Effects Of Ginseng Total Saponins Research Articles

Protective effects of ginseng total saponins on reward-directed operant conditioning in hindlimb suspension rats

ObjectiveTo explore the therapeutic effects of ginseng total saponins (GTSs) on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment. MethodsFifty specific pathogen-free (SPF) male Wistar rats were randomized into control, hindlimb suspension (HLS), Huperzine A (HLS-Hup A 0.1 mg/kg), low-dose GTSs (HLS-GTSs 100 mg/kg), and high-dose GTSs (HLS-GTSs 200 mg/kg) groups, based on the completion time of reward-directed conditioning tasks. Except for rats in the control group, the others were subjected to HLS and treated with drugs (day 20 – 58), received reflex test under the condition of rewarding, and underwent Nissl body staining and Western blot detection on hippocampal. ResultsAfter modeling, rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning task Ⅰ (P < 0.05) when compared with the control group, which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups (P > 0.05). In the reward-directed operant conditioning task Ⅱ, the HLS group rats demonstrated a marked decrease in the number of lever presses (P < 0.05) and nose pokes (P < 0.01) when compared with the control group rats; the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes (P < 0.05), while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses (P < 0.05) when compared with the HLS group rats. In visual signal discrimination task, compared with the control group rats, the HLS group rats showed decrease in the indexes of the visual signal discrimination (P < 0.01), while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it (P < 0.01). In reward extinction experiment, the number of lever presses in HLS rats significantly increased when compared with the control group (P < 0.01); compared with the HLS group, HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease (P < 0.05). The expressions of N-methyl-D-aspartic acid receptor 1 (NR1) and phosophorylated N-methyl-D-aspartic acid receptor 2B (p-NR2B) proteins were markedly decreased in rats in the HLS group (P < 0.05 and P < 0.01, respectively), while that of NR2B protein maintained the same (P > 0.05). GTSs increased the expression levels of p-NR2B (P < 0.01). ConclusionGTSs improved the learning and memory ability of complex operations by regulating the NR1/NR2B phosphorylation pathways in rats.

Target engagement of ginsenosides in mild cognitive impairment using mass spectrometry-based drug affinity responsive target stability

BackgroundMild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. MethodsThe candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC–MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a protein–protein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. ResultsWe screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. ConclusionThis study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

Preventive Effects of Ginseng Total Saponins on Chronic Corticosterone-Induced Impairment in Astrocyte Structural Plasticity and Hippocampal Atrophy.

To further explore the underlying antidepressant mechanism of ginseng total saponins (GTS), this study observed the effects on hippocampal astrocyte structural plasticity and hippocampal volume in the corticosterone-induced mouse depression model. Corticosterone (20mg/kg/day) was administered subcutaneously for 5weeks, and GTS (12.5, 25, and 50mg/kg/day; namely GTSL, GTSM, and GTSH) or fluoxetine (10mg/kg/day) were given intragastrically during the last 3weeks. On day 33 and day 34, depression-like behavior was observed via a forced swimming test and a tail suspension test, respectively. At 6h after the last dose of corticosterone (day 35), all mice were sacrificed followed by serum corticosterone assays, stereological analysis of hippocampal glial fibrillary acidic protein-positive (GFAP+ ) astroctyes and hippocampal volume, and hippocampal glycogen tests. Results showed that all doses of GTS ameliorated depression-like behavior and the decrease in hippocampal glycogen without normalizing hypercortisolism. Moreover, GTSH and GTSM reversed the corticosterone-induced reduction in the total number of hippocampal GFAP+ astrocytes and hippocampal volume. Additionally, GTSH alleviated the diminished protrusion length and somal volume of GFAP+ astrocytes induced by corticosterone. These findings imply that the effects of GTS on corticosterone-induced depression-like behavior may be mediated partly through the protection to hippocampal astrocyte structural plasticity. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-stress effects of ginseng total saponins on hindlimb-unloaded rats assessed by a metabolomics study

Ethnopharmacological relevanceGinseng, the roots and rhizomes of Panax ginseng C.A. Mey. (Araliaceae), is used as a tonic herb for thousands of years in Asian countries. Saponins are recognized as its major active ingredients and reportedly can ease disorders caused by various adverse stimuli. Nevertheless, it is unclear whether ginseng saponins have beneficial effects on stress caused by microgravity. Aim of the studyThis study aimed to assess the anti-stress effects and corresponding mechanisms of ginseng total saponins (GTSs) on simulated microgravity (SM) hindlimb-unloaded rats using a metabolomics method. Materials and methodsThe stressed rats were induced by hindlimb unloading for 7 continuous days. Levels of plasma corticosterone (CORT) and weights of immune organs including the thymuses, spleens, and adrenal glands were determined. Urinary metabolic profiles of the rats under the simulated microgravity condition with and without GTSs intervention were compared using an ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) based metabolomics method. Multivariate statistical analysis including Principal Component Analysis (PCA) and Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA) were performed. ResultsCompared with control (66.22±10.40ng/mL), the plasma CORT level of the SM rats (82.67±13.64ng/mL) were significantly (p<0.05) elevated, and GTSs could restore this elevation to a lower level (77.75±14.35ng/mL). GTSs could also significantly alleviate the atrophy of the thymuses and the spleens, as well as the hypertrophy of the adrenal glands of the SM rats. Urinary metabolic profiling showed comprehensive metabolic variation among the three groups. A series of metabolic pathways including taurine and hypotaurine, purine and pyridine, and amino acid were affected. Eleven potential biomarkers such as taurine, adenine, and valine were identified. GTSs could correct the disturbed metabolic pathways and restore the variation of these potential markers. ConclusionGTSs can exert anti-stress effects by reducing the secretion of plasma CORT, enhancing the immune function, and restoring an array of disturbed metabolic pathways and metabolites. The findings of this study provide crucial evidence of a link between metabolic imbalance and microgravity, and reveal a molecular basis for the anti-stress benefits of GTSs in the management of microgravity-related disorders.

LC/MS-based metabolomics strategy to assess the amelioration effects of ginseng total saponins on memory deficiency induced by simulated microgravity

Microgravity-induced memory deficiency seriously affects learning and memory ability of the astronaut during spaceflight, with few effective countermeasures. Panax ginseng C. A. Mey. has been used as a nootropic herb for thousands of years in Asian countries. Saponins are recognized as its major active components. Previous studies have shown that ginseng saponins offer protection against memory deficits caused by various factors. Nevertheless, the underlying mechanisms of their nootropic effects are still largely unknown. In this study, we evaluated the memory-improving effects of ginseng total saponins (GTS) on simulated microgravity hindlimb-unloaded rats using a metabolomics approach. After being exposed to a 7-days hindlimb unloading (HU), variations of plasmatic and hippocampal metabolic profiles of rats with and without GTS intervention were examined by a liquid chromatography–mass spectrometry (LC–MS) based untargeted metabolomics method. Subsequently, 8 hippocampal neurotransmitters were determined using a LC–MS/MS method. Finally, a LC–MS/MS based targeted metabolomics was performed to validate biomarkers found in the untargeted analysis. Besides, to support the metabolomics results, passive avoidance (PA) test, Nissl staining, and plasmatic corticosterone (CORT) levels determination were performed. The results showed that HU could lead to variations of 7 neurotransmitters and significantly different plasmatic and hippocampal metabolic profiles. GTS could restore most of the imbalanced neurotransmitters, especially glutamic acid and acetylcholine, and correct the levels of various disturbed learning and memory relevant biomarkers such as asparagine, phenylalanine, tyrosine, tryptophan, and choline. In addition, GTS could markedly ameliorate HU-induced memory deficiency, protect hippocampal neurons from damage, and down-regulate elevated CORT levels. In conclusion, GTS exhibits memory-improving effects mainly through regulating the metabolism of amino acids, neurotransmitters, choline, kynurenine, and sphingolipids. The findings of this study not only can deepen our understanding of the underlying molecular mechanisms of MG-induced memory disorders, but also provide scientific evidence for choosing ginseng as a countermeasure against MG-induced memory deficiency.

Treatment with ginseng total saponins improves the neurorestoration of rat after traumatic brain injury

Ethnopharmacological relevanceGinseng, the root of Panax ginseng C.A. Meyer, is a traditional medicinal herb that has been widely used in Asia for the treatment of many diseases through its effects of reinforcing vitality, strengthening the bodily resistance to pathogenic factors, engendering body liquids and allaying thirst, relieving uneasiness of the body and mind and benefiting intelligence, reducing body weight and prolonging life. Ginsenosides are the most important biologically active substances in ginseng. Many reports have suggested that ginsenosides could exert prominent neuroprotective and neurotrophic effects, promote neural stem/progenitor cell (NSC) proliferation and promote neurite outgrowth and neuronal network formation. The present study aimed to investigate whether treatment with ginsenosides could facilitate NSC proliferation in the hippocampal formation after traumatic brain injury (TBI) and contribute to the recovery of neurological functions including learning and memory. Materials and methodsThe modified Feeney׳s method was used to induce a TBI in rats. Ginseng total saponins (GTS) were treated intraperitoneally twice a day for 1 week after the TBI. The neurological functions, morphology of the hippocampus, expression of nerve growth-related factors and number of NSCs in the hippocampal formation ipsilateral to the trauma were determined. ResultsWe determined 1) GTS (5–80mg/kg) treatment after a TBI improved the recovery of neurological functions, including learning and memory, and reduced cell loss in the hippocampal area. The effects of GTS at 20, 40, 60, and 80mg/kg were better than the effects of GTS at 5 and 10mg/kg. 2) GTS treatment (20mg/kg) after a TBI increased the expression of NGF, GDNF and NCAM, inhibited the expression of Nogo-A, Nogo-B, TN-C, and increased the number of BrdU/nestin positive NSCs in the hippocampal formation. ConclusionsGTS treatment in rats after a TBI alleviated the secondary brain injury and ameliorated the neurological functions with an effective dose limit of 5–80mg/kg. GTS regulated the expression of nerve growth-related factors and improved the proliferation of neural stem/progenitor cells, which might facilitate neural regeneration and tissue repair, and might contribute to the recovery of neurological functions, including learning and memory. These effects of GTS might provide a foundation for the use of ginseng as a medicinal herb to enhance intelligence, reduce the aging process and prolong life in the traditional medicine.

Effect of intraperitoneal administered ginseng total saponins on hyperalgesia induced by repeated intramuscular injection of acidic saline in rats.

The aim of this study was to assess the antinociceptive activity of ginseng total saponins (GTS) on hyperalgesia induced by repeated intramuscular injections of acidic saline in rats and to examine the mechanisms involved. Rats were injected intraperitoneally with a 0.9% saline vehicle or various doses of GTS after the development of hyperalgesia. Rats were then injected with N-methyl-D-aspartate (NMDA) or naloxone 10 min before GTS injection. The mechanical withdrawal threshold (MWT) was assessed with von Frey filaments. The MWT was significantly increased after intraperitoneal injection of 100 mg/kg and 200 mg/kg of GTS when compared with the MWT after the development of hyperalgesia. Injection of GTS with NMDA showed a significant decrease in the MWT when compared with GTS injection. GTS showed an antinociceptive activity against chronic muscle-induced pain, and the effect of GTS may be mediated by NMDA.

Ginseng Total Saponins Reverse Corticosterone-Induced Changes in Depression-Like Behavior and Hippocampal Plasticity-Related Proteins by Interfering with GSK-3β-CREB Signaling Pathway

This study aimed to explore the antidepressant mechanisms of ginseng total saponins (GTS) in the corticosterone-induced mouse depression model. In Experiment 1, GTS (50, 25, and 12.5 mg kg−1 d−1, intragastrically) were given for 3 weeks. In Experiment 2, the same doses of GTS were administrated after each corticosterone (20 mg kg−1 d−1, subcutaneously) injection for 22 days. In both experiments, mice underwent a forced swimming test and a tail suspension test on day 20 and day 21, respectively, and were sacrificed on day 22. Results of Experiment 1 revealed that GTS (50 and 25 mg kg−1 d−1) exhibited antidepressant activity and not statistically altered hippocampal protein levels of brain-derived neurotrophic factor (BDNF) and neurofilament light chain (NF-L). Results of Experiment 2 showed that GTS (50 and 25 mg kg−1 d−1) ameliorated depression-like behavior without normalizing hypercortisolism. The GTS treatments reversed the corticosterone-induced changes in mRNA levels of BDNF and NF-L, and protein levels of BDNF NF-L, phosphor-cAMP response element-binding protein (Ser133), and phosphor-glycogen synthase kinase-3β (Ser9) in the hippocampus. These findings imply that the effect of GTS on corticosterone-induced depression-like behavior may be mediated partly through interfering with hippocampal GSK-3β-CREB signaling pathway and reversing decrease of some plasticity-related proteins.

The antidepressant effects of ginseng total saponins in male C57BL/6N mice by enhancing hippocampal inhibitory phosphorylation of GSK-3β.

Ginseng total saponins (GTS) are principal bioactive ingredients of Panax ginseng. In this study, we investigated the antidepressant effect of GTS on the corticosterone-induced mouse depression model and explored the underlying mechanism. Corticosterone (20 mg kg(-1) d(-1)) was subcutaneously administered for 22 d to induce the model, before doses of GTS (12.5, 25, and 50 mg kg(-1) d(-1)) or fluoxetine (10 mg kg(-1) d(-1)) were subsequently given by gavage. On day 20 and 21, depression-like behavior was observed via a forced swimming test and a tail suspension test respectively. At 6 h after the last dose of corticosterone (day 22), all mice were sacrificed followed by serum corticosterone assays and Western blot analysis. The results showed that GTS (25 and 50 mg kg(-1) d(-1))treatments relieved depression-like behavior without altering the elevated serum corticosterone levels. Furthermore, GTS treatments raised the down-regulated levels of hippocampal glycogen synthase kinase-3β (GSK-3β) inhibitory phosphorylation. In contrast, fluoxetine (10 mg kg(-1) d(-1)) treatment reversed the increased corticosterone level and had no effect on the decreased GSK-3β inhibitory phosphorylation. These findings confirmed the antidepressant effect of GTS in the corticosterone-induced mouse depression model. Enhancing GSK-3β inhibitory phosphorylation may be one of the underlying mechanisms.

Antihyperalgesic effects of ginseng total saponins in a rat model of incisional pain

BackgroundThe aim of this study was to assess whether intraperitoneal administration of ginseng total saponins (GTS) has antihyperalgesic effects in a rat model of incisional pain. The proinflammatory responses and reversal of the antihyperalgesic effect of GTS by N-methyl-d-aspartate (NMDA) or naloxone were also evaluated. Materials and methodsRats were injected intraperitoneally with 0.9% saline vehicle or various doses of GTS before or after a plantar incision. Paw withdrawal in response to application of the von Frey filament with the lowest bending force marked the mechanical withdrawal threshold (MWT). Blood samples were collected for the assessment of serum interleukin (IL)-1β and IL-6 levels. The IL levels were measured using an enzyme-linked immunosorbent assay kit. Rats were injected intraperitoneally with NMDA or naloxone before the GTS injection to assess the reversal of the antihyperalgesic effect of GTS. ResultsThe MWT measured 2 h after the plantar incision increased significantly after the postincision administration of 50, 100, or 200 mg/kg of GTS compared with the MWT at 2 h after plantar incision. The MWT also increased significantly after the preincision injection of 100 or 200 mg/kg of GTS compared with the MWT of the vehicle control. Administration of GTS suppressed the postincision rise in serum IL-1β levels and NMDA inhibited the increase in the MWT compared with GTS alone. ConclusionsIntraperitoneal administration of GTS before or after surgery induces antihyperalgesic effects in a rat model of incisional pain. The effects on mechanical hyperalgesia may be associated with anti-inflammatory cytokines and NMDA signaling.

Protective effects of ginseng total saponins against hepatic ischemia/reperfusion injury in experimental obstructive jaundice rats

Context: Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is one of the most extensively used herbs for stroke and chronic debilitating conditions in East Asian countries. Ginsenosides (GS) are the main bioactive compounds for ginseng's efficacy, but the mechanisms have not been fully clarified.Objective: To investigate hepatoprotective effects of GS against ischemia/reperfusion (IR) injury in the experimental obstructive jaundice rats.Materials and methods: GS was fed to cholestatic rats with IR injury daily for 6 d at a dose of 1.10 g/kg. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by colorimetric method. Apoptosis was measured quantitatively by the terminal transferase UTP nick end-labeling method. Protein expression of Bax and Bcl-2 was detected by immunohistochemistry.Results and discussion: After intervention of GS to cholestatic rats with IR injury, the levels of activating blood flow were significantly improved, and the levels of serum ALT were decreased 1.7-times, AST decreased 1.3-times, but SOD activities were increased 1.1-times compared with those of the model rats. It could also reverse histopathological changes and inhibit IR-induced apoptosis of hepatic tissues via decrease of Bax/Bcl-2 ratio (from 2.87 ± 0.57 to 1.65 ± 0.29). Oral administration of GS in a dosage of 26.4 g/kg did not lead to toxic effects in rats.Conclusion: GS attenuated the IR injury in the presence of cholestasis and could be considered for the clinical treatment of cholestasis.

Treatment with ginseng total saponins reduces the secondary brain injury in rat after cortical impact

The present study was designed to investigate the neuroprotective effect of ginseng total saponins (GTSs) and its underlying mechanisms in a rat model of traumatic brain injury (TBI). Rats were injected with GTSs (20 mg/kg, i.p.) or vehicle for 14 days after TBI. Neurological functions were determined using beam balance and prehensile traction tests at 1-14 days after trauma. Brain samples were extracted at 1 day after trauma for determination of water content, Nissl staining, enzyme-linked immunosorbent assay, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling, and measurement of oxidative stress variables and inflammatory cytokines. Moreover, the dose response of the neuroprotective effect and time window of the efficacy of GTSs were also determined. We found that treatment of GTSs 1) improved the neurological function with an effective dosage of 5-80 mg/kg and an efficacy time window of 3-6 hr after TBI; 2) reduced brain water content and neuronal loss in the hippocampal CA3 area; 3) increased the activity of superoxide dismutase and decreased the activity of nitric oxide synthase and the amount of malondialdehyde and nitric oxide; 4) down-regulated interleukin-1β, interleukin-6, and tumor necrosis factor-α and upregulated interleukin-10 in the cortical area surrounding the injured core; and 5) inhibited the apoptotic cell death and expression of caspase-3 and bax and raised the expression of bcl-2. These findings suggest that administration of GTSs after TBI could reduce the secondary injury through inhibiting oxidative and nitrative stress, attenuating inflammatory response, and reducing apoptotic cell death.

Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy

BackgroundThe effectiveness of ginseng in preventing and treating various central nervous system (CNS) diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly explained. Anti-inflammatory approaches are becoming promising therapeutic strategies for depression and other CNS diseases; however, previous studies have focused largely on anti-inflammatory therapies directed at the central nervous system. It is thus of interest to determine whether ginsenosides, characterized by poor brain distribution, are also effective in treating lipopolysaccharide- (LPS) induced depression-like behavior and neuroinflammation.MethodsIn an LPS-induced depression-like behavior model, the antidepressant effects of ginseng total saponins (GTS) were assessed using a forced swimming test, a tail suspension test, and a sucrose preference test. The anti-inflammatory efficacies of GTS in brain, plasma, and LPS-challenged RAW264.7 cells were validated using ELISA and quantitative real-time PCR. Moreover, indoleamine 2,3-dioxygenase (IDO) activity in the periphery and brain were also determined by measuring levels of kynurenine/tryptophan.ResultsGTS significantly attenuated LPS-induced depression-like behavior. Moreover, LPS-induced increases in 5-HT and tryptophane turnover in the brain were significantly reduced by GTS. IDO activities in brain and periphery were also suppressed after pretreatment with GTS. Furthermore, GTS-associated recovery from LPS-induced depression-like behavior was paralleled with reduced mRNA levels for IL-1β, IL-6, TNF-α, and IDO in hippocampus. Poor brain distribution of ginsenosides was confirmed in LPS-challenged mice. GTS treatment significantly decreased production of various proinflammatory cytokines in both LPS-challenged mice and RAW264.7 cells.ConclusionThis study suggests that the anti-depression efficacy of GTS may be largely attributable to its peripheral anti-inflammatory activity. Our study also strengthens an important notion that peripheral anti-inflammation strategies may be useful in the therapy of inflammation-related depression and possibly other CNS diseases.

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.

Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression

Ginseng total saponins (GTS) are the major active components of Panax ginseng C.A. Meyer, which has been used as a popular tonic herb for 2000 years in Far East countries. In the present study, two classic animal models: the forced swimming test (FST) and the chronic mild stress (CMS) model were used to evaluate the antidepressant-like activities of GTS. It was observed that GTS at doses of 50 and 100 mg/kg significantly reduced the immobility time in the FST in mice after 7-day treatment. GTS also reversed the reduction in the sucrose preference index, decrease in locomotor activity as well as prolongation of latency of feeding in the novelty environment displayed by CMS rats. In addition, HPLC-ECD and immunohistochemical staining analysis indicated that the CMS-induced decrease in monoamine neurotransmitter concentration and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were almost completely reversed by GTS. In conclusion, GTS exerts antidepressant-like effects in two highly specific and predictive animal models of depression. The activity of GTS in antidepression may be mediated partly through enhancing the monoamine neurotransmitter concentration and BDNF expression in the hippocampus.

Effects of ginseng total saponins on nerve growth factor expression in rat with estradiol valerate-induced polycystic ovaries

To investigate the effect of ginseng total saponins (GTS) on expression of nerve growth factor in rat with polycystic ovaries. A total of thirty rats were randomly divided into normal control group, untreated group and GTS group. Polycystic ovaries were induced by a single intramuscular injection of 4 mg estradiol valerate (EV) in rats of the untreated group and GTS group. The rats in the GTS group were administered 50 mg/kg GTS every other day by intraperitoneal injection for 30 days after the EV injection. The expressions of NGF in the ovaries, pituitary and hippocampus were observed by method of immunohistochemistry. Comparison with the normal control group revealed that the expressions of NGF in ovaries, pituitary and hippocampus of rats in the untreated group were increased (P<0.05). The ovarian morphology of the GTS group was almost as normal as that of the normal control group. As compared with the untreated group, the expression of NGF in ovaries of the rats in GTS group was obviously decreased (P<0.05), while the expression of NGF in pituitary and hippocampus showed on difference. GTS can decrease the expression of NGF in ovary tissue in rats with polycystic ovaries induced by EV, which may be its mechanism in lessening the polycystic ovary.

Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine

We have reported that ginseng total saponin (GTS) inhibited the development of physical and psychological dependence on morphine. However, the possible molecular mechanisms of GTS are unclear. Therefore, this study was undertaken to understand the possible molecular mechanism of GTS on the inhibitory effects of morphine-induced dependence. It has been reported that the up-regulated cAMP pathway in the LC of the mouse brain after repeated administration of morphine contributes to the feature of withdrawals. GTS inhibited up-regulation of cAMP pathway in the LC after repeated administration of morphine in this experiment. GTS inhibited cAMP levels and protein expression of protein kinase A (PKA). In addition, GTS inhibited the increase of cAMP response element binding protein (CREB) phosphorylation. Therefore, we conclude that the inhibitory effects of GTS on morphine-induced dependence might be mediated by the inhibition of cAMP pathway.

Inhibitory Effects of Ginseng Total Saponins on Behavioral Sensitization and Dopamine Release Induced by Cocaine

Many studies have suggested that the behavioral and reinforcing effects of cocaine can be mediated by the central dopaminergic systems. It has been shown that repeated injections of cocaine produce an increase in locomotor activity, the expression of the immediate-early gene, c-fos, and the release of dopamine (DA) in the nucleus accumbens (NAc), which is one of the main dopaminergic terminal areas. Several studies have shown that behavioral activation and changes in extracellular dopamine levels in the central nervous system induced by psychomotor stimulants are prevented by ginseng total saponins (GTS). In order to investigate the effects of GTS on the repeated cocaine-induced behavioral and neurochemical alterations, we examined the influence of GTS on the cocaine-induced behavioral sensitization and on c-Fos expression in the brain using immunohistochemistry in rats repeatedly treated with cocaine. We also examined the effect of GTS on cocaine-induced dopamine release in the NAc of freely moving rats repeatedly treated with cocaine using an in vivo microdialysis technique. Pretreatment with GTS (100, 200, 400 mg/kg, i.p.) 30 min before the daily injections of cocaine (15 mg/kg, i.p.) significantly inhibited the repeated cocaine-induced increase in locomotor activity as well as the c-Fos expression in the core and shell in a dose-dependent manner. Also, pretreatment with GTS significantly decreased the repeated cocaine-induced increase in dopamine release in the NAc. Our data demonstrate that the inhibitory effects of GTS on the repeated cocaine-induced behavioral sensitization were closely associated with the reduction of dopamine release and the postsynaptic neuronal activity. The results of the present study suggest that GTS may be effective for inhibiting the behavioral effects of cocaine by possibly modulating the central dopaminergic system. These results also suggest that GTS may prove to be a useful therapeutic agent for cocaine addiction.

Effects of Ginsenosides, Active Ingredients of Panax ginseng, on Development, Growth, and Life Span of Caenorhabditis elegans

The backbone structure of ginsenosides, active ingredients of Panax ginseng, is similar with that of sterol, especially cholesterol. Caenorhabditis elegans (C. elegans) is one of free living nematodes and is well-established animal model for biochemical and genetic studies. C. elegans cannot synthesize de novo cholesterol, although cholesterol is essential requirement for its growth and development. In the present study, we investigated the effects of ginseng total saponins (GTS) on the average brood size, growth, development, worm size, and life span of C. elegans in cholesterol-deprived and -fed medium. Cholesterol deprivation caused damages on normal growth, reproduction, and life span of worms throughout F1 to F3 generations. GTS supplement to cholesterol-deprived medium restored the growth, reproduction, and life span of worms as much as cholesterol alone-fed medium. GTS co-supplement to cholesterol-fed medium not only promoted worm reproduction but also induced bigger worms and faster growth than cholesterol-fed medium. In study to identify which ginsenosides are responsible for life span restoring effects of GTS, we found that ginsenoside Rc supplement not only restored life span of worms grown in cholesterol-deprived medium but also prolonged life span of worms grown in cholesterol-fed medium. Worms grown in medium supplemented with ginsenoside Rb(1) or Rc to cholesterol-deprived medium exhibited strong filipin staining, in which filipin forms tight and specific complexes with 3beta-hydroxy sterols. These results show a possibility that ginsenosides could be utilized by C. elegans as a sterol substitute and further indicate that ginsenoside Rc is the component of Panax ginseng that prolongs the life span of C. elegans.

Effects of Ginseng Total Saponins on Pacemaker Currents of Interstitial Cells of Cajal from the Small Intestine of Mice

Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of ginsenosides on gastrointestinal (GI) motility. We studied the modulation of pacemaker activities by ginseng total saponins in the interstitial cells of Cajal (ICC) using the whole cell patch-clamp technique. Externally applied ginseng total saponins (GTS) produced membrane depolarization in the current-clamp mode and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid or niflumic acid abolished the generation of pacemaker currents, but only treatment with flufenamic acid inhibited the GTS-induced tonic inward currents. The tonic inward currents induced by GTS were not inhibited by the intracellular application of guanosine 5'-[beta-thio]diphosphate trilithium salt. Pretreatment with a Ca(2+)-free solution, with U-73122, an active phospholipase C inhibitor, and with thapsigargin, a Ca(2')-ATPase inhibitor of the endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the GTS-induced action. However, treatment with chelerythrine and calphostin C, protein kinase C inhibitors, did not block the GTS-induced effects on the pacemaker currents. These results suggest that ginsenosides modulate the pacemaker activities of the ICC, and the ICC can be targets for ginsenosides, and their interaction can affect intestinal motility.