Enterovirus A71(EV-A71)is the major causative pathogen for severe hand-foot-mouth disease(HFMD),a predominantly childhood-associated communicable disease.The mechanisms that children manifest severe disease progressio...Enterovirus A71(EV-A71)is the major causative pathogen for severe hand-foot-mouth disease(HFMD),a predominantly childhood-associated communicable disease.The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized,which hinders the development of effective therapy against this disease.Herein,using the newborn mouse model of EV-A71 infection,we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection,and EV-A71 infection dramatically impaired T-cell immune response.Moreover,the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection,as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection.To further assess the relationship between T-cell immunity and HFMD,we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children.Furthermore,we found that the treatment of newborn mice with Astragaloside A,a saponin from the medicinal herb Astragalus membranaceus,showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner.In conclusion,these findings uncover the interaction between EV-A71 infection and T-cell immunity,provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD,and find a promising immunotherapeutic strategy to treat this viral disease.展开更多
Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput seq...Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.展开更多
Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms....Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms.Methods Adult-male Sprague-Dawley rats(230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test(hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ(5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8 th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior softwaresystem. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-px) and catalase(CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta(IL-1β) and tumor necrosis factor-alpha(TNF-α) in tissue lysates were assayed with ELISA.Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ significantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia’s rats. Conclusion Our findings suggest that AS-Ⅳ might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.展开更多
A reliable and accurate HPLC/UV method was developed for the quantitative determination of astragaloside IV in ＇Huang-Qi-Si-Wu＇ Capsules, a widely used prescription of traditional Chinese medicines （TCM）. The chro...A reliable and accurate HPLC/UV method was developed for the quantitative determination of astragaloside IV in ＇Huang-Qi-Si-Wu＇ Capsules, a widely used prescription of traditional Chinese medicines （TCM）. The chromatographic separation conditions employed for HPLC/UV were optimized using a Hypersil-ODS column （250 mm^4.6 mm, 5.0 pm） with isocratic elution. Acetonitrile-water （32：68, v/v） were used as the mobile phase pumped at a flow rate of 1.0 mL/min and a detection wavelength at 203 nm was used. The method was fully validated with respect to linearity, precision, accuracy, specificity and robustness. The validated method was applied successfully to the quantification of astragaloside IV in the extract of ＇Huang-Qi- Si-Wu＇ Capsules from different production batches. The results indicate that the established HPLC/UV method is suitable for the quantitative analysis and quality control of ＇Huang-Qi-Si-Wu＇ Capsules and other related botanical drugs.展开更多
[Objective] This study aimed to establish a method for determining the content of Astragaloside IV in Yupingfeng oral solution.[Method] The HPLC-ELSD method was adopted.The chromatographic column was Venusil MP（4.6 m...[Objective] This study aimed to establish a method for determining the content of Astragaloside IV in Yupingfeng oral solution.[Method] The HPLC-ELSD method was adopted.The chromatographic column was Venusil MP（4.6 mm × 150 mm,5 μm）.The mobile phase was acetonitrile-water（35∶65）.The ELSD evaporator tube temperature was 65 ℃.N2 was used as the carrier gas（pressure,30 psi）.[Result] When the content of Astragaloside IV ranged from 0.5 to 5.0 μg,the Astragaloside IV content showed a good linear relationship with peak area（r=0.999,n=6）.The average recovery was 96.36%,and the RSD was 2.46%.[Conclusion] This method is accurate and reliable,and can be applied in the quality control of Yupingfeng oral solution.展开更多
OBJECTIVE: To review the pharmacological effects and mechanisms of action of Astragaloside IV in Huangqi (Radix Astragali Mongolici). METHODS: Aticles focusing on Astragaloside IV in English and Chinese in databases w...OBJECTIVE: To review the pharmacological effects and mechanisms of action of Astragaloside IV in Huangqi (Radix Astragali Mongolici). METHODS: Aticles focusing on Astragaloside IV in English and Chinese in databases were collected and reviewed in order to summarize the latest extraction separation, pharmacokinetics, and the pharmacological effects of astrageloside IV. RESULTS: Protective effects of Astrageloside IV on the cardiovascular system, immune, digestive, nervous system were identified, and the action mechanisms were associated with regulation of the calcium balance, anti-oxydant, antiapoptosis, antivirus, and so on. CONCLUSION: Astrageloside IV has broad application prospects, especially in cardiovascular diseases, digestive diseases, cancer and other modern high incidence, high-risk diseases, and could be developed as a medicine.展开更多
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 ...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 m RNA expression of nephrin and podocin was measured in the kidney tissues using the real-time q PCR,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 m RNA 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.展开更多
AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gas...AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside Ⅳ.CONCLUSION Astragaloside Ⅳ can inhibit the pathological functions of GCAFs by correcting their dysregulation of micro RNA expression,and it is promisingly a potent therapeutic agent regulating tumor microenvironment.展开更多
3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol （astragaloside IV）, the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. Thi...3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol （astragaloside IV）, the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside IV could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneally injected with 10, 5, 2.5 mg/kg astragaloside IV per day for 8 consecutive days Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 ex- pression was upregulated in mouse spinal cord segments L4-6 after intervention with 10, 5, 2.5 mg/kg astragaloside IV per day in a dose-dependent manner. Luxol fast blue staining and elec- trophysiological detection suggested that astragaloside IV elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside IV con- tributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.展开更多
This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h ...This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h and treated with AS IV at 50, 100, and 150 μmol·L-1 for various durations. Cell viability was determined by MTT. The content of released TNF-α and IL-6 from cardiomyocytes were evaluated by enzyme-linked immunosorbent assay(ELISA). The levels of superoxidase dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase(LDH), and creatine phosphate kinase(CK) were measured by using commercial available kits. The mR NA and protein expression levels of NF-κB p65 were measured by RT-PCR and Western blotting, respectively. And the NF-κB p65 activity was measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150 μmol·L-1 markedly inhibited the release of TNF-α and IL-6 and decreased NF-κB expression, compared with the model group. Moreover, the improved SOD activity and decreased MDA, LDH and CK levels were detected after AS IV treatment. In summary, AS IV could increase the activities of antioxidant enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory mediators involved in the inflammatory responses. These results demonstrated that AS IV could prevent LPS-induced injury in cardiomyocytes.展开更多
Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long time.AstragalosideⅣ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi extract.Many experimental mo...Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long time.AstragalosideⅣ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi extract.Many experimental models have shown that AS-Ⅳexerts broad beneficial effects on cardiovascular disease,nervous system diseases,lung disease,diabetes,organ injury,kidney disease,and gynaecological diseases.This review demonstrates and summarizes the structure,solubility,pharmacokinetics,toxicity,pharmacological effects,and autophagic mechanism of AS-Ⅳ.The autophagic effects are associated with multiple signalling pathways in experimental models,including the PI3KI/Akt/m TOR,PI3KⅢ/Beclin-1/Bcl-2,PI3K/Akt,AMPK/m TOR,PI3K/Akt/m TOR,SIRT1–NF-κB,PI3K/AKT/AS160,and TGF-β/Smad signalling pathways.Based on this evidence,AS-Ⅳcould be used as a replacement therapy for treating the multiple diseases referenced above.展开更多
AIM: To reveal the profile of astragalosides for better quality evaluation of Radix Astragali, this study was aimed to investigate the transformation of astragalosides under different conditions. METHOD: Seven major a...AIM: To reveal the profile of astragalosides for better quality evaluation of Radix Astragali, this study was aimed to investigate the transformation of astragalosides under different conditions. METHOD: Seven major astragalosides were selected for evaluation under acidic, neutral and alkaline conditions. The transformation in real plant samples was also examined and the products were characterized by LC-ESI-TOF/MS. RESULTS: In weak acidic solution, all of the astragalosides are stable. In addition, the transformation ratios of the astragalosides under neutral and alkaline conditions were also obtained. CONCLUSION: In neutral solution, malonylastragaloside I was transformed to astragaloside I; and in alkaline solution, substituent group(s) in the xylose moiety of all the astragalosides were eliminated. Since astragalosdie IV is the basic skeleton structure of the astrgalosides, it is a common transformation product of other astragalosides.展开更多
Objective:To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta(IL-1β)and neuropeptide Y(NPY)based on pharmacodynamics in rats.Methods:The animal model was b...Objective:To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta(IL-1β)and neuropeptide Y(NPY)based on pharmacodynamics in rats.Methods:The animal model was built by transient middle cerebral artery occlusion(MCAO).The method for evaluating the concentrations of the FA-Pr-AI components in rat plasma was established by using HPLC and the expression levels of IL-1βand NPY were determined by ELISA.A new mathematics method of the trend of percentage rate of change(PRC)was used to assess the correlation between pharmacokinetics(PK)and pharmacodynamics(PD).Results:FA-Pr-Al in combination reduced neurological deficits,decreased infarct volume and inhibited the expression levels of IL-1βand NPY(all P<0.05)compared with the model group.FA,Pr and Al all displayed two compartment open models in rats.Clockwise hysteresis loops were obtained by time-concentration-effect curves.IL-1βand NPY level changes in the plasma followed an opposite trend to the plasma concentration tendency after C_(max)was reached.Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min.Conclusions:The pharmacokinetics of FA-PrAl in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury,and the components of FA-Pr-Al may have a synergistic pharmacological effect.Astragaloside may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.展开更多
Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis(AS).If these conditions are disordered,it will inevitably lead to plaque formation and even ruptu...Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis(AS).If these conditions are disordered,it will inevitably lead to plaque formation and even rupture.Astragaloside IV(AsIV)and salvianolic acid B(Sal B)are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza,respectively,and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies.However,it is still unknown if the combination of AsIV and Sal B(AsIV+Sal B)can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect.To clarify the role of AsIV+Sal B in AS,we observed the efficacy of each group(Control,Model,AsIV,Sal B,and AsIV+Sal B)by biomolecular assays,such as observing the pathological morphology of the aorta by oil red O staining,evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test,and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS.Results showed that AsIV,Sal B and AsIV+Sal B decreased the deposition of lipid in the arterial wall,so as to exert the effect of anti-oxidant stress and vascular endothelial protection,where the inhibitory effect of AsIV+Sal B was the most obvious.Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline.AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism.AsIV+Sal B is mainly related to the regulation of the citrate cycle(TCA cycle),alanine,aspartic acid,and glutamate metabolism,cysteine,and methionine metabolism.Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination.In conclusion,we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS,and succinic acid and methionine are the synergistic metabolites.展开更多
OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS...OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.展开更多
OBJECTⅣE:To compare the phenotype and adipogenic and osteogenic differentiation capacities of adiposederived mesenchymal stem cells(AMSCs)isolated from patients with psoriasis vulgaris and healthy donors,and to explo...OBJECTⅣE:To compare the phenotype and adipogenic and osteogenic differentiation capacities of adiposederived mesenchymal stem cells(AMSCs)isolated from patients with psoriasis vulgaris and healthy donors,and to explore the effects of astragalosideⅣ,a Traditional Chinese Medicine,on the immunoregulatory function of AMSCs.METHODS:AMSCs were isolated from human adipose tissue and cultured for three generations in vitro.Cell phenotype and cell cycle analysis were performed by flow cytometry.Adipogenic and osteogenic differentiation of AMSCs was examined by lipid(oil red O)and alkaline phosphatase staining,respectively.Expression of inflammatory mediators was examined by real-time quantitative polymerase chain reaction analysis,and proliferation was quantified using the cell counting kit-8 assay.RESULTS:Expression of CD29,CD44,and CD73 was higher in AMSCs from healthy donors than psoriasis patients,while the reverse was true for expression of CD45,CD31,and HLA-DR.AMSCs from psoriasis patients had a greater ability to undergo adipogenic differentiation than cells from healthy donors,whereas there was no significant difference in osteogenic differentiation between AMSCs from the two sources.Compared with AMSCs from healthy donors,psoriasis patient-derived AMSCs expressed lower levels of the anti-inflammatory cytokines interleukin-10 and transforming growth factor-β(TGF-β)and the immune checkpoint ligand programmed cell death 1 ligand 1(PDL1)(P<0.05)and higher levels of the pro-inflammatory cytokines tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Incubation of AMSCs from psoriasis patients with astragalosideⅣhad no significant effect on proliferation but increased the expression of TGF-βand PDL1 and decreased the expression of IFN-γand TNF-α.CONCLUSION:AMSCs from patients with psoriasis vulgaris display abnormal proliferation and adipogenesis and an enhanced pro-inflammatory phenotype.These defects were normalized by treatment with astragalosideⅣ,suggesting that this Traditional Chinese Medicine may be useful for restoring the immunoregulatory function of AMSCs and immune homeostasis in patients with psoriasis vulgaris.展开更多
[Objectives] The content of astragaloside in Astragalus membranaceus(Fisch.) Bge.var.mongholicus(Bge.) Hisao from three different regions was determined.[Methods] Referring to the method recorded in the Chinese Pharma...[Objectives] The content of astragaloside in Astragalus membranaceus(Fisch.) Bge.var.mongholicus(Bge.) Hisao from three different regions was determined.[Methods] Referring to the method recorded in the Chinese Pharmacopoeia(2015 edition),the content of astragaloside IV in A.membranaceus was determined by HPLC.[Results] There were great differences in the astragaloside IV content of A.membranaceus among different regions.The content of astragaloside IV in A.membranaceus cultivated in Inner Mongolia was highest(0.155%),followed by that(0.143%) in A.membranaceus cultivated in Gansu,and the content of astragaloside IV in A.membranaceus cultivated in Shanxi was lowest(0.080%).The contents of astragaloside IV in A.membranaceus from different regions were all in line with the standard(not less than 0.040%) of Chinese Pharmacopoeia(2015 edition).[Conclusions]The content of astragaloside IV in A.membranaceus cultivated in three different regions met the medicinal standards.展开更多
Objective: Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that A...Objective: Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the heart from myocardial ischemic injury, but the mechanisms of action are unknown. ATP-sensitive potassium (KATP) channels are activated during ischemia and exert a compensatory protective effect on cardiomyocytes. We therefore examined the effects of AsIV on KATP channel currents and channel expression in isolated rat ventricular cardiomyocytes after ischemia-reperfusion injury. Methods: Forty Wistar rats were divided into five groups: control group, ischemia-reperfusion (IP) group, IP + glibenclamide group, IP + pinacidil group and IP + AsIV group. The ischemia-reperfusion injury model was established in enzymatically isolated ventricular cardiomyocytes by perfusion with calcium-free Tyrode solution for 10 min, arrest for 30 min, and reperfusion for 45 min. The different drugs were applied for 10-15 min, and the KATP channel current (IKATP) was recorded with voltage-clamp mode by whole-cell patch-clamp technique. Protein and mRNA expression of the KATP channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B was quantified using western blotting and real-time PCR. Results: The KATP current in IP group was significantly greater than that in control group (211.45±33.67 vs 83.51±23.67 pA; P<0.01). Glibenclamide (10 μmol/L) blocked KATP currents, whereas both AsIV (1 mg/L) and the known channel opener pinacidil (50 μmol/L) significantly increased IKATP (P<0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P<0.01 vs IP group). Conclusion: The protective effects of AsIV in ischemia-reperfusion injury may be related to the up-regulation of several KATP channel subunits and facilitation of KATP currents.展开更多
OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),ir...OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),irradiation+AS-IV(20 mg/kg)group(IR+AS-20)and irradiation+AS-IV(40 mg/kg)group(IR+AS-40).One month after intraperitoneal injection of AS-IV,the mice were irradiated with 8Gry Co60γ,the blood was collected for biochemical analysis,and the liver was collected for hematoxylin-eosin staining,immunofluorescence and electron microscopic observation,oxidative stress,and Western blot analysis.RESULTS:The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate aminotransferase levels in serum induced by radiation;AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation;in addition,AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein(TXNIP)and nod-like receptor protein 3(NLRP3)inflammasome in liver tissue after radiation;The expression of TXNIP,NLRP3 inflammasome,apoptosisassociated speck-like protein containing a CARD,cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group.CONCLUSIONS:These findings suggested that Co60γradiation can cause structural and functional damage to the liver,which may be related to the NLRP3 mediated inflammatory pathway;AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.展开更多
基金supported by the National Natural Science Foundation of China(32200130 to Chong Wang and 82372228 to Yi Xu)the 2023-2024 Annual Scientific Research Project of Traditional Chinese Medicine from Hubei Provincial Administration of Traditional Chinese Medicine(ZY2023Q050 to Chong Wang)Hubei Province Natural Science Funds(2023AFA008 to Xi Zhou).
文摘Enterovirus A71(EV-A71)is the major causative pathogen for severe hand-foot-mouth disease(HFMD),a predominantly childhood-associated communicable disease.The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized,which hinders the development of effective therapy against this disease.Herein,using the newborn mouse model of EV-A71 infection,we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection,and EV-A71 infection dramatically impaired T-cell immune response.Moreover,the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection,as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection.To further assess the relationship between T-cell immunity and HFMD,we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children.Furthermore,we found that the treatment of newborn mice with Astragaloside A,a saponin from the medicinal herb Astragalus membranaceus,showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner.In conclusion,these findings uncover the interaction between EV-A71 infection and T-cell immunity,provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD,and find a promising immunotherapeutic strategy to treat this viral disease.
基金supported by grants from Open Project of Gansu Traditional Chinese Medicine Research Center(No.zyzx-2020-10)Gansu Province Youth Science and Technology Foundation Program(No.21JR7RA652)+1 种基金Gansu Province Higher Education Research(No.2018A-049)Gansu Province Higher Education Research(No.2021B-163).
文摘Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.
基金Supported by the Natural Science Foundation of Shaanxi Province of China(2015JQ8299)National Science Foundation of China(81703842)Traditional Chinese Medicine Scientific Research Projects of Shaanxi Province of China(JCMS032)
文摘Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms.Methods Adult-male Sprague-Dawley rats(230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test(hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ(5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8 th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior softwaresystem. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-px) and catalase(CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta(IL-1β) and tumor necrosis factor-alpha(TNF-α) in tissue lysates were assayed with ELISA.Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ significantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia’s rats. Conclusion Our findings suggest that AS-Ⅳ might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.
基金Scientific and Technological Innovation Project Foundation of Shanxi,China(Grant No.20090321099)
文摘A reliable and accurate HPLC/UV method was developed for the quantitative determination of astragaloside IV in ＇Huang-Qi-Si-Wu＇ Capsules, a widely used prescription of traditional Chinese medicines （TCM）. The chromatographic separation conditions employed for HPLC/UV were optimized using a Hypersil-ODS column （250 mm^4.6 mm, 5.0 pm） with isocratic elution. Acetonitrile-water （32：68, v/v） were used as the mobile phase pumped at a flow rate of 1.0 mL/min and a detection wavelength at 203 nm was used. The method was fully validated with respect to linearity, precision, accuracy, specificity and robustness. The validated method was applied successfully to the quantification of astragaloside IV in the extract of ＇Huang-Qi- Si-Wu＇ Capsules from different production batches. The results indicate that the established HPLC/UV method is suitable for the quantitative analysis and quality control of ＇Huang-Qi-Si-Wu＇ Capsules and other related botanical drugs.
基金Supported by General Program of Science and Technology Plan of Beijing Municipal Commission of Educational(KM201410020007)~~
文摘[Objective] This study aimed to establish a method for determining the content of Astragaloside IV in Yupingfeng oral solution.[Method] The HPLC-ELSD method was adopted.The chromatographic column was Venusil MP（4.6 mm × 150 mm,5 μm）.The mobile phase was acetonitrile-water（35∶65）.The ELSD evaporator tube temperature was 65 ℃.N2 was used as the carrier gas（pressure,30 psi）.[Result] When the content of Astragaloside IV ranged from 0.5 to 5.0 μg,the Astragaloside IV content showed a good linear relationship with peak area（r=0.999,n=6）.The average recovery was 96.36%,and the RSD was 2.46%.[Conclusion] This method is accurate and reliable,and can be applied in the quality control of Yupingfeng oral solution.
文摘OBJECTIVE: To review the pharmacological effects and mechanisms of action of Astragaloside IV in Huangqi (Radix Astragali Mongolici). METHODS: Aticles focusing on Astragaloside IV in English and Chinese in databases were collected and reviewed in order to summarize the latest extraction separation, pharmacokinetics, and the pharmacological effects of astrageloside IV. RESULTS: Protective effects of Astrageloside IV on the cardiovascular system, immune, digestive, nervous system were identified, and the action mechanisms were associated with regulation of the calcium balance, anti-oxydant, antiapoptosis, antivirus, and so on. CONCLUSION: Astrageloside IV has broad application prospects, especially in cardiovascular diseases, digestive diseases, cancer and other modern high incidence, high-risk diseases, and could be developed as a medicine.
基金supported by the National Sciences Foundation of China(Nos.81273968 and 81471027)Ministerial projects of the National Working Commission on Aging(QLB2014W002)the“Four Hundreds Project of 301 Hospital(YS201408)
文摘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 m RNA expression of nephrin and podocin was measured in the kidney tissues using the real-time q PCR,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 m RNA 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.
基金Supported by the National Natural Science Foundation of China,No.81760552the Program of the Inner Mongolia Natural Science Foundation,No.2016MS0824 and No.2015MS0896+1 种基金the Program of“Keji Baiwan Gongcheng”of Inner Mongolia Medical University,No.YKD2015KJBW008the Supporting Program for Outstanding Youth in Science and Technology of Inner Mongolia Autonomous Region,No.NJYT-17-B30
文摘AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside Ⅳ.CONCLUSION Astragaloside Ⅳ can inhibit the pathological functions of GCAFs by correcting their dysregulation of micro RNA expression,and it is promisingly a potent therapeutic agent regulating tumor microenvironment.
文摘3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol （astragaloside IV）, the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside IV could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneally injected with 10, 5, 2.5 mg/kg astragaloside IV per day for 8 consecutive days Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 ex- pression was upregulated in mouse spinal cord segments L4-6 after intervention with 10, 5, 2.5 mg/kg astragaloside IV per day in a dose-dependent manner. Luxol fast blue staining and elec- trophysiological detection suggested that astragaloside IV elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside IV con- tributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Nanjing University of Chinese Medicine Natural Science Foundation for the Youth(No.12XZR06)+1 种基金Anhui Province Natural Science Foundation(No.1408085MH146)Anhui University of Chinese Medicine Natural Science Foundation(No.2015qn023)
文摘This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h and treated with AS IV at 50, 100, and 150 μmol·L-1 for various durations. Cell viability was determined by MTT. The content of released TNF-α and IL-6 from cardiomyocytes were evaluated by enzyme-linked immunosorbent assay(ELISA). The levels of superoxidase dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase(LDH), and creatine phosphate kinase(CK) were measured by using commercial available kits. The mR NA and protein expression levels of NF-κB p65 were measured by RT-PCR and Western blotting, respectively. And the NF-κB p65 activity was measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150 μmol·L-1 markedly inhibited the release of TNF-α and IL-6 and decreased NF-κB expression, compared with the model group. Moreover, the improved SOD activity and decreased MDA, LDH and CK levels were detected after AS IV treatment. In summary, AS IV could increase the activities of antioxidant enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory mediators involved in the inflammatory responses. These results demonstrated that AS IV could prevent LPS-induced injury in cardiomyocytes.
基金Supported by Project of Zhejiang Traditional Chinese Medicine Technology,No.2018ZA063Chinese National Natural and Science Foundation,No.81700552Natural Science Fund Committee of Zhejiang Province,No.LQ20C200010。
文摘Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long time.AstragalosideⅣ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi extract.Many experimental models have shown that AS-Ⅳexerts broad beneficial effects on cardiovascular disease,nervous system diseases,lung disease,diabetes,organ injury,kidney disease,and gynaecological diseases.This review demonstrates and summarizes the structure,solubility,pharmacokinetics,toxicity,pharmacological effects,and autophagic mechanism of AS-Ⅳ.The autophagic effects are associated with multiple signalling pathways in experimental models,including the PI3KI/Akt/m TOR,PI3KⅢ/Beclin-1/Bcl-2,PI3K/Akt,AMPK/m TOR,PI3K/Akt/m TOR,SIRT1–NF-κB,PI3K/AKT/AS160,and TGF-β/Smad signalling pathways.Based on this evidence,AS-Ⅳcould be used as a replacement therapy for treating the multiple diseases referenced above.
基金supported by the National Natural Science Foundation of China(No.81222052)the Excellent Young Scientist Fund of Jiangsu(BK20130025)the Program for New Century Excellent Talents in University(NCET-11-0737)
文摘AIM: To reveal the profile of astragalosides for better quality evaluation of Radix Astragali, this study was aimed to investigate the transformation of astragalosides under different conditions. METHOD: Seven major astragalosides were selected for evaluation under acidic, neutral and alkaline conditions. The transformation in real plant samples was also examined and the products were characterized by LC-ESI-TOF/MS. RESULTS: In weak acidic solution, all of the astragalosides are stable. In addition, the transformation ratios of the astragalosides under neutral and alkaline conditions were also obtained. CONCLUSION: In neutral solution, malonylastragaloside I was transformed to astragaloside I; and in alkaline solution, substituent group(s) in the xylose moiety of all the astragalosides were eliminated. Since astragalosdie IV is the basic skeleton structure of the astrgalosides, it is a common transformation product of other astragalosides.
基金supported by the National Science Foundation of China(81274176)the Clinical Medicine Special Foundation of China(12012064)+1 种基金the National Science Foundation of Province(LY13H280008)the Science and Technology Department of public welfare project(2014C33212)
文摘Objective:To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta(IL-1β)and neuropeptide Y(NPY)based on pharmacodynamics in rats.Methods:The animal model was built by transient middle cerebral artery occlusion(MCAO).The method for evaluating the concentrations of the FA-Pr-AI components in rat plasma was established by using HPLC and the expression levels of IL-1βand NPY were determined by ELISA.A new mathematics method of the trend of percentage rate of change(PRC)was used to assess the correlation between pharmacokinetics(PK)and pharmacodynamics(PD).Results:FA-Pr-Al in combination reduced neurological deficits,decreased infarct volume and inhibited the expression levels of IL-1βand NPY(all P<0.05)compared with the model group.FA,Pr and Al all displayed two compartment open models in rats.Clockwise hysteresis loops were obtained by time-concentration-effect curves.IL-1βand NPY level changes in the plasma followed an opposite trend to the plasma concentration tendency after C_(max)was reached.Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min.Conclusions:The pharmacokinetics of FA-PrAl in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury,and the components of FA-Pr-Al may have a synergistic pharmacological effect.Astragaloside may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.
基金supported by the National Natural Science Foundation of China(No.81974566)the Taishan Scholar Construction Project Grant Project(No.ts201712042)。
文摘Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis(AS).If these conditions are disordered,it will inevitably lead to plaque formation and even rupture.Astragaloside IV(AsIV)and salvianolic acid B(Sal B)are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza,respectively,and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies.However,it is still unknown if the combination of AsIV and Sal B(AsIV+Sal B)can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect.To clarify the role of AsIV+Sal B in AS,we observed the efficacy of each group(Control,Model,AsIV,Sal B,and AsIV+Sal B)by biomolecular assays,such as observing the pathological morphology of the aorta by oil red O staining,evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test,and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS.Results showed that AsIV,Sal B and AsIV+Sal B decreased the deposition of lipid in the arterial wall,so as to exert the effect of anti-oxidant stress and vascular endothelial protection,where the inhibitory effect of AsIV+Sal B was the most obvious.Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline.AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism.AsIV+Sal B is mainly related to the regulation of the citrate cycle(TCA cycle),alanine,aspartic acid,and glutamate metabolism,cysteine,and methionine metabolism.Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination.In conclusion,we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS,and succinic acid and methionine are the synergistic metabolites.
基金National Natural Science Foundation of China(81530100,81673802,81673712,81822049)。
文摘OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.
基金Supported by the National Natural Science Foundation of China Project:Exploring the Immune Mechanism of Kaixuan Jiedu Method in the Treatment of Psoriasis based on the Hypoxia Sensing Pathway Mediating Th17/Treg Imbalance(No.82074448)
文摘OBJECTⅣE:To compare the phenotype and adipogenic and osteogenic differentiation capacities of adiposederived mesenchymal stem cells(AMSCs)isolated from patients with psoriasis vulgaris and healthy donors,and to explore the effects of astragalosideⅣ,a Traditional Chinese Medicine,on the immunoregulatory function of AMSCs.METHODS:AMSCs were isolated from human adipose tissue and cultured for three generations in vitro.Cell phenotype and cell cycle analysis were performed by flow cytometry.Adipogenic and osteogenic differentiation of AMSCs was examined by lipid(oil red O)and alkaline phosphatase staining,respectively.Expression of inflammatory mediators was examined by real-time quantitative polymerase chain reaction analysis,and proliferation was quantified using the cell counting kit-8 assay.RESULTS:Expression of CD29,CD44,and CD73 was higher in AMSCs from healthy donors than psoriasis patients,while the reverse was true for expression of CD45,CD31,and HLA-DR.AMSCs from psoriasis patients had a greater ability to undergo adipogenic differentiation than cells from healthy donors,whereas there was no significant difference in osteogenic differentiation between AMSCs from the two sources.Compared with AMSCs from healthy donors,psoriasis patient-derived AMSCs expressed lower levels of the anti-inflammatory cytokines interleukin-10 and transforming growth factor-β(TGF-β)and the immune checkpoint ligand programmed cell death 1 ligand 1(PDL1)(P<0.05)and higher levels of the pro-inflammatory cytokines tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Incubation of AMSCs from psoriasis patients with astragalosideⅣhad no significant effect on proliferation but increased the expression of TGF-βand PDL1 and decreased the expression of IFN-γand TNF-α.CONCLUSION:AMSCs from patients with psoriasis vulgaris display abnormal proliferation and adipogenesis and an enhanced pro-inflammatory phenotype.These defects were normalized by treatment with astragalosideⅣ,suggesting that this Traditional Chinese Medicine may be useful for restoring the immunoregulatory function of AMSCs and immune homeostasis in patients with psoriasis vulgaris.
基金Supported by Tianjin Natural Science Fund(17JCYBJC29800)Tianjin Agricultural College Various Talents Funding Plan Project(J01009030702)+1 种基金Science and Technology Project in the Field of Social Development of Binhai New Area,TianjinAgricultural Science and Technology Plan Project of Baodi District,Tianjin(201838)
文摘[Objectives] The content of astragaloside in Astragalus membranaceus(Fisch.) Bge.var.mongholicus(Bge.) Hisao from three different regions was determined.[Methods] Referring to the method recorded in the Chinese Pharmacopoeia(2015 edition),the content of astragaloside IV in A.membranaceus was determined by HPLC.[Results] There were great differences in the astragaloside IV content of A.membranaceus among different regions.The content of astragaloside IV in A.membranaceus cultivated in Inner Mongolia was highest(0.155%),followed by that(0.143%) in A.membranaceus cultivated in Gansu,and the content of astragaloside IV in A.membranaceus cultivated in Shanxi was lowest(0.080%).The contents of astragaloside IV in A.membranaceus from different regions were all in line with the standard(not less than 0.040%) of Chinese Pharmacopoeia(2015 edition).[Conclusions]The content of astragaloside IV in A.membranaceus cultivated in three different regions met the medicinal standards.
基金supported by Key Project of Shanghai Education Commission (No.07ZZ56)National Natural Science Foundation of China (No.30873340)+1 种基金National 11th-Five Year Research Program of China (No.2007BAI20B078)Program for Innovative Research Team in University of Shanghai Education Commission
文摘Objective: Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the heart from myocardial ischemic injury, but the mechanisms of action are unknown. ATP-sensitive potassium (KATP) channels are activated during ischemia and exert a compensatory protective effect on cardiomyocytes. We therefore examined the effects of AsIV on KATP channel currents and channel expression in isolated rat ventricular cardiomyocytes after ischemia-reperfusion injury. Methods: Forty Wistar rats were divided into five groups: control group, ischemia-reperfusion (IP) group, IP + glibenclamide group, IP + pinacidil group and IP + AsIV group. The ischemia-reperfusion injury model was established in enzymatically isolated ventricular cardiomyocytes by perfusion with calcium-free Tyrode solution for 10 min, arrest for 30 min, and reperfusion for 45 min. The different drugs were applied for 10-15 min, and the KATP channel current (IKATP) was recorded with voltage-clamp mode by whole-cell patch-clamp technique. Protein and mRNA expression of the KATP channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B was quantified using western blotting and real-time PCR. Results: The KATP current in IP group was significantly greater than that in control group (211.45±33.67 vs 83.51±23.67 pA; P<0.01). Glibenclamide (10 μmol/L) blocked KATP currents, whereas both AsIV (1 mg/L) and the known channel opener pinacidil (50 μmol/L) significantly increased IKATP (P<0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P<0.01 vs IP group). Conclusion: The protective effects of AsIV in ischemia-reperfusion injury may be related to the up-regulation of several KATP channel subunits and facilitation of KATP currents.
基金Supported by Natural Science Foundation-Funded Project:Molecular Mechanism of the Brain AQP4 Adaptation to the Extreme Hhypoxia in the Qinghai-Tibet Plateau Animal(No.31760271)。
文摘OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),irradiation+AS-IV(20 mg/kg)group(IR+AS-20)and irradiation+AS-IV(40 mg/kg)group(IR+AS-40).One month after intraperitoneal injection of AS-IV,the mice were irradiated with 8Gry Co60γ,the blood was collected for biochemical analysis,and the liver was collected for hematoxylin-eosin staining,immunofluorescence and electron microscopic observation,oxidative stress,and Western blot analysis.RESULTS:The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate aminotransferase levels in serum induced by radiation;AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation;in addition,AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein(TXNIP)and nod-like receptor protein 3(NLRP3)inflammasome in liver tissue after radiation;The expression of TXNIP,NLRP3 inflammasome,apoptosisassociated speck-like protein containing a CARD,cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group.CONCLUSIONS:These findings suggested that Co60γradiation can cause structural and functional damage to the liver,which may be related to the NLRP3 mediated inflammatory pathway;AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.
