Astragaloside Group Research Articles

Effect of astragaloside on expression of smac, cytochrome C and caspase-3 in hepatic tissue of acute hepatic failure induced by D-Gal NLPS

This study assessed astragaloside IV’s effect on liver Smac, Cytochrome C (Cyt-C) and Caspase-3 expression in acute liver failure in mice. Mice were randomly assigned into normal group, model group, model+astragaloside (1%) group and model+astragaloside (5%) group. Mice were given by gavage of astragaloside (50 mg/kg/d, 250 mg/kg/d) for 2 d before making the model in model + astragaloside group and model+astragaloside group. Equal dose of normal saline was administrated to the other groups. Except for the normal group, mice in the other groups were intraperitoneally injected with D-GalN/LPS for 48 h. The mice were at the end killed after the final intraperitoneal injection for 2 hours. Hepatic apoptosis and expressions of hepatic Smac, Cyt-C and caspase-3 were then analyzed. Mice exhibited less hepatocyte apoptosis and lower content of hepatic Cyt-C expression in both the model+astragaloside and model+astragaloside groups (P <0.01). D-GalN/LPS significantly enhanced Caspase-3 and Smac mRNA. Moreover, astragaloside suppressed the activity of Caspase-3 and decreased hepatic Smac mRNA expression in mice (P <0.01). Astragaloside IV can reduce the content of Cyt-C and down-regulate the expression of Smac and caspase-3, thereby protecting acute liver failure.

Evaluation of astragaloside IV in hepatic fibrosis: A meta-analysis.

To evaluate the effect of astragaloside IV for hepatic fibrosis.The multiple databases like Pubmed, Embase, Cochrane databases, and China National Knowledge database were used to search for the relevant studies, and full-text articles involved in the evaluation on effect of astragaloside IV for hepatic fibrosis. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted.Finally, 7 eligible studies were eventually satisfied the included criteria. Alanine aminotransferase (ALT) in model was higher than astragaloside group (mean difference [MD] = −58.01, 95% confidential interval (CI) [−93.97, −22.05], P = .002; I2 = 99%). The meta-analysis suggested that aspartate aminotransferase (AST) in model group was more than that in astragaloside group (MD = −39.94, 95% CI [−129.38, 49.50], P = .38; I2 = 100%). Model group had higher α - smooth muscle actin (α-SMA) than astragaloside group (MD was −1.13, P of heterogeneity <.0001, I2 = 94%, Z = 5.18, P of over effect <.0001). Transforming growth factor β (TGF-β) in model group was higher than that in astragaloside group (MD was −0.55, P of heterogeneity <.00001, I2 = 97%, Z = 2.54, P of over effect = .01). Limited publication bias was observed in this study.Astragaloside IV is a potential clinical drug for the treatment of liver fibrosis considering liver function and hepatic fibrosis related protein factor in experimental rats are improved.

Treatment with astragaloside IV reduced blood glucose, regulated blood lipids, and protected liver function in diabetic rats.

ObjectivesTo investigate the effects of astragaloside IV on blood glucose, blood lipids, and liver function in diabetic rats.MethodsFifty diabetic rats were randomly placed into five groups (n = 10 each): the diabetes mellitus (DM) group received intragastric saline, the metformin hydrochloride group received intragastric metformin hydrochloride, and the astragaloside-30, -60, and -120 groups received intragastric astragaloside 30 mg/kg, 60 mg/kg, and 120 mg/kg for 28 days, respectively. Ten non-diabetic rats received intragastric saline as controls.ResultsRelative to the DM group, fasting blood glucose, triglyceride, total cholesterol, serum alanine transaminase, and serum aspartate aminotransferase levels decreased in the astragaloside-60 and astragaloside-120 groups; serum alkaline phosphatase decreased solely in the astragaloside-120 group. Serum superoxide dismutase (SOD), glutathione (GSH-Px), and catalase (CAT) levels were elevated, while maleic dialdehyde (MDA) decreased in the astragaloside-120 group, relative to the DM group. Relative to the DM group, the liver index and liver cell apoptosis rate were reduced, while histopathological changes in liver tissue were ameliorated in the astragaloside groups; moreover, liver tissue SOD, GSH-Px, and CAT levels were increased, while liver tissue MDA was reduced.ConclusionsAstragaloside IV can lower blood glucose, regulate blood lipids, and protect liver function in diabetic rats.

Effects of Astragaloside on Biological Characteristics of Non-Small Cell Lung Cancer Cells via the Phosphatidylinositol 3-Kinase/Protein Kinase B/Mechanistic Target of Rapamycin Pathway

To evaluate the effects of astragaloside on the proliferation, invasion, migration and apoptosis of nonsmall cell lung cancer A549 cells and phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway. After A549 cells were treated with 0, 10, 20, 40, 60, 80 and 100 μmol/l astragaloside for 24 h, the survival rate was measured by methyl thiazolyl tetrazolium assay and the half maximal inhibitory concentration was calculated. Astragaloside at half maximal inhibitory concentration was added. Cell invasion, migration and apoptosis were detected by transwell assay, wound healing assay and flow cytometry, respectively. The effects of astragaloside on the expressions of phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway-related proteins were detected by western blotting. After different concentrations of astragaloside were added, cell proliferation declined with increasing concentration. Half maximal inhibitory concentration against A549 cell proliferation was 32.2 μmol/l. Compared with blank control group; cell proliferation; invasion and migration were significantly weakened, while apoptosis was enhanced in astragaloside group. The expressions of phosphorylation of phosphatidylinositol 3-kinase, phosphorylation of protein kinase B and phosphorylation of mechanistic target of rapamycin proteins in astragaloside group were significantly lower than those in blank control group. Astragaloside inhibits the proliferation, invasion and migration, and promotes the apoptosis of nonsmall cell lung cancer A549 cells dose-dependently. Inhibiting phosphorylation of phosphatidylinositol 3-kinase, phosphorylation of protein kinase B and phosphorylation of mechanistic target of rapamycin expressions in the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway may be one of the mechanisms of astragaloside.

Encapsulation of Astragaloside with Matrix Metalloproteinase-2-Responsive Hyaluronic Acid End-Conjugated Polyamidoamine Dendrimers Improves Wound Healing in Diabetes.

Impaired wound healing that occurs in diabetics can result in many life-threatening complications associated with excessive expression of matrix metalloproteinases (MMPs), which mediate the proteolysis of major matrix constituents. In this study, the dendrimer polyamidoamine (PAMAM) and the polysaccharide hyaluronic acid (HA) were connected through the substrate polypeptide (Gly-PLGLAG-Cys) of MMP-2 to obtain the MMP-2-responsive nanocarrier HA-pep-PAMAM. Insoluble astragaloside (ASI) was encapsulated in this nanocarrier to achieve controlled release at the site of intractable wounds. The HA-pep-PAMAM-ASI was successfully prepared with an average diameter of 142.3 ± 28.9 nm. Immunohistochemical staining of the skin revealed that the hard-to-heal wounds of diabetic mice showed stronger expression of MMP-2 than the wounds of normal mice. HA-pep-PAMAM-ASI achieved 73.9% release in the presence of MMP-2, but only 13.5% in PBS. A dose-dependent effect of H₂O₂ on the proliferation of BJ and HaCaT cells was observed, and HA-pep-PAMAM-ASI treatment had the best antioxidant capacity with MMP-2 pretreatment. HA-pep-PAMAM-ASI significantly increased GSH levels and reduced reactive oxygen species (ROS) levels to achieve antioxidant effects. The MMP-2-pretreated HA-pep-PAMAM-ASI group showed more improved cell proliferation and migration abilities. Compared with ASI group, the expression of all wound-repair-related genes in the group of HA-pep-PAMAM-ASI was significantly increased, and HA-pep-PAMAM-ASI showed a pronounced in vivo therapeutic effect. Therefore, our results revealed that enzyme-responsive MMP-2-loaded PAMAM nanoparticles could promote wound healing in diabetes and may be a promising biomaterial for treatment.

Effect of astragaloside IV on cognitive dysfunction in rats with cerebrally infarcted via TGF-β / Smad signaling pathway

Cerebral infarction is an acute cerebrovascular disease caused by abnormal blood circulation in the brain. In the present study, we investigate the effect of astragaloside IV on cognitive dysfunction in cerebrally infarcted rats via transforming growth factor-β (TGF-β) / Smad signaling pathway. For this purpose, 45 rats were divided into three groups including astragaloside, model, and control. 30 of 45 healthy adult male SD rats were randomly selected to establish an acute cerebral infarction model. 15 modeled rats were enrolled as a model and astragaloside group, and another 15 rats as a blank control group. The rats in the astragaloside group were fed with astragaloside IV according to 1.08 g/kg body weight, and those in the blank group and model group were given matching normal saline. The levels of TGF-β, Smad1, Smad3 and Smad7 of TGF-β/Smad signaling transduction pathway at T0 (week 0), T1 (week 3) and T2 (week 6) were determined by enzyme-linked immunosorbent assay (ELISA). The modified neurological severity score (mNSS) was used to evaluate the improvement of cognitive dysfunction in rats. The mNSS of rats with cerebral infarction in the astragaloside group was lower than that in the control group and model group (P&lt; 0.05). While the levels of TGF-β, Smad1, Smad3 and Smad7 in the astragaloside group were higher than those in the control group and model group (P&lt; 0.05). Astragaloside IV plays an important role in improving cognitive dysfunction in rats with cerebral infarction while affecting the levels of TGF-β, Smad1, Smad3 and Smad7 and activating TGF-β / Smad signaling pathway.

Astragaloside IV protects rat renal ischemia-reperfusion injury by regulating Th1/Th2 imbalance

Objective To investigated the protective effect and immunology mechanism of Astragaloside Ⅳ(Ast) on rat renal ischemia-reperfusion injury model. Methods The SD rats were randomly divided into four group as the control, sham-operation, renal ischemia-reperfusion injury, and Ast treatment groups. Rat serum and urine were collected and detective for kidney function and interleukin cytokines. The kidney tissue was collected for histology exam. The rats in astragaloside group were intraperitoneally injected with 100 mg/kg astragaloside, and the other three groups were intraperitoneally injected with an equal volume of normal saline. The models of renal ischemia-reperfusion injury were prepared to generate in model and astragaloside groups, after 30 minutes of astragaloside injection. The rats with renal ischemia-reperfusion injury model were sacrificed after 24 hours, and the level of blood-urine creatinine, neutrophil gelatinase-associated lipocalin and Kidney damage molecule-1 were determined. The level of Th1 type cytokines (TNF-α, IFN-γ, IL-2) and Th2 type cytokines (IL-4, IL-5, IL-10) in serum were measured by using ELISA. The protein and gene expression of TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10 in renal tissue were tested by western blot and PCR, respectively. The pathological changes and apoptosis of renal tissue in each group were detected by HE staining and TUNEL staining, respectively. The expression of CD20 protein in renal tissue was determined by immunohistochemistry. Results Compared with the model group, Ast treatment reduced serum creatinine (58.74 ± 9.44 μmol/L vs. 85.03 ± 23.48 μmol/L), increased creatinine clearance rate (0.81 ± 0.13 ml/min vs. 0.37 ± 0.08 ml/min), and reduce urine neutrophil gelatinase-associated lipocalin (NGAL) (579.34 ± 11.70 pg/ml vs. 827.60 ± 14.48 pg/ml), kidney injury molecule-1 (KIM-1) (105.06 ± 2.10 pg/ml vs. 151.67 ± 3.06 pg/ml) (P<0.05). Compared with the model group, Ast treatment alleviated renal tubular epithelial cell injury and significantly decreased the apoptosis (14.36 ± 1.36% vs. 28.63 ± 2.03%) (P < 0.05), and significantly decreased the serum TNF-α (361.44 ± 9.66 pg/ml vs. 515.93 ± 10.61 pg/ml), IFN-γ (64.11 ± 1.21 pg/ml vs. 93.51 ± 2.15 pg/ml), IL-2 (388.33 ± 1.21 pg/ml vs. 557.82 ± 15.29 pg/ml), IL-4 (60.89 ± 1.21 pg/ml vs. 95.56 ± 2.75 pg/ml), IL-5 (94.02 ± 2.81 pg/ml vs. 147.07 ± 3.50 pg/ml), and IL-10 (52.62 ± 2.51 pg/ml vs. 78.22 ± 3.24 pg/ml) (P<0.01). Compared with the model group, Ast treatment significantly decreased the kidney TNF-α mRNA (1.89 ± 0.59 vs. 2.87 ± 0.97), IFN-γ mRNA (3.11 ± 1.02 vs. 5.98 ± 1.52), IL-2 mRNA (1.68 ± 0.44 vs. 4.09 ± 1.65), IL-4 mRNA (2.41 ± 0.81 vs. 4.69 ± 1.62), IL-5 mRNA (1.56 ± 0.19 vs. 2.92 ± 0.55), IL-10 mRNA (1.45 ± 0.14 vs. 2.85 ± 0.32) (P<0.01). The ratio of IL-4 to IFN-γ was basically restored to the level of sham operation group (1.05 ± 0.02 vs. 1.02 ± 0.06) (P<0.01), and CD20 cells in renal tissue was reduced. Conclusions The Th1 and B lymphocytes play an important role in renal ischemia reperfusion injury, and Th2 cells play a protective role. Astragaloside can regulate the imbalance of Th1/Th2 in the early stage after acute renal injury, and alleviate renal tubular injury. Key words: Reperfusion injury; Astragaloside Ⅳ; Th1-Th2 balance; Antigens, CD20; Rats

Astragaloside attenuates the progression of prostate cancer cells through endoplasmic reticulum stress pathways.

Astragaloside (As) has been demonstrated extensively to serve roles in a variety of tumor types, including glioma, lung cancer, colorectal cancer, breast cancer and cervical cancer, and has therefore been widely used in Traditional Chinese Medicine. To the best of our knowledge, the present study was the first to investigate the efficacy of the Traditional Chinese Medicine astragaloside on tumor growth and the apoptosis of prostate cancer cells. In addition, further investigation into the underlying molecular mechanisms via the endoplasmic reticulum (ER) stress pathway was also performed. In the present study, the human prostate cancer DU-145 cell line was employed as an experimental model in vitro and cells were divided into five treatment groups: Dimethyl sulfoxide (DMSO) group (control), low-dose astragaloside group (L-As; 20 nmol/l), moderate-dose astragaloside group (M-As; 50 nmol/l), high-dose astragaloside group (H-As, 100 nmol/l) and ER stress suppressor group (tauroursodeoxycholic acid; TUDCA). The proliferative ability and apoptosis rate of the DU-145 cells were detected via Cell Counting kit-8 methods and flow cytometry, respectively. Furthermore, the ER stress factors [binding immunoglobulin protein (BiP), C/EBP homologous protein (CHOP) and caspase-12] were assessed through reverse transcription polymerase chain reaction. Additionally, the protein expression levels of inositol-requiring enzyme 1 (IRE1), phosphorylated protein kinase R-like ER kinase (p-PERK), iron-regulated transcriptional activator Aft (AFT)4 and AFT6 were measured detected by western blot analysis. Administration of As significantly reduced the cell viability and promoted apoptosis (P<0.05) in a dose-dependent manner. Expression of ER-stressed genes BiP, CHOP and caspase-12 mRNA was increased by As administration, while TUDCA treatment led to a lower mRNA expression of these genes, compared with the control group. Results of western blot analysis indicated that the protein expression of IRE1, AFT4 and AFT6 was upregulated in the H-As group, and that the ratio of p-PERK/PERK was also higher than in the other groups. The administration of As demonstrated significant therapeutic effects on the proliferation of prostate cancer cells, as well as the expression of related proteins and genes. The results of the present study suggested future clinical potential of As for the treatment of prostate cancer.

Astragaloside protects myocardial cells from apoptosis through suppression of the TLR4/NF-κB signaling pathway.

Astragaloside is a monomer isolated from Astragalus membranaceus, a flowering plant in the family Fabaceae. The aim of the present study was to investigate the anti-apoptotic affect of astragaloside on myocardial cells through the TLR4/NF-κB signaling pathway. Astragaloside, NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and Toll-like receptor 4 (TLR4) blocking antibody solution were prepared in vitro, and myocardial cells were incubated and cultured in serum-free medium overnight. Cells were divided into five groups: the normal control group, serum-free group, astragaloside group, TLR4 blocking antibody group and NF-κB inhibitor PDTC group. The myocardial cell apoptosis in each group was detected using flow cytometry, and the expression levels of TLR4 and NF-κB were detected via western blotting. The apoptosis rate in the serum-free group was significantly higher than that in the normal control group. The apoptosis rate of myocardial cells in the TLR4 blocking antibody group and NF-κB inhibitor PDTC group was lower than that in the serum-free group. In addition, the myocardial cell apoptosis was more obviously decreased in the astragaloside group, and the protein expression levels of TLR4 and NF-κB in the serum-free group were significantly higher than those in normal control group. The protein expression levels of TLR4 and NF-κB in the astragaloside group were obviously lower than those in the serum-free group, and the protein expression levels of TLR4 and NF-κB in the TLR4 blocking antibody group and NF-κB inhibitor PDTC group were decreased. In conclusion, astragaloside reduced myocardial cell apoptosis and protected myocardial cells, which may be one of the mechanisms of a traditional Chinese medicine monomer in treating heart failure.

Protective Effects and Mechanisms of Shenhua Tablet () on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury.

To investigate the protective effects and potential mechanisms of Shenhua Tablet (, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI). Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg-1•d-1), low- and high-dose SHT (1.5 and 3.0 g•kg-1•d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiffstaining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay. Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05). TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.

Astragaloside attenuates myocardial injury in a rat model of acute myocardial infarction by upregulating hypoxia inducible factor-1α and Notch1/Jagged1 signaling

The present study aimed to investigate the mechanisms underlying the cardioprotective effect of Astragaloside against myocardial injury following myocardial infarction (MI) in a rat model. Male Wistar rats were subjected to left anterior descending branch ligation. The rats that survived 24 h (n=18) were randomly and equally assigned to three groups: MI model group, and 2.5 and 10 mg/kg/day Astragaloside group. A further six rats underwent identical surgical procedures without artery ligation, serving as sham controls. Following 28 days of treatment, the left ventricle was harvested for morphological analysis, and mRNA and protein expression levels of hypoxia inducible factor-1α (HIF-1α), Notch1 and Jagged1 were measured. Treatment with Astragaloside attenuated pathological changes in the myocardium. Compared with untreated MI rats, rats treated with Astragaloside exhibited significantly increased mRNA expression levels of HIF-1α, Notch1 and Jagged1 (all P<0.01). HIF-1α demonstrated a dose-dependent effect (P<0.05). Astragaloside (10 mg/kg/day) significantly increased HIF-1α (P<0.05), Notch1 (P<0.01) and Jagged1 (P<0.01) protein expression levels. Additionally, 2.5 mg/kg Astragaloside significantly increased Jagged1 protein expression levels compared with untreated MI rats. Furthermore, there was a dose-dependent effect of Astragaloside treatment (P<0.01). These findings suggested that the cardioprotective effects of Astragaloside against myocardial injury following MI may involve upregulation of HIF-α, Notch1 and Jagged1 signaling, implicating these molecules as therapeutic targets for the treatment of MI.

Effect of astragaloside on mRNA expression of PI3K/Akt/mTOR signal transduction in anemia model mice induced by chemotherapy

To study the influence of astragaloside on mRNA expression of PI3K/Akt/mTOR signal transduction in anemia model mice induced by chemotherapy, 48 male BALB/c mice which were 6-7 week old were picked as the research objects and randomly divided into four groups, blank group, model group, astragaloside group and astragaloside IV group. Each group was 12 mice. Chemotherapy anemia model was established by cyclophosphamide. The mice were drawn blood from eyeball after 14 days treatment. The QPCR was used to test the mRNA concentrations of Akt, PI3K, BCL-xl, bad, FoxO, mTOR, PTEN in mouse spleen. In comparison of blank group, astragaloside group and astragaloside IV group,the erythrocyte counting and values of Hb in model group were significantly lower (P<0.05). The volumes mRNA of Akt,PI3K,BCL-xl,bad,mTOR were lower in blank group, compared with other groups (P<0.05 or P<0.01). The similar trend in astragaloside IV group except PI3K, comparing with blank group (P<0.05 or P<0.01). The contents of these five genes were no significant differentiations between astragaloside group and blank group. The statistics were obvious between astragaloside group and astragaloside IV group (P<0.05 or P<0.01). The concentrations of FoxO, PTEN were higher in model group,compared with blank group and astragaloside group (P<0.05 or P<0.01), but no difference with astragaloside IV group. Comparing with blank group, the volumes of these two genes were increased in astragaloside IV group (P<0.05), FoxO was higher in astragaloside group (P<0.05), but PTEN was not significant. There was no the same as astragaloside group and Astragaloside IV group. Therefore, astragaloside could increase the contents of Akt, PI3K, BCL-xl, bad, mTOR (P<0.01), decrease the concentrations of FoxO, PTEN (P<0.05). The changes in cyclophosphamide-induced anemia were highly significant by astragaloside. It could be related to the mRNA expression of PI3K/Akt/mTOR Signal Transduction.

Protective effects of astragaloside in rats with adriamycin nephropathy and underlying mechanism

The present study was designed to determine the mechanism underlying the treatment of nephrotic syndrome using astragaloside by observing the effects of astragaloside on the expression of nephrin and podocin proteins and genes in kidneys of rats with adriamycin nephropathy. The rats were injected with adriamycin and, after successful model establishment, randomly divided into a model group, a Methylprednisolone (MP) group, and an astragaloside group. The 24-h complete urine samples were collected. Biochemical indicators were monitored, and kidney tissues were collected for pathological analysis using light microscopy and electron microscopy. The mRNA expression of nephrin and podocin was measured in the kidney tissues using the real-time qPCR, and the protein expression levels of nephrin and podocin were detected using Western blot analysis. At the end of 12 weeks of drug intervention, the urinary protein level was lower in the MP and astragaloside groups than that in the model group (P = 0.008 and P = 0.01, respectively). Serum albumin was higher in the MP and astragaloside groups than in the model group (P < 0.001 and P = 0.012, respectively). Podocytes in the MP group were nearly normal, and fusion of podocytes in the astragaloside group was significantly less than that in the control group. The nephrin and podocin mRNA and protein expression levels in the intervention groups were higher (P < 0.05) than that in the model group. Due to the increased expression of podocyte-related nephrin and podocin proteins, astragaloside maintained slit diaphragm integrity and decreased the level of proteinuria in rats with adriamycin nephropathy.

Effects of Compound Shenhua Tablet (复方肾华片) on renal tubular Na+-K+-ATPase in rats with acute ischemic reperfusion injury

To observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI). Fifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope. Compared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a superior effect as compared with the astragaloside group and the SHT low-dose group. The SHT effectively alleviated RIRI caused by ischemic reperfusion, promoted the recovery of the polarity of renal tubular epithelial cells, and protected the renal tubules. The therapeutic effects of SHT were superior to those of astragaloside as a single agent.

Effects of Fufang Shenhua Tablet (复方肾华片) on the expression of toll-like receptors during acute kidney injury induced by ischemia-reperfusion in rats

To investigate the impact of a traditional Chinese medicinal compound known as Fufang Shenhua Tablet (SHP) on the expression of Toll-like receptors (TLRs) during renal ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI) in rats. A total of 28 Wistar rats were randomly divided into five groups: (1) pseudo-operation control group, (2) ischemia-reperfusion model group, (3) Astragaloside group, (4) high-dose SHP group, and (5) low-dose SHP group. There were four rats in the pseudo-operation group and six rats in each of the other groups. The accepted ischemia-reperfusion model was established after a 7-day gavage intervention, and pathological changes and renal function were observed, using an enzyme-linked immunosorbent assay (ELISA) to detect interleukin 8 (IL-8) and interferon gamma (IFN-γ) levels, as well as immunohistochemical staining to detect altered levels of TLR2 and TLR4 expression in renal tissue. After 24 h, renal pathological damage and the expression levels of serum creatinine (Scr), IL-8, IFN-γ, TLR2, and TLR4 were significantly higher in the model group as compared with the pseudo-operation group (P<0.05). In addition, at 24 h the above indicators decreased significantly in the Astragaloside group, high-dose SHP group and low-dose SHP group as compared with the ischemia-reperfusion model group (P< 0.05). TLR2 and TLR4 expression levels were significantly reduced in the SHP treatment and Astragaloside group as compared with the pseudo-operation group (P<0.05). Further, the high-dose SHP group showed significantly less renal damage score and decreased levels of TLR expression than those of low-dose SHP group and Astragaloside group (all P<0.05). SHP can alleviate the renal structural and functional damage caused by IRI-induced AKI in rats by reducing the damage of renal pathology, which may reduce inflammatory cytokine levels by downregulating the expression of TLRs in renal tissue in a dose-dependent manner.

Protective effects of astragaloside against ultraviolet A-induced photoaging in human fibroblasts

In this study, we aim to investigate the protective effects of astragaloside on ultraviolet A (UVA)-induced photoaging in human fibroblasts and its possible mechanisms. Subconfluent fibroblasts were cultured and divided into normal control group, astragaloside group, UVA irradiation group and UVA plus astragaloside group. The cells were shammed or irradiated with 10 J/cm(2) of UVA irradiation and treated with 20 μg/mL astragaloside. The aging condition was determined by histochemical staining of senescence-associated β-galactosidase (SA-β-gal). Concentration of transforming growth factor-β1 (TGF-β1) in the supernatant was determined by enzyme-linked immunosorbent assay, and mRNA levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by real-time polymerase chain reaction. UVA irradiation raised the proportion of SA-β-gal-positive cells in comparison with the normal control group (P<0.05). Astragaloside treatment was shown to decrease the level of SA-β-gal compared with the UVA group. With UVA irradiation, the concentration of TGF-β1 in the supernatant decreased, and astragaloside treatment recovered the content of TGF-β1 compared with the UVA irradiation alone (P<0.05). UVA irradiation also up-regulated the mRNA levels of MMP-1 and TIMP-1 (P<0.05). Astragaloside decreased the mRNA level of MMP-1 compared with the UVA irradiation alone, while the TIMP-1 expression increased (P<0.05). Astragaloside can protect the skin from UVA irradiation. The mechanism involved may be related with TGF secretion and decrease of collagen degradation.

Effects of astragalosides and Panax notoginseng saponins combination on oxidative stress of cerebral ischemic reperfusion injury in mice

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 (P<0.01), activity of SOD and content of GSH were decreased (P<0.01). Compared with the untreated group, content of MDA in the AST group was decreased (P<0.01) and activity of SOD was increased (P<0.01), however, contents of GSH and NO and activity of NOS had no obvious changes (P>0.05). Contents of MDA and NO in the PNS group was decreased as compared with the untreated group (P<0.01), but activities of SOD and NOS and content of GSH had no changes (P>0.05). Contents of MDA and NO and activity of NOS in brain tissues in the edaravone group were decreased (P<0.01, P<0.05), and activity of SOD was increased (P<0.05), while content of GSH had no changes (P>0.05). Contents of MDA and NO and activity of NOS in brain tissue in the AST and PNS combination groups were decreased (P<0.01, P<0.05), the activity of SOD increased (P<0.01, P<0.05), the content of GSH increased (P<0.01, P<0.05), and activity of SOD and content of GSH were increased (P<0.01, P<0.05). The results of analysis of variance of factorial design showed that there were interactions between AST (110 mg/kg) and PNS (115 mg/kg) (P<0.01). 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.

A comparative study on the therapeutic effect of Astragaloside ("Equation missing" ) and Perindopril in treating CVB3-infected cardiomyocytes in rats) and Perindopril in treating CVB3-infected cardiomyocytes in rats

Objective: To compare the therapeutic effects of Astragaloside and Perindopril on myocardial sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) activity and the SERCA type 2 mRNA level in Coxsack-ievirus B3 (CVB3)-infected cardiomyocytes.Methods: Cultured cardiomyocytes of rats were divided into normal, model, Astragaloside and Perindopril groups. The model, Astragaloside and Perindopril groups were infected with CVB3. Meanwhile, the Astragaloside and the Perindopril groups were treated with Astragaloside (10 μg/ml) and Perindopril (1.3 μg/ml) respectively. Cytopathic effect (CPE), cardiac troponin I (cTnI), the SERCA activity and mRNA level of the SERCA type 2 were observed after 96 hours.Results: The CPE and cTnI of model group were significantly higher than those of normal, Astragaloside and Perindopril groups (P 0.05).Conclusion: Astragaloside and Perindopril were able to reverse the down-regulations of cardiac SERCA activity and mRNA expression caused by virus infection to alleviate the cardiomyocyte injury.