Astragalosides Treatment Research Articles

Study on the Mechanism of Radix Astragali against Renal Aging Based on Network Pharmacology.

Radix Astragali is widely used in the traditional Chinese medicine with the effect of antiaging. The purpose of this study is to explore the main active ingredients and targets of Radix Astragali against renal aging by network pharmacology and further to verify the mechanism of the main active ingredients in vitro. TCMSP, ETCM, and TCMID databases were used to screen active ingredients of Radix Astragali. Targets of active ingredients were predicted using BATMAN-TCM and cross validated using kidney aging-related genes obtained from GeneCards and NCBI database. Pathways enrichment and protein-protein interaction (PPI) analysis were performed on core targets. Additionally, a pharmacological network was constructed based on the active ingredients-targets-pathways. HK-2 cell was treated with D-galactose to generate a cell model of senescence. CCK-8 and β-galactosidase were used to detect the effect of Radix Astragali active components on cell proliferation and aging. ELISA was used to detect the expression of senescence-associated secreted protein (TGF-β and IL-6) in the cell culture supernatant. Western blot was used to detect the expression of key proteins in the SIRT1/p53 pathway. Five active ingredients (Astragaloside I, II, III, IV and choline) were identified from Radix Astragali, and all these active ingredients target a total of 128 genes. Enrichment analysis showed these genes were implicated in 153 KEGG pathways, including the p53, FoxO, and AMPK pathway. 117 proteins and 572 interactions were found in PPI network. TP53 and SIRT1 were two hub genes in PPI network, which interacted with each other. The pharmacological network showed that the five main active ingredients target on some coincident genes, including TP53 and SIRT1. These targeted genes were involved in the p53, FoxO, and AMPK pathway. Proliferation of HK-2 cells was increased by Astragaloside IV treatment compared with that of the D-Gal treatment group. However, the proliferation of the SA-β-gal positive cells were inhibited. The expression of TGF-β and IL-6 in the D-Gal group was higher than that in the normal group, and the treatment of Astragaloside IV could significantly reduce the expression of TGF-β and IL-6. The expression of SIRT1 in the Astragaloside IV group was higher than that in the D-Gal group. However, the expression of p53 and p21 was less in the Astragaloside IV group than that in the D-Gal group. This study suggested that Astragaloside IV is an important active ingredient of Radix Astragali in the treatment of kidney aging via the SITR1-p53 pathway.

Astragaloside Attenuates Atherosclerosis Coupled Inflammation Through miR-101/Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1)/p38 Signaling in Mice

This study aimed at elucidating the effect of astragaloside on atherosclerosis coupled inflammation and potential mechanism in mice. C57BL/6J mice were maintained in high-fat diet (HFD) for 12 weeks to induce atherosclerosis, with or without treatment with astragaloside (50 mg/kg). In turn, serum biochemical parameters in mice were also evaluated. Multiple tissue stain assay, including HE, were employed to assess the pathological alterations in arteries, and blood inflammation mediators were examined using ELISA. Expressions of microRNA101 (miR-101), p-p38 and mitogen-activated protein kinase phosphatase-1 (MKP-1) in the arteries were evaluated by qPCR and Western blot. Finally, AML-193 cells were transfected by miR-101 mimics and inhibitors. Expression of miR-101, MKP-1 and downstream inflammation cytokines were then analyzed. High-fat diet (HFD) mice with astragaloside treatment exhibited reduced atherosclerotic plaques size evaluated by oil red o, improved hepatocyte steatosis, and increased collagen fibers in atherosclerotic plaques for more stable plaque. Further, astragaloside treatment suppressed miR-101 transcription and enhanced MKP-1 expression, thus restraining the secretion of inflammation factors in vitro. Moreover, the inhibited impact of astragaloside in inflammatory factors production was ineffective in the presence of miR-101 mimics in AML-193 cells stimulated by LPS. Astragaloside exerted an anti-inflammatory role through miR-101/MKP-1/p38 signaling, for reducing atherosclerotic plaques and alleviate inflammation damage in mice and AML-193 cell.

Metabolomics analysis delineates the therapeutic effects of Huangqi decoction and astragalosides on α-naphthylisothiocyanate (ANIT) -induced cholestasis in rats

Ethnopharmacological relevanceCholestasis caused by bile secretion and excretion disorders is a serious manifestation of liver disease. With limited treatment methods, it affects millions of people worldwide. Huangqi decoction (HQD), an effective traditional Chinese medicine, is used to treat chronic cholestatic liver diseases. However, the action mechanisms of it were not fully elucidated. Aim of the studyWe aim to investigate the therapeutic effect of HQD, and its active component, astragalosides, against α-naphthylisothiocyanate (ANIT)-induced cholestasis in rats based on targeted metabolomics analysis and revel the potential mechanism. Materials and methodsThe therapeutic effect of HQD and astragalosides on ANIT-induced cholestasis model rats were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The levels of bile acids (BAs) and free fatty acids (FFAs) in serum and liver tissues were measured by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQMS). qRT-PCR and Western blot analysis were used to measure the expression of nuclear hormone receptor, membrane receptor and BA transporter protein in cholestatic rats before and after HQD and astragalosides treatment. ResultsThe obtained data showed that the administration of ANIT caused obvious cholestasis with significantly increased intrahepatic retention of hydrophobic BAs and altered FFAs, which were consistent with the liver histopathological and serum biochemical findings. HQD and astragalosides treatment were able to attenuate ANIT-induced BAs and FFAs perturbation, ameliorate the impaired liver function, histopathological ductular reaction, and lipid peroxidation damage by ANIT. Elevated mRNA and protein expression of transporters related to BA metabolism and genes related to lipogenesis and lipid oxidation metabolism in cholestasis were attenuated or normalized by HQD and astragalosides treatment. ConclusionsIntervention by ANIT can significantly change the homeostasis of BAs and FFAs. HQD and astragalosides exerted a hepatoprotective effect against cholestatic liver injury by restoring the altered BA and FFA metabolism through the improvement of BA transporter, nucleus hormone receptor, and membrane receptor.

Effect of astragaloside on diaphragm cell apoptosis in chronic obstructive pulmonary disease.

PurposeThis study aimed to discuss the effects and relative mechanisms of astragaloside (AST) on diaphragm cell apoptosis in mice with chronic obstructive pulmonary disease (COPD).Materials and methodsThe mouse models of COPD were established by passive smoking. The pathological changes in lung and diaphragm tissues were observed by hematoxylin and eosin staining and evaluating the number of apoptotic cells of the diaphragm via a terminal deoxynucleotidyl transferase dUTP nick‐end labeling assay. The relative protein expression levels of AKT, p‐AKT, caspase‐3, and caspase‐9 were measured through immunohistochemistry and Western blot assay.ResultsIn comparison with the normal control mice, the pathological change and number of apoptotic cells deteriorated in the lung and diaphragm tissues of COPD model mice. With AST supplement, the pathological change and the number of apoptotic cells significantly improved (p < .05). With AKT inhibitor intervention, the effects of AST treatment disappeared. p‐AKT, caspase‐3, and caspase‐9 protein expression was stimulated in the model group but was depressed in the AST‐treated groups.ConclusionOur in vivo study revealed that AST improved COPD‐induced diaphragm apoptosis by regulating and depressing AKT activities.

Effect of astragalosides on long non-coding RNA expression profiles in rats with adjuvant-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which occurs in ~1.0% of the general population. Increasing studies have suggested that long non-coding RNAs (lncRNAs) may serve important roles in various biological processes and may be associated with the pathogenesis of different types of disease, including RA. Astragalosides (AST) has been used as a traditional Chinese medicine for the treatment of RA. However, the mechanism underlying its therapeutic effect has remained unclear to date. Thus, there is an urgent need to elucidate the possible mechanism of AST in the treatment of RA from the perspective of lncRNAs. In the present study, the lncRNAs and mRNAs of a vehicle group, animal model group and AST treatment (control) group were determined by Arraystar Rat lncRNA/mRNA microarray. The differentially expressed genes with a fold change >1.5 and P<0.05 were selected and analyzed. Gene Ontology (GO) and pathway analysis was performed using the Database for Annotation, Visualization and Integration Discovery, and the coding-non-coding gene co-expression network was drawn based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. Based on node degree and the correlation between bioinformatics analysis and RA, the critical differentially expressed lncRNAs were selected, analyzed and verified by reverse transcription-quantitative PCR (RT-qPCR) analysis. The results showed that, following AST treatment, up to 75 lncRNAs and 247 mRNAs were found to be differentially expressed among the three groups. GO and pathway analysis manifested that 135 GO terms and 17 pathways were enriched by differentially expressed genes. Four lncRNAs (MRAK012530, MRAK132628, MRAK003448 and XR_006457) were selected as the critical lncRNAs and their trend in expression showed consistency between the RT-qPCR and microarray data. In conclusion, AST had a regulatory effect on differentially expressed lncRNAs during the development of RA, and four lncRNAs could be selected as critical therapeutic targets of AST.

Astragaloside exerts anti-photoaging effects in UVB-induced premature senescence of rat dermal fibroblasts through enhanced autophagy

BackgroundAstragalus membranaceus is a fundamental herb in Traditional Chinese Medicine and has attracted significant attention due to its anti-inflammatory, and longevity effects. However, its anti-photoaging property remains to be defined. Autophagy plays important roles in regulating cell homeostasis and aging processes. Whether regulation of autophagy could be an efficient way for anti-photoaging is still unclear. ObjectiveTo investigate the effects and the possible mechanism of astragaloside on anti-photoaging in UVB-induced photoaging cell model. MethodsPrimary rat dermal fibroblasts were prepared by repeated exposures to UVB irradiation. The expression levels of cytokines and signal molecules were determined by RT-PCR and western blot. SA-β-gal staining was performed to indicate senescence level. Intracellular reactive oxygen species and mitochondrial membrane potential were monitored by fluorescent probes DCFH-DA and JC-1. The cell viability was determined using Cell Counting Kit-8. ResultsAstragaloside increases the expression of collagen-I (Col1) downregulated by UVB. UVB-induced oxidative stress and photoaging could be inhibited by astragaloside. The degradation of Col1 caused by UVB irradiation through activated ERK and p38 signals could be suppressed by astragaloside. Importantly, autophagy was induced by astragaloside. Col1 could be further accumulated by chloroquine but decreased by 3-methyladenine in photoaged cell after treatment of astragaloside. ConclusionAutophagy play essential roles, at least partially, in modulating the formation and degradation of Col1 in photoaging cell model. Astragaloside increases the accumulation of Col1 and protects UVB-induced photoaging cells through not only ERK and p38 inhibition but also autophagy activation, indicating the potential application of astragaloside for anti-photoaging therapy.

EFFECT OF ASTRAGALOSIDE ON VITAMIN D-RECEPTOR EXPRESSION AFTER ENDOTHELIN-1-INDUCED CARDIOMYOCYTE INJURY.

Background:Astragaloside, which is one of the main components of Astragalus membranaceus, has been widely used in the treatment of congestive heart failure in China, and it can protect cardiomyocytes. Its mechanism of action remains unclear. Therefore, the present study was carried out to investigate the influence of astragaloside on rat cardiomyocytes stimulated with endothelin-1 (ET-1), and explored the underlying mechanism.Materials and Methods:ET-1 was used to stimulate primary rat cardiomyocytes and establish a cardiomyocyte hypertrophy model. Different astragaloside doses were administered in combination with ET-1. Cardiomyocyte hypertrophy and apoptosis were examined using transmission electron microscopy (TEM) and flow cytometry, respectively. The molecular mechanism was explored by analyzing the mRNA of the vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1(CYP27B), cytochrome P450 family 24 subfamily A member 1(CYP24A) and renin mRNA levels by quantificational real-time polymerase chain reaction(qRT-PCR).Results:Rat cardiomyocyte hypertrophy model was established successfully. Astragaloside administration significantly affected cell apoptosis and significantly inhibited ET-1-induced cardiomyocyte hypertrophy in a dose-dependent manner. Astragaloside treatment affected the expression of signaling molecules in the vitamin D axis.Conclusion:Astragaloside inhibits ET-1-induced cardiomyocyte hypertrophy. This effect can be reversed by regulating the levels of the relevant factors in the vitamin D axis.

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.

Effects of astragaloside IV on lung injury and inflammation after hemorrhagic shock and resuscitation in rats

Objective To investigate the effects of astragaloside Ⅳ on lung injury and inflammation after hemorrhagic shock and resuscitation in rats. Methods Twenty-four male Sprague Dawley rats were randomly divided in 3 groups, including Sham group, hemorrhagic shock-resuscitation group (HS-R group) and astragaloside Ⅳ+ hemorrhagic shock-resuscitation group (AGS+ HS-R group). Hemorrhagic shock was induced by blood drawing from the femoral artery, and the resuscitation was performed by infusion of shed blood and two-fold volume saline. The operations for Sham group were the same with HS-R group, except that the blood drawing and fluid resuscitation were not performed. The rats in AGS+ HS-R group were subjected to hemorrhagic shock, and 20 mg/kg of astragaloside Ⅳ was intraperitoneally injected at the onset of resuscitation. Two h after resuscitation, histological changes were observed under light microscope, and myeloperoxidase (MPO) activities were determined with a commercial kit. The protein levels of cytoplasmic high mobility group protein B1 (HMGB1) as well as Toll-like receptor 4 (TLR4) and phospho-p38 mitogen activated protein kinase (p-p38MAPK) protein expression levels were detected by Western blotting. The protein levels of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β were examined by enzyme linked immunosorbent assay (ELISA). Results Histological results showed that the lung injury after hemorrhagic shock and resuscitation was attenuated by the treatment of astragaloside Ⅳ. As compared with HS-R group [(8.2±1.6) U/g], the treatment of astragaloside Ⅳ [(5.2±0.9) U/g] decreased MPO activities by 36.6% (P<0.01). In addition, the astragaloside Ⅳ treatment also down-regulated the expression levels of cytoplasmic HMGB1 as well as TLR4 and p-p38MAPK by 24.9%, 27.5%, and 23.7%, respectively (P<0.01 or P<0.05). The results of ELISA suggested that the lung protein levels of TNF-α, and IL-1β after hemorrhagic shock and resuscitation were decreased by 66.3%, and 44.3% respectively (P<0.01). Conclusion Astragaloside Ⅳ might attenuate the lung injury after hemorrhagic shock and resuscitation via inhibition of HMGB1/TLR4 signaling. Key words: Astragaloside Ⅳ; Hemorrhagic shock; Lung injury; Inflammatory response

Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction.

The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty-four hours after surgery, the rats were divided into low-dose, high-dose, control and sham surgery groups (n=8 per group). The low- and high-dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post-treatment. Twenty-four hours post-surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST-treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low- and high-dose groups was noted, however, an increase in the bFGF expression levels was detected in the high-dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST-treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST-induced increase in angiogenesis in rat models of MI.

Astragalosides from Radix Astragali benefits experimental autoimmune encephalomyelitis in C57BL /6 mice at multiple levels.

BackgroundRadix Astragali is famous for its beneficial effect on inflammation associated diseases. This study was to assess the efficacy of astragalosides (AST) extracted from Radix Astragali, on the progression of experimental autoimmune encephalomyelitis (EAE), and explore its possible underlying molecular mechanisms.MethodsEAE was induced by subcutaneous immunization of MOG35–55. Infiltration of inflammatory cells was examined by HE staining. ROS level was detected by measuring infiltrated hydroethidine. Leakage of blood brain barrier (BBB) was assessed using Evan’s blue dye extravasation method. Levels of inflammatory cytokines were measured using ELISA kits. Activities of total-SOD, GSH-Px, and iNOS and MDA concentration were measured using biochemical analytic kits. Gene expression was detected using real-time PCR method. Protein expression was assayed using western blotting approach.ResultsAST administration attenuated the progression of EAE in mice remarkably. Further studies manifested that AST treatment inhibited infiltration of inflammatory cells, lessened ROS production and decreased BBB leakage. In peripheral immune-systems, AST up-regulated mRNA expression of transcriptional factors T-bet and Foxp3 but decreased that of RORγt to modulate T cell differentiation. In CNS, AST stopped BBB leakage, reduced ROS production by up-regulation of T-SOD, and reduced neuroinflammation by inhibition of iNOS and other inflammatory cytokines. Moreover, AST inhibited production of p53 and phosphorylation of tau by modulation of the Bcl-2/Bax ratio.ConclusionsAST orchestrated multiple pathways, including immuno-regulation, anti-oxidative stress, anti-neuroinflammation and anti-neuroapoptosis involved in the MS pathogenesis, to prevent the deterioration of EAE, which paves the way for the application of it in clinical prevention/therapy of MS.

Role of BCL-2, caspase-3 and NF-κB in astragaloside inducing apoptosis of human NB4 cells

This study was purposed to investigate the apoptosis-inducing effect of astragalosides on acute promyelocytic leukemia(APL) cell line NB4 and its mechanism. NB4 cells were treated with different concentrations (200, 300, 400 µg /ml) of astragalosides for 48 h. The cell proliferation was assayed by using CCK-8 method; the cell apoptosis was analyzed by flow cytometry with Annexin V-FITE/PI double staining. The mRNA expression of BCL-2 and the relative activity of BCL-2, NF-κB and caspase-3 were detected by RT-PCR and Western blot, respectively. The results showed that after treated with astragalosides for 48 h, astragalosides inhibited NB4 cell proliferation in concentration-dependent way, the apoptosis rate of NB4 cells gradually elevated from 4.69% to 40.85% with the increasing of astragalosides concentration. Simultaneously, the mRNA expression of BCL-2 was down-regulated, Western blot analysis showed that the protein expression levels of BCL-2 and NF-κB decreased after astragalosides treatment, while caspase-3 protein expression level increased. It is concluded that the molecular mechanism of the astragalosides-induced apoptosis in NB4 cells may be associated with down-regulation of the expression of BCL-2 and NF-κB, finally the relative activity of caspase-3 activated.

Beneficial effect of astragalosides on stroke condition using PC12 cells under oxygen glucose deprivation and reperfusion.

Astragalosides (AST) are reported to be neuroprotective in focal cerebral ischemic models in vivo. In this study, the direct effect of AST against oxygen and glucose deprivation (OGD) including neuronal injury and the underlying mechanisms in vitro were investigated. 5 h OGD followed by 24 h of reperfusion [adding back oxygen and glucose (OGD-R)] was used to induce in vitro ischemia reperfusion injury in differentiated rat pheochromocytoma PC12 cells. AST (1, 100, and 200 µg/mL) were added to the culture after 5 h of the OGD ischemic insult and was present during the reoxygenation phases. A key finding was that OGD-R decreased cell viability, increased lactate dehydrogenase, increased reactive oxygen species, apoptosis, autophagy, functional impairment of mitochondria, and endoplasmic reticulum stress in PC12 cells, all of which AST treatment significantly reduced. In addition, AST attenuated OGD-R-induced cell loss through P38 MAPK activation a neuroprotective effect blunted by SB203580, a specific inhibitor of P38 MAPK. Our data suggest that both apoptosis and autophagy are important characteristics of OGD-R-induced PC12 death and that treating PC12 cells with AST blocked OGD-R-induced apoptosis and autophagy by suppressing intracellular oxidative stress, functional impairment of mitochondria, and endoplasmic reticulum stress. Our data provide identification of AST that can concomitantly inhibit multiple cells death pathways following OGD injuries in neural cells.

Protective effects of astragalosides on dexamethasone and Aβ25–35 induced learning and memory impairments due to decrease amyloid precursor protein expression in 12-month male rats

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptide deposition are found to be correlated with dementia progression in patients with AD. The astragalosides (AST) was extracted from traditional Chinese herb Astragalus membranaceous. In this study, 12months male rats were treated with Aβ25–35 (10μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg, ig) and AST (8, 16 and 32mg/kg, ig) or ginsenoside Rg1 (Rg1, 5mg/kg, ig) for 14days. We investigated the protective effect of AST against DEX+Aβ25–35 injury in rats and its mechanisms of action. Our results indicate that DEX+Aβ25–35 can induce learning and memory impairments and increase APP and Aβ1–40 expression. AST (16, 32mg/kg) or Rg1 (5mg/kg) treatment significantly improve learning and memory, down-regulate the mRNA levels of APP and β-secretase, decrease expression of APP and Aβ1–40 in hippocampus. The results indicated that DEX might increase hippocampal vulnerability to Aβ25–35 and highlight the potential neuronal protection of AST.

The Effect of Treatment and Mechanism of Astragaloside on Chronic Viral Myocarditis with Coxsackievirus B3 in BALB/C Mice

Objective: To Observe the effect of the treatment and mechanism of cardiac apoptosis of astragaloside on chronic viral myocarditis with CVB3 in Balb/c mice. Methods: Four-week-old Balb/c mice were randomly divided into three groups as follows: astragaloside treatment group, model of viral cardiomyopathy group, and normal control group. The model group and control group were fed with drinking water while astragaloside treatment group with drinking water containing astragaloside at concentration of 300mg/L for 3 months. Survival rates were determined, myocardial histopathology, Collagen volume fraction (CVF) and apoptosis of heart tissue, levels of Bax,Bcl-2 and CVB3-RNA levels (realtime RT-PCR) were detected on 3 months later respectively. Results: The survival rate on 3 months was significantly improved in mice treated with Astragaloside in treatment group than that of model group (p< 0.05). Astragaloside treatment also significantly attenuated histological myocardial lesion, reduced the myocardial CVF and apoptosis, decreased myocardial CVB3-RNA levels (P< 0.01 or p< 0.05, respectively). The Astragaloside significantly induced the expression levels of Bcl-2 protein (p< 0.05) and mRNA (p< 0.05), reduced the expression level of Bax protein (p< 0.05) and mRNA (0.63±0.13 vs 0.79±0.12, p< 0.05) than that in viral cardiomyopathy group.respectly. Conclusion: Astragaloside is a potent agent with a highly significant effect on chronic viral myocarditis in the Balb/c murine with CVB3. and could reduce the apoptosis of viral myocarditis. Which mechanism may be partly up-regulated expretion of Bcl-2 and down-regulated expression of gene Bax.

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.

Protective Effect of Astragaloside on Focal Cerebral Ischemia/Reperfusion Injury in Rats

This study was to observe the neurological protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats and to explore its possible mechanism. Male SD rats received right middle cerebral artery occlusion for 120 min and AST (40 mg/kg) was orally administered. The rats were decapitated 1, 3, 7, and 14 days after reperfusion. The neurological deficit score, infarct volume and water content of brain were measured; the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and nitric oxide synthase (NOS), and the content of malondialdehyde (MDA), lactate (LD) and nitric oxide (NO) of brain tissue were detected too. The expression of inducible nitric synthase (iNOS), nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) mRNA were measured by RT-PCR or real-time PCR. AST could significantly reduce the neurological deficit score; infract volume and water content, increase SOD and LDH activities, decrease NOS activity and MDA, LD and NO content. AST treatment could down-regulate expression of iNOS mRNA, while, NGF and TrkA mRNA were up-regulated. Our data suggest that AST have the protective effects on focal cerebral ischemia in rats at the different reperfusion time points, the mechanism may be related to the antioxidation, regulated the expressions of iNOS, NGF and TrkA mRNA.

A novel antioxidant agent, astragalosides, prevents shock wave-induced renal oxidative injury in rabbits

Extracorporeal shock-wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms, including small vessel injury and free radical formation. Our previous studies have demonstrated that Astragalus membranaceus (AM), a traditional Chinese herb, could significantly alleviate shock wave-induced renal oxidative injury, and its renoprotective effects were superior to those of varapamil, a calcium antagonist, which were considered to be a powerful agent in treating renal damage during ESWL. However, the effective antioxidant ingredient of this herb in the setting of lithotripsy remains unclear. Astragalosides, the major components of AM, was demonstrated to have superior antioxidation properties both in vitro and in vivo. Therefore, in this study we further investigate the potential effects of astragalosides on the shock wave-induced oxidative stress in rabbit kidney. Thirty male rabbits were randomly assigned to two groups, each consisting of 15 rabbits: (1) control group, (2) astragaloside-treated group. Each group of animals underwent 1,500 shock waves to the right kidney. Peripheral blood, urine and kidney tissue samples were collected pre- and post-ESWL. The level of urinary N-acetyl-beta-glucosaminidase (NAG), serum creatinine, serum or homogenates malondialdehyde (MDA) and superoxide dismutase (SOD), respectively, were detected. Histological alterations were also examined through light microcopy and transmission electron microscopy. In the control group, shock wave significantly increased the level of MDA and decreased SOD activity in both blood and renal homogenates (P<0.05, respectively). The comparison between the control and astragalosides group demonstrated that astragalosides could significantly decrease the level of MDA (P<0.05) and inhibit the decline of SOD activity (P<0.05). After exposure to shock waves, the activity of urinary NAG increased significantly in the control group (P<0.05). However, the concentration of serum creatinine did not change significantly. The comparison between the control and astragalosides group demonstrated that astragalosides significantly reduced the shock wave-induced leakage of NAG into the urine (P<0.05). Histological examination also showed that renal morphological impairments were much milder in astragaloside-treated rabbits than those of the control group. Our results indicated that astragaloside treatment provided significant protection against shock wave-induced renal oxidative injury.

Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia

Astragalus membranaceus is a herbal medicine that has been used clinically in stroke patients in China for decades, but its potential neuroprotective effect against ischemic brain injury has not been experimentally tested. In this study, we investigated the effect of Astragaloside IV, a purified extract from Astragalus membranaceus, in a murine model of focal cerebral ischemia/reperfusion produced by transient (1.5 h) middle cerebral artery occlusion. As determined at 72 h after ischemia, post-ischemic treatment of Astragaloside IV (20 or 40 mg/kg) markedly and significantly ( P<0.03 vs. vehicle-treated animals) reduced infarct volume. Astragaloside IV treatment also decreased the levels of malondialdehyde, an indicator of lipid peroxidation, and increased the levels of the antioxidant enzymes glutathione peroxidase and superoxide dismutase in ischemic tissues. The results presented here provide the first evidence of a neuroprotective effect of Astragaloside IV in the model of ischemic brain injury. We suggest that the anti-infarction effect by Astragaloside IV may be derived at least in part from its antioxidant properties.