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
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
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
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
[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
Heart failure has become a global public health problem that seriously threatens human health.Due to "multi-target" effect,traditional Chinese medicine has unique advantages in the treat.ment of heart failur...Heart failure has become a global public health problem that seriously threatens human health.Due to "multi-target" effect,traditional Chinese medicine has unique advantages in the treat.ment of heart failure.Astragaloside Ⅳ is one of the main active ingredients of astragalus membrana.ceus.It has the functions of protecting the heart and neovascularization,anti-inflammation,anti-oxida.tion,regulating energy metabolism,neuroprotection and anti-cancer effects.This article reviews the recent progresses of astragaloside Ⅳ in the treatment of heart failure.Data show that astragaloside Ⅳ can inhibit heart fibrosis,attenuate excessively activation of renin-angiotensin system,increase energy metabolism,promote positive inotropic action,inhibit myocardial cell apoptosis,etc,which are all involved in the protective role of astragalosideⅣ in rodents or cellular models of heart failure.Astragalo.side Ⅳ may be a potential active ingredient in traditional Chinese medicine for the treatment of heart failure.展开更多
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.
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 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.
文摘Heart failure has become a global public health problem that seriously threatens human health.Due to "multi-target" effect,traditional Chinese medicine has unique advantages in the treat.ment of heart failure.Astragaloside Ⅳ is one of the main active ingredients of astragalus membrana.ceus.It has the functions of protecting the heart and neovascularization,anti-inflammation,anti-oxida.tion,regulating energy metabolism,neuroprotection and anti-cancer effects.This article reviews the recent progresses of astragaloside Ⅳ in the treatment of heart failure.Data show that astragaloside Ⅳ can inhibit heart fibrosis,attenuate excessively activation of renin-angiotensin system,increase energy metabolism,promote positive inotropic action,inhibit myocardial cell apoptosis,etc,which are all involved in the protective role of astragalosideⅣ in rodents or cellular models of heart failure.Astragalo.side Ⅳ may be a potential active ingredient in traditional Chinese medicine for the treatment of heart failure.
基金This research was supported by grants from the Scienceand Technology Development Foundation of Department of Education of Shan-dong Province(J05L02)the Natural Science Foundation of Qingdao City(04-2-JZ-97)
