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astragaloside Ⅳ inhibits pathological functions of gastric cancer-associated fibroblasts

World Journal of Gastroenterology 2017年第48期23卷 8512-8525页

作者： Zhen-Fei Wang Da-Guang Ma Zhe Zhu Yong-Ping Mu Yong-Yan Yang Li Feng Hao Yang Jun-Qing Liang Yong-Yan Liu Li Liu Hai-Wen Lu Laboratory for Tumor Molecular Diagnosis Affiliated People’s Hospital of Inner Mongolia Medical UniversityHuhhot 010020Inner Mongolia Autonomous Region Department of cytotherapy for tumors Affiliated People’s Hospital of Inner Mongolia Medical University Department of Abdominal Tumor Surgery Affiliated People’s Hospital of Inner Mongolia Medical University Department of Radiotherapy Affiliated People’s Hospital of Inner Mongolia Medical University Central Laboratory People’s Hospital of Wuhai City Affiliated Hospital of Inner Mongolia Medical University Huhhot 010050Inner Mongolia Autonomous Region

AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying *** 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 *** GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P 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

关键词： astragaloside Ⅳ Gastric cancer-associated fibroblasts Proliferation Migration Invasion Micro RNA

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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 2015年第B11期31卷 136-137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, 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.

关键词： astragaloside IV obesity high-fat diet appetite leptin receptor neuropeptide Y

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Pharmacokinetic and pharmacodynamic analysis of ferulic acidpuerarin-astragaloside in combination with neuroprotective in cerebral ischemia/reperfusion injury in rats

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Asian Pacific Journal of Tropical Medicine 2015年第4期8卷 299-304页

作者： Li-Jun Ge Shou-Yan Fan Jie-Hong Yang Yi Wei Zhen-Hong Zhu Yi-Jia Lou Ying Guo Hai-Tong Wan Yi-Qiang Xie Institute of Pharmacology Toxicology and Biochemical PharmaceuticsZhejiang University College of Life Science Zhejiang Chinese Medical University Department of Basic Medical Hainan Medical University Research Department Hainan Medical University

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 ***: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 ***,Pr and Al all displayed two compartment open models in *** hysteresis loops were obtained by time-concentration-effect ***-1βand NPY level changes in the plasma followed an opposite trend to the plasma concentration tendency after C_(max)was ***'s PRC value was significantly higher than those of FA and puerarin between 120 to 180 ***: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 *** may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.

关键词： Ferulic acid Puerarin astragaloside Interleukin-1β Neuropeptide Y

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astragaloside in cancer chemoprevention and therapy

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Chinese Medical Journal 2023年第10期136卷 1144-1154页

作者： Yaning Wang Zhuo Zhang Zhaohua Cheng Wei Xie Hanjiao Qin Jiyao Sheng Department of Hepatobiliary and Pancreatic Surgery Second Hospital of Jilin UniversityChangchunJilin 130041China Department of Orthopedics China-Japan Union Hospital of Jilin UniversityChangchunJilin 13033China Department of Ophthalmology Second Hospital of Jilin UniversityChangchunJilin 130041China Department of Radiotherapy Second Hospital of Jilin UniversityChangchunJilin 130041China

Tumor chemoprevention and treatment are two approaches aimed at improving the survival of patients with *** ideal anti-tumor drug is that which not only kills tumor cells but also alleviates tumor-causing risk factors,such as precancerous lesions,and prevents tumor *** herbal monomers are considered to be ideal treatment agents due to their multi-target *** has been shown to possess tumor chemoprevention,direct anti-tumor,and chemotherapeutic drug sensitization *** this paper,we review the effects of astragaloside on tumor prevention and treatment and provide directions for further research.

关键词： astragaloside Carcinoma Chemoprevention Anti-tumor Tumor recurrence

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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

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中国免疫学杂志 2019年第23期35卷 2848-2852页

作者：刘建春张红珍郭文娟柴智尉杰忠于婧文肖保国马存根山西中医药大学神经生物学研究中心国家中医药管理局多发性硬化益气活血重点实验室晋中030619 山西大同大学脑科学研究所中枢神经炎症变性疾病新药创制省市共建山西省重点实验室培育基地大同037009 复旦大学附属华山医院神经病学研究所上海200025

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... 详细信息

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(Pastragaloside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(Pastragaloside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。

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

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Chinese Journal of Natural Medicines 2016年第4期14卷 270-277页

作者： WANG Na WEI Ri-Bao LI Qing-Ping YANG Xi CHEN Xiang-Mei Department of Nephrology Chinese PLA General Hospital Chinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina 100853

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 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 astragaloside maintained slit diaphragm integrity and decreased the level of proteinuria in rats with adriamycin nephropathy.

关键词： astragaloside Adriamycin nephropathy Podocyte Nephrin Podocin

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astragaloside regulates the growth and invasion activity of colon cancer cells in vitro: the experimental study

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Journal of Hainan Medical University 2018年第19期24卷 1-4页

作者： Qiang Li Rong-Chi Mao Hui Huang Pharmacy Department the First People's Hospital of Ziyang Sichuan ProvinceZiyangSichuan Province641300China

Objective: To study the regulating effects of astragaloside on the growth and invasion activity of colon cancer cells in vitro. Methods: Lovo colon cancer cell lines were cultured and randomly divided into the control group treated with DMEM without drug or serum and the astragaloside groups treated with serum-free DMEM containing 10 μmol/L, 20 μmol/L and 40μmol/L astragaloside. The cell proliferation activity, the number of invasive cells as well as the expression of proliferating genes and invasion genes were measured after 24 h of treatment. Results: 24 h after treatment, the cell proliferation activity, the number of invasive cells as well as CCND1, β-catenin, ADAM17, MMP11, VEGF and ZEB2 mRNA expression of different concentrations of astragaloside groups were obviously lower than those of blank control group while WTX, PERK, ATF6, TIMP1 and E-cadherin mRNA expression were significantly higher than those of blank control group, and the higher the concentration of astragaloside, the more significant the decreasing trend of the cell proliferation activity, the number of invasive cells as well as CCND1, β-catenin, ADAM17, MMP11, VEGF and ZEB2 mRNA expression and the increasing trend of the WTX, PERK, ATF6, TIMP1 and E-cadherin mRNA expression. Conclusion: astragaloside can significantly inhibit the growth and invasion of colon cancer cells in vitro.

关键词： Colon cancer astragaloside Proliferation Invasion

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astragaloside Ⅳ derivative HHQ16 ameliorates infarction-induced hypertrophy and heart failure through degradation of lncRNA4012/9456

Astragaloside Ⅳ derivative HHQ16 ameliorates infarction-ind...

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2023年全国心血管药理学学术会议

作者： Jingjing Wan Zhen Zhang Chennan Wu Saisai Tian Yibei Zang Ge Jin Qingyan Sun Pin Wang Xin Luan Yili Yang Xuelin Zhan Lingyu Linda Ye Dayue Darrel Duan Xia Liu Weidong Zhang School of Pharmacy Second Military Medical University China Institute of Pharmaceutical Industry Key Laboratory of Medical Immunology and Institute of Immunology Second Military Medical University Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine State Key Laboratory of Medicinal Chemical Biology College of PharmacyNankai University Key Laboratory of Autoimmune Diseases and Precision Medicine People's Hospital of Ningxia Hui Autonomous Region Department of Pharmacology University of Nevada Reno School of Medicine Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College

Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction(MI) heart failure(HF).Here,we report a novel small molecule HHQ16,an optimized derivative of astragaloside IV,effectively reversed infarction-induced myocardial remodeling and improved cardiac function via directly acting on the cardiomyocyte to reverse *** effect of HHQ16 was associated with a strong inhibition of a newly discovered Egr2-affiliated transcript lnc9456 in the *** minimally expressed in normal mouse heart,lnc9456 was dramatically upregulated in the heart subjected to left anterior descending coronary artery ligation(LADL) and in cardiomyocytes subjected to hypertrophic *** critical role of lnc9456 in cardiomyocyte hypertrophy was confirmed by specific overexpression and knockout in vitro.A physical interaction between lnc9456 and G3BP2 increased NF-κB nuclear translocation that triggers hypertrophy-related ***16 physically bound to lnc9456 with a high-affinity and induced its ***-specific lnc9456 overexpression induced,but knockout prevented LADL-induced,cardiac hypertrophy and ***16 reversed the effect of lnc9456 overexpression while lost its protective role when lnc9456 deletion,further confirming lnc9456 as the bona fide target of *** further identified the human ortholog of lnc9456,also an Egr2-affiliated transcript,***,lnc4012 was significantly upregulated in hypertrophied failing hearts of patients with dilated ***16 also specifically bound to lnc4012 and caused its degradation and antagonized its hypertrophic *** degradation of pathological increased lnc4012/lnc9456 by small molecules might serve as a novel promising strategy to regress infarction-induced cardiac hypertrophy and HF.

关键词： astragaloside derivative HHQ16 ameliorates infarction-induced hypertrophy and heart failure through degradation of lncRNA4012/9456 lncRNA

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Content Determination of astragaloside Ⅳ in Astragalus from Three Different Regions by HPLC

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Medicinal Plant 2018年第6期9卷 15-18,22页

作者： Wei XIN Jiangli NIE Ye HAN Yi PEI Nan YANG Yujie LANG Xi ZHA College of Horticulture and Landscape Architecture Tianjin Agricultural University

[Objectives] The content of astragaloside in Astragalus membranaceus(Fisch.) ***(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 *** was determined by HPLC.[Results] There were great differences in the astragaloside IV content of *** among different *** content of astragaloside IV in *** cultivated in Inner Mongolia was highest(0.155%),followed by that(0.143%) in *** cultivated in Gansu,and the content of astragaloside IV in *** cultivated in Shanxi was lowest(0.080%).The contents of astragaloside IV in *** 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 *** cultivated in three different regions met the medicinal standards.

关键词： Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hisao astragaloside IV HPLC Content determination

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Influence of astragaloside on gastric mucosa of stress ulcer rats

Influence of astragaloside on gastric mucosa of stress ulcer...

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两岸三地药理学与临床药理学术会议

作者： LI Yan-wu (Institute of PiWei, Guangzhou University of Chinese medicine, Guangzhou 510405, China)

Objective To investigate the effect of astragaloside (AST) on the gastric mucosal injury of water immersion restraint stress ulcer *** The stress ulcer model was made by water immersion and re- *** gastric mucosal injury index was *** SOD activity,the MDA contents and the gene expression of melatonin receptor 1 and 2 were detected in gastric *** Compared with the normal group,the model group showed mucous edema,hyperemia and even ulcer *** 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 *** administration of AST,the gastric mucosal ulcer index and MDA con- tents 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 *** the mechanism of the gastric mucosal protection should be concerned with regulat- ing the melatonin receptor and lessening the injury of oxygen free radical.

关键词： astragaloside oxygen free radical melatonin receptor stress ulcer

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