Effect Of Ginseng Total Saponin Research Articles

Ginseng total saponin modulates the changes of α-actinin-4 in podocytes induced by diabetic conditions

BackgroundThe actin cytoskeleton in podocytes is essential for the maintenance of its normal structure and function. Its disruption is a feature of podocyte foot-process effacement and is associated with proteinuria. α-Actinin-4 in podocytes serves as a linker protein binding the actin filaments of the cytoskeleton. MethodsTo investigate the effect of ginseng total saponin (GTS) on the pathological changes of podocyte α-actinin-4 induced by diabetic conditions, we cultured mouse podocytes under normal glucose (5mM) or high glucose (HG, 30mM) conditions, with or without the addition of advanced glycosylation end products (AGE), and treated with GTS. ResultsIn confocal imaging, α-actinin-4 colocalized with the ends of F-actin fibers in cytoplasm, but diabetic conditions disrupted F-actin fibers and concentrated α-actinin-4 molecules at the peripheral cytoplasm. GTS upregulated α-actinin protein in a time- and dose-dependent manner, and suppressed the receptor for AGE levels in western blotting. Diabetic conditions, including HG, AGE, and both together, decreased cellular α-actinin-4 protein levels at 24 h and 48 h. Such quantitative and qualitative changes of α-actinin-4 protein induced by diabetic conditions were mitigated by GTS. ConclusionThese findings imply that both HG and AGE have an influence on the distribution and amount of α-actinin-4 in podocytes that can be recovered by GTS.

Ginseng total saponin modulates podocyte p130Cas in diabetic condition

Proteinuric conditions demonstrate structural and compositional changes of the foot processes and slit diaphragms between podocytes. p130Cas in podocytes serves as an adapter protein anchoring glomerular basement membrane to actin filaments of podocyte cytoskeleton. To investigate the effect of ginseng total saponin (GTS) on the pathologic changes of podocyte p130Cas induced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, control); 2) high glucose (HG, 30 mM); 3) advanced glycosylation endproducts (AGE)-added; or 4) HG plus AGE-added conditions and treated with GTS. In confocal imaging, p130Cas colocalized with zonula occludens-1 and synaptopodin connecting to F-actin. However, diabetic conditions relocalized p130Cas molecules at perinuclear cytoplasmic area and reduced the intensity of p130Cas. In Western blotting, diabetic conditions, especially HG plus AGE-added condition, decreased cellular p130Cas protein levels at 24 and 48 h. GTS improved such quantitative and qualitative changes. These findings imply that HG and AGE have an influence on the redistribution and amount of p130Cas of podocytes, which can be reversed by GTS.

Ginseng total saponin regulates podocyte P-cadherin/β-catenin unit in diabetic condition

Proteinuric conditions demonstrate structural and compositional changes of the foot processes and slit diaphragms between podocytes. β-Catenin in podocytes serves as an adapter protein anchoring P-cadherin of slit diaphragms to actin filaments of podocyte cytoskeleton. To investigate the effect of ginseng total saponin (GTS) on the pathologic changes of podocyte P-cadherin/β-catenin unit induced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, = control); 2) high glucose (HG, 30 mM); 3) advanced glycosylation end products (AGE)-added; or 4) HG plus AGE-added conditions and treated with GTS. In confocal imaging, β-catenin colocalized with P-cadherin at intercellular junction area, predominantly. However, diabetic conditions relocalized and concentrated both molecules at perinuclear cytoplasmic area. In Western blotting, diabetic conditions, especially HG plus AGE-added condition, also decreased cellular β-catenin protein levels at 6, 24, and 48 hours. GTS improved such quantitative and qualitative changes of β-catenin. These findings imply that HG plus AGE have an influence on the redistribution and amount of P-cadherin/β-catenin unit of podocytes, which can be reversed by GTS.

Ginseng Total Saponin Improves Podocyte Hyperpermeability Induced by High Glucose and Advanced Glycosylation Endproducts

Early diabetic nephropathy is characterized by glomerular hyperpermeability as a result of impaired glomerular filtration structure caused by hyperglycemia, glycated proteins or irreversible advanced glycosylation endproducts (AGE). To investigate the effect of ginseng total saponin (GTS) on the pathologic changes of podocyte ZO (zonula occludens)-1 protein and podocyte permeability induced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, = control); 2) high glucose (HG, 30 mM); 3) AGE-added; or 4) HG plus AGE-added conditions and treated with GTS. HG and AGE increased the dextran filtration of monolayered podocytes at early stage (2-8 hr) in permeability assay. In confocal imaging, ZO-1 colocalized with actin filaments and β-catenin at cell contact areas, forming intercellular filtration gaps. However, these diabetic conditions suppressed ZO-1 immunostainings and disrupted the linearity of ZO-1. In Western blotting, diabetic conditions also decreased cellular ZO-1 protein levels at 6 hr and 24 hr. GTS improved such quantitative and qualitative changes. These findings imply that HG and AGE have an influence on the redistribution and amount of ZO-1 protein of podocytes thereby causing hyperpermeability at early stage, which can be reversed by GTS.

The effects of ginseng total saponin, panaxadiol and panaxatriol on ischemia/reperfusion injury in isolated rat heart

The aim of the present study was to evaluate the protective effect of ginseng total saponin, panaxadiol and panaxatriol, which are the major components of Panax ginseng, against myocardial ischemia/reperfusion (I/R) injury in isolated rat hearts. Rats were orally administered once a day with total saponin (20mg/kg), panaxadiol (5mg/kg) and panaxatriol (5mg/kg) for consecutive 7days. On day 8, the hearts were isolated and perfused with Krebs-Henseleit bicarbonate buffer solution using Langendorff apparatus. After 30min of global ischemia, hearts were reperfused for 30min. Myocardial function, coronary flow and biochemical parameters, such as lactate dehydrogenase (LDH), creatine kinase (CK), adenosine triphosphate (ATP), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Total saponin and panaxatriol significantly improved I/R-induced myocardial dysfunction by increasing left ventricular development pressure, (−dP/dt)/(+dP/dt) and time to contracture. Moreover, the increases in the levels of LDH, CK and MDA and the decrease in the levels of GSH were attenuated by total saponin and panaxatriol. However, the ATP levels did not affected by total saponin, panaxadiol and panaxatriol pretreatment. Our findings suggest that pretreatment with ginseng total saponin, especially panaxatriol, ameliorates I/R-induced myocardial damage and this protection is caused by reducing oxidative stress.

Effects of ginseng saponin on acute cocaine-induced alterations in evoked dopamine release and uptake in rat brain nucleus accumbens

In traditional medicine, Panax ginseng has been used to treat various behavioral effects of psychostimulants (e.g., cocaine) and other drugs of abuse and to ameliorate withdrawal symptoms. The neurochemical bases for this efficacy, however, remain to be elucidated. We previously used the real-time fast-scan cyclic voltammetry in rat nucleus accumbens slices to demonstrate that cocaine not only enhances DA release evoked by single-pulse electrical stimulation and inhibits DA uptake during application but also further increases the release upon washout (termed a “rebound” release enhancement). In the present study, we determined whether co-application and washout of ginseng total saponin (GTS), the active ingredient of Panax ginseng, with cocaine attenuate cocaine-induced enhancement of evoked DA release, DA uptake inhibition and/or withdrawal-associated rebound enhancement. Cocaine rapidly potentiated the DA release within the first 10 min of application, and acute cocaine withdrawal caused a rebound increase. Co-application of GTS with cocaine inhibited the release enhancement and subsequently prevented the rebound increase during acute withdrawal. The effect of GTS was concentration-dependent. In contrast, GTS had no significant effects on the cocaine-mediated DA uptake inhibition. These results suggest that the attenuation of the cocaine-induced enhancement of impulse-dependent DA release, rather than uptake inhibition, might be one of the pharmacological bases for attenuation of behavioral effects of cocaine and amelioration of acute withdrawal symptoms by ginseng.

Ginseng Total Saponin Enhances the Phagocytic Capacity of Canine Peripheral Blood Phagocytesin Vitro

The clinical and pharmacological activities of ginseng are known to modulate immune function, metabolic processes and neuro-endocrine system activities. Ginseng saponins are the principle active ingredients in the formation of immune stimulating complexes. The objective of this study was to evaluate the in vitro effect of ginseng total saponin (GTS) on the phagocytic capacity of canine peripheral blood phagocytes. GTS itself did not cause any direct effect on the phagocytic capacity of peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) but not peripheral blood monocytes. However, the phagocytic capacity of PMN and monocytes, but not PBMC, was enhanced by the culture supernatant from PBMC treated with GTS. The phagocytic capacity of PMN and monocytes was also increased by treatment with recombinant canine (rc) tumor necrosis factor (TNF)-alpha. The ability of the culture supernatant from GTS-treated PBMC to stimulate the phagocytic capacity of phagocytes was inhibited by addition of anti-rc TNF-alpha polyclonal antibody (pAb) prior to the culture. The amount of TNF-alpha in the culture supernatant from PBMC was shown to increase upon treatment of GTS as compared with that of vehicle-treated PBMC culture supernatant. These results suggest that GTS has an immunoenhancing effect on the phagocytic capacity of canine peripheral blood phagocytes, which is mainly mediated by TNF-alpha released from GTS-stimulated PBMC.

The antistress effect of ginseng total saponin and ginsenoside Rg3 and Rb1 evaluated by brain polyamine level under immobilization stress

The present study aims to demonstrate the ability of ginseng total saponin (GTS), ginsenosides Rg3 and Rb1 to reduce brain polyamine levels in immobilization-stressed gerbil mice. A previous study reported that ginsenosides had an anti-stress property. So, we tested the anti-stress effect of ginseng by investigating the brain level of polyamine, a well-known stress stimuli marker. We determined the brain polyamine levels under 30-min immobilization stress in pretreating GTS (100 mg kg −1, oral), ginsenosides Rg3 and Rb1 (10 mg kg −1, oral, respectively). Then, we compared polyamine levels between the non-stressed mouse and the stressed mouse which had taken saline orally to check the placebo effect. Putrescine (PUT) levels were significantly increased ( P < 0.01) in the stressed condition, but it was reduced in pretreatment of GTS, ginsenosides Rg3 ( P < 0.01, respectively) and Rb1 ( P < 0.001) under 30-min immobilization stressed-mouse. However, other polyamine levels did not change regardless of stressed condition or GTS-, ginsenosides Rg3- and Rb1-treated stressed condition. These results mean that only PUT could be a marker for stress and GTS, ginsenosides Rg3 and Rb1 administration lead to an anti-stress effect. Thus, our studies indicate that GTS, ginsenosides Rg3 and Rb1 may play a neuroprotective role in the immobilization-stressed brain.

홍삼사포닌이 좌골신경 재생에 미치는 영향

실험적으로 좌골신경에 압궤손상을 유발한 흰쥐에 홍삼사포닌을 투여하여 손상된 말초신경의 회복에 미치는 홍삼사포닌의 효과를 광학현미경과 전자현미경적 관찰을 통한 조직ㆍ형태학적 평가를 실시한 결과 다음과 같은 결론을 얻었다. 1. 손상된 신경재생에 가장 유효한 홍삼사포닌의 농도를 확인하기 위하여 50 mg/kg, 100mg/kg, 150mg/kg의 홍삼사포닌을 3주간 투여한 결과 150 mg/kg의 홍삼사포닌이 가장 효과적이었다. 2. 홍삼사포닌이 신경재생에 미치는 영향을 알아보고자 150 mg/kg의 홍삼사포닌을 1주 간격으로 1주부터 3주까지 투여한 결과 총 유수신경섬유 수는 홍삼사포닌 투여군에서는 1주에서 2주 사이에 급격히 증가를 하고 3주에서는 약간 감소하는 경향을 나타내었으나 대조군에서는 1주에서 3주까지 꾸준히 증가하는 경향을 나타내었다. 총 유수신경섬유 수가 홍삼사포닌 투여군에 비하여 대조군이 현저히 적은 양이지만 증가하는 양상을 보이는 것은 축삭절단만 시키고 신경 연결을 완전히 절단하지 않았기 때문에 어느 정도 자연회복이 이루어지고 있음을 의미한다. 그러나 홍삼사포닌 투여군에서는 대조군 보다 많은 수의 유수신경섬유 수를 가지고 이로 인해 홍삼사포닌은 말초신경 손상 시 재생에 효과가 있음을 알 수 있다. 특히 홍삼사포닌 투여군에서 1주와 2주 사이에 큰 차이를 나타내는 것은 신경 재생의 초기 단계에 효과를 나타내는 것으로 생각된다. 이상의 결과를 종합하면 말초신경 손상 시 홍삼사포닌을 투여하는 것은 자연 회복의 속도를 촉진시키는 효과가 있으므로 신경손상 시 홍삼사포닌을 투여하는 방법을 임상에 적용한다면 조기에 신경재생을 유도할 수 있을 것이라고 사료된다.다.X>$_4$</TEX> ratio도 대조그룹 대비 RFEY-1.0, RFEY-3.0, RFEY-5.0의 투여그룹은 각각 39.5%, 67.3% 및 96.3%의 유의적인 증가효과가 인정되었다. 이상의 실험 결과를 종합해 볼 때 장미열매 추출물을 주재로 한 장미 요구르트의 항스트레스작용은 매우 효과적일 것으로 기대된다.cetate, jupinene, <TEX>$\delta$</TEX>-cadinene, germa acrene, farnesol 등이 검출되었고 원자방출검출기 (AED)를 이용하여 분석한 결과, 특이적인 황화합물 및 질소화합물 등이 검출되지 않았다.한 수술 전 평가 등을 통해 중장기 개통률을 향상시킬 수 있다.25^{\circ}C$</TEX>에서 49.30% (76.66mg/kg)로 나타나 주로 <TEX>$25^{\circ}C$</TEX> 이하에서 발현한 것으로 나타났다. 3. 배양온도에서 검지 된 뷰틸산의 량은 6일 동안 돈분에서 1,463.87mg/kg, 계분에서 96.72mg/kg, 우분에서 129.18mg/kg이 발현되었으며 돈분의 경우 93.31%(1,365.95mg/kg)가 <TEX>$25^{\circ}C$</TEX>에서 발현되었고 이 중 87.92%가 3일령, 4일령과 6일령에 집중적으로 나타났다. 계분의 경우 <TEX>$37^{\circ}C$</TEX> 처리구에서 76.60%(74.09 mg/kg)로 발현되었고 이 중 88%가 1일령, 2일령과 5일령에 집중적으로 나타났다. 우분의 경우 61.55%(79.51mg/kg)가 <TEX>$25^{\circ}C$</TEX>에서 발현되었고 이 중 89.6%가 1일령, 3일령과 4일령에 집중적으로 나타났다. 4. We investigated the effect of ginseng total saponin (GTS) on the regeneration process of experimentally crush injured rat sciatic nerves. The bilateral sciatic nerves of fifty adult male Sprague-Dawley rats were compressed surgically with a straight hemostat for 30 seconds with 1 mm width. Twenty rats were divided into four groups to test the dose-dependent effect of GTS (0, 50, 100, or 150 mg/kg, i.p.). Saline for vehicle control group or GTS dissolved in saline was administerd for three weeks. After that period of time, the numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs were examined and analyzed using image analysis system to confirm a morphological effect of GTS. We found that the most effective concentration of GTS for the regeneration of damaged sciatic nerve was 150 mg/kg. In another set of experiment, thirty rats were divided into two groups as saline-treated vehicle group and GTS-treated group (150 mg/kg, i.p.) for three weeks. Every week we examined the numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs using image analysis system to evaluate the effect of GTS on injured nerves. We found that the regeneration of damaged sciatic nerves was facilitated in GTS-treated group compared to saline-treated group until two weeks. However, after that period of time we could not observe the significant difference between saline-treated group and GTS-treated group. These results suggest that GTS is a useful adjuvant therapy for the regeneration of the peripheral nerve injury in short period of treatment.

A novel activation of Ca(2+)-activated Cl(-) channel in Xenopus oocytes by Ginseng saponins: evidence for the involvement of phospholipase C and intracellular Ca(2+) mobilization.

1. The signal transduction mechanism of ginsenosides, the active ingredients of ginseng, was studied in Xenopus oocytes using two-electrode voltage-clamp technique. Ginseng total saponin (GTS), i.e., an unfractionated mixture of ginsenosides produced a large outward current at membrane potentials more positive than -20 mV when it was applied to the exterior of oocytes, but not when injected intracellularly. The effect of GTS was concentration-dependent (EC(50): 4.4 microg ml(-1)) and reversible. 2. Certain fractionated ginsenosides (Rb(1), Rb(2), Rc, Rf, Rg(2) and Ro) also produced an outward current in a concentration-dependent manner with the order of potency of Rf>Ro>Rb(1)=Rb(2)>Rg(2)>Rc. Other ginsenosides (Rd, Re and Rg(1)) had little or no effect. 3. The GTS effect was completely blocked by bath application of the Ca(2+)-activated Cl(-) channel blocker niflumic acid and by intracellular injection of the calcium chelator BAPTA or the IP(3) receptor antagonist heparin. Also, the effect was partially blocked by bath-applied U-73122, a phospholipase C (PLC) inhibitor and by intracellularly injected GTP gamma S, a non-hydrolyzable GTP analogue. Whereas, it was not altered by pertussin toxin (PTX) pretreatment. 4. These results indicate that: (1) interaction of ginsenosides with membrane component(s) at the extracellular side leads to Ca(2+)-activated Cl(-) channel opening in Xenopus oocyte membrane; and (2) this process involves PLC activation, the release of Ca(2+) from the IP(3)-sensitive intracellular store and PTX-insensitive G protein activation.

Effect of ginseng total saponin on extracellular dopamine release elicited by local infusion of nicotine into the striatum of freely moving rats.

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using an in vivo microdialysis technique. In order to further characterize the mechanism by which GTS affects DA release, the effect of GTS on K(+)-induced DA release was also examined. Local infusion of nicotine (1, 5, and 10 mM) into the striatum produced a dose-dependent increase in extracellular DA in dialysate samples (maximal response = 154.0 +/- 10.8%, 308.1 +/- 55.7%, and 499.9 +/- 77.9% over basal levels, respectively). GTS (100 mg/kg i.p.) had no effect on basal levels of extracellular DA. However, GTS inhibited maximal DA release induced by intrastriatal infusion of nicotine (1, 5, and 10 mM) by 35.3%, 36.6%, and 58.5%, respectively. Intra-striatal infusion of high K+ solution (100 mM) produced an increase in extracellular DA in the striatum (maximal response = 796.6 +/- 98.8% over basal levels). However, GTS had no effect on the K(+)-induced increase in extracellular DA. The present study demonstrated that GTS inhibited striatal DA release stimulated by local infusion of nicotine. This may reflect the blocking effect of GTS on the striatum-related behavior induced by nicotine as well as other psychostimulants. The results also suggest that GTS may act on presynaptic nicotinic acetylcholine receptors or receptor-operated Na+ channels in dopaminergic nerve terminals, but not on voltage-sensitive ion channels.

Modulatory effect of ginseng total saponin on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the rat

Several studies have demonstrated that behavioral activation induced by psychostimulants is prevented by ginseng total saponin (GTS), which has been known to act on the central dopaminergic system. In an attempt to investigate whether the effect of GTS is through its inhibitory action on the elevated dopaminergic transmission, we examined the effect of GTS on nicotine-induced dopamine (DA) release in the nucleus accumbens (NA) of freely moving rats using in vivo microdialysis. Systemic injection of nicotine (3 mg/kg; i.p.) produced a mild increase in extracellular DA of dialysates samples in the NA (132±13% over basal levels at the peak). GTS (100 mg/kg; i.p.) had no effect on resting levels of extracelluar DA. However, an increase in accumbens DA release produced by systemic nicotine was completely blocked by systemic pre-treatment with GTS (100 mg/kg; i.p.). In addition, the effect of GTS on nicotine-induced tyrosine hydroxylase (TH) and immediate early gene expression in ventral tegmental area (VTA) or NA regions was examined. A single injection of nicotine increased TH mRNA level at VTA region. GTS, which did not affect the basal TH mRNA expression, attenuated nicotine-induced TH mRNA expression. Nicotine slightly increased both c-fos and c-jun mRNA level and GTS, which did not affect the basal c-fos and c-jun mRNA expression, further enhanced nicotine-induced c-fos and c-jun mRNA level at both VTA and NA regions. Our results suggest that GTS may have an inhibitory action against nicotine-induced DA release in NA region and TH mRNA expression in VTA region. GTS may exert an potentiative effect on both c-fos and c-jun mRNA expression at NA region through inhibiting the release of DA in NA.

Acute and Chronic Effects of Ginseng Total Saponin and Amphetamine on Fixed-Interval Performance of Rats

The effect of ginseng total saponin (GTS) on amphetamine (AMPH)-induced disruption of fixed-interval (Fl) responding in rats was examined. GTS (50 mg/kg) significantly improved the temporal responding impaired by 2 mg/kg of AMPH. A higher dose of 100 mg/kg GTS disrupted performance when given alone; this disruption was reversed by a low dose of AMPH (0.5 mg/kg) and tolerance developed to the effects of GTS with its repeated administration. Neurochemical analysis revealed that GTS (50 mg/kg) attenuated the increase in striatal dopamine caused by AMPH leading to the conclusion that brain dopamine may partially mediate the behavioral effects of GTS.

Effect of ginseng total saponin on bovine adrenal tyrosine hydroxylase.

Ginseng total saponin (GTS) can modulate dopaminergic activity at both presynaptic and postsynaptic dopamine receptors (Kim et al., 1998). The present study investigated the effect of GTS on the bovine adrenal tyrosine hydroxylase (TH), which catalyze L/tyrosine to DOP. GTS inhibited the bovine adrenal TH by 42.4, 51.5 and 55.3% at concentrations of 40, 80 and 100 micrograms/ml, respectively. The IC50 value of GTS was 77.5 micrograms/ml. GTS exhibited noncompetitive inhibition with a substrate L-tyrosine. The Ki value was 155 micrograms/ml.