 부신 chromaffin 세포에 있어GTS와 진세노사이드가 Ca++전류와 deltaCm에 억제효과가 있음을 발견하였다. 이러한 결과는 인삼 사포닌이 부신 chromaffin세포로부터 catecholamine분비를 조절하고 이 조절이 인삼의 항 스트레스 효과의 세포학적 기초가 될 것 이다
PMID: 9667819 [PubMed - indexed for MEDLINE]

8.Neurosci Res. 1997 Jul;28(3):191-200.
Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root.
Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, Peng H, Aburaya J, Ishihara K, Sakanaka M.Department of Anatomy, Ehime University School of Medicine, Japan.
Our previous study showed that the oral administration of red ginseng powder before but not after transient forebrain ischemia prevented delayed neuronal death in gerbils, and that a neuroprotective molecule within red ginseng powder was ginsenoside Rb1. However, it remains to be clarified whether or not ginsenoside Rb1 acts directly on the ischemic brain, and the mechanism by whichginsenoside Rb1 protects the ischemic CA1 neurons is not determined. Without elucidation of the pharmacological property of ginsenoside Rb1, the drug would not be accepted as a neuroprotective agent. The present study demonstrated that the intracerebroventricular infusion of ginsenoside Rb1 after 3.5 min or 3 min forebrain ischemia, precluded significantly the ischemia-induced shortening of response latency in a step-down passive avoidance task and rescued a significant number of hippocampal CA1 neurons from lethal ischemic damage. The intracerebroventricular infusion of ginsenoside Rb1 did not affect hippocampal blood flow or hippocampal temperature except that it caused a slight increase in hippocampal blood flow at 5 min after transient forebrain ischemia. Furthermore, ginsenoside Rb1 at concentrations of 0.1-100 fg/ml (0.09-90 fM) rescued hippocampal neurons from lethal damage caused by the hydroxyl radical-promoting agent FeSO4 in vitro, and the Fenton reaction system containing p-nitrosodimethylaniline confirmed the hydroxyl radical-scavenging activity of ginsenoside Rb1. These findings suggest that the central infusion of ginsenoside Rb1 after forebrain ischemia protects hippocampal CA1 neurons against lethal ischemic damage possibly by scavenging freeradicals which are overproduced in situ after brain ischemia and reperfusion. The present study may validate the empirical usage of ginseng root over thousands of years for the prevention of cerebrovascular diseases.
 전뇌 허혈 후 Rb1의 주입은  뇌 허혈 및 재 관류 후 과잉 생산되는 자유기를 청소하여 치명적인 허혈 손상으로부터  해마 CA1신경을 보호한다.
9.Int J Artif Organs. 2002 Nov;25(11):1103-8.
Ginsenoside Rb1 enhances peripheral nerve egeneration across wide gaps in silicone rubber chambers.Chen YS, Wu CH, Yao CH, Chen CT.Laboratory of Biomaterials, Institute of Chinese Medical Science, China Medical College, Taichung, Taiwan. yuehsc@mail.cmc.edu.twSilicone rubber chambers filled with collagen containing ginsenoside Rb1 (GRb1) were used to repair lesioned rat sciaticnerves with 15-mm gaps between stumps. Six weeks after implantation, histology of the nerve regenerated in the chambers filled with GRb1 and collagen contained larger axons than those in the chambers with collagen only. This study showed that the GRb1 could exert a positive influence on nerve regeneration when using silicone rubber tubes
9.ol Pharm Bull. 1994 Apr;17(4):509-13.
Malonylginsenoside Rb1 potentiates nerve growth factor (NGF)-induced neurite outgrowth of cultured chick embryonic dorsal root ganglia.Nishiyama N, Cho SI, Kitagawa I, Saito H.Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.Effects of malonylginsenoside Rb1 (GRb1-m) isolated from dried root of Panax ginseng C. A. Meyer (Araliaceae) on neuronal survival and neurite outgrowth were compared with those of ginsenoside Rb1 (GRb1) using organ culture of chick embryonic dorsal root ganglia (DRG) and cell culture of DRG neurons. In the organ culture, nerve growth factor (NGF) showed neurite outgrowth promoting effect. GRb1-m (30 microM) significantly potentiated this NGF-induced neurite outgrowth with similar potency to that of GRb1 (30 microM). Low density cell culture of DRG neurons was employed to minimize the contribution of contaminating non-neuronal cells. NGF (10 ng/ml) prolonged duration of neuronal survival. Neither GRb1-m nor GRb1 (1-30 microM) changed the prolongation effect of NGF, nor did NGF show a significant effect on the neurite elongation and re-elongation after axotomy by laser beam irradiation. However, GRb1-m (10 microM) potentiated initial neurite elongation when co-treated with NGF. In the process of re-elongation of neurites, GRb1-m (1, 30 microM) also promoted it in the presence of NGF. These results suggest, first, that GRb1-m potentiates NGF-induced neurite outgrowth of chick embryonic DRGs and DRG neurons, but behaves in a slightly different manner from GRb1, and, second, that the effects of the two saponins may work primarily on neurons causing the potentiation of NGF-induced neurite outgrowth
10.Neural Transm. 2004 Jan;111(1):37-45. Epub 2003 Dec 03.
Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected mesencephalic dopaminergic cells.
Radad K, Gille G, Moldzio R, Saito H, Ishige K, Rausch WD.Institute for Medical Chemistry, Veterinary Medical University, Vienna, Austria
.Ginsenosides Rb1 and Rg1 are the main active ingredients of Panax ginseng C.A. Meyer (Araliaceae). They appear to exert protection against ischaemia and anoxic damage in animal models, suggesting an antioxidative and cytoprotective role. In our study, primary cultures from embryonic mouse mesencephalon are applied to examine the effects of these two ginsenosides on neuritic growth of dopaminergic cells and their survival affected by 1-methyl-4-phenylpyridinium-iodide (MPP(+)). Ginsenoside Rb1(at 10 microM) enhanced the survival of dopaminergic neurons by 19% compared to untreated control. MPP(+) (at 1 microM) significantly reduced the number of dopaminergic neurons and severely affected neuronal processes. Both ginsenosides counteracted these degenerations and significantly protected lengths and numbers of neurites of TH(+) cells. Both compounds however could not prevent the cell loss caused by MPP(+). Our study thus indicates partial neurotrophic and neuroprotective actions of ginsenosides Rb1 and Rg1 in dopaminergic cell culture.PMID: 14714214 [PubMed - indexed for MEDLIN
11.Am J Chin Med. 2003;31(5):665-73.
Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneration.
Tsai CC, Lu MC, Chen YS, Wu CH, Lin CC.School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan. tsaicc@mail.cmc.edu.twA high-dose of nerve growth factor (NGF) mixed with ginsenoside Rb1 (GRb1) was encapsulated by collagen and placed in silicone rubber chambers, which were used to repair dissected Sprague-Dawley rat sciatic nerves with 15 mm gaps. Six weeks after surgery, no axons or Schwann cells were seen in these chambers. By comparison, nerves treated with collagen-GRb1 alone had regenerated axons and Schwann cells in their endoneurial areas. We suggest that excessive NGF may not promote but, rather, suppress developing nerves.PMID: 14696670 [PubMed - indexed for MEDLINE
12.Exp Neurol. 2002 Feb;173(2):224-34. 
 Neuroprotective effectsof ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro.Liao B, Newmark H, Zhou R.Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, USA.Spinal cord injury is a major cause of disability and results in many serious physical, psychological, and social difficulties. Numerous studies have shown that traumatic spinal cord injuries (SCI) lead to neuronal loss and axonal degeneration in and around the injury site that cause partial disability or complete paralysis(마비). An important strategy in the treatment of SCI is to promote neuron survival and axon outgrowth, making possible the recovery of neural connections. Using an in vitro survival assay, we have identified ginsenosides Rb1 and Rg1, extracted from ginseng root (Panax ginseng C. A. Meyer), as efficient neuroprotective agents for spinal cord neurons. These compounds protect spinal neurons from excitotoxicity induced by glutamate and kainic acid, as well as oxidative stress induced by H(2)O(2). The neuroprotective effects are dose-dependent. The optimal doses are 20-40 microM for ginsenosides Rb1 and Rg1. The effects are specific for Rb1 and Rg1, since a third ginsenoside, Re, did not exhibit any activity. Ginseng has been used for thousands of years in the treatment of neurological disorders and other diseases in Asia. Ginsenosides Rb1 and Rg1 represent potentially effective therapeutic agents for spinal cord injuries. (c)2002 Elsevier Science (USA).PMID: 11822886 [PubMed - indexed for MEDLINE] 
Rg1과Rb1은 척추손상에 충분히 효과적인 치료 물질이다.(Re는 효과 무)
13.Biol Pharm Bull. 2004 Mar;27(3):433-6.
Ginsenoside Rh2 reduces ischemic brain injury in rats.
Park EK, Choo MK, Oh JK, Ryu JH, Kim DH.College of Pharmacy, Kyung Hee University, Hoegi, Dongdaemun-ku, Seoul, Korea.
Ginseng was incubated under mildly acidic conditions and its inhibitory effect on a rat ischemia-reperfusion model was investigated. When ginseng was treated with 0.1% hydrochloric acid at 60 degrees C, its protopanaxadiol saponins were transformed to diasteromeric ginsenoside Rg3 and Delta20-ginsenoside Rg3. When the transformed ginseng extract, of which the main component was ginsenosides Rg3, was treated with human intestinal microflora, the main metabolite was ginsenoside Rh2. Orally administered acid-treated ginseng (AG) extract and ginsenoside Rh2 potently protect ischemia-reperfusion brain injury. The ginsenoside Rh2 also inhibited prostaglandin-E2 synthesis in lipopolysaccharide-stimulated RAW264.7 cells, but showed no in vitro antioxidant activity. These results suggest that AG and ginsenoside Rh2 can improve ischemic brain injury.PMID: 14969341 
[PubMed - indexed for MEDLINE
14.Brain Res. 2006 Jul 10; [Epub ahead of print]

Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway.

? Xue JF, Liu ZJ, Hu JF, Chen H, Zhang JT, Chen NH. 

Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Medical College of Chinese People's Armed Police Force, Tianjin 300162, PR China.

Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), has been extensively used in traditional oriental medicine for the prevention and treatment of aging-related disorders for over 2000 years. Accumulating evidence suggests that ginsenosides such as Rg1 and Rb1, which are the pharmacologically active ingredients of ginseng, modulate neurotransmission. Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release. All synapsins contain a short amino-terminal domain A that is highly conserved and phosphorylated by cAMP-dependent protein kinase (PKA), which plays a key role in regulating neurotransmitter release. In the present study, we demonstrated that both Rg1 and Rb1 increased neurotransmitter release in undifferentiated and differentiated PC12 cells. However, in the presence of the PKA inhibitor H89, Rg1, but not Rb1, still induced neurotransmitter release. Moreover, Rb1, but not Rg1, enhanced the phosphorylation of synapsins via PKA pathway. In summary, Rb1 promotes neurotransmitter release by increasing the phosphorylation of synapsins through the PKA pathway, whereas the similar effects observed with Rg1 are independent of the phosphorylation of synapsins.
PMID: 16836988 [PubMed - as supplied by publisher]

Rb1은 신경세포 자극전달부의 phosphoryration을 조정하여 신경전달물질의 방출을 증진한다.
고려인삼은 2000년 넘게 동양의 전통의학에서 노화와 관련된 장애의 예방 및 치료에 폭넓게 사용되어 왔다. 축적된 증거는 인삼의 중요 약리성분인 Rg1과 Rb1 신경전달을 조절하는 진세노사이드라고 생각된다. 신경세포 자극 전달부에는 신경전달물질 방출조정에 필수적인 phosphoprotein이  풍부하다 모든 신경세포 자극전달부에는  신경전달 물질의 방출 조절에 열쇠역할을 하는 cAMP의존 단백질 활소(PKA)에 의해 부 인산화반응(인산 함유 물질의 에스테르반응)되고 높은 비율로 전환되는  짦은 아미노 말단 영역 A을 지니고 있다.
이번 연구에서 우리는 Rb1과 Rg1이 모두 분화 또는 미분화된 PC12세포에서 신경전달물질 방출을 일으키는 것을 보여주었다. 그러나 PKA저해제인 H89의 존재 하에서 Rb1이 아니라 Rg1이 여전히 신경전달 물질 방출을 유도하였다. 더구나 Rg1이 아닌 Rb1은 PKA 경로를 경유하여 신경세포자극전달부의 부 인산화 반응을 높였다.
요약하면 Rb1은 PKA 경로를 통하여 신경세포 자극전달부의 부 인산화 반응을 일으켜 신경전달물질의 방출을 증진하는 반면 Rg1은 신경세포 자극 전달부의 부 인산화 반응하고는 관련 없이 유사한 효과가 있음이 관찰되었다.

15.Planta Med. 2006 Jun;72(7):627-33. Epub 2006 Apr 28.
Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells.

? Bae EA, Kim EJ,Park JS, Kim HS, Ryu JH, Kim DH. College of Pharmacy, Kyung Hee University, Seoul, Korea.

The anti-inflammatory effect of ginsenosides Rg3 and Rh2, which improves ischemic brain injury induced by middle cerebral artery occlusion, was investigated in lipopolysaccharide (LPS) and IFN-gamma-induced murine BV-2 microglial cells. Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM. The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences. However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
PMID: 16673329 [PubMed - in process]

Rg3와 Rh2는 lipopolysaccharide/interferon-gamma로 자극된 BV-2 소교세표에서 AP-1와 protein kinase A경로의 활성을 억제한다.
Rg3와 Rh2의  중뇌 동맥 폐색에 의해 유도된 허혈성 뇌 상처를 개선시키는  항 염 작용에 대한 효과를 lipopolysaccharide (LPS) and IFN-gamma-induced murine BV-2 microglial에서 연구되었다.Rh2는 NO의 생성을 억제하였다(IC 50 치수는 17microM) Rh2의 NO억제효과는 NO합성(iNOS)유전자의 출현과 mRNA와 단백질의 감소와 관련되어있다. 나아가 Rh2는 COX-2의 출현,LPS/IFN-gamma으로 유도된 BV-2세포에서  전구 염증물질인  TNF-alpha와 IL-1beta의 출현을 억제한 반면 항염증 물질인 cytokine IL-10의 출현을 증가시켰다. 전기이동 분석법에서 Rh2는 의미있게 AP-1 DNA로 유도된 LPS/IFN-gamma의 결합력을 억제한 반면 CRE에 결합된 단백질을 증가시켰으나 NF-kappaB 의 결합력에는 영향이 없었다. 따라서 Rh2의 항 염효과는  AP-1과 Kinase A경로에 의존한 것으로 보인다.
Rg3의 LPS/IFN-gamma-activated BV-2 세포에 대한 효과는 Rh2보다 못하였다. 이들 발견은 생체 내에서 Rg3의 항 허혈효과는 Rg3의 장내 세균총의 대사물인  Rh2로부터 기인했을 것이라 추측된다(Rh2의 항 허혈효과는 뇌 소교세포에 있어 항 염 효과라고 생각된다)

16. Eur J Pharmacol. 2006 Apr 24;536(1-2):69-77. Epub 2006 Feb 28
20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons.
? Lee E, Kim S, Chul Chung K, Choo MK, Kim DH, Nam G, Rhim H. Biomedical Research Center, Korea Institute of Science and Technology (KIST), 39-1 Hawholgok-dong Sungbuk-gu, Seoul 136-791, Republic of Korea.

Most herbal medicines that are orally administrated have been known to be metabolized before they are absorbed from the gastrointestinal tract. We, therefore, examined the effects of 20(S)-ginsenosides Rb1, Rg1 and Rg3, the three most commonly studied ginsenosides in the central nervous system, and their main metabolites on NMDA receptors using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques. Among the nine ginsenosides tested, 20(S)-ginsenoside Rh2 (20(S)-Rh2) along with 20(S)-ginsenoside Rg3 (20(S)-Rg3) produced the highest inhibitory effect in cultured hippocampal neurons. Although 20(S)-Rg3 and 20(S)-Rh2 selectively targeted NMDA receptors with similar potency, they produced additive effects and seemed to modulate different NMDA receptor regulatory sites. As a competitive antagonist, 20(S)-Rh2 seems to inhibit the receptor via its interaction with polyamine-binding sites, and 20(S)-Rg3 does so using glycine-binding sites. Therefore, these results suggest that the treatment of 20(S)-Rh2, a newly identified active ingredient of ginseng, might be a novel preventive candidate in treating neurodegenerative disorders.
 인삼에서 새롭게 밝혀진 활성 성분인 20(S)-ginsenoside Rh2는 배양된 쥐의 해마 신경에서  NADA수용체를 억제한다
대부분의 생약은 경구 투여 후 위장 관에서 흡수되기 전 대사되는 것으로 알려져 있다. 따라서 우리는 20(s)-Rb1,Rg1,Rg3의 중추신경계에 대한 효과와  perforated whole-cell patch-clamp기술과 fura-2-based 디지털 이미지를 이용하여 NADA 수용 체에 그들의 대사 물을 조사하였다.9개의 진세노사이드 실험 중 20(S)-Rh2와 20(S)-Rg3가  함께 배양된 해마 신경에서 가장 높은 억제효과를 보였다. 비록 20(S)-Rg3 와 20(S)-Rh2이  유사한 힘으로  NADA수용 체에 선택적이었지만 그들은 상가 효과를 나타냈고 다른 NADA수용 체 조절 부위를 조정하는 것으로 보였다. 경쟁적 길항제로서20(S)-Rh2은  polyamine-binding 부위와 상호 작용하여 수용 체를 억제하는 것으로 보이며 20(S)-Rg3는 glycine-binding 부위에서 동일한 작용을 하는 것 같다.따라서 이들 결과는  인삼의 새롭게 밝혀진 활성 성분인 20(S)-Rh2 는 신경퇴행성 장애의 치료에 새로운 예방 후보물질일 것이다.

17. Zhongguo Zhong Yao Za Zhi. 2002 May;27(5):371-3.
[Protective effects and its mechanism of panaxatriol saponins isolated from Panax notoginseng on cerebral ischemia
Yao XH, Li XJ.Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.
OBJECTIVE: To study the protective effects and its mechanism of Panaxatriol Saponins isolated from Panax notoginseng (PTS) on focal cerebral ischemia in rat brain. METHOD: The influences of PTS on cerebral water content and three specific proteins (VEGF, HSP70 and transferrin) related with cerebral ischemia were studied with unilateral(편) occlusion of the middle cerebral artery (MCAO) and Western Blot. RESULT: PTS 12.5 mg.kg-1 i.p. x 7 d (5 d before MCAO and 2 d after MCAO) inhibited the increase of cerebral water content caused by MCAO and influenced contents of HSP70 and transferrin, but had no influence on VEGF protein level. CONCLUSION: PTS shows a protective effect on focal cerebral ischemia in rat brain by alleviating cerebral edema, up-regulating the expression of HSP70, down-regulating transferrin and maintaining blood-brain barrier.

쥐에 있어PPT계열은  부종을 경감하여 뇌 허혈에 보호효과를 보인다.
PMID: 12774330 [PubMed - indexed for MEDLINE] 

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