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Cerebral ischemia-reperfusion (CIR) is a serious complication often associated with cerebral ischemia. The purpose of this study was to explore the therapeutic effect of nourishing qi, activating blood circulation, and inducing resuscitation (Borneol with astragaloside IV and Panax notoginseng total saponins, BAP) on CIR. Neurological function score system was used to determine the neurological function. The survival of nerve cells was detected by Nissl staining. The levels of IL-1β, IL-18, IL-4, and IL-10 were detected by ELISA. The expression of GSDMD, GSDMD-N, Nrf2, and HO-1 proteins in hippocampus tissues was measured by immunohistochemistry (IHC). Western blot, RT-qPCR, or immunofluorescence (IF) were used to detect the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), pro-Caspase-1, Caspase-1, Nrf2, and HO-1 expression. Lactate dehydrogenase (LDH) level was analyzed by LDH release assay. Cell viability was determined by cell counting kit-8 (CCK8). Apoptosis was detected by flow cytometry. BAP significantly promoted the recovery of nerve function, the activity of nerve cells, and the expression of Nrf2, HO-1, IL-4, and IL-10 in rat hippocampus tissues after CIR. BAP has an obvious inhibitory effect on the expression of NLRP3, pro-Caspase-1, and Caspase-1 proteins, the release of IL-1β and IL-18 factors, and neuronal pyroptosis in hippocampal tissues. BAP also promoted IL-4 and IL-10 levels, and the activity of SH-SY5Y cells. The IL-1β, IL-18, NLRP3, pro-Caspase-1, Caspase-1, GSDMD, and GSDMD-N expressions were significantly inhibited by BAP in vitro, which was reversed by Nrf2 knockdown. This study confirmed that BAP alleviated rat CIR and inhibited the pyroptosis of SH-SY5Y cells by regulating the Nrf2/HO-1 signaling pathway. This study provided new directions and ideas for the treatment of CIR.

Objective To study the effect of borneol combined with astragaloside IV and Panax notoginseng saponins (BAP) on promoting neurogenesis by regulating microglia polarization after cerebral ischaemia–reperfusion(CI/R) in rats. Methods A focal CI/R injury model was established. Evaluated the effects of BAP on ischaemic brain injury, on promoting neurogenesis, on inhibiting Inflammatory microenvironment and TLR4/MyD88/NFκB signalling pathway. A microglia oxygen-glucose deprivation reoxygenation (OGD/R) model was established that evaluated the effects of BAP on regulating the polarization of microglia and inflammatory microenvironment. Results BAP can inhibit the expression of TLR4, MyD88 and NFκB proteins, reduce IL-1β and increase IL-10, reduce M1 type microglia and increase M2 microglia. The proliferation of neural stem cells increased, synaptic gap decreased, synaptic interface curvature increased, expression of SYN and PSD95 proteins increased, which improved the neurological dysfunction and reduced the volume of cerebellar infarction and nerve cell injury. Conclusion BAP can reduce CI/R injury and promote neurogenesis, the effect is related to inhibition of the activation of TLR4/MyD88/NFκB, regulating the polarization of microglia from M1 type to M2 type and inhibition of inflammatory response.

Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking.To assess the efficacy of RIC for acute moderate ischemic stroke.This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.ClinicalTrials.gov Identifier: NCT03740971.

Pyroptosis and necroptosis are closely associated with the mechanism underlying cerebral ischemia-reperfusion (I/R) injury. The combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) has remarkable effects on the alleviation of cerebral I/R damage. However, whether inhibition of pyroptosis and necroptosis is the mechanism underlying the beneficial effects of this drug combination on cerebral I/R injury remains unclear. To explore the effects and mechanisms of drug treatment, middle cerebral artery occlusion was performed to induce I/R injury in rats, which was verified based on neurological deficit score (NDS), infarct volume and H&E staining. Activation of pyroptosis and necroptosis was detected by western blot analysis of associated proteins. The results of the present study demonstrated that treatment with AST IV and PNS, either alone or in combination, significantly reduced the NDS, cerebral infarct volume and cell injury rate in the cerebral cortex of rats. The treatments also improved pathological injury to the cerebral cortex and reduced the levels of proteins associated with pyroptosis and necroptosis. These effects were stronger in the combination drug group compared with groups treated with a single drug alone. The findings of the present study suggested that the combination of AST IV and PNS exhibited stronger neuroprotective effects in I/R injury than either drug alone, and that the underlying mechanism was associated with inhibition of pyroptosis and necroptosis.

Myocardial ischaemia reperfusion injury (MIRI) is considered the primary cause of death in patients with cardiovascular diseases. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be involved in the pathogenesis of MIRI. However, whether lncRNA ROR and miR-124-3p play roles in MIRI and the underlying mechanism remain undetermined. HCMs were exposed to hypoxic conditions for 2 h followed by re-oxygenation (H/R) treatment. Expression of miR-124-3p and lncRNA ROR in HCMs was measured by qRT-PCR. TRAF6 expression was evaluated by qRT-PCR and western blotting. ELISA and qRT-PCR were conducted to assess the production of TNF-α, IL-6, and IL-1β. The interaction between miR-124-3p and TRAF6, as well as between miR-124-3p and lncRNA ROR, was verified by dual-luciferase reporter assay. Cell apoptosis was detected by flow cytometry analysis. Our data revealed that miR-124-3p was significantly downregulated, while TRAF6 and lncRNA ROR were upregulated in both MIRI rat model and H/R treated HCMs. Overexpression of miR-124-3p reversed the H/R-induced cell apoptosis and upregulation of TNF-α, IL-6, and IL-1β. Mechanistically, miR-124-3p bound and negatively regulated TRAF6 expression in HCMs. Moreover, TRAF6 overexpression significantly blocked the effects of miR-124-3p mimics on cell apoptosis and inflammatory response of HCMs, which involved the NF-κB pathway. Further analysis showed that lncRNA ROR sponged and negatively regulated miR-124-3p in HCMs. Overexpression of IL-1β was demonstrated to promote H/R induced cell apoptosis in HCMs. In addition, overexpression of ROR further enhanced the H/R-induced inflammation and cell apoptosis through its action on miR-124-3p. The lncRNA ROR/miR-124-3p/TRAF6 axis regulated the H/R-induced cell apoptosis and inflammatory response of HCMs.

To explore the main active components and effects of cell cycle regulation mechanism of Astragali radix (AR) and Angelicae sinensis radix (ASR) on oxidative damage in vascular endothelial cells, a model of oxidative damage in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL) treatment was developed. Based on the “knock-out/knock-in” model of the target component, cell viability, intracellular reactive oxygen species (ROS), and lactate dehydrogenase (LDH) leakage were assessed by Cell Counting Kit-8 assay, fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA), and colorimetric assay, respectively, to evaluate the protective effect of the active components of AR and ASR (astragaloside IV (AS IV), astragaloside I (AS I), formononetin (FRM), calycosin (CAL), calycosin-7-O-β-D glucoside (CLG), and ferulic acid (FRA)) against oxidative damage. The cell cycle and expression of genes encoding cyclins and cyclin-dependent kinases (CDKs) were observed using flow cytometry and quantitative real-time polymerase chain reaction. The results showed that the combination of active components (ACC) significantly inhibited the decrease in cell viability as well as the increase in ROS and LDH release in HUVECs induced by ox-LDL treatment. AS IV and FRM promoted the proliferation of HUVECs but the proliferation index was decreased in the AS I and FRA groups; this inhibitory effect was counteracted by the ACC. The ACC reduced and increased the proportion of positive cells in G1 and S phases, respectively, followed by the upregulation of cyclin A (CCNA), cyclin E (CCNE), and CDK2 mRNA expression and downregulation of cyclin B (CCNB), cyclin D1 (CCND1), CDK1, CDK4, and CDK6 mRNA expression, which significantly mitigated inhibition of HUVECs proliferation induced by ox-LDL treatment. Taken together, AS IV, AS I, FRM, CAL, CLG, and FRA were the primary pharmacodynamic substances of AR and ASR that alleviated oxidative injury in HUVECs. ACC mitigated the upregulation of intracellular ROS levels and LDH release induced by ox-LDL treatment, which promoted the cell cycle procession of HUVECs by regulating the expression of genes encoding cyclins and CDKs and thus preventing oxidative damage in HUVECs.

The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1. Meanwhile, AST IV and Rg1 alone increased cell survival and decreased lactate dehydrogenase (LDH) leakage induced by OGD/R, reduced autophagosomes and the LC3 II positive patch, down-regulated the LC3 II/LC3 I ratio and up-regulated the p62 protein; the 1:1 combination enhanced these effects. Mechanistic study showed that Rg1 and the 1:1 combination increased the phosphorylation of PI3K I, Akt and mTOR; the effects of the combination were greater than those of the drugs alone. AST IV and the 1:1 combination suppressed the expression of PI3K III and Becline-1, and the combination elevated Bcl-2 protein expression; the effects of the combination were better than those of the drugs alone. These results suggest that after 2 h-OGD followed by reoxygenation for 24h, PC12 cells suffer excessive autophagy and damage, which are blocked by AST IV or Rg1; moreover, the combination of AST IV and Rg1 at a 1:1 ratio of their IC50 concentrations has a synergistic inhibition on autophagic injury. The synergistic mechanism may be associated with the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways.

The present study was aimed to investigate the protective effect and anti-inflammation mechanism of astragaloside IV (AST-IV) on cerebral ischemia and reperfusion injury. Following the establishment of cerebral ischemia and reperfusion model in rats by modified suture method, neurological deficit scores and cerebral infarct volume were used to evaluate the pharmacological effect of AST-IV against cerebral ischemia-reperfusion injury. Western blot was used to detect the expression levels of NLRP3, pro-Caspase-1, Caspase-1, pro-IL-1β, IL-1β, pro-IL-18, IL-18, phosphorylated and total nuclear factor kappa B (NF-κB)/p65 protein in the brain tissue. The results showed that compared with model group, the intervention of AST-IV decreased the neurological deficit scores, reduced the cerebral infarct volume, decreased the levels of NLRP3, Caspase-1, pro-IL-1β, IL-1β, pro-IL-18 and IL-18, and inhibited the expression of phosphorylated NF-κB in brain tissue. The results suggest that AST-IV has a protective effect against cerebral ischemia and reperfusion injury, and its mechanism is related to inhibiting the phosphorylation of NF-κB and NLRP3 inflammasome activation.

Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g·kg-1), Angelica (3.00 g·kg-1), and combinations of Astragalus and Angelica at different ratios, including 10 : 1 (Astragalus 9.81 g·kg-1+Angelica 0.98 g·kg-1), 5 : 1 (Astragalus 9.00 g·kg-1+Angelica 1.80 g·kg-1), 2 : 1 (Astragalus 7.71 g·kg-1+Angelica 3.08 g·kg-1), 1 : 1 (Astragalus 5.40 g·kg-1+Angelica 5.40 g·kg-1), 1 : 2.5 (Astragalus 3.08 g·kg-1+Angelica 7.71 g·kg-1), 1 : 5 (Astragalus 1.80 g·kg-1+Angelica 9.00 g·kg-1), and 1 : 10 (Astragalus 0.98 g·kg-1+Angelica 9.81 g·kg-1). Our results suggested that Astragalus mixed with Angelica synergistically promoted hematopoiesis best when the combination ratio of Astragalus and Angelica was 1 : 1, 1 : 2.5 or 1 : 5; moreover, the effect of Angelica was greater than that of Astragalus. The potential mechanisms of the combinations of Astragalus and Angelica that promote hematopoiesis include the dissolution of the effective components, promoting the synthesis and secretion of hematopoietic growth factor (HGF) and the proliferation of hematopoietic progenitor cells (HPCs).

Pyroptosis is a form of inflammatory programmed cell death activated by caspase-1 and caspase-4/5/11, and involves in the pathogenesis of infectious diseases and nervous system diseases. Pyroptosis is mediated by canonical inflammasome pathway and non-canonical inflammasome pathway. The canonical inflammasome pathway is activated in stroke and aggravates brain injury. Inhibition of inflammasome, caspase-1, IL-1β and IL-18 ameliorates brain injury. These studies indicate that canonical inflammasome pathway contributes to post-stroke brain injury, therefore, pyroptosis has become a potential therapeutic target for preventing excessive cell death during stroke. We reviewed the relationship between pyroptosis and stroke to provide some perspectives on future researches in this field.

To explore the effects and molecular mechanisms of the combination between total Astragalus extract (TAE) and total Panax notoginseng saponins (TPNS) against cerebral ischemia-reperfusion injury.C57BL/6 mice were randomly divided into sham-operated group, model group, TAE (110 mg/kg) group, TPNS (115 mg/kg) group, TAE-TPNS combination group and Edaravone (4 mg/kg) group, treated for 4 days, then, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery (CCA) ligation for 20 min followed by reperfusion for 1 and 24 h.TPNS could increase adenosine triphosphate (ATP) level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate (ADP) contents and NaThe combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.

The aim is to study the effect of astragaloside Ⅳ (AST Ⅳ) combined with Panax notoginseng saponins (PNS) on cerebral ischemia-reperfusion injury, and to probe the synergistic mechanism through the pharmacokinetics of the four major components such as AST Ⅳ, ginsenoside Rg₁ (Rg₁), ginsenoside Rb₁ (Rb₁), notoginsenoside R₁ (R₁) in cerebral ischemia-reperfusion rats. Following the establishment of cerebral ischemia/reperfusion model in rats by modified suture method, neurological function score, cerebral infarction area and pathomorphology were used to evaluate the pharmacological effect that the combination of AST Ⅳ and PNS antagonized cerebral ischemia-reperfusion injury; the contents of AST Ⅳ, Rg₁, Rb₁, R₁ in rat plasma of different time points were determined with ultra performance liquid chromatography tandem massspectrometry (UPLC-MS/MS), pharmacokinetic parameters were calculated and pharmacokinetics changes of the main effective components were analyzed. The results showed that AST Ⅳ, PNS alone and their combination could reduce the cerebral infarction area of rats, relieve the behavioral scores of neurologic deficit, improve the pathological changes after cerebral ischemia, the effects of the combination were better. Among AST Ⅳ, Rg₁, Rb₁, R₁, the area under the curve (AUC) was significantly increased, the mean residence time of (MRT0-t) was delayed, the peak concentration (Cmax) was significantly raised, the apparent volume of distribution (Vz/F) was reduced, and the clearance rate in vivo was significantly slowed. It suggested that AST Ⅳ combined with PNS has synergistic enhancement on anti-cerebral ischemia/reperfusion injury, moreover, make the pharmacokinetic behavior of the main effective components change, the mechanism may be associated with prolonging the retention time of the effective components in cerebral ischemia condition, elevating the bioavailability.

The aim is to study the effect and its mechanism of Astragalus Radix combined with Angelicae Sinensis Radix on the proliferation of hematopoietic stem cells(HSCs) in senescence model. After drug-containing plasma of rats was prepared via intragastric administration, HSCs of mice were cultured in vitro, and then they were divided into blank control group, model group, blank plasma group, Astragalus Radix + Angelicae Sinensis Radix 1∶1 group and 10∶1 group, Angelicae Sinensis Radix plasma group, and Astragalus Radix plasma group. HSCs senescence model was induced by using tert-butyl hydrogen peroxide(t-BHP), and intervened by drug-containing plasma. Cells senescence rate was tested by SA-β-galactosidase staining method; cell cycle distribution was determined by flow cytometry; Cyclin D1, P21, and P53 mRNA were measured with RT-PCR, and Cyclin D1 protein expression was measured by Western blot. Results showed that after being induced by t-BHP, senescence rate of HSCs was increased; cell proliferation ability was decreased; count of G₀/G₁ phase cells was increased; count of G₂/M+S phase cells was reduced; Cyclin D1 expression was down-regulated while P53, P21 expression was up-regulated, which were reversed by Astragalus Radix + Angelicae Sinensis Radix 1∶1 and 10∶1, single Angelicae Sinensis Radix, and single Astragalus Radix plasma. Furthermore, the above effects were most obvious in Astragalus Radix+Angelicae Sinensis Radix 1∶1 group. These results suggested that t-BHP can promote HSCs senescence and reduce cell proliferation ability. Angelicae Sinensis Radix, Astragalus Radix and their combinations can inhibit HSCs senescence, promote HSCs proliferation as well as cell cycle conversion; moreover, the effects of 1∶1 Astragalus Radix+Angelicae Sinensis Radix were strongest. The mechanisms may be related to up-regulating the expression of cell cycle positive regulator, down-regulating the expression of cell cycle negative regulator, thus promoting the cells to enter the proliferation phase from the stationary phase.

Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g·kg

Lung functional impairment caused by acute pancreatitis (AP) is the primary contributor to AP‑associated mortality. Previous studies have reported that AP‑associated lung injury is associated with systemic inflammatory response syndrome and oxidative stress. In the present study, the protective effects of Danhong injection (DHI), a widely used Chinese Traditional Medicine preparation, on AP‑associated lung injury in rats was examined. The myeloperoxidase activity, malondiadelhyde level and superoxide dismutase activity determination demonstrated the anti‑inflammatory and anti‑oxidative properties of DHI. The results of western blotting and reverse‑transcription‑semi‑quantitative polymerase chain reaction indicated that DHI could protect rats against AP‑associated lung injury, and the protective effect was associated with the suppression of nuclear factor‑κB activation and cell adhesion molecule expression, and the reduction of neutrophil infiltration and oxidative stress levels. As demonstrated by HE staining, DHI inhibited the pancreas and lung tissue injury. Therefore, DHI could be a potential candidate for the treatment of patients with AP‑associated lung injury.

A decreased plasma level of soluble form of the receptor for advanced glycation end products (sRAGE) in patients with Alzheimer's disease (AD) has been reported. However, no evidence has shown whether the sRAGE plasma level of AD patients may differentiate from other types of dementia.Our study assessed sRAGE concentrations in the following 121 individuals in Chongqing area: 36 patients with AD, 12 with vascular dementia (VaD), 14 with mixed dementia (MD), 24 with other dementia (OD) including Parkinson's disease dementia, frontotemporal dementia, paralytic dementia and 35 cognitively normal controls. The total plasma level of sRAGE was determined using sandwich ELISA method.sRAGE concentration in AD is significantly decreased compared with healthy controls. However, the receiver operating characteristic curve analysis of sRAGE between the AD and the control shows a low diagnostic accuracy.Our results demonstrate that sRAGE may assist the diagnosis of AD from normal individuals, but cannot differentiate AD from VaD, MD or OD.

This paper was aimed to explore the effects of glycosides, the effective component of Buyang Huanwu decoction, and its main active components such as astragaloside Ⅳ, amygdalin, peoniflorin and their combinations on vascular smooth muscle cells (VSMC) proliferation, clarify the major active materials of anti-VSMC proliferation and investigate the mechanisms via the signal transduction pathway. Plasma containing drug was prepared via oral administration in rats. VSMCs of rats aorta were cultured, and then VSMC proliferation was stimulated by using platelet derived growth factor (PDGF).The plasma containing drug was added to detect the activity of cell proliferation, cell cycle and related protein expressions of signaling pathway such as extracellular signal-regulated kinase (ERK), phos-phatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and Janus kinase/signal transducer and activator of transcription (JAK/STAT). After being stimulated by PDGF, the proliferation activity of VSMC was strengthened (P

Objective To explore the effects and mechanisms of combining astragaloside IV (the effective component of Astragalus membranaceus) with notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1 (the effective components of Panax notoginseng) against oxidative injury in PC12 cells induced by cobalt chloride (CoCl₂). Methods CoCl₂ was used to stimulate PC12 cells to induce injury after transdifferentiation with nerve growth factor. Then the PC12 cells were divided into 10 groups and cultured with corresponding drugs. After culture, apoptotic cells were tested by using Hocchst 33258 fluorescent staining, the level of mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 fluorescent staining and the content of reactive oxygen species (ROS) in PC12 cell was measured by dichlorofluorescin diacetate fluorescent staining. Results CoCl₂ induced apoptosis along with the obvious decrease of MMP as well as overproduction of ROS in PC12 cells. Astragaloside IV, ginsenosides Rg1, ginsenosides Rb1 and notoginsenoside R1 had inhibition effects in different degree on PC12 cell apoptosis induced by CoCl₂, reduced the overproduction of ROS and the decrease of MMP. The effects of the combination were better than those of active component alone. Conclusion Active components extracted from Astragalus and Panax notoginseng can inhibit PC12 cell apoptosis induced by oxidative injury, furthermore, the effects were enhanced by combination of these components, which may be associated with jointly antagonizing the generation of ROS and raising MMP.

This aim of this study was to explore the effects and molecular mechanisms of Astragalus extract against cerebral ischemia injury through the energy metabolism and apoptosis pathways of c‑Jun N-terminal kinase (JNK) signal transduction. After the bilateral common carotid artery of C57BL/6 mice was occluded for 20 min followed by 1-h reperfusion, the ATP content, total adenine nucleotides (TAN), energy charge (EC), and sodium potassium ATPase (Na(+)-K(+)‑ATPase) activity were decreased markedly in brain tissues. Astragalus extract markedly increased the ATP and ADP levels, EC value, and Na(+)-K(+)-ATPase activity. Twenty-four and 48 h after reperfusion, the neurocyte survival rate decreased and apoptosis rate increased, while the expression of phosphorylated JNK1/2, cytochrome c (Cyt C), and cysteine aspartic acid-specific protease (caspase)-9 and -3 were significantly enhanced in brain tissues. Astragalus extract significantly increased neurocyte survival and decreased the apoptosis rate as well as down-regulated the expression of p-JNK1/2, Cyt C, caspase-9, and caspase-3. These results suggest that Astragalus extract has neuroprotective effects against nerve injury after cerebral ischemia-reperfusion, and the underlying mechanism may be associated with improved cellular energy metabolism, inhibition of JNK signal transduction pathway activation, and then suppression of the mitochondrial apoptosis pathway.

To investigate the influence of astragaloside (AST) and Panax notoginseng saponins (PNS) combination on oxidative stress of brain tissues in C57BL/6 mice with cerebral ischemia-reperfusion injury.Eighty C57BL/6 mice were randomly divided into sham-operated group, untreated group, high-dose combination group (AST at a dose of 220 mg/kg plus PNS at a dose of 230 mg/kg), medium-dose combination group (AST at a dose of 110 mg/kg plus PNS at a dose of 115 mg/kg), low-dose combination group (AST at a dose of 55 mg/kg plus PNS at a dose of 57.5 mg/kg), AST (110 mg/kg) group, PNS (115 mg/kg) group and edaravone (4 mg/kg) group. AST and PNS were administered by gavage once daily for 4 days and edaravone was administered by intraperitoneal injection twice daily for 4 days. On the fourth day, bilateral common carotid arteries were ligated for 20 minutes to induce cerebral ischemia, followed by 60 minutes of reperfusion. Ischemic brain tissue was used to prepare tissue homogenate, then contents of malonaldehyde (MDA), glutathione (GSH) and nitric oxide (NO), and activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in the homogenate were detected. Two x two analysis of variance of factorial design was used to analyze whether there was an interaction between AST at 110 mg/kg and PNS at 115 mg/kg.Compared with sham-operated group, contents of MDA and NO, and activity of NOS in the untreated group were remarkably increased (P0.01), activity of SOD and content of GSH were decreased (P0.01). Compared with the untreated group, content of MDA in the AST group was decreased (P0.01) and activity of SOD was increased (P0.01), however, contents of GSH and NO and activity of NOS had no obvious changes (P0.05). Contents of MDA and NO in the PNS group was decreased as compared with the untreated group (P0.01), but activities of SOD and NOS and content of GSH had no changes (P0.05). Contents of MDA and NO and activity of NOS in brain tissues in the edaravone group were decreased (P0.01, P0.05), and activity of SOD was increased (P0.05), while content of GSH had no changes (P0.05). Contents of MDA and NO and activity of NOS in brain tissue in the AST and PNS combination groups were decreased (P0.01, P0.05), the activity of SOD increased (P0.01, P0.05), the content of GSH increased (P0.01, P0.05), and activity of SOD and content of GSH were increased (P0.01, P0.05). The results of analysis of variance of factorial design showed that there were interactions between AST (110 mg/kg) and PNS (115 mg/kg) (P0.01).Combination of AST (110 mg/kg) and PNS (115 mg/kg) has a restraint effect on the early oxidative stress injury in the brain after ischemia-reperfusion, and the combination has a synergistic or additive effect.

To explore the effects of alkaloids and glycosides extracted from Buyang Huanwu Decoction (BYHWD), a compound of traditional Chinese herbal medicine, on aortic intimal hyperplasia and the expression of the proliferating cell nuclear antigen (PCNA) in rats with aortic intimal injuries.The vessel restenosis model was established by denuding aortic endothelium with domestic balloon catheter in rats. Drugs were administered intragastrically on the first day after operation. The injured segments of aorta were taken on the fifteenth day after operation to determine the degree of intimal hyperplasia and observe the expression of PCNA.Aortic intimal hyperplasias were very obvious on the fifteenth day after operation. The media hyperplasias in the drug-treated groups were not significant (P0.05), but the intimal hyperplasia were remarkable as compared with that in the sham-operated group (P0.01). The degrees of intimal hyperplasia in BYHWD, alkaloids, glycosides and atorvastatin groups were less than that in the untreated group (P0.01). There was significant difference of PCNA expression between the untreated group and the sham-operated group (P0.01). The expressions of PCNA in alkaloids, glycosides, and atorvastatin groups were higher than that in the sham-operated group (P0.01, P0.05), but still lower than that in the untreated group (P0.01). The expression of PCNA in BYHWD group was higher than that in the sham-operated group (P0.01), and no significant difference was found between the BYHWD group and the untreated group (P0.05).Alkaloids and glycosides extracted from BYHWD can inhibit intimal hyperplasia induced by denuding arterial endothelium with domestic balloon catheter in rats. Alkaloids and glycoside may be among basal substances in BYHWD inhibiting intimal hyperplasia of blood vessel, the effect of which may relate to down-regulating the expression of PCNA.

To investigate the effects of Panax notoginseng saponins (PNS) on mRNA expressions of interleukin-1 beta (IL-1 beta), interleukin-1 receptor type I (IL-1RI), interleukin-1 receptor antagonist (IL-1ra), intercellular adhesion molecule-1 (ICAM-1), cysteinyl-aspartate specific protease-1 (caspase-1), caspase-3 and caspase-8 after cerebral ischemia-reperfusion in rats.Focal cerebral ischemia reperfusion in rats was induced by the method of nylon monofilament via the internal carotid artery. PNS was administered intraperitoneally respectively five minutes before cerebral ischemia and twelve hours after cerebral ischemia. After cerebral ischemia for two hours followed by reperfusion for twenty two hours, the mRNA expressions of IL-1 beta, IL-1RI, IL-1ra, ICAM-1, caspase-1, caspase-3 and caspase-8 in brain tissue were determined by reverse transcription polymerase chain reaction assay.After cerebral ischemia for two hours followed by reperfusion for twenty two hours, the mRNA expression levels of IL-1 beta, IL-1RI, IL-1ra, ICAM-1, caspase-1, caspase-3 and caspase-8 in brain tissue in the untreated group were obviously elevated as compared to those in the sham-operation group (P0.05 or P0.01). The mRNA expression levels of IL-1 beta, IL-1RI, IL-1ra in brain tissue in the PNS group were lower than those in the untreated group, but higher than those in the sham-operation group, and without statistical differences as compared to those in the sham-operation group and in the untreated group (P0.05). The mRNA expression level of caspase-3 in brain tissue in the PNS group was significantly lower than that in the untreated group (P0.05), but PNS had no effect on the mRNA expression levels of ICAM-1, caspase-1 and caspase-8 in brain tissue.PNS can inhibit the mRNA expression of caspase-3, slightly inhibit the mRNA expressions of IL-1 beta and its correlative inflammatory factors in brain tissue. The protective effects of PNS on cerebral injury induced by ischemia-reperfusion may be related to inhibiting the mRNA expressions of caspase-3, IL-1 beta and its correlative inflammatory factors in brain tissue.

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-[Formula: see text]B) inhibitor protein [Formula: see text] (p-I[Formula: see text]Ba) in brain tissues were up-regulated, and the nuclear translocation rate of NF-[Formula: see text]B 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[Formula: see text]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-[Formula: see text], and ICAM-1 mRNA, respectively, Notoginsenoside R1 reduced both TNF-[Formula: see text] and ICAM-1 mRNA, and the combination of the 4 effective components had inhibitory effects on the expressions of TNF-[Formula: see text], IL-1[Formula: see text], and ICAM-1 mRNA. Astragaloside IV, Ginsenoside Rg1, Notoginsenoside R1, and 4 effective components combination were able to restrain the phosphorylation of I[Formula: see text]B[Formula: see text], and relieve the nuclear translocation rate of NF-[Formula: see text]B. Moreover, the effects of the combination are greater than those of active components alone. All drugs could suppress the phosphorylation of JAK1 induced by I/R; meanwhile the expression of p-STAT1 exhibited a decrease in Ginsenoside Rg1 and four active components combination groups. The decreases of p-JAK1 and p-STAT1 in the four active components combination group were more obvious than those in active components alone groups. Astragaloside IV, Ginsenoside Rg1, and Notoginsenoside R1 further augmented GRP78 expression caused by I/R, Notoginsenoside R1 attenuated caspase-12 protein expression, Astragaloside IV and Ginsenoside Rg1 lessened the phosphorylation of JNK1/2, and the four active components combination was capable of up-regulating GRP78 protein while down-regulating the expressions of caspase-12 and p-JNK1/2. Similarly, the effects of the four active components combination were greater than those of effective components alone. These suggested that the combination of the main active components of Astragalus and Panax notoginseng could strengthen protective effects on cerebral ischemia injury via anti-apoptosis and anti-inflammation, and the mechanisms might be associated with restraining the activation of NF-[Formula: see text]B and JAK1/STAT1 signal pathways and regulating endoplasmic reticulum stress (ERS) after cerebral ischemia.

Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents, playing an important homeostatic role in cell survival, differentiation and development to maintain homeostasis. Autophagy is involved in tumors as well as neurodegenerative, cardiovascular and cerebrovascular diseases. Recently, active compounds from traditional Chinese medicine (TCM) have been found to modulate the levels of autophagy in tumor cells, nerve cells, myocardial cells and endothelial cells. Ischemic stroke is a major cause of neurological disability and places a heavy burden on family and society. Regaining function can significantly reduce dependence and improve the quality of life of stroke survivors. In healthy cells, autophagy plays a key role in adapting to nutritional deprivation and eliminating aggregated proteins, however inappropriate activation of autophagy may lead to cell death in cerebral ischemia. This paper reviews the process and the molecular basis of autophagy, as well as its roles in cerebral ischemia and the roles of TCM in modulating its activity.

Objectives Total Panax notoginseng saponin (TPNS) is extracted from Panax notoginseng. Our previous studies suggested that TPNS could inhibit intimal hyperplasia. This study discussed the impact of TPNS on the proliferation of vascular smooth muscle cells (VSMCs) and revealed the associated mechanisms through cell cycle-related factors and extracellular regulated protein kinase (ERK) signal transduction pathway. Methods A VSMC proliferation model induced by platelet-derived growth factor (PDGF) was established to observe the effects of rat drug-containing plasma on VSMC proliferation. Key findings After being stimulated by PDGF, the proliferating cell nuclear antigen (PCNA) and c-fos content increased, while up-regulation of cyclinD1, cyclin-dependent kinase-4 (CDK4) and down-regulation of p21 protein were observed. These changes were inhibited by atorvastatin and TSPN drug-containing plasma, and the inhibitive activity in both groups was not significant. Furthermore, both atorvastatin and TSPN could obviously inhibit the activation of PDGF-induced P-ERK1/2 and increase the content of MKP-1, there were also no significant differences. Conclusions These results suggested that atorvastatin and TPNS could inhibit VSMC proliferation by inhibiting the activation of ERK signalling pathway.

By analyzing current research status and considering our own previous research results, we hold that research on active substance of Chinese herbal formula should be focused on the effect of active components according to its functions, thus determining the main effective components of traditional Chinese medicine (TCM) compound prescriptions. Study of compatibility of effective components should be carried out and compound prescriptions composed of effective components should be developed. It is a pivotal way to deepen research on active components of TCM compound prescription by further analyzing the compatibility of effective components and the relationship between functional components and active components by multilink and multitarget methods.

Buyang Huanwu Decoction (BYHWD) was a commonly used traditional Chinese medicine for the treatment and prevention of ischemic cardiovascular and cerebral disease. Previous studies had shown that BYHWD alkaloids and glycosides could inhibit intimal hyperplasia and vascular smooth muscle cell (VSMC) proliferation after injury caused by balloon catheter. The present study aims to explore the mechanisms by which cell cycle was affected by BYHWD and its components. Primary rat VSMC was treated with platelet-derived growth factor (PDGF) and cell cycle phase and extracellular-signal regulated protein kinase (ERK) transduction pathway factors were measured. PDGF-treated cells were associated with a significant increase in the number of cells in the G(2)/M phase and S phase, and in the expression of P-ERK1/2, proliferating cell nuclear antigen (PCNA), c-fos, cyclinD(1) and cyclin-dependent kinase-4, as well as a decrease in the number of cells in the G(0)/G(1) phase, and in the expression of cyclin-dependent kinase inhibitor P21 protein and mitogen-activated protein kinase phosphatase-1 (MKP-1). Treatment with plasma of rats fed seven doses of BYHWD crude extract (22.2g/kg), BYHWD alkaloids (1.66g/kg), BYHWD glycosides (14.2g/kg) or the negative control atorvastatin (20mg/kg) inhibited these changes. All drug-containing plasma had similar activity to the mitogen activated protein kinase (MAPK)/ERK antagonist PD098059 which inhibited PDGF-induced expression of P-ERK1/2 and enhanced MKP-1. These suggest that BYHWD and its components may prevent VSMC proliferation by interfering with the ERK transduction pathway.

OBJECTIVE To investigate the effect of astragalosides (AST) and Panax notoginseng saponins (PNS) compatibility on the expression of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metal11oproteinase-1 (TIMP-1) after cerebral ischemia/reperfusion (I/R) injury in mice, to probe into its anti-ischemic brain injury protection mechanism. METHOD C57BL/6N mice were randomly divided into sham-operation group, model group, AST and PNS compatibility of high, medium and low-dose group, AST group, PNS group and edaravone group. Cerebral ischemia-reperfusion injury were prepared by bilateral common carotid artery ligation for 20 min followed by 24 hours reperfusion after administration for 4 days. Pathomorphism was detected with HE staining and the expression of MMP-9 and TIMP-1 protein in brain was detected by western-blot. RESULT The neuronal survival rate in the drug groups was significantly higher than the control group (P < 0.01), and the effect of the-middle dose compatibility group was more obvious. Factorial analysis manifested that AST110 mg x kg(-1) and PNS115 mg x kg(-1) compatibility had a synergistic interaction (P < 0.01). The expression of MMP-9 protein in the drug groups was lower than the model group significantly (P < 0.01 or P < 0.05), but the expression of TIMP-1 protein was higher than the model group significantly (P < 0.01 or P < 0.05), and the effect of the-middle dose compatibility group was more obvious, the two drugs had the stacking interaction (P < 0.05). CONCLUSION AST110 mg x kg(-1) and PNS115 mg x kg(-1) compatibility has a synergistic effect against ischemia-reperfusion injury in mice by accommodating MMP-9/TIMP-1 probably.

Aim of the study: the effect of total saponins of “panax notoginseng root” on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats Materials and methods Sprague-Dawley rats were randomly divided into sham-operated, control, TSPN and atorvastatin group. Rat aorta intima in all groups were injured by insertion of domestic balloon catheter into the aortae except sham-operated rats. Drugs were administrated orally from the second day after vascular injury and continued for 14 days. The injured segments of aortae were collected on the sixteenth day after operation to observe the morphological changes of vascular structure and to examine the expressions of proliferating cell nuclear antigen(PCNA), cyclinD1, cyclinE, collagen I(Col-I), fibronect(FN), matrix metalloproteinase-9(MMP-9) and tissue inhibitor metalloproteinase-1(TIMP-1). Results: TPNS significantly inhibited the vascular intimal hyperplasia. TPNS significantly lowered the expression of PCNA, cyclinE, cyclinD1, FN and MMP-9. TPNS had no significant impacts on the expression of Col-I and TIMP-1. Conclusions: Our studies indicated that TSPN could inhibit vessel restenosis after vascular intimal injury, and its mechanisms may be related to the blockage of the excessive proliferation of VSMC, the reduction of ECM protein deposition in the endometrium, and the degradation of ECM protein.

Aim of the study The inhibitive effect of BuYang HuanWu Decoction (BYHWD) and its major components on vascular intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix protein. Materials and methods Sprague-Dawley rats were randomly divided into sham-operated, control, alkaloid, glycoside, BYHWD and atorvastatin groups. Rat aorta intima in all groups were injured by insesion of domestic balloon catheter into the aortae except sham-operated rats. Drugs were administrated orally from the second day after vascular injury and continued for 14 days. The injured segments of aortae were collected on the sixteenth day after operation to observe the morphological changes of vascular structure and to examine the expressions of proteins in vascular cells associated with cell cycle including proliferating cell nuclear antigen(PCNA), cyclinD1 and cyclinE, and extracellular matrix(ECM) proteins including collagen I (Col-I) and fibronectin (FN), further to discover the involved biologically active substances and the potential mechanisms. Results Alkaloid and glycosid isolated from BYHWD were more effective than BYHWD in the inhibition of intimal hyperplasia and the expressions of PCNA, cyclinD1, cyclinE, Col-I and FN, suggesting that alkaloid and glycoside may be the main components of BYHWD responsible for the observed inhibition of excessive hyperplasia of vascular intima. Conclusions The mechanism associated with the anti-hyperplasia activity of BYHWD and its effective components may be related to the blockage of cell cycles of VSMC, and the inhibition of the ECM protein synthesis, even the increased degradation of ECM proteins.

To establish the mathematical kinetic model of the components extracted from the FTMC (formulae of the traditional Chinese medicine) and analyze parameters of the astragaloside IV extracted from the BYHWD (Buyang Huanwu decoction).The model, including algebra and differential groups, have been set up according to the FICK discipline and Noyes-whitney soluted theories, as well as two transfer diffusive processes ((1) from protoplasate to apoplasmic, also from material compartment interior cell membrane to outside compartment; (2) apoplasmic to solution, also from outside compartment to solvent compartment) on components extraction from the FTMC. The equation groups, according to laplace transform, have been given a expression as solutions, which indicate the quantitative changes of the component concentration in solvent vs. time. The model kinetic parameters have been analyzed, meanwhile the parameters of the astragaloside IV in the BYHWD under 100 degrees C, extracted by water, have been analyzed by way of this model:It has been established a mathematical model that consists of three parts of e exponent. The kinetic parameters: M, alpha, N, beta, L, pi, K, k1', k2', rho1, rho2, tmax, Cmax, AUC, w0, P, D of the BYHWD were respectivelly 0.061 27% , 0.280 2 min(-1), - 1.027% , 0.008 965 min(-1), 1.077%, 0.002 665 min(-1), 3.451 x 10(-3) min(-1), 3.188 x 10(-3) min(-1), 0.375 9 min(-1), 1.420 min, 0.754 7 min, 184.9 min, 0. 0572 1 mg x mL(-1), 289.9 min, 0.070 11%, 46.24%, 22. 35%.The kinetic model, applied to isolated system, can have been of the rule of multiplex linear. Each parameters can be analyzed completely.

To compare effects of different point combinations of Zusanli (ST 36) for improving acute gastric mucosa injury and study on the mechanism.One hundred rats were randomly divided into 10 groups, Zusanli (ST 36) group (group A); Zusanli and Neiguan (PC 6) group (group B); Zusanli and Zhongwan (CV 12) group (group C); Zusanli and Gongsun (SP 4) group (group D); Zusanli, Neiguan and Zhongwan group (group E); Zusanli, Neiguan and Gongsun group (group F); Zusanli, Zhongwan and Gongsun group (group G); Zusanli and Neiguan, Zhongwan, Gongsun group (group H); model group (group I); blank control group (group J), 10 rats in each group. Gastric mucosa injury model was made by intragastric infusion of dehydrated alcohol (0. 6 mL/100 g). The gastric mucosa injury index (UI), epidermal growth factor (EGF), nitric oxide (NO) and gastrin (GAS) contents were detected.Contents of EGF and NO were significantly increased and GAS content decreased in all of the EA groups as compared with those in the model group (P0. 01 or P0. 05), with no significant differences among group A, B and D, and significant differences as group A compared with group C, F and group H compared with other EA groups.Different point combinations of Zusanli (ST 36) can improve acute gastric mucosa injury, with the strongest effect in the Zusanli and Neiguan, Zhongwan, Gongsun group.

To study the effect of Sanhuang Jiangtang recipe (SJR) on renin-angiotensin system in local myocardium in diabetic rats.Rats were made into diabetes model by intraperitoneally administering of streptozocin, and medicated through gastrogavage with SJR (50 g/kg), gliclazide (20 mg/kg), captopril (15 mg/kg) and nitrendipine (30 mg/kg) respectively, for successive 8 weeks, started from 2 weeks after modeling. Levels of fasting blood sugar (FBS), serum insulin (Ins), heart/body weight ratio (H/BW), myocardial angiotensin II (Ang II), angiotensin converting enzyme (ACE) and aldosterone (ALD) were determined. And the mRNA expression of type I angiotensin receptor (AT1R) in myocardium were detected by RT-PCR assay.As compared with those in the normal rats, levels of FBS, H/BW, Ang II, ACE, ALD and AT1R mRNA expression were higher (all P0.05) and level of serum Ins was lower (P0.01) in the model rats. SJR, gliclazide, captopril and nitrendipine could slightly reduce the blood sugar level in model rats, but with no increase of serum Ins. All the four drugs could reduce H/BW, Ang II, ACE and AT1R mRNA expression. SJR and captopril could also decrease the ALD content in myocardium.Cardiac hypertrophy has been induced in 10 weeks after diabetic modeling. Activation of local myocardial RAS is related to the genesis of diabetic cardiomyopathy. SJR, gliclazide, captopril and nitrendipine could antagonize the genesis of diabetic cardiomyopathy, the mechanism is related to the inhibition of RAS activation in local myocardium.

To study the effects of Bu Yang Huan Wu Decoction on astrocytes after cerebral ischemia and reperfusion.Cerebral ischemia model in gerbils was produced by ligating bilateral common carotid artery. The dynamic expressin of GFAP were determined by immunochemistry after cerebyal ischemia for 15 min followed by reperfusion for 24 hours and 48 hours.GFAP positive reactions reached a peak after cerebral ischemia for 15 min followed by reperfusion for 24 hours. Bu Yang Huan Wu Decoction decreased the expression. GFAP positive reactions decreased after cerebral ischemia for 15 min followed by reperfusion for 48 hours, Bu Yang Huan Wu Decoction increased the expression.The regulation of Bu Yang Huan Wu Decoction on astrocytes after cerebral ischemia and reperfusion may be related to repairing process after cerebral ischemia.

To compare the effects of Buyang Huanwu Decoction (BYHWD) and its active regions combination on brain heat shock protein 70 (HSP70) expression.Cerebral ischemia model gerbils produced by ligating bilateral common carotid artery were injected intraperitoneally by BYHWD and its active regions combination separately. HSP70 mRNA expression was determined by Northern blot test and protein expression determined by Western blot test 48 hrs after ischemia for 15 min and reperfusion.The level of HSP70 mRNA and protein expression in ischemic/reperfusion brain tissue increased significantly. BYHWD and its active regions combination could decrease the HSP70 mRNA expression obviously, the inhibition effect of BYHWD was more significant than that of its active regions combination, but neither of them showed any effect on HSP70 protein expression.BYHWD and its active regions combination might down-regulate HSP70 mRNA expression in ischemic brain tissue through its anti-ischemic effect.

Background: Astragalus and Panax notoginseng are traditional Chinese medicines used for the treatments of cardio-cerebrovascular ischemic diseases, astragaloside IV (AST IV) and ginsenoside Rg1 (Rg1), ginsenoside Rb1 (Rb1), notoginsenoside R1 (R1) are their active components. Objective: The purpose of this work was to investigate the effect of AST IV combined with Rg1, Rb1, R1 on energy metabolism in brain tissues after cerebral ischemia-reperfusion in mice. Materials and Methods: C57BL/6 mice were randomly divided into 11 groups, treated for 3 days. At 1 h after the last administration, the model of cerebral ischemia-reperfusion injury was established, and brain tissues were detected. Results: All drugs increased the contents of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and the level of total adenine nucleotides (TAN), the combinations increased energy charge (EC), the effects of four active components combination were better. The phosphorylation of AMP-activated protein kinaseα1/2 (p-AMPKα1/2) was increased in AST IV, R1, four active components combination, AST IV + Rg1 and AST IV + R1 groups, the increased effect of four active components combination was greater than that of the active components alone and AST IV + Rb1. All drugs increased glucose transporter 3 (GLUT3) mRNA and protein, and the increases of four active components combination were more obvious than those of the active components alone or some two active components combinations. Conclusion: Four active components combination of Astragalus and P. notoginseng have the potentiation on improving of energy metabolism, the mechanism underlying might be associated with promoting the activation of AMPKα1/2, enhancing the expression of GLUT3, thus mediating glucose into nerve cells, increasing the supply and intake of glucose.

Background: Astragalus and Panax notoginseng are traditional Chinese Medicines used for the treatments of ischemic cerebrovascular disease, being often combined together in China and achieving a good effect. Objective: The objective of this study is to investigate the effects of astragaloside-IV (AST-IV) (the effective component of Astragalus ) combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 (the effective components of P. notoginseng ) on oxidative stress injury after cerebral ischemia-reperfusion in mice, and to explore the mechanisms through nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Materials and Methods: C57BL/6 mice were randomly grouped after treated for 3 days, the model of cerebral ischemia-reperfusion injury was established, and the brain tissues were detected. Results: AST-IV combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 could increase significantly the survival rate of nerve cell; decrease the contents of malondialdehyde, nitric oxide, increase the activity of superoxide dismutase and the level of glutathione; Nrf2 was down-regulated in the cytoplasm while up-regulated in nucleus, nuclear translocation rate raised as well as HO-1 messenger ribonucleic acid and protein expressions increased. The effects of four active components combination were better than those of the active components alone. Conclusion: Active components of Astragalus and P. notoginseng had the effects against cerebral ischemia-reperfusion injury, which were related to the antioxidative stress after cerebral ischemia-reperfusion. AST-IV combined with ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 could strengthen the antagonism effects on ischemia-reperfusion and oxidative stress injury, the mechanism underlying might be associated with jointly activating Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion.