Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin （DCX）＋ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX＋ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX＋ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.

Panax notoginseng saponins preconditioning protects rat liver grafts from ischemia/reper- fusion injury via an antiapoptotic pathway

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of primary graft dysfunction and renders an al- lograft more immunogenic in orthotopic liver transplanta- tion (OLT). Panax notoginseng saponins (PNS) has been re- ported to exert protective effects against I/R injury to vari- ous organs. The objective of this study is to investigate whether PNS preconditioning protects rat liver grafts from I/R injury via an antiapoptotic pathway. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation ( OLT) and were divided into PNS preconditioning group (group P) and normal saline control group (group N) randomly according to whether PNS (50 mg/kg) was injected intra- venously 1 hour before liver grafts harvesting, and sham group (group S). The animals were separately killed 2, 6 and 24 hours after reperfusion. Plasma samples were collect- ed for test of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Liver tissues were collected to de- tect histological changes, apoptosis and the expression of TNF-α, Bcl-2 and Caspase-3 mRNA. RESULTS: The serum levels of ALT and AST and the apop- tosis index (AI) of liver tissue in group P were lower than in group N significantly 2, 6 and 24 hours after reperfusion. Compared with group N, the expression of TNF-a and Caspase-3 mRNA was reduced significantly in group P 2 and 6 hours after reperfusion and the expression of Bcl-2 mRNA was enhanced significantly in group P 6 and 24 hours after reperfusion. CONCLUSIONS: PNS preconditioning protects liver grafts from I/R injury effectively in rat OLT via an antiapoptotic pathway. The antiapoptotic mechanisms of PNS may in- clude inhibiting the expression of TNF-a and Caspase-3 and enhancing the expression of Bcl-2.

Panax notoginseng saponins influence on transplantation of neural stem cell-derived dopaminergic neurons in a rat model of Parkinson’s disease

BACKGROUND： Dopaminergic neurons differentiated from neural stem cells have been successfully used in the treatment of rat models of Parkinson＇s disease; however, the survival rate of transplanted cells has been low. Most cells die by apoptosis as a result of overloaded intracellular calcium and the formation of oxygen free radicals. OBJECTIVE： To observe whether survival of transplanted cells, transplantation efficacy, and dopaminergic differentiation from neural stem cells is altered by Panax notoginseng saponins （PNS） in a rat model of Parkinson＇s disease. DESIGN, TIME AND SETTING： Cellular and molecular biology experiments with randomized group design. The experiment was performed at the Animal Experimental Center, First Hospital of Sun Yat-sen University from April to October 2007. MATERIALS： Thirty-two adult, healthy, male Sprague Dawley rats, and four healthy Sprague Dawley rat embryos at gestational days 14-15 were selected. The right ventral mesencephalon was injected with 6-hydroxydopamine to establish a model of Parkinson＇s disease. 6-hydroxydopamine and apomorphine were purchased from Sigma, USA. METHODS： Neural stem cells derived from the mesencephalon of embryonic rats were cultivated and passaged in serum-free culture medium. Lesioned animals were randomly divided into four groups （n = 8）： dopaminergic neuron, dopaminergic neuron ＋ PNS, PNS, and control. The dopaminergic neuron group was injected with 3 μL cell suspension containing dopaminergic neurons differentiated from neural stem cells. The dopaminergic neurons ＋ PNS group received 3 μ L dopaminergic cell suspension combined with PNS （250 mg/L）. The PNS group received 3 μL PNS （250 mg/L）, and the control group received 3 μL DMEM/F12 culture medium. MAIN OUTCOME MEASURES： The rats were transcardially perfused with 4% paraformaldehyde at 60 days post-grafting for immunohistochemistry. The rats were intraperitoneally injected with apomorphine （0.5 mg/kg） to induce rotational behavior. RESULTS： Cell counts of tyrosine hydroxylase-positive neurons in the dopaminergic neuron ＋ PNS group were （732±82.6） cells/400-fold field. This was significantly greater than the dopaminergic neuron group [（326 ± 34.8） cells/400-fold field, P 〈 0.01]. Compared to the control group, the rotational asymmetry of rats that received dopaminergic neuron transplants was significantly decreased, beginning at 20 days after operation （P 〈 0.01）. Rotational asymmetry was further reduced between 10-60 days post-surgery in the dopaminergic neuron ＋ PNS group, compared to the dopaminergic neuron group （P 〈 0.01）. CONCLUSION： Panax notoginseng saponins can increase survival and effectiveness of dopaminergic neurons differentiated from neural stem cells for transplantation in a rat model of Parkinson＇s disease.

Effect of Panax notoginseng saponins on the expression of beta-amyloid protein in the cortex of the parietal lobe and hippocampus, and spatial learning and memory in a mouse model of senile dementia

BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin （Syp） was tested by real time PCR and RT-PCR. RESULTS： The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group （P 〈 0.05）. CONCLUSION： These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer＇s disease. The therapeutic effects of PNS for Alzheimer＇s disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.

Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease

BACKGROUND： Modem pharmacological studies have demonstrated that Panax notoginseng saponins （PNS） can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer＇s disease （AD） remains unclear. OBJECTIVE： Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN： A completely randomized grouping design, controlled animal experiment. SETTING： Center of Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS： Ninety healthy Wistar rats of both genders, 15-month-old （n =75） and 3-month-old rats as young controls （n =15）, were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd （permission No. Z53021485, Yuxi, Yunan Province, China）. Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS： This study was performed at the Center of Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each： model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose （5 mL/kg） every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μ L ibotenic acid （5 g/L） bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension （0.3 mg/kg） was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES： After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency （time-to-platform）, number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS： Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test： Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups （both P 〈 0.05）. No significant differences in these two indices were measured among the administration groups （all P 〉 0.05）. Results of spatial probe test： Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups （P 〈 0.05）. There were no significant differences in these two indices among the administration groups （P 〉 0.05）. CONCLUSION： PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.

Yizhijiannao Granule and a combination of its effective monomers,icariin and Panax notoginseng saponins,inhibit early PC12 cell apoptosis induced by beta-amyloid(25-35)

One of our previous studies showed that Yizhijiannao Granule,a compound Chinese medicine, effectively improved the clinical symptoms of Alzheimer’s disease.In the present study,we established a model of Alzheimer’s disease using beta-amyloid（25-35）in PC12 cells,and treated the cells with Yizhijiannao Granule and its four monomers,i.e.,icariin,catechin,Panax notoginseng saponins,and eleutheroside E.Flow cytometry showed that Yizhijiannao Granule-containing serum, icariin,Panax notoginseng saponins,and icariin＋Panax notoginseng saponins were protective against beta-amyloid（25-35）-induced injury in PC12 cells.Icariin in combination with Panax notoginseng saponins significantly inhibited early apoptosis of PC12 cells with beta-amyloid （25-35）-induced injury compared to icariin or Panax notoginseng saponins alone.The effects of icariin＋Panax notoginseng saponins were similar to the effects of Yizhijiannao Granule.The findings indicate that two of the effective monomers of Yizhijiannao Granule,icariin and Panax notoginseng saponins,can synergistically inhibit early apoptosis of PC12 cells induced by beta-amyloid（25-35）.

Effects of Panax notoginseng saponins on hydrogen peroxide-induced apoptosis in cultured rabbit bone marrow stromal cells

Objective To investigate the effects of Panax notoginseng saponins(PNS)on hydrogen peroxide(H2O2)-induced apoptosis in cultured rabbit bone marrow stromal cells(BMSCs).Methods BMSCs from 3-month-old New Zealand rabbits were isolated and cultured by the density gradient centrifugation combined with adherent method.The cultured BMSCs were divided into three groups:normal control,H2O2 treatment(100μmol/L),and PNS pretreatment(0.1g/L).Intracellular reactive oxygen species(ROS)levels as the index of oxidative stress were measured by using 2’7’-dichlorodihydrofluorescein diacetate.Flow cytometry was used to observe the apoptosis of BMSCs by staining with annexinV-FITC/PI.The protein expression of Bax in BMSCs was analyzed by Western blotting.Activity of caspase-3 enzyme was measured by spectrofluorometry.Results Pretreatment with PNS significantly decreased intracellular ROS level induced by H2O2(P<0.01).PNS markedly attenuated H2O2-induced apoptosis rate from 38.68% to 19.24%(P<0.01).PNS reversed H2O2-induced augmentation of Bax expression.Furthermore,PNS markedly reduced the altered in activity of caspase-3 enzyme induced by H2O2(P<0.01).Conclusion PNS has a protective effect on hydrogen peroxide-induced apoptosis in cultured rabbit BMSCs by scavenging ROS and decreasing Bax expression and caspase-3 activity.

Neuroprotective effect of panax notoginseng saponins and its main components

Stroke is the third leading cause of death and the first cause of adult disability in industrial countries [1]. It is charicaterized by hemiplegia, hemianopsia, aphasia, mouth askew and sever sequelae. It is considered that an ischemic disease without any specific treatment method and few effective drugs such as tPA (human tissue-type plasminogen activator) and Edarovone with specific therapeutic window will cause a lot of disadvantages if being used inaccurate. Root of Panax notoginseng (PN) which is one of traditional Chinese medicines (TCMs), was first found in “Shennong’s Classic of Materia Medica” around 200 AD. Panax notogineng saponins(PNS) is a multi-components mixture containing ginseng and saponins as the most important bioactive components which are commonly used in clinical treatment. Also, ginseng and saponins form the main components of many herbal medicines in the market, e.g., Xueshuantong injection [2], Xuesaitong injection [3], Xuesaitong soft capsule [4] and so on. The main monomers of Panax notoginseng saponins (PNS) are Ginsenoside-Rb1, Gensenoside-Rg1, Gensenoside-Re, Gensenoside-Rd and Panax notoginseng saponins-R1 [5]. In this review, we found some important points as well as shortcomings that require special consideration. We therefore highlighted the advances in neuro-protection of PNS and its main monomers in the area of experimental research.

Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors

Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic（T10） spinal cord transection, and injected Panax notoginseng saponins（100 mg/kg） or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan（BBB） scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor（NGF） and brain-derived neurotrophic factor（BDNF）. Our results show that at 7–30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function.

Dammarane-type saponins from steamed leaves of Panax notoginseng

Four new dammarane-type triterpenoid saponins,namely notoginsenosides SFt1-SFt4(1-4)were isolated from the steamed leaves of Panax notoginseng(Burk.)F.H.Chen(Araliaceae),together with 17 known saponins.Their structures were established on the basis of detailed spectroscopic analyses and acidic hydrolysis.The known ginsenosides Rk2 and Rh3 were obtained from P.notoginseng for the first time.All of these new saponins showed no in vitro cytotoxicity against five human cancer cell lines(HL-60,SMMC-7712,A-549,MCF-7,and SW480).

Effects of Panax notoginseng saponins on apoptosis induced by hydrogen peroxide in cultured rabbit bone marrow stromal cells via altering the oxidative stress level and down-regulating caspase-3

Objective： To investigate the effects of Panax notoginseng saponins （PNS） on hydrogen peroxide （H2O2）-induced apoptosis in cultured rabbit bone marrow stromal cells （BMSCs）. Methods： The effects of different concentrations of PNS on proliferation and early osteoblast differentiation of BMSCs were determined by the MTT assay and an alkaline phosphatase （ALP） assay. An optimal effective concentration of PNS was determined and used in subsequent experiments. The cultured BMSCs were divided into three groups： untreated control, H2O2 treated, and PNS pretreatment of H2O2 treated. The oxidative stress level was assessed by superoxide dismutase （SOD） and malondialdehyde （MDA） assays. Flow cytometry was used to determine BMSC apoptosis by staining with annexinV-FITC/propidium iodide （PI）. The activity of caspase-3 enzyme was measured by spectrofluorometry. Results： PNS （0.1g/L） significantly increased both BMSC proliferation rate and ALP activity, while it decreased the indicators of oxidative stress, caspase-3 activity, and the apoptosis rate of BMSCs induced by H2O2.. Conclusion： PNS, acting as a biological antioxidant, had a protective effect on H2O2-induced apoptosis in cultured rabbit BMSCs by decreasing oxidative stress and down-regulating caspase-3.

Comparison of pharmacokinetics of different oral Panax notoginseng saponins using ultra-high performance liquid mass spectrometry

Objective:To discuss and compare the plasma pharmacokinetics after three oral Panax notoginseng saponin(PNS)administrations in beagle dogs.PNS is the main active ingredient of the traditional Chinese medicine(TCM)Panax notoginseng.Although its outstanding therapeutic efficacy has been demonstrated by various researchers,its broader application is restricted by the low bioavailability of PNS.Methods:An ultra-high performance liquid chromatographyetandem mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of notoginsenoside R1,ginsenoside Rg1,ginsenoside Rb1,ginsenoside Rd,and ginsenoside Re in beagle dog plasma was developed and validated.The plasma samples were subjected to liquideliquid extraction with acetone and methanol,and separated on an ACQUITY C18 column(100×2.1 mm ID,1.7 mm)using acetonitrile and water as the mobile phase with a run time of 4.5 min.Results:The analytes were detected without interference in Selected Reaction Monitoring mode with positive electrospray ionization.The validated method was successfully used in comparative pharmacokinetic studies of the five saponins in beagle dogs after oral administration of three PNS preparations.Blood samples were collected up to 192 h after administration and pharmacokinetic parameters were calculated using DAS 3.20 and SPSS 17.0.The AUC_(0-t)values of Re and R1 were significantly higher in soft capsules than in hard capsules.However,the AUC_(0-t)values between hard and soft capsules were not significantly different for the other three componentsdRb1,Rd and Rg1.Conclusion:Our intuitive analysis suggests that the bioavailability of PNS in soft capsules is greater than in hard capsules.

Panax notoginseng saponins promotes cerebral recovery from ischemic injury by downregulating LINGO-1 and activating the EGFR/PI3K/AKT signaling pathways in vivo

Objective:Panax notoginseng saponins (PNS),extracted from rhizome of the herb Radix et Rhizoma Notoginseng (Panax notoginseng (Burk.) F.H.Chen),was recently discovered to have beneficial effects against neurological damage.This study investigated the effects of PNS on cerebral ischemia and elucidated the molecular mechanisms underlying these effects.Methods:Middle cerebral artery occlusion rats were treated with PNS (3.6 mg/100 g or 7.2 mg/100 g per day) for 7 days,the gene of LINGO-1 was measured and the expression of protein synaptophysin,postsynaptic density protein 95,LINGO-1 and p-EGFR/p-PI3K/p-AKT were investigated.The weight and mNSS score of Sprague-Dawley rats in each group were recorded every day during the 7 days.Results:PNS promoted middle cerebral artery occlusion rats' weight and the recovery of neural function.PNS significantly decreased ischemia-induced LINGO-1 protein expression.PNS also elevated EGFR/PI3K/AKT phosphorylation levels.Conclusion:PNS promoted cerebral recovery from ischemic injury by accelerating synapse reconstruction and inhibiting the neuron growth negative regulatory protein LINGO-1 and activating the epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in vivo.

Advances in Researches of Extraction, Separation, and Purification Technologies for Total Saponins of Panax notoginseng

Total saponins of Panax notoginseng have the functions of promoting blood circulation and removing phlegm, thus they have high medicinal value. There are many different extraction methods in the extraction and separation of total saponins of P. notoginseng . The extraction methods of total saponins of P. notoginseng are mainly divided into traditional extraction methods, modern extraction methods and compound extraction methods.

Effects of Paeonol Combined with Panax Notoginseng Saponins on Nrf2/ARE Pathway in Rats with Diabetic Cardiomyopathy

[Objectives]To investigate whether paeonol(Pae)combined with panax notoginseng saponins(PNS)can protect the myocardium of rats with diabetic cardiomyopathy(DCM)through improving the antioxidant capacity of the rats by activating the Nrf2/ARE pathway.[Methods]The rats were fed with high-fat and high-sugar diet for 6 weeks,and combined with intraperitoneal injection of small-dose STZ to build a type II diabetes model;the model rats were randomly divided into a model group,a Pae group of 80 mg/kg,and a PNS group of 100 mg/kg,a Pae 80 mg/kg+PNS 100 mg/kg,and a metformin group 157.5 mg/kg;rats of normal group and model group were injected with an equal volume of sodium carboxymethyl cellulose(1%),10 rats in each group.After 8 weeks,3 rats in the model group were taken for histopathological examination.Changes in myocardial fibrosis and myocardial collagen formation indicated that the building of DCM model was successful.qRT-PCR and Western blot were used to detect the expression levels of Nrf2,HO-1,Col-I,and Col-III in myocardial tissue of each group of rats.[Results]Compared with the normal group,the mRNA and protein expression levels of Nrf2 and HO-1 in myocardial tissue of the DCM group rats were significantly reduced,and the mRNA and protein expression levels of Col-I and Col-III were significantly increased;compared with the DCM group,the mRNA and protein expression levels of Nrf2 and HO-1 in the myocardial tissue of each drug group increased to varying degrees,and the combined drug group increased more significantly than that of the single drug group;the mRNA and protein expression levels of Col-I and Col-III were reduced to varying degrees,and the combined drug group declined more significantly than that of the single drug group.[Conclusions]Paeonol combined with panax notoginseng saponins can up-regulate the expression of Nrf2 and HO-1 in myocardial tissue,inhibit the expression of type I and type III collagen.The mechanism may be related to improving the DCM myocardial fibrosis through activating the Nrf2/ARE pathway.

The neuroprotective role of Panax notoginseng saponins in APP/PS1 transgenic mice through the modulation of cerebrovascular

Background:Panax notoginseng saponins(PNS)is extracted from Sanqi(Panax notoginseng),which is a valuable herb and has been widely used in traditional Chinese medicine for the treatment of cerebrovascular diseases and pain.PNS has been proved to promote blood circulation and angiogenesis by inhibiting platelet aggregation.In our previous study,PNS accompanied with geniposide can prevent Alzheimer’s disease(AD).However,the efficacy of PNS and its potential mechanism in AD remain unclear.Methods:Amyloid precursor protein/presenilin-1(APP/PS1)transgenic(Tg)mice were used as AD-like animal models.Wild-type mice and APP/PS1 transgenic were administrated with saline solution while mice in PNS treatment group were administrated with PNS at a dosage of 17 mg/kg/day for three months.Morris water maze(MWM)was applied to evaluate the spatial learning and memory and step-down test was used to evaluate the cognitive function.1%Thioflavin-S staining was used to calculate the average number amyloid plaques in cortex and hippocampus.CD31 staining was detected to observe the density of cerebrovascular in hippocampus areas and CD105 staining was further detected to evaluate angiogenesis.Laser Doppler PeriFlux 5000 was further measured the change of cerebrovascular blood flow.ChemDraw was used to draw the molecular structures of five main ingredients of PNS.AlzPlatform were used to estimate the potential targets of PNS.Results:By a bench of behavioral tests,PNS showed a better tendency in proving cognitive functions.In addition,the amyloid plaques in both cortex and hippocampus were significantly reduced after PNS intervention(P<0.05 and P<0.001 respectively).Furthermore,the density of cerebrovascular in the hippocampus areas was increased under PNS administration(P<0.001),which accompanied with angiogenesis in dentate gyrus areas and cerebrovascular blood flow promotion(P<0.05).By AlzPlatform docking serve,we screened five major ingredients of PNS-R1,Rd,Rb1,Re and Rg1.These screening data suggested that vascular related proteins could be the one of potential targets of PNS,such as platelet activating factor receptor and vasopressin V1a receptor.Conclusion:By modulating cerebrovascular function,PNS can reduce the deposition of amyloid plaques and exhibit the role of neuroprotection in a preventive strategy.

Recent Progress in Structural Modification and Activities on Panax notoginseng Saponins

This paper reviews recent progress in the structural modification and activities on Panax notoginseng saponins(PNS).PNS can not only improve the function of cardio-cerebral system,central nervous system and immune system,but also reveal anticancer,anti-aging and anti-oxidation activities.In order to solve the problem of low bioavailability and poor absorbability of PNS in vivo,usually,the researchers modified the structure of PNS with three methods:glycoside cleavage(including acid hydrolysis,sulfation,etc.),biotransformation method(including enzyme hydrolysis,microbial transformation)and combinatorial chemical method.It was found that the structural modification sites of PNS were single,mainly aimed at C-3,C-6 and C-20,which provided a new perspective for the structural modification of PNS.Therefore,structural modification on PNS with high yield and ready availability are significant in the discovery of new active ingredients and industrialization.Derivatives of PNS are applied to research of structure-activity relationship,which is beneficial to the development of new medicines.

Atherosclerosis lesion is accelerated by persistent systemic inflammation but attenuated by saponins from Panax Notoginseng in rabbits

ObjectiveTo 在 rabbits.MethodsThirty 兔子在这进程上在动脉粥样硬化和人参属 Notoginseng (PNS ) 的 saponins 的效果探索坚持的全身的发炎的角色随机并且同等地被划分成 6 个组，即，控制，高脂肪的食谱，发炎，阿司匹林， PNS 和简单发炎的组。所有动物除了在控制组和简单发炎的组用高脂肪的饮食被喂 8 个星期之外。基于那，在发炎，阿司匹林和 PNS 组的兔子与酵母多糖注射被对待(10 mg/kg， i.p ) 。生理盐水在控制组被给兔子。除酵母多糖注射以外，在阿司匹林和 PNS 组的动物与阿司匹林被管理(12 mg/kg， i.g ) 并且 PNS (120 mg/kg， i.g ) 分别地。在简单发炎的组的动物与酵母多糖注射被对待(10mg/kg， i.p ) 并且有正常的美联储节食。在主动脉的动脉粥样硬化损害被染色的苏丹 IV 观察。肝磷脂以后的脂蛋白脂肪分解酵素( LPL )的浆液全部的胆固醇，甘油三酸酯( TG )，TNF-和活动与高脂肪的食谱组，一起在一夜的 fast.ResultsCompared 以后在 第4 和 第8 星期的结束被测量动脉粥样硬化损害的区域，浆液 TG 和 TNF 显著地在发炎组的兔子增加了，并且 LPL 的活动显著地被减少。浆液 TNF- 水平否定地与肝磷脂以后的 LPL 的活动被相关(r = 0.708， P 【 0.01 ) 。动脉粥样硬化，浆液 TG 和 TNF 的区域在发炎组与那相比在阿司匹林和 PNS 组减少了，并且 LPL 的活动显著地被增加。与控制组相比，浆液 TG 和 TNF- 显著地在简单发炎的组被增加，当 LPL 活动被减少时。动脉粥样硬化患者损害没在全身的发炎能加速的简单发炎的 group.ConclusionsPersistent 发生在主动脉的动脉粥样硬化损害的形成，它部分取决于肝磷脂以后的脂蛋白脂肪分解酵素的活动减少。PNS 能改进发炎引起的变化。

Effects of panax notoginseng saponins on apoptosis, inflammation and oxidative stress in rats with propofol-induced cognitive impairment

Objective: To study the effects of panax notoginseng saponins(PNS) on apoptosis, inflammation and oxidative stress in rats with propofol-induced cognitive impairment. Methods: 7-day-old SD rats were chosen as experimental animals and randomly divided into control group, propofol group and PNS intervention group, propofol group were given intraperitoneal injection of propofol, and PNS intervention group were given panax notoginseng saponins intervention on the basis of intraperitoneal injection of propofol. The brain tissues of three groups of rats were collected 7 d after modeling and intervention to measure the expression of apoptotic molecules, inflammatory molecules and oxidative stress molecules. Results: Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Bax inhibitor 1 (BI-1), DNA dioxygenase (TET2), peroxidoreductin 6 (PRDX6), heat shock protein 70 (HSP70) mRNA expression in brain tissues of propofol group were lower than those of control group whereas Bcl-2 related X protein (Bax), glycoprotein 78 (GRP78), caspase-3 containing cysteine, nuclear factor-κB (NF-κB), interleukin-1β(IL-1β), tumor necrosis factor-a(TNF-a), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), NADPH oxidase 2 (NOX2), malondialdehyde (MDA) mRNA expression were higher than those of control group;BDNF, NGF, BI-1, TET2, PRDX6 and HSP70 mRNA expression in brain tissues of PNS intervention group were higher than those of propofol group whereas Bax, GRP78, Caspase-3, NF-κB, IL-1β, TNF-α, nNOS, iNOS, NOX2 and MDA mRNA expression were lower than those of propofol group. Conclusion: Panax notoginseng saponins can reduce the apoptosis, inflammation and oxidative stress in rats with propofol-induced cognitive impairment.

ERβ modulation and non-modulation of ERα by administration of geniposide and panax notoginseng saponins in SH-SY5Y cells

Objective:To illustrate the effect of geniposide (GP) and panax notoginseng saponins (PNS) on estrogen receptors (ER) including ERα and ERβ within the cytoplasm and nucleus of SH-SY5Y cells.Methods:Immunofluorescence was used to observe the distribution of ERα and ERβ in cytoplasm and nucleus,but Western blot was only for ERβ detection.q-PCR was applied to detect NR3C1,S100A6 and LGALS1downstream mRNA gene expression levels of ER.Results:Through analyzing fluorescence intensity under the administration of GP and PNS in SHSY5Y cells,we found that the distribution of ERα has not been affected.We also discovered that GP and/or PNS significantly stimulated the transportation of ERβ into the nucleus in a timedependent manner (all P <.001).When SH-SY5Y cells were treated with supplements of GP,PNS,GP + PNS at 15 minutes,30 minutes and 45 minutes,the distribution of ERβ in the nucleus significantly increased compared with that in control group (all P <.001).Evidently,treatment with GP,PNS,GP + PNS was able to significantly increase the levels of ERβ protein within the nucleus compared with control group at both 30 minutes and 45 minutes intervals (all P <.001).Furthermore,GP and PNS showed signs of activating to NR3C1 and LGALS1,two genes downstream of ER.It is possible that the 5100A6 gene mainly encoded the downstream gene in ERα's signaling pathway,which was not affected after the treatment of GP and/or PNS.Conclusion:The distribution and expression of ERβ has been modulated under the administration of GP + PNS within the SH-SY5Y cells,whereas ERα has not.GP and PNS in combination may play an estrogenic-like effect with selectivity on ERβ modulation.