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Functional characterization of a cycloartenol synthase and four glycosyltransferases in the biosynthesis of cycloastragenol-type astragalosides from Astragalus membranaceus 被引量:2
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作者 Yangyang Duan Wenyu Du +5 位作者 Zhijun Song Ridao Chen Kebo Xie Jimei Liu Dawei Chen Jungui Dai 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第1期271-283,共13页
Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi,of which cycloastragenol-type glycosides are the most typical and major bioactive compounds.This kind of compounds exhibit vario... Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi,of which cycloastragenol-type glycosides are the most typical and major bioactive compounds.This kind of compounds exhibit various biological functions including cardiovascular protective,neuroprotective,etc.Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis,re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides.However,the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps.Herein,guided by transcriptome and phylogenetic analyses,a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus.AmCAS1,the first reported cycloartenol synthase from Astragalus genus,is capable of catalyzing the formation of cycloartenol;AmUGT15,AmUGT14,AmUGT13,and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation,3-O-glucosylation,25-O-glucosylation/O-xylosylation and 2’-O-glucosylation of cycloastragenol glycosides,respectively.These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants,also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production. 展开更多
关键词 Cycloastragenol-type astragalosides Cycloartenol synthase GLYCOSYLTRANSFERASE BIOSYNTHESIS Astragalus membranaceus
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Transformation of astragalosides from Radix Astragali under acidic,neutral,and alkaline extraction conditions monitored by LC-ESI-TOF/MS 被引量:7
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作者 CHU Chu LIU E-Hu +1 位作者 QI Lian-Wen LI Ping 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2014年第4期314-320,共7页
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
关键词 TRANSFORMATION Radix Astragali LC-TOF/MS astragalosides
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Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide
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作者 Hai-long LI Li-hua SHAO +6 位作者 Xi CHEN Meng WANG Qi-jie QIN Ya-li YANG Guang-run ZHANG Yang HAI Yi-hong TIAN 《Current Medical Science》 SCIE CAS 2024年第4期854-863,共10页
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
关键词 PC12 cells astragaloside IV INFLAMMATION DNA damage
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Astragalus membranaceus(Fisch.)Bge.administered by dissolving microneedles achieves systemic therapeutic effects at low doses Author links open overlay panel
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作者 Yiwen Chen Zihan Zhou +3 位作者 Luzheng Zhang Zifan Ding Pengyue Li Cong Yan 《Journal of Traditional Chinese Medical Sciences》 CAS 2024年第3期340-350,共11页
Objective:To determine the main components of Astragalus membranaceus(Fisch.)Bge(A.membranaceus,Huang Qi),Astragaloside IV(AIV)and Astragalus polysaccharides(AP),to characterize their properties,evaluate their in vivo... Objective:To determine the main components of Astragalus membranaceus(Fisch.)Bge(A.membranaceus,Huang Qi),Astragaloside IV(AIV)and Astragalus polysaccharides(AP),to characterize their properties,evaluate their in vivo efficacy,and to analyze drug diffusion using dissolving microneedle(DMN)technology in vivo.Methods: Respectively,AIV-and AP-loaded DMNs comprising chitosan(CTS)and polyvinyl alcohol(PVA)were prepared via dual-mold forming.Their morphology,mechanical properties,in vivo solubility,and skin irritation characteristics were tested.In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice,in vivo diffusion of AIV and AP by DMNs and conventional methods was compared,and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured.Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles(MNs)at low doses(50%–17%of intraperitoneal AIV injection and 12%–4%of intravenous AP injection)reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models,increased the thymus index,and achieved equivalent or better systemic therapeutic effects.Compared with injections,AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs,resulting in highly localized aggregation within 48 h,reducing the initial explosive effect of the drug,and achieving stable and slow drug release.Conclusion: The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine(TCM)perspective,thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs. 展开更多
关键词 Dissolving microneedle Astragaloside IV Astragalus polysaccharides In vivo diffusion Rheological properties Acupuncture IMMUNOSUPPRESSION Drug delivery
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Astragaloside IV Ameliorates Inflammatory Damage in Mice with Acute Liver Failure
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作者 Ying Yang Meng Hong +1 位作者 Wenwen Lian Zhi Chen 《Chinese Medicine》 2023年第4期221-241,共21页
Acute liver failure is a life-threatening clinical syndrome with a high mortality rate. Currently, the research on Astragaloside IV in liver diseases primarily focuses on liver cancer, and there is limited understandi... Acute liver failure is a life-threatening clinical syndrome with a high mortality rate. Currently, the research on Astragaloside IV in liver diseases primarily focuses on liver cancer, and there is limited understanding of its mechanism in acute liver failure’s innate immunity. Therefore, this study aims to investigate the potential protective effect of Astragaloside IV on acute liver failure and its impact on innate immune cells. The study employed D-GalN/LPS-induced acute liver failure mouse models and employed various techniques such as a range of molecular and analytical techniques. The experimental results demonstrated that treatment with Astragaloside IV significantly reduced the inflammatory response, alleviated liver injury, and improved the survival rate of mice with acute liver failure induced by D-GalN/LPS. Further investigations revealed that AS-IV played a beneficial role by regulating the proportion of CD11b<sup>+</sup>Ly6C<sup>hi</sup> monocytes and the secretion of inflammatory cytokines and anti-inflammatory metabolites. These findings suggest that the pharmacological mechanism of AS-IV may involve targeted regulation of CD11b<sup>+</sup>Ly6C<sup>hi</sup> monocytes in both peripheral blood and liver. The implications of this study’s results are twofold. Firstly, they provide a basis for the clinical application of AS-IV in treating liver failure, offering potential therapeutic benefits. Secondly, they serve as a reference for further development of safer and more effective modified compounds. 展开更多
关键词 Astragaloside IV Acute Liver Failure INFLAMMATION MONOCYTE AUTOPHAGY
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Astragaloside Ⅳ Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats 被引量:14
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作者 潘艳芳 贾晓涛 +1 位作者 宋二飞 彭小忠 《Chinese Medical Sciences Journal》 CAS CSCD 2018年第1期29-37,共9页
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
关键词 amyloid-βprotein astragalosideⅣ spatial learning and memory OXIDATIVE stress NEUROINFLAMMATION
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黄芪甲苷孵育的脂肪源性干细胞对顺铂诱导的急性肾损伤小鼠的保护作用 被引量:11
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作者 姜燕 王葳 +3 位作者 李泽争 程劲 王巍巍 张金元 《中国中西医结合肾病杂志》 2014年第2期114-117,I0003-I0005,共7页
目的:建立顺铂诱导的急性肾损伤(AKI)小鼠模型,尾静脉输注人脂肪源性干细胞(hADSC)及黄芪甲苷孵育的人脂肪源性干细胞(Ast-hADSC),探讨其对AKI小鼠肾损伤的修复作用。方法:应用PKH26标记hADSC及Ast-hADSC;雄性BALB/C裸鼠随机分为4组(nor... 目的:建立顺铂诱导的急性肾损伤(AKI)小鼠模型,尾静脉输注人脂肪源性干细胞(hADSC)及黄芪甲苷孵育的人脂肪源性干细胞(Ast-hADSC),探讨其对AKI小鼠肾损伤的修复作用。方法:应用PKH26标记hADSC及Ast-hADSC;雄性BALB/C裸鼠随机分为4组(normal组、model组、hADSC及Ast-hADSC干预组),干预组及模型组腹腔注射顺铂建立AKI模型,于建模后24 h尾静脉输注100μl hADSC及Ast-hADSC悬液,模型组给予等量生理盐水。分别留取建模后24 h及静脉输注后1 d、3 d、7 d、14 d小鼠血清及肾组织标本,检测血Scr、BUN水平,HE染色观察肾组织病理变化,TUNEL法检测肾小管上皮细胞凋亡,激光共聚焦观察hADSC及Ast-hADSC在小鼠肾组织的分布。结果:模型组小鼠Scr、BUN、肾组织病理改变及细胞凋亡区域均显著高于正常组及细胞干预组,其中Scr、BUN分别在第3天、第7天达到最高值,肾小管损伤严重;相同时间点Ast-hADSC组肾组织病理改变及细胞凋亡区域较hADSC组明显降低,至14 d可基本恢复至正常水平;激光共聚焦显示PKH26标记的hADSC及Ast-hADSC于14 d在小鼠肾组织有少量表达,其中少量红色荧光与肾小管上皮细胞呈融合状态。结论:hADSC移植可减轻AKI小鼠肾脏结构和功能的损伤;经Ast孵育后,可在一定程度上提高hADSC对受损肾组织的修复作用。 展开更多
关键词 急性肾损伤 顺铂 黄芪甲苷 脂肪源性干细胞 ASTRAGALOSIDE
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基于综合评分的中药复方“鼻敏康”提取工艺研究 被引量:3
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作者 毋桂花 李莉 +2 位作者 王颖莉 张梦萱 张伟 《世界科学技术-中医药现代化》 北大核心 2013年第8期1837-1842,共6页
目的:优选中药复方“鼻敏康”的最佳提取工艺并建立黄芪甲苷的HPLC-ELSD含量测定方法。方法:采用加热回流法,乙醇为提取溶剂,以浸膏率及黄芪甲苷含量为指标,对乙醇浓度、提取时间、液料比和提取次数进行单因素考查,优选出对浸膏... 目的:优选中药复方“鼻敏康”的最佳提取工艺并建立黄芪甲苷的HPLC-ELSD含量测定方法。方法:采用加热回流法,乙醇为提取溶剂,以浸膏率及黄芪甲苷含量为指标,对乙醇浓度、提取时间、液料比和提取次数进行单因素考查,优选出对浸膏率及黄芪甲苷含量较大影响的3个因素,按照L9(34)安排正交试验优选复方制剂鼻敏康的提取工艺。黄芪甲苷含量测定采用Diamonstil C18(250 mm&#215;4.6 mm,5μm)色谱柱,流动相为水(A)-乙腈(B),洗脱梯度:0-45 min,22%B;45-60 min,22%-32%B,流速1.0 mL&#183;min-1,漂移管温度100℃,载气为N2,载气流速2.5 L&#183;min-1,柱温:30℃。结果:复方制剂鼻敏康最佳提取工艺为8倍量70%乙醇,每次1.5 h,提取3次,结果表明乙醇浓度和提取次数存在显著性影响,最终确定提取工艺为8倍量70%乙醇,每次加热回流1.5 h,提取2次;黄芪甲苷含量测定线性范围为0.87-8.72μg,回归方程 Y=1.5454X+5.8759,r =0.9997,平均收率95.05%,RSD值为2.64%。结论:优选的提取工艺稳定合理可行,适用于工业生产。 展开更多
关键词 鼻敏康 提取工艺 正交试验 黄芪甲苷 ASTRAGALOSIDE
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Studies on Biologically Active Principles of Huangqi,Root of Astragalus membranaceous,Isolation and Detection of Constituents Scavenging Superoxide Anion
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作者 刘星堦 江明华 +4 位作者 喻正坤 郑基蒙 龚志铭 张静华 戴瑞鸿 《Journal of Chinese Pharmaceutical Sciences》 CAS 1993年第1期80-84,共5页
本文使用黄嘌呤-黄嘌呤氧化酶—鲁米诺化学发光体系和化学发光检测法研究了黄芪中各成分的清除超氧阴离子自由基的能力,以药物抑制发光强度50%的浓度(IC_(50))为指标。经研究证明,黄芪总皂甙部分(N)具有较强的活性,IC_(50)为185μg/ml,... 本文使用黄嘌呤-黄嘌呤氧化酶—鲁米诺化学发光体系和化学发光检测法研究了黄芪中各成分的清除超氧阴离子自由基的能力,以药物抑制发光强度50%的浓度(IC_(50))为指标。经研究证明,黄芪总皂甙部分(N)具有较强的活性,IC_(50)为185μg/ml,再经进一步导向分离并鉴定证明,黄芪甙Ⅲ,Ⅳ和Ⅵ的 IC)_(50)分别为80、50和11μg/ml,从而证明黄芪的抗心力衰竭的有效成分可能为黄芪总皂甙部分。 展开更多
关键词 Astragalus membranaceous astragalosides and Oxygen free radical scavenger Superoxide anion Chemiluminescence
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Determination of Astragaloside IV in Yupingfeng Oral Solution by HPLC-ELSD Method
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作者 王建舫 张倩 穆祥 《Agricultural Science & Technology》 CAS 2015年第2期197-199,共3页
[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
关键词 HPLC ELSD Yupingfeng oral solution Astragaloside IV
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Astragaloside 对实验性自身免疫性脑脊髓炎小鼠的防治作用研究 被引量:4
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作者 刘建春 张红珍 +5 位作者 郭文娟 柴智 尉杰忠 于婧文 肖保国 马存根 《中国免疫学杂志》 CAS CSCD 北大核心 2019年第23期2848-2852,共5页
目的:探讨Astragaloside对实验性自身免疫性脑脊髓炎(EAE)小鼠的保护作用及机制。方法:采用髓鞘MOG 35-55诱导C57BL/6雌性小鼠建立EAE模型,随机分为EAE对照组、Astragaloside高、低剂量组。造模的第3天起,采用腹腔注射给药,持续25 d。EA... 目的:探讨Astragaloside对实验性自身免疫性脑脊髓炎(EAE)小鼠的保护作用及机制。方法:采用髓鞘MOG 35-55诱导C57BL/6雌性小鼠建立EAE模型,随机分为EAE对照组、Astragaloside高、低剂量组。造模的第3天起,采用腹腔注射给药,持续25 d。EAE对照组给予PBS;Astragaloside高、低剂量组分别给予Astragaloside溶液30 mg/(kg·d),15 mg/(kg·d);各组小鼠给药0.2 ml/(次·只),每天记录小鼠症状、体征、体重变化和临床评分。HE染色检测脊髓炎细胞浸润。ELISA法检测外周血中IL-1β、IL-17、TNF-α、IL-10的表达量。Western blot法检测脊髓组织中ROCKⅡ、P-MYPT1、p-NF-κB/p65的表达变化。结果:与EAE对照组比较,Astragaloside高、低剂量组均可明显降低平均最高临床评分,减轻EAE临床症状(P<0.01,P<0.05),高剂量组治疗效果优于低剂量组;Astragaloside可抑制中枢神经系统炎症细胞浸润,显著降低血清中IL-1β、IL-17的表达(P<0.05,P<0.001),增加血清IL-10水平(P<0.05),明显抑制ROCKⅡ、P-MYPT1、p-NF-κB/p65的表达(P<0.05)。结论:Astragaloside可通过抑制Rock通路和调节细胞因子的表达改善EAE的临床症状。 展开更多
关键词 实验性自身免疫性脑脊髓炎 ASTRAGALOSIDE 炎性因子 ROCK通路
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Astragaloside Ⅳ inhibits pathological functions of gastric cancer-associated fibroblasts 被引量:16
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作者 Zhen-Fei Wang Da-Guang Ma +8 位作者 Zhe Zhu Yong-Ping Mu Yong-Yan Yang Li Feng Hao Yang Jun-Qing Liang Yong-Yan Liu Li Liu Hai-Wen Lu 《World Journal of Gastroenterology》 SCIE CAS 2017年第48期8512-8525,共14页
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
关键词 ASTRAGALOSIDE GASTRIC cancer-associated FIBROBLASTS Proliferation Migration INVASION Micro RNA
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The mechanism of astragaloside Ⅳ promoting sciatic nerve regeneration 被引量:14
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作者 Xiaohong Zhang Jiajun Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第24期2256-2265,共10页
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
关键词 neural regeneration traditional Chinese medicine peripheral nerve injury astragaloside IVgrowth-associated protein-43 sciatic nerve nerve myelin sheath myelinated nerve axonsneuroregeneration
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Pharmacokinetic and pharmacodynamic analysis of ferulic acidpuerarin-astragaloside in combination with neuroprotective in cerebral ischemia/reperfusion injury in rats 被引量:5
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作者 Li-Jun Ge Shou-Yan Fan +6 位作者 Jie-Hong Yang Yi Wei Zhen-Hong Zhu Yi-Jia Lou Ying Guo Hai-Tong Wan Yi-Qiang Xie 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2015年第4期299-304,共6页
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
关键词 Ferulic acid PUERARIN ASTRAGALOSIDE INTERLEUKIN-1Β NEUROPEPTIDE Y
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Review of the pharmacological effects of astragalosideⅣand its autophagic mechanism in association with inflammation 被引量:8
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作者 Ying Yang Meng Hong +1 位作者 Wen-Wen Lian Zhi Chen 《World Journal of Clinical Cases》 SCIE 2022年第28期10004-10016,共13页
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
关键词 AstragalosideⅣ Pharmacological effect AUTOPHAGY INFLAMMATION
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Effect of astragaloside Ⅳ on lipid and glucose metabolism in acute myocardial infarction through PPARγ pathway 被引量:2
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作者 ZHANG Qian WANG Xiao-ping +2 位作者 WANG Yong LI Chun WANG Wei 《中国药理学与毒理学杂志》 CAS 北大核心 2019年第9期680-681,共2页
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
关键词 acute MYOCARDIAL INFARCTION astragalosideⅣ lipid and glucose metabolism PPARγpathway
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Content Determination of Astragaloside Ⅳ in Astragalus from Three Different Regions by HPLC 被引量:2
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作者 Wei XIN Jiangli NIE +4 位作者 Ye HAN Yi PEI Nan YANG Yujie LANG Xi ZHA 《Medicinal Plant》 CAS 2018年第6期15-18,22,共5页
[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
关键词 ASTRAGALUS membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hisao ASTRAGALOSIDE IV HPLC CONTENT determination
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Molecular Mechanism of Induction on Apoptosis of Human Esophageal Cancer HCE-4 Cells by Active Components from Astragalus membranaceus 被引量:2
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作者 Jiaru WANG Yinghua LUO +8 位作者 Xianji PIAO Chang LIU Yi ZHANG Hao WANG Jinqian LI Wanting XU Yang LIU Yiqin WU Chenghao JIN 《Medicinal Plant》 CAS 2018年第1期63-66,共4页
[Objectives] To investigate the pharmacologic effects of active components from A. membranaceus on human esophageal cancer HCE-4 cells and its apoptosis mechanism. [Methods] The viabilities of HCE-4 cells were measure... [Objectives] To investigate the pharmacologic effects of active components from A. membranaceus on human esophageal cancer HCE-4 cells and its apoptosis mechanism. [Methods] The viabilities of HCE-4 cells were measured by MTT assay. The induction of active components from A. membranaceus on apoptosis of HCE-4 cells was detected by Annexin V-FITC/PI double staining. The apoptotic-related protein expression levels were determined by Western blotting. [Results] Formononetin and astragaloside IV suppressed the proliferation of HCE-4 cells in a dose-dependent manner. The Annexin V-FITC/PI double staining results showed that formononetin and astragaloside IV could induce HCE-4 cells apoptosis in a time-dependent manner. The Western blotting results showed that formononetin and astragaloside IV could significantly down-regulate p-AKT,pro-caspase-3,and increase cle-caspase-3 protein expression in HCE-4 cells. [Conclusions]Active components from A. membranaceus such as formononetin and astragaloside IV significantly inhibited the proliferation of human esophageal cancer HCE-4 cells by inducing mitochondrial dependent apoptosis via AKT signaling pathway. 展开更多
关键词 Human esophageal cancer HCE-4 cells FORMONONETIN Astragaloside IV Astragalus root extract APOPTOSIS AKT signal path way
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Astragaloside IV prevents high-fat diet induced obesity partially through enhancing leptin signaling transduction
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期136-137,共2页
Aim To investigate the effects of astragaloside IV (ASI) on high-fat diet (HFD) induced obese mice. Methods The male mice aged 6 weeks were randomly divided into three groups (u- 18/group), namely control group,... Aim To investigate the effects of astragaloside IV (ASI) on high-fat diet (HFD) induced obese mice. Methods The male mice aged 6 weeks were randomly divided into three groups (u- 18/group), namely control group, model group and ASI-treated group. Control group were fed with standard diet, whereas the other two groups were given high fat diet. ASI-treated mice were daily intraperitoneally injected with ASI (25 nag · kg^-1). Mean- while, the other group mice were treated with saline. Body weight of mice was monitored every week and lasted for 13 weeks. Serum cholesterol and triglyceride content were measured with respective kits. Serum leptin level was deter- mined by ELISA kit. Expression of leptin receptor in hypothalamus was measured by Western blot assay. Gene ex- pression of neuropeptide Y (NPY) and agouti-related protein (AGRP) in hypothalamus was detected by qPCR assay. In addition, leptin receptor-deficient db/db mice were given intraperitoneally with ASI (25 mg ~ kg-1) or saline for 13 weeks (u- 8/group). Results ASI blocked body weight gain, suppressed appetite, improved leptin resistance, lowered serum triacylglycerol (TG) and total cholesterol (TC) contents, reduced accumulation of fat tissues and pre- vented enlargement of adipose cells in HFD fed mice. Furthermore, ASI increased the protein expression level of lep- tin receptor in hypothalamus, and inhibited the mRNA expression levels of NPY and AGRP. However, ASI could not decrease body gain in leptin receptor - deficient db/db mice as well as the mRNA expression levels of NPY and AGRP. Conclusion The study suggested that ASI could efficiently prevent HFD-induced obesity in C57BL/6 mice,which was partially mediated through enhancing leptin signaling transduction. 展开更多
关键词 ASTRAGALOSIDE IV OBESITY HIGH-FAT diet APPETITE LEPTIN receptor NEUROPEPTIDE Y
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Influence of astragaloside on gastric mucosa of stress ulcer rats
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作者 LI Yan-wu(Institute of PiWei,Guangzhou University of Chinese medicine,Guangzhou 510405,China) 《沈阳药科大学学报》 CAS CSCD 北大核心 2008年第S1期111-111,共1页
Objective To investigate the effect of astragaloside(AST)on the gastric mucosal injury of water immersion restraint stress ulcer rat.Methods The stress ulcer model was made by water immersion and restraint.The gastric... Objective To investigate the effect of astragaloside(AST)on the gastric mucosal injury of water immersion restraint stress ulcer rat.Methods The stress ulcer model was made by water immersion and restraint.The gastric mucosal injury index was observed.The SOD activity,the MDA contents and the gene expression of melatonin receptor 1 and 2 were detected in gastric mucosa.Results Compared with the normal group,the model group showed mucous edema,hyperemia and even ulcer damage.The injury index and the MDA content of gastric mucosa in model group were significantly increased(P<0.05),the SOD activity of gastric obviously depressed(P<0.01),and the melatonin receptor 1 and 2 mRNA expressions of damaged gastric mucosa were also lower.After administration of AST,the gastric mucosal ulcer index and MDA contents relieved obviously(P<0.01,P<0.05),the SOD activity and the expressions of melatonin receptor 1 and 2 mRNA raised up(P<0.01,P<0.05).Conclusions AST could prevent the gastric mucosal damage of rat in stress ulcer.And the mechanism of the gastric mucosal protection should be concerned with regulating the melatonin receptor and lessening the injury of oxygen free radical. 展开更多
关键词 ASTRAGALOSIDE OXYGEN free RADICAL MELATONIN RECEPTOR stress ULCER
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