notoginsenoside-r1 and Disease-Models--Animal

Chronic unpredictable mild stress (CUMS) can cause a series of depressive symptoms in depression patients. Recently, notoginsenoside R1 (NGR1) has been reported to play crucial roles in the anti-inflammatory, antioxidant, and anti-apoptotic. However, the role and mechanisms of NGR1 in improving symptoms of depressive behavior remain unknown. Evaluating and identifying its value and exploring the mechanisms of NGR1 on CUMS-induced depressive behavior were the aims of this study. Here, rats were separated into five different groups and treated with or without different concentrations of the NGR1. Then, the body weight, sucrose preference rate, immobility time, crossing number, rearing number, and grooming number were determined to evaluate the effect of NGR1 on improving the depressive behavior of CUMS rats. Subsequently, the morphology of hippocampal neurons and protein expression of brain-derived neurotrophic factor in each group were examined by hematoxylin and eosin staining and western blot to show the neuroprotective effects of NGR1. Furthermore, the mRNA and protein expression of TNF-α, IL-6, and IL-1β were also detected by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay to verify the anti-inflammatory effects of NGR1 on CUMS rats. In addition, the cell apoptosis-related proteins were examined to reveal that NGR1 can inhibit cell apoptosis in CUMS rats. Moreover, it was confirmed that NGR1 attenuated the symptoms of depressive behavior by mediated PI3K/Akt/NF-κB pathway. Together, this study shows that NGR1 improves depressive behavior induced by chronic stress in rats through activation of PI3K/AKT/NF-κB pathway.

Topics: Animals; Depression; Disease Models, Animal; Ginsenosides; Hippocampus; Humans; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Stress, Psychological

Ischemic stroke is a syndrome of severe neurological responses that cause neuronal death, damage to the neurovascular unit and inflammation. Notoginsenoside R1 (NG-R1) is a neuroprotective drug that is commonly used to treat neurodegenerative and cerebrovascular diseases. However, its potential mechanisms on the regulation of small molecule metabolism in ischemic stroke are largely unknown. The aim of this study was to explore the potential mechanisms of NG-R1 on the regulation of small molecule metabolism after ischemic stroke. Here, we found that NG-R1 reduced infarct size and improved neurological deficits by ameliorating neuronal damage and inhibiting glial activation in MCAO/R rats. Furthermore, using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), we clarified that NG-R1 regulated ATP metabolism, the tricarboxylic acid (TCA) cycle, the malate-aspartate shuttle, antioxidant activity, and the homeostasis of iron and phospholipids in the striatum and hippocampus of middle cerebral artery occlusion/reperfusion (MCAO/R) rats. In general, NG-R1 is a promising compound for brain protection from ischemic/reperfusion injury, possibly through the regulation of brain small molecule metabolism.

Topics: Animals; Apoptosis; Brain; Disease Models, Animal; Energy Metabolism; Ginsenosides; Infarction, Middle Cerebral Artery; Ischemic Stroke; Male; Neuroprotective Agents; Predictive Value of Tests; Rats, Sprague-Dawley; Reperfusion Injury; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors

Cervical Spondylotic Myelopathy (CSM) is one of the most serious spinal cord disorders in adults. Pharmacological modulation of ion channels is a common strategy to interfere with CSM and prevent neuronal damage.. Here, we investigated the effects of Jingshu Keli (JSKL), a traditional Chinese herbal formula, on CSM-related gait abnormality, mechanical allodynia and thermal hyperalgesia, and assessed the neuronal mechanisms of JSKL on cultured brainstem cells. Behavioral tests and patch clamp recordings were performed to make this assessment.. In our study, we found that JSKL significantly recovered the gait performance (P<0.001) and decreased the levels of mechanical pain in 18.9% (P<0.01) and thermal pain in 18.1% (P<0.05). Further investigation suggested that JSKL and its containing ginsenoside Rb1 (GRb1), notoginsenoside R1 (NGR1) reduced the action potential frequency in 38.5%, 27.2%, 25.9%, and hyperpolarized resting membrane potential in 15.0%, 13.8%, 12.1%, respectively. Kir channels, not KV channels and KCa channels, were the major intermediate factors achieving treatment effects. Finally, immunostaining results showed that the phosphorylation of Kir3.1 was promoted, whereas the total expression level did not change.. Our study reveals a novel strategy of treating CSM by using Traditional Chinese Medicines (TCMs) containing active components.

Topics: Animals; Disease Models, Animal; Drugs, Chinese Herbal; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Gait; Ginsenosides; Hyperalgesia; Male; Medicine, Chinese Traditional; Pain Measurement; Rats; Rats, Sprague-Dawley; Spinal Cord Diseases

BACKGROUND This study investigated the effect and mechanism of notoginsenoside R1 (NGR1) on chronic atrophic gastritis (CAG) in a rat model. MATERIAL AND METHODS To perform our investigation, a rat model of CAG was established, and then rats were treated with various doses of NGR1. After treatment, hematoxylin-eosin (HE) staining was used for histopathological observation and further scoring. Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of gastrointestinal hormones, inflammatory factors, gastric mucosal destruction factors, and gastric mucosal-protective factors. Gene and protein expressions were measured using quantitative real-time PCR and Western blot assay, respectively. RESULTS Results indicated that NGR1 relieved rat CAG. NGR1 treatment significantly increased the levels of gastrin (GAS) and somatostatin (SS) and reduced motilin (MTL) in the serum of CAG rats. The serum levels of interleukin (IL)-1β and IL-6 were significantly reduced by NGR1 treatment in CAG rats in a dose-dependent manner. Additionally, the increased levels of prostaglandin (PG)E2, nitric oxide synthase (NOS), and endothelin (ET) in CAG rats were significantly decreased by NGR1 administration. Moreover, the decreased level of secretory IgA (sIgA) and glutathione (GSH) in rats caused by MNNG was notably increased by NGR1 treatment. No significant changes were found in glutathione disulfide (GSSG) secretion. Finally, we found that the increased Bcl-2 expression and reduced Bax expression in the stomach tissues of rats caused by MNNG were eliminated by NGR1 treatment. CONCLUSIONS NGR1 exerts a protective effect on CAG, and it is a multi-target, multi-linked, comprehensive process.

Topics: Animals; Chronic Disease; Disease Models, Animal; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Ginsenosides; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Somatostatin

Restenosis caused by neointimal hyperplasia significantly decreases long-term efficacy of percutaneous transluminal angioplasty (PTA), stenting, and by-pass surgery for managing coronary and peripheral arterial diseases. A major cause of pathological neointima formation is abnormal vascular smooth muscle cell (VSMC) proliferation and migration. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and has reported cardioprotective, neuroprotective and anti-inflammatory effects. However, its role in modulating VSMC neointima formation remains unexplored. Herein, we report that NGR1 inhibits serum-induced VSMC proliferation and migration by regulating VSMC actin cytoskeleton dynamics. Using a mouse femoral artery endothelium denudation model, we further demonstrate that systemic administration of NGR1 had a potent therapeutic effect in mice, significantly reducing neointimal hyperplasia following acute vessel injury. Mechanistically, we show that NGR1's mode of action is through inhibiting the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Taken together, this study identified NGR1 as a potential therapeutic agent for combating restenosis after PTA in cardiovascular diseases.

Topics: Animals; Cell Movement; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Ginsenosides; Humans; Hyperplasia; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

Aseptic periprosthetic osteolysis is a complication induced by wear particles after hip joint replacement, which shortens the service life of prostheses. Although many methods have been applied to prevent this complication, the results were not always successful. In the present study, we explored the prophylactic effect of notoginsenoside R1 (NG-R1) on a Ti particle-induced mouse calvarial osteolysis model and the inhibitory effect on RANKL-mediated osteoclastogenesis and osteoclast bone resorption. Our results indicated that intraperitoneal injection of NG-R1(10 or 20mg/kg/day), a constituent of notoginseng, alleviates Ti particle-induced mouse calvarial osteolysis after twelve days post-treatment. In vitro, we observed that NG-R1 inhibits RANKL-mediated mitogen-activated protein kinases (MAPKs), including the phosphorylation levels of JNK1/2, P38, ERK1/2 and NF-kappa B (NF-κB) signalling pathways, and suppresses RANKL-mediated osteoclastogenesis and osteoclast bone resorption. These results suggest that NG-R1 may be a promising therapeutic agent for preventing wear particle-induced periprosthetic osteolysis.

Topics: Animals; Arthroplasty, Replacement; Bone Resorption; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Ginsenosides; Humans; Male; Metal Nanoparticles; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoclasts; Osteolysis; Postoperative Complications; Prosthesis Failure; RANK Ligand; RAW 264.7 Cells; Signal Transduction; Titanium

This study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.. The in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.. R1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.. R1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.

Topics: Animals; Blood Vessels; Cell Movement; Cell Proliferation; Collagen; Disease Models, Animal; Drug Combinations; Ginsenosides; Human Umbilical Vein Endothelial Cells; Humans; Laminin; Neovascularization, Physiologic; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proteoglycans; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor Receptor-2; Zebrafish

Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases.. We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro.. H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (± dP/dt max/min).. NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P-PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardiac dysfunction.. We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1.

Topics: Animals; Cell Line; Cell Survival; Disease Models, Animal; Endoplasmic Reticulum Stress; Gene Expression Regulation; Ginsenosides; Male; Membrane Potential, Mitochondrial; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Signal Transduction

Notoginsenoside R1 (R1) is the main bioactive component in Panax notoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of R1 on inflammatory bowel disease (IBD). The present study demonstrated that R1 alleviated the severity of dextran sulfate sodium-induced colitis in mice by decreasing the activity of myeloperoxidase, the production of cytokines, the expression of proinflammatory genes, and the phosphorylation of IκB kinase, IκBα, and p65 in the colon. Further studies indicated that R1 dose-dependently activated human/mouse pregnane X receptor (PXR), a known target for decreasing inflammation in IBD, and upregulated the expression of genes involved in xenobiotic metabolism in colorectal cells and the colon. Ligand pocket-filling mutant (S247W/C284W or S247W/C284W/S208W) of the human PXR abrogated the effect of R1 on PXR activation. Time-resolved fluorescence resonance energy transfer PXR competitive binding assay confirmed R1 (ligand) binding affinity. In addition, PXR overexpression inhibited nuclear factor-κB (NF-κB)-luciferase activity, which was potentiated by R1 treatment. PXR knockdown by small interfering RNA demonstrated the necessity of PXR in R1-induced upregulation of the expression of xenobiotic-metabolizing enzymes and downregulation of NF-κB activity. Finally, the anti-inflammatory effect of R1 was confirmed in trinitrobenzene sulfonic acid-induced colitis in mice. These findings suggest that R1 attenuates experimental IBD possibly via the activation of intestinal PXR signaling.

Topics: Animals; Anti-Inflammatory Agents; Colon; Disease Models, Animal; Female; Gene Expression; Ginsenosides; HT29 Cells; Humans; Inflammatory Bowel Diseases; Interleukin-6; Mice, Inbred C57BL; NF-kappa B; Peroxidase; Pregnane X Receptor; Receptors, Steroid; Signal Transduction; Tumor Necrosis Factor-alpha

Notoginsenoside R1 (NTR1) is the main active ingredient of the well-known traditional Chinese herbal medicine Panax notoginseng, the root of Panax notoginseng (Burk.) F. H. Chen. Studies demonstrated that NTR1 may have some neuronal protective effects. Alzheimer's disease (AD) is a neurodegenerative disease characterized by β -amyloid protein (Aβ) deposition, neurofibrillary tangle formation and neuronal loss. This study was designed to explore the protective effect of NTR1 on an APP/PS1 double-transgenic mouse model of AD and investigate the possible mechanism. The 3-month-old mice were fed with 5 mg/(kg•d), 25 mg/(kg•d) NTR1 or vehicle via oral gavage for 3 months and changes in behavior, neuropathology, and amyloid pathology were investigated. The mice with NTR1 treatment showed significant amelioration in the cognitive function and increased choline acetyl transferase expression, as compared to the vehicle treated mice. NTR1 treatment inhibited Aβ accumulation and increased insulin degrading enzyme expression in both APP/PS1 mice and N2a-APP695sw cells, suggesting that of NTR1 may exert its protective effects through the enhancement of the Aβ degradation. Furthermore, our data showed that the increased level of peroxisome proliferator-activated receptor γ (PPARγ) and the up-regulation of insulin degrading enzyme induced by NTR1 were inhibited by administration of GW9662 (a PPARγ antagonist), indicating that the effect of NTR1 was mediated, at least in part, by PPARγ. Thus, our findings provide the evidences that NTR1 has protective effect on AD mouse model and NTR1 may be a potential candidate for AD treatment.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Anilides; Animals; Cell Line, Tumor; Central Nervous System Agents; Choline O-Acetyltransferase; Cognition; Disease Models, Animal; Ginsenosides; Humans; Insulysin; Male; Mice, Inbred C57BL; Mice, Transgenic; Neuroprotective Agents; PPAR gamma; Presenilin-1; Random Allocation; Up-Regulation

Notoginsenoside R1 (NR1) is the main bioactive component in panaxnotoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of NR1 on antihypertension and the underlying mechanisms are still not clear. This study is aim to investigate the effect and elicit the mechanism of NR1 in antihypertension. Firstly, to assess the ability of NR1 in antihypertension, NR1 was injected in spontaneously hypertensive rats (SHR) via the vena caudalis. Then we examined the rats systolic blood pressure and inducible nitric oxide synthase (iNOS) activation in rats thoracoabdominal aortic. To further investigate the molecular mechanism of NR1 reduce blood pressure, primary SHR and WYK rat vascular endothelial cells (RVECs) were used for next study. LncRNAs related to hypertension were gained from bioinformatics analysis. The role of LncRNAs was finally characterized in RVECs by siRNA. Our results showed that NR1 significantly reduce blood pressure in SHR and induce nitric oxide (NO) generation through increasing the phosphorylation of iNOS. Through bioinformatics analysis and knockdown LncRNA AK094457 in RVECs, we also found LncRNA AK094457 promoted iNOS expression and NO concentration. Thus, we conclude that NR1 reduces the caudal blood pressure of SHR through induction of iNOS regulated by long non-coding RNA AK094457. These findings may have important implications for understanding the mechanisms of NR1 regulation blood pressure.

Topics: Animals; Antihypertensive Agents; Aorta; Blood Pressure; Cells, Cultured; Computational Biology; Disease Models, Animal; Endothelial Cells; Enzyme Activation; Gene Expression Profiling; Ginsenosides; Hypertension; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Rats, Inbred SHR; Rats, Inbred WKY; RNA Interference; RNA, Long Noncoding; Time Factors; Transfection

Astragalus and Panax notoginseng are commonly used to treat cardio-cerebrovascular diseases in China and are often combined together to promote curative effect. We speculate that the enhancement of the combination on anticerebral ischemia injury may come from the main active components. The purpose of this work was to probe the effects and mechanisms of Astragaloside IV (the active component of Astragalus) combined with Ginsenoside Rg1, Ginsenoside Rb1, and Notoginsenoside R1 (the active components of P. notoginseng) to antagonize ischemia/reperfusion (I/R) injury via inflammation and apoptosis. C57BL/6 mice were randomly divided into sham, model, Astragaloside IV, Ginsenoside Rg1, Ginsenoside Rb1, Notoginsenoside R1, four active components combination, and Edaravone groups. After administration for 3 days, bilateral common carotid arteries (CCA) were occluded with artery clip for 20[Formula: see text]min followed by reperfusion for 24[Formula: see text]h. Our results showed that the survival rate of nerve cell in hippocampal CA1 decreased while the apoptotic rate increased, and the level of caspase-3 protein in brain tissues was elevated, the expressions of TNF-a, IL-1, and ICAM-1 mRNA as well as phosphorylated nuclear factor kappa B (NF-κB) inhibitor protein α (p-IκBa) in brain tissues were up-regulated, and the nuclear translocation rate of NF-κB was raised. Additionally, the protein expressions of phosphorylated tyrosine kinase 1 (p-JAK1), phosphorylated signal transducer and activator of transcription-1 (p-STAT1), glucose regulated protein 78 (GRP78), caspase-12, and phosphorylated c-Jun N-terminal kinases 1/2 (p-JNK1/2) in brain tissues were also significantly strengthened after I/R for 24 h. All drugs could increase neurocyte survival rate in hippocampal CA1, decrease the apoptotic rate, and inhibit caspase-3 protein expression, in contrast, the effects of four active components combination were better than those of active components alone. In addition, Astragaloside IV and Ginsenoside Rg1 could down-regulate the level of TNF-α, and ICAM-1 mRNA, respectively, Notoginsenoside R1 reduced both TNF-α and ICAM-1 mRNA, and the combination of the 4 effective components had inhibitory effects on the expressions of TNF-α, IL-1β, and ICAM-1 mRNA. Astragaloside IV, Ginsenoside Rg1, Notoginsenoside R1, and 4 effective components combination were able to restrain the phosphorylation of IκBα, and relieve the nuclear translocation rate of NF-κB. Moreover, the eff

Topics: Animals; Apoptosis; Astragalus Plant; Brain Ischemia; CA1 Region, Hippocampal; Cell Survival; Disease Models, Animal; Drug Combinations; Endoplasmic Reticulum Chaperone BiP; Ginsenosides; Inflammation; Janus Kinase 1; Male; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; NF-kappa B; Panax notoginseng; Phytotherapy; Reperfusion Injury; Saponins; STAT1 Transcription Factor; Triterpenes

To establish an HPLC-UV method for determining pharmacokinetic difference of notoginsenoside R1 between normal rats and ischemic rats.. 48 male SD rats were randomly divided into normal group and acute myocardial ischemia( AMI) model group induced by pituitrin and each group was classified into high,middle and low-dose of groups with notoginsenoside R1 (200, 100 and 50 mg/kg) respectively. Blood samples were collected at different points in time after they were administered once by gavage and separated by Waters symmetry C18 column (250 mm x 4.6 mm, 5 µm) under the detective wavelength 203 nm, the mobile phase was acetonitrile-water with icariin as the internal standard and the pharmacokinetic parameters were calculated by DAS 2. 0.. Notoginsenoside R1 had good linearity in the ranges of 0.2~125 µg/mL (R2 = 0.9997) with SNR 1:3 and the lowest detection limit was 0.053 µg/mL, the extraction rate, RSDs of within-day and between-day, specificity, accuracy and precision accorded with the require-ment of bio-sample pretreatment. Compared to the normal group, AUC0-t, and AUC0-∞ was significantly increased (P < 0.01) and the terminal half-life was prolonged markedly (P < 0.01) in AMI group.. The method is simple, accurate and had high specificity and sensitivity, that could be applied in quantitative determination of notoginsenoside R1 and research of pharmacokinetics; the relative bioavailability of notoginsenoside R1 is increased significantly in AMI group,which indicates that notoginsenoside R1 has better effect in model rat.

Topics: Animals; Disease Models, Animal; Ginsenosides; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley

Atherosclerosis is the primary cause of cardiovascular diseases and stroke. The current study evaluated the interventional effects of a naturally occurring compound Notoginsenoside R1 (NR1) on atherosclerosis in ApoE-/- mice.. The atherosclerotic lesion was significantly alleviated by NR1 treatment and this attenuation was marked by reduction in lipid deposition, fibrosis and oxidative stress. Increased serum levels of GSH and SOD and decreased level of MDH were observed in NR1-treated ApoE-/- mice. NR1 treatment also significantly decreased the levels of CHO, TG, ox-LDL and increased the level of HDL. Additionally, the levels of inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced in NR1-treated ApoE-/- mice. Furthermore, significantly increased aortic expression of miR-26a, miR-21, miR-126a, miR-132, miR-146 and miR-155 and decreased expression of miR-20a and miR-92a were observed in the vehicle-treated ApoE-/- mice. While NR1 treatment led to a significant reduction in the expression of miR-21, miR-26a, miR-126 and increased expression of miR-20a.. Collectively, our results demonstrated for the first time the anti-atherosclerotic effects of NR1, which could be in part mediated through its multiple targeting effects on inflammation, oxidative stress, lipid metabolism and microRNA expression. These results therefore justify further evaluation of NR1 as a therapeutic agent treating atherosclerosis.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cytokines; Disease Models, Animal; Gene Expression Regulation; Ginsenosides; Inflammation Mediators; Lipid Metabolism; Lipids; Mice, Inbred C57BL; MicroRNAs; Oxidative Stress

Neurodegeneration and synaptic dysfunction observed in Alzheimer's disease (AD) have been associated with progressive decrease in neuronal activity. Here, we investigated the effects of Notoginsenoside R1 (NTR1), a major saponin isolated from Panax notoginseng, on neuronal excitability and assessed the beneficial effects of NTR1 on synaptic and memory deficits under the Aβ-enriched conditions in vivo and in vitro. We assessed the effects of NTR1 on neuronal excitability, membrane ion channel activity, and synaptic plasticity in acute hippocampal slices by combining electrophysiological extracellular and intracellular recording techniques. We found that NTR1 increased the membrane excitability of CA1 pyramidal neurons in hippocampal slices by lowering the spike threshold possibly through a mechanism involving in the inhibition of voltage-gated K(+) currents. In addition, NTR1 reversed Aβ1-42 oligomers-induced impairments in long term potentiation (LTP). Reducing spontaneous firing activity with 10 nM tetrodotoxin (TTX) abolished the protective effect of NTR1 against Aβ-induced LTP impairment. Finally, oral administration of NTR1 improved the learning performance of the APP/PS1 mouse model of AD. Our work reveals a novel mechanism involving in modulation of cell strength, which contributes to the protective effects of NTR1 against Aβ neurotoxicity.

Topics: Amyloid; Amyloid beta-Peptides; Animals; Disease Models, Animal; Ginsenosides; Hippocampus; Long-Term Potentiation; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Neurons; Potassium; Tetrodotoxin