Total Panax notoginseng saponin inhibits balloon injury-induced neointimal hyperplasia in rat carotid artery models by suppressing pERK/p38 MAPK pathways

Total Panax notoginseng saponin (TPNS) is the main bioactivity compound derived from the roots and rhizomes of Panax notoginseng (Burk.) F.H. Chen. The aim of this study was to investigate the effectiveness of TPNS in treating vascular neointimal hyperplasia in rats and its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups, sham (control), injury, and low, medium, and high dose TPNS (5, 10, and 20 mg/kg). An in vivo 2F Fogarty balloon-induced carotid artery injury model was established in rats. TPNS significantly and dose-dependently reduced balloon injury-induced neointimal area (NIA) (P<0.001, for all doses) and NIA/media area (MA) (P<0.030, for all doses) in the carotid artery of rats, and PCNA expression (P<0.001, all). The mRNA expression of smooth muscle (SM) α-actin was significantly increased in all TPNS groups (P<0.005, for all doses) and the protein expression was significantly increased in the medium (P=0.006) and high dose TPNS (P=0.002) groups compared to the injury group. All the TPNS doses significantly decreased the mRNA expression of c-fos (P<0.001). The medium and high dose TPNS groups significantly suppressed the upregulation of pERK1/2 protein in the NIA (P<0.025) and MA (P<0.004). TPNS dose-dependently inhibited balloon injury-induced activation of pERK/p38MAPK signaling in the carotid artery. TPNS could be a promising agent in inhibiting cell proliferation following vascular injuries.

Xueshuantong for Injection (Lyophilized, ) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, , XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats.@*METHODS@#Diabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-β1 (TGF-β1)-Smad2/3 signaling pathway were evaluated at last.@*RESULTS@#There was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-β1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01).@*CONCLUSIONS@#XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-β/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.

Characterization analysis technique of Panax notoginseng saponin subcomponents for prevention and treatment of myocardial ischemia based on their structure and effect differences / 中国中药杂志

According to the structure and effect differences of Panax notoginseng saponin components(PNSC), subcomponent division and network pharmacological characterization were conducted to provide a research basis for the medicinal properties of P.notoginseng saponin subcomponents and the technical design of unit preparations. PNSC were screened by the TCMSP database and subcomponents were classified according to systematic clustering. Then the subcomponents obtained were subjected to target prediction and attribution analysis by PharmMapper server, GeneCards, DisGeNET and HOME-NCBI-GENE database. A subcomponent target interaction network was constructed by using the STRING database. KEGG and GO enrichment analysis were performed on each subcomponent target using the DAVID database. The subcomponents-targets-pathways visualization network was constructed by Cytoscape. The subcomponent targets and pathways involved were compared to analyze the differences in anti-myocardial ischemic drug mechanisms and the rationality of subcomponent division. Eighteen compounds of PNSC were screened out, and classified into three subcomponents A, B, and C according to their properties, involving 67 targets and 17 common anti-myocardial ischemic pathways directly or indirectly related to myocardial ischemia. Subcomponent A had the highest number of targets and the target interaction was dense, possibly indicating its key role in the mechanism of pharmacodynamics. Subcomponents A, B, and C had similar basic structures, and KEGG and GO analysis showed that they all can enhance the heart function and protection of cardiomyocytes by inhibiting apoptosis, promoting angiogenesis and regulating inflammatory response to play the effect on myocardial ischemia. This study fully reflected the differences in the efficacy of various subcomponents in preventing and treating myocardial ischemia due to the different physical properties of P. notoginseng saponin subcomponents. To some extent, the differences in the efficacy of each subcomponent in the prevention and treatment of myocardial ischemia could verify the rationality of the division of P. notoginseng saponin subcomponents according to the structural properties, realizing the characterization of P. notoginseng saponin subcomponents based on structure and effect differences.

Pharmacokinetic Study on Xuesaitong Dispersible Tablets and Common Tablets in Beagle Dogs in Vivo / 中国药学杂志

OBJECTIVE: To compare the pharmacokinetic parameters of Xuesaitong dispersible tablets and common tablets in Beagle dogs. METHODS: Using double cycle crossover trial, six Beagle dogs were treated with single oral dose of 100 mg of Xuesaitong dispersible tablets and conventional tablets and determining the pharmacokinetic parameters of ginsenoside Rb1 and Rg1 in Xuesaitong dispersible tablets and conventional tablets in Beagle dog plasma. RESULTS: The ginsenoside Rb1 and Rg1 peak concentration of Xuesetong dispersible tablets in Beagle dog plasma was significantly higher than that of Xuesaitong tablets, the ginsenoside Rg1 peak time of Xuesaitong dispersible tablets in Beagle dog plasma was significantly earlier than that of Xuesaitong tablets. Additionally, the ginsenoside Rb1 peak time exhibited ahead of the trend, which is in line with the characteristics of rapid disintegration and absorption of preparation in vivo. CONCLUSION: The plasma exposure in two preparation of ginsenoside Rb1 and Rg1 in Beagle dog holds fairly basic and no significant difference. But the ρmax of the main ingredients of Panax ginseng saponins Rb1 and Rg1 in Xuesaitong dispersed tablets, is significantly higher than that of the film coated tablets, and peak time is significantly shortened, which could promote the drug absorption.

Degradation of total saponins of Panax notoginseng by intestinal flora of rats in vitro / 中草药

Objective To investigate the degradation of three kinds of saponins (notoginseng saponin R1, ginsenoside Rg1, and ginsenoside Rb1) from total saponins of Panax notoginseng (tPNS) by intestinal flora in male and female rats in vitro. Methods tPNS were incubated for 24 h with male and female rats intestinal flora separately in vitro under anaerobic environment. The content of three kinds of saponins was measured at different treatment time. Results The results showed that the intestinal flora both in male and female rats all had the degradation action against ginsenosides Rb1, in which the degradation of male rats was slightly faster than that of female rats. But the intestinal flora both in male and female rats had no obvious degradation to notoginseng saponin R1 and ginsenoside Rg1. Conclusion Under the condition of in vitro, tPNS can be degraded by rats intestinal flora, of which Rb1 was degraded most, while notoginseng saponin R1 and ginsenoside Rg1 were more stable.

Effects of radix notoginseng saponin dispersible tablets combined with rivaroxaban in treatment of tibial fracture after operation and its effects on joint function and the leves of inflammatory factors / 中国生化药物杂志

Objective To study curative efficacy of radix notoginseng saponin dispersible tablets combined with rivaroxaban in treatment of tibial fracture after operation and its effects on joint function and the leves of inflammatory factors .Methods 90 patients of tibial fracture who received therapy from March 2014 to March 2016 in our hospital were selected.According to random number table,all elective surgery,those patients were divided into the observation group (n=45) and the control group (n=45),the control group was treated with radix notoginseng saponin dispersible tablets,while the observation group was treated combined with rivaroxaban.After two weeks of treatment, the hemorheology, inflammatory factors, joint function were compared between two groups.Results The patient swelling time and bed time in the observation group were shorter than the control group (P<0.05);after treatment,the levels of red cell volume, whole blood viscosity,fibrinogen in the observation group were lower than the control group (P<0.05);the levels of tumor necrosis factor TNF-α, IL-1,IL-6 in the observation group were lower than the control group (P<0.05);after treatment three months and six months,the Baird-Jackson scores in the observation group were higher than the control group (P <0.05).Conclusion Radix notoginseng saponin dispersible tablets combined with rivaroxaban is well for tibial fracture after operation,which can improve hemorheology,reduce the level of inflammatory factors,promote joint functional recovery.

Advances in pharmacological studies of Panax notoginseng saponins on brain ischemia-reperfusion injury / 药学学报

Sanqi in Chinese herbal medicine is the root and rhizoma of Panax notoginseng (Burk.) F.H.Chen, which belongs to genus Panax in the Araliaceae family and is widely used as a tonic medicine in the traditional Chinese medicine. The main active constituents of sanqi are Panax notoginseng saponins, including ginsenoside Rg1, Rb1 and notoginsenoside R1. A wide variety of pharmaceutical applications of Panax notoginseng saponins have been reported in the regulation of blood circulation system, cardiovascular system and nervous system. Ischemic stroke, the most common form of stroke, leads to a high risk of morbidity and disability, which evolves serious medical, social and economic problems. Ischemia-reperfusion injury is the most important part in the progress of ischemic stroke. Abnormal energy metabolism, disturbance of the ion metabolism, free radical injury, inflammatory reactions all participate in the complex pathological mechanisms of ischemiareperfusion injury. Over the past few decades, substantial studies demonstrated that Panax notoginseng saponins possessed a significant protective effect on ischemia-reperfusion injury. However, little is known about the underlying mechanisms of the protective effects. In order to develop a new medicine from Panax notoginseng, we provide a review of the major literatures on the pharmaceutical actions and molecular mechanisms of Panax notoginseng and Panax notoginseng saponins in the protection of ischemia-reperfusion injury.

Protective effects and underlying mechanisms of Panax notoginseng saponins against SH-SY5Y cell apoptosis induced by 6-hydroxydopamine / 药学学报

The aim of this study is to investigate the protective effects of Panax notoginseng saponins (PNS) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in SH-SY5Y cells and the possible underlying mechanisms. Cell viability was examined by MTT assay. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured using the respective assay kits. Apoptosis was measured by TUNEL kit, JC-1 and ROS was measured by staining with fluorescent dyes. The activation of caspase-3 was measured with the caspase-3 assay kit. The expression of nuclear protein Nrf2 and HO-1 were determined by Western blot. PNS had significant protective effects against 6-OHDA-induced apoptosis in SH-SY5Y cells in a time- and dose-dependent manner. PNS could attenuate 6-OHDA-induced suppression of SOD, GAT, GSH-Px (PPP<0.01). Moreover, PNS pretreatment increased the expression of the nuclear Nrf2 and up-regulate HO-1. The protective effects of PNS could be inhibited by HO-1 inhibitor SnPP. In conclusion, PNS has significant protective effects against 6-OHDAinduced apoptosis in SH-SY5Y cells. The possible mechanisms of PNS are due to PNS-mediated activation of Nrf2, up-regulation of HO-1 and inhibition of oxidative stress.

Apoptosis of rat superficial renal medulla cells after femoral fracture and the protective role of panax notoginseng saponins / 西安交通大学学报(医学版)

Objective To study the effects of panax notoginseng saponins (PNS)on rat superficial renal medulla cells after femoral fracture and to discuss the protective role of PNS in renal injury after fracture. Methods We divided 102 Wistar rats randomly into simple fracture group (n =36),fracture and medication group (n =36)and normal control group (n =30).In the former two groups 6 rats were respectively executed at 1,6,12, 24,36,48 h after fracture modeling,while 5 rats in normal control group were executed at the corresponding time points.Regular HE staining was used to observe pathological changes and TUNEL was used for apoptotic cells.And immunohistochemistry and in situ hybridization were used to detect the expressions of Bcl-2 and Bax in superficial renal medulla tissues.Results In simple fracture group,mild granular degeneration could be seen in renal tubular epithelial cells of superficial renal medulla and the interstitial small vessels were slightly expanded and congested. Compared with simple fracture group,the lesions were slighter in fracture and medication group.In simple fracture group,Bcl-2 and Bcl-2 mRNA expressions were significantly higher than those in normal control group at 1 -36 h (P <0.01).Bax expression was higher than that in normal control group at 12-36 h (P <0.01),and Bax mRNA expression was higher than that in normal control group after 6 h after fracture (P < 0.01 ).In fracture and medication group,Bcl-2 expression was obviously higher than that in simple fracture group at 1 h (P <0.01),and Bcl-2 mRNA expression was higher than that in simple fracture group at 1 -48 h (P <0.01).Bax and Bax mRNA expressions were both lower than those in simple fracture group at 1 - 48 h (P < 0.01 ).Conclusion Fracture trauma has significant influences on protein expression and mRNA transcription of Bcl-2 and Bax in superficial renal medulla.PNS can upregulate anti-apoptosis gene Bcl-2 and downregulate pro-apoptosis gene Bax,thus playing the role of inhibiting tissue cell apoptosis.

Quality analysis for Xueshuantong injections / 中国药学杂志

OBJECTIVE: To evaluate the quality of Xueshuantong injections and the feasibility of the current legal quality standards through testing 84 batches of samples from five factories.

Study on Percolation Extraction Process of Panax Notoginseng / 中国中医药信息杂志

Objective To optimize the conditions for the percolation extraction process of Panax notoginseng(Burk.) F.H.Chen.Methods Conditions for the percolation were studied by orthogonal experimental design as guided by the contents of total notoginseng saponin and total amino acids.Results The percolate rate,concentration and quantity of alcohol had significant effects on the process.Conclusion The optimum condition for the extraction of Panax notoginseng was adding 12 times amount of 50% alcohol and percolating at a rate of 1～3 mL/(min?kg).

Determination of Ginseng Saponin Rg_1,Rb_1,Re and Notoginseng Saponin R_1 in Tangzhiqing Capsule by HPLC / 中药新药与临床药理

Objective To establish a method of determining effective components in Tangzhiqing Capsule.Methods Gin- seng saponin Rg_1,Rb_1,Re and notoginseng saponin R_1 in the capsule were separated and purified by D_(101)macroporous absorption resin,and then determined by HPLC.Results The linearity arrange of ginseng saponin Rg_1,Re,Rb_1 and no- toginseng saponin R_1 were 1.88～11.28?g,1.76～10.56?g,0.294～1.764?g,0.752～2.256?g and the recov- eries were 101.51%(RSD=0.75%),100.58%(RSD=0.46%),100.29%(RSD=1.01%),98.64% (RSD = 0.73%)respectively.Conclusion The method is simple,feasible and reproducible,and can be used for the determination of effective components in Tangzhiqing Capsule.

Studies on process for extraction of Panax notoginseng by orthogonal experiments / 中草药

Object To optimize the conditions for the extraction of Panax notoginseng (Burk ) F H Chen Methods Conditions for the extraction were studied by orthogonal experimental design as guided by the content of total notoginseng saponin present in the extract Results Significant effect was observed in 3 different experimental conditions Conclusion The optimum condition for the extraction of P notoginseng was to soak the drug in 75% alcohol for 24 h and then percolate at a rate of 1~3 ml/min to collect an amount corresponding to about 10 times of the quantity of P notoginseng

Panax notoginseng saponin liposomes:Characterization of pharmaceutics and pharmacokinetics on pulmonary instillation in rats / 中草药

Object To prepare Panax notoginseng saponin (PNS) liposomes and investigate their characterization of pharmaceutics and pulmonary pharmacokinetics in rats. Methods The film-disperion method was used to prepare PNS liposomes by investigating its form, vesicle size, entrapping efficiency and stability. The study of pulmonary pharmacokinetics in rats was carried out by pulmonary instillation. Results The entrapment of PNS liposomes was 78.50%. The mean vesicle size was 1.5 ?m with uniform externality. The drug leakage from PNS liposomes was slow. Low temperature was required for its storage. The pulmonary pharmacokinetics parameters were as follows: T 1/2 ?=7.00 h, T 1/2 ?=27.72 h, AUC= 2 218.9 ?g?h/mL, the absolute bioavailability was 70.14%. Conclusion PNS liposomes with high entrapment and stability can prolong its circulation in blood and improve the PNS bioavailability via lung approach.

Preparation and in vitro evaluation of dispersible tablet of total notoginseng saponin / 中成药

AIM: To establish the preparative method of dispersible tablet of total notoginseng saponin (DTTNS) by powder direct compression,and to evaluate it pharmaceutical characteristics. METHODS: The effect of factors on the disintegration of DT-TNS was investigated by single factor method,and the formulation was optimized through orthogonal design. RESULTS: The disintegration time of DT-TNS containing 40% total notoginseng saponin was within 1 min while the formulation mainly consisted of 49% MCC as filler,12% of PVPP mixed with 3% L-HPC as disintegrating agent. In addition,the dissolution of DT-TNS was almost finished in 10-15 min. CONCLUSION: The preparative method of DT-TNS by powder direct compression is simple,with short disintegration time and high dissolution rate.

Determination of ginseng saponin Rg_1,Rb_1 and notoginseng saponin R_1 in Qianjin Shenanning Pills by HPLC / 中成药

AIM:To establish a method of determining effective components in Qianjin Shenanning Pills(Flemingia Philippinensis Merr.et Rolfe,Radix et Rhizoma Ginseng rubra,Radix et Rhizowa Notoginseng,etc). METHODS: The contents of ginseng saponin Rg_1,Rb_1 and notoginseng saponin R_1 were determined by HPLC. RESULTS: The four effective components could be separated and purified by macroporous adsorptive resins of D_(101) and n-butanol,and their contents could be determined. CONCLUSION: The method is simple,feasible and reproducibility is good,it can be used as quality control in medicinal preparation.

Effects of Panax notoginseng saponin on macrophage inflammatory protein-1? and monocyte chemoattractant protein-1 in plasma in rats with pulmonary fibrosis / 第三军医大学学报

Objective To investigate the effects of Panax notoginseng saponin (PNS) on macrophage inflammatory protein 1?(MIP 1?) and monocyte chemoattractant protein 1(MCP 1) in plasma in rats with pulmonary fibrosis. Methods The dynamic changes of the contents of MIP 1?and MCP 1 in plasma were determined with ELISA. Results The contents of MIP 1? and MCP 1 in plasma were significantly higher in PF group than those in PNS group at most time points(125 pg/ml and 298 pg/ml), and correlated with the development of fibrosis. The contents of MIP 1? and MCP 1, close to those in the control group, were inhibited obviously in PNS group. Conclusion PNS may have effect on the prevention and cure of fibrosis by minimization of the alveolar inflammation due to the effective inhibition of the contents of MIP 1? and MCP 1 in plasma.