Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Karyotype Analysis of Angelica sinensis (Oliy.) Diels

The seeds of tested Angelica sinensis （Oliy.）Diels were purchased from the planting base of Hebsi Anguo Traditional Chinese Medicine Market. With the root tips of germinated Angelica sinensis seeds treated with GA3 as materials, karyotype analysis was performed by photomicrographic technology and conventional chromosome preparation method. The results showed that the chromosome number of A. sinensis was 2 n=2.2, which accords with previous studies; and no satellites were observed, and the chromosome karyotype was 2A, with the asymmetrical karyotype coefficient （AS.K%） of 54：85%. The total length of the chromosomes was 113.4 pro, and total volume of chromosomes was 83.21 μm3.

正交试验优化当归趁鲜切片的加工工艺

目的通过药物成分含量检测与正交试验相结合的方式,确定当归趁鲜切片的工艺流程及工艺参数。方法先考察鲜当归杂质处理方法、切片的厚度及其干燥的方式对当归趁鲜切制外观性状、内在结构和药物成分(阿魏酸、挥发油)含量的影响。然后采用L_(9)(3^(4))正交试验,对当归饮片中阿魏酸含量进行分析,选出当归趁鲜切制的最适宜工艺条件。结果通过正交试验优化得到最适宜当归趁鲜饮片加工工艺为:首先将鲜当归除去芦头、须根和泥沙,并用水洗净其表面泥土和杂质,稍晾至没有水滴下滴时,放入温棚日晒干燥,直到当归归须和归尾(直径在5 mm以内)已干燥,归身变软,再将全当归切成4 mm薄片,最后放置在温棚日晒干燥,即得当归饮片,其饮片中阿魏酸含量为0.2211%,挥发油含量为0.9%;当归趁鲜切制最适宜工艺所得的当归饮片质量优于传统方法所得的质量(阿魏酸含量为0.1930%,挥发油含量为0.8%)。结论所得的加工工艺合理、可行,为后期当归趁鲜切片工艺研究奠定基础。

栽培方式对航天诱变当归SP_(2)繁种特性的影响

当归3年完成正常生活史,繁种周期长,成种株率低。为提高当归新品种选育效率,将搭载“长征7号”运载火箭在太空运行22 h(命名为航归22 h)和搭载“神舟十一号”宇宙飞船在太空运行33 d(命名为航归33 d)的当归种子作为SP0种子,以未搭载种子为对照(CK),经育苗栽培获得SP_(2)种苗。采用留苗和移栽2种栽培方式,测定进入第3年繁种年的SP_(2)群体的种株率、农艺性状和种果重。结果表明,CK群体未能进入繁种期而被淘汰,太空诱变获得的2个群体均进入正常繁种年。航归22 h的返青株成活率较航归33 d提高14.65个百分点,成种株率提高19.7个百分点。与移栽航归33 d、留苗航归22 h和33 d群体相比较,移栽航归22 h的繁殖特性有明显改善,单株果重分别增加1527.5%、428.2%和377.7%,根重分别增加235.3%、256.8%和265.2%,根长分别增加44.5%、36.7%和6.0%,根粗分别增加83.3%、83.7%和83.9%。航归SP_(2)代群体性状综评指数大小依次为移栽航归22 h(0.8133)>留苗航归33 d(0.4083)>留苗航归22 h(0.2378)>移栽航归33 d(0.0334)。综上,太空搭载种子对当归具有诱变效应,运载火箭搭载时间短,群体诱变效应更佳,选育效率更高;采用移栽和留苗互补栽培可保障繁种的安全性。本研究结果为当归新品系扩繁提供了科学技术依据。

Differentially Expressed Genes in Heads and Tails of Angelica Sinensis diels： Focusing on Ferulic Acid Metabolism

Objective： To explore the scientific connotation of the discrepant pharmaceutical activities between the head and tail of Angelica sinensis diels（AS）, an important herb extensively utilized in Chinese medicine, by the approach of transcriptome sequencing. Methods： Ten samples of AS were randomly collected in Min County, Gansu Province of China. Transcriptome sequencing of AS was accomplished in a commercial ILLumina Hi Seq-2000 platform. The transcriptome of each head and tail of AS were fixed in a gene chip, and detected under the procedure of Illumina Hi Seq-2000. Differentially expressed unigenes between the heads and tails of AS were selected by Shanghai Biotechnology Corporation（SBC） online analysis system, based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and relevant bioinformatic database. Results： Totally 63,585 unigenes were obtained from AS by high-throughput sequencing platform. Among which 3359 unigenes were identified as differentially expressed unigenes between the heads and tails of AS by SBC analysis system scanning. Of which 15 differentially expressed unigenes participate in the metabolic regulation of phenylpropanoid biosynthesis（PB） pathway and ferulic acid metabolites, in response to the distinguished pharmaceutical actions of the heads and tails of AS. Conclusion： Different content of ferulic acid in the heads and tails of AS is related to the differentially expressed genes, particularly involved in the PB pathway.

应用Proofman-LMTIA技术双重检测当归和东当归

通过梯型熔解温度核酸等温扩增技术(Ladder-shape melting temperature nucleic acid isothermal amplification,LMTIA)与校对酶介导探针(Proofreading enzyme-mediated probe cleavage,Proofman)联合的方法对当归和东当归进行双重检测。以ddH2O为阴性模板,当归和东当归基因组DNA为阳性模板,测定当归和东当归引物的最适温度、灵敏度及稳定性,并进行了真实样品检测。结果表明,应用Proofman-LMTIA双重检测当归和东当归,引物测定的最适温度为62℃,当归引物灵敏度低至10 pg/μL,东当归引物灵敏度低至1 pg/μL,具有良好的稳定性。7份市售当归样品经检测均为当归。该研究可为当归和东当归的鉴别提供一种新的检测方法。

未来气候条件下当归适生区预测及时空变化分析

目的 研究未来气候变化对当归适生区分布的影响及时空变化趋势,为当归生产规划提供参考。方法 利用最大熵(MaxEnt)模型和ArcGIS软件对当前(1970-2000年)和未来(2041-2060年、2061-2080年、2081-2100年)不同气候情景下(SSP126和SSP585)当归的适生区分布进行预测,利用质心位移法绘制适生区移动轨迹,分析当归适生区的时空演变趋势。结果 当前气候条件下当归总适生区面积约为148.13×10^(4) km^(2),海拔、年均降水量、最冷季度平均温度是影响当归分布的主要环境因子,其中海拔的影响最大,贡献率为49.1%。未来SSP126和SSP585气候情景下,当归总适生区面积先增加后减少,均在2050年达到最大值,高适生区和极高适生区受气候影响较大,新增适生区主要集中在青海东部的高海拔地区,适生区质心均向高纬度方向移动。SSP126情景下适生区面积在2081-2100年又有所增加。结论 未来气候条件下当归适生区向高纬度方向移动,温度升高可能是导致其适生区变化的重要因素,可进行相关生产规划。

不同加工过程中当归化学成分变化的研究进展

当归经过不同的加工会对其化学成分产生不同程度的影响。因此,就近20年来不同加工方式对当归化学成分的含量变化进行文献综述,并对当归加工过程中化学成分变化规律进行探讨,最后对当归的功能性食品及产品的开发进行展望。该文对当归药食价值的深入挖掘、品质提升、工艺创新、新产品开发等具有一定的参考价值。

品种及种苗规格对当归成药期质量和经济效益的影响

当归是甘肃省定西市品牌大宗道地药材之一,但生产中的早薹问题导致其成药期质量下降,已成为制约当地当归产业发展的最大瓶颈。为了筛选出适宜在当地种植的最佳当归品种和种苗,以岷归系列品种为试材,采用二因素随机区组设计,研究了不同当归品种及其种苗规格对成药期当归质量和经济收益的影响。结果表明,选择移栽单株鲜重约0.7 g、主根长7.1 cm、侧根数少于0.2条/株的岷归4号种苗,是最适宜获得当归主要农艺性状较优、早薹率低、抗病性较强、产量及经济收益高的种植方案。应用该种苗种植时,当归单株鲜根重最重,为69.3 g;鲜根折合产量最高,为11800.0 kg/hm2;经济纯收益最高,为67600.0元/hm2;产投比最优,为21.1元/元。建议在定西地区及类似区立地条件下,优先选择岷归4号小种苗。

覆膜方式和移栽密度对当归生长及产量的影响

为了改进高寒阴湿区当归栽培技术,提高当归产量和效益,以不同覆膜方式和移栽密度为因子,采用双因素随机区组试验,定期测定当归生长指标、抽薹率并统计产量。结果表明,在临夏高寒阴湿地区,不同覆膜方式和移栽密度对当归生长及产量有一定的影响。覆盖黑膜有利于提高当归株高、根直径及产量,并使当归抽薹率和折干率较低;覆盖白膜有利于当归根长的生长。在株距20 cm、行距25 cm的密度条件下对当归生长和产量较好,鲜产最高达17469.45 kg/hm^(2),干产最高达4991.25 kg/hm^(2)。综合考虑各因素,在高寒阴湿区种植当归用黑膜覆盖为好,移栽密度以株距20 cm、行距25 cm为宜。

环保酵素对当归种苗质量性状及产量的影响

环保酵素是以废弃果蔬、植物、厨余垃圾等为原料发酵制得的含有特定生物活性成分的产品,富含各种酶、有机酸、矿物质和微生物,是一种环保高效的土壤改良材料。为了探明酵素改良土壤和供肥作用对当归生长的影响,给当归种苗绿色标准化繁育提供参考。以岷归5号为指示品种,采用单因素随机区组法设计,以田园土和含环保酵素的营养土按体积比2∶1、1∶1的基质培育种苗,以不施酵素为对照,研究了不同用量环保酵素对当归种苗质量性状及产量的影响。结果表明,以田园土和含环保酵素营养土体积比为2∶1的基质更有利于提高当归种苗质量性状和产量,有利于增加当归一级种苗数。其中百苗鲜重和根冠比分别较不施酵素增加14.13%、29.13%;当归折合产量最高,为1520.82 kg/hm^(2),较不施酵素增产13.06%。

甘南州洮河流域当归种植气候分析及区划研究

利用1980—2021年甘南州洮河流域自动站(碌曲、卓尼、临潭)资料,运用气候分析、种植区划和模糊数学方法对洮河流域绿色道地药材当归气候生态种植区划和品质区划进行了研究。结果表明:1980—2021年,除了碌曲、临潭年日照时数呈下降趋势外,3个站点的年平均气温、年降水量、年相对湿度、≥0℃年积温均呈上升趋势;根据当归种植适宜性,将甘南州洮河流域划分为最适宜种植区、适宜种植区、次适宜种植区、可种植区、不宜种植区;根据当归品质等级,将其分为品质好区、品质较好区、品质一般区、品质较差区、品质差区;同时运用模糊数学方法,结合Fuzzy模型进行计算后,得出了气候生态适宜性与生产布局存在一定吻合的结论,为当归生产基地建设提供了科学的参考依据。

当归药材道地性的RAPD分析

目的 从 DNA分子水平上探讨当归药材道地性的生物学基础。方法 对来自不同产地的 18个当归样品 ,提取其基因组 DNA,并进行 RAPD分析。对筛选出的 10个引物的 RAPD结果进行聚类分析 ,得出 18个当归样品的聚合树状图。结果 显示地理分布距离越小 ,当归的遗传差异越小 ;反之 ,越大。但生态环境特别是小生境对当归遗传差异的作用亦不可忽视。

当归的研究进展

对近年在当归植物学、药理学、栽培学等方面的研究工作作一概述。就当归生地育苗。

当归补血汤中不同组分对正常及血虚小鼠免疫功能的影响

目的 比较当归补血汤中的不同组分对正常及血虚小鼠模型的免疫调节作用。方法 采用 MTT法测 T、B淋巴细胞的增殖率 ;分光光度法检测脾细胞中抗体的生成 ;用乙酰苯肼和环磷酰胺制备小鼠血虚模型。结果 黄芪中的 4个不同组分对正常小鼠均具有增强 T、B淋巴细胞增殖率及促进抗体生成作用 ,而当归中的 3个不同组分则作用各异 ,但是对血虚模型小鼠均表现出明显的免疫调节作用。体外实验发现 :在 2 .5～ 2 5 0 μg/m L 浓度范围内 ,黄芪黄酮、黄芪皂苷以及黄芪和当归的挥发油部分均表现为良好的双向免疫调节作用 ,而黄芪和当归的多糖组分则为明显的浓度依赖性作用方式。

炮制对当归药材有效成分的影响

目的建立当归药材及其炮制品的高效液相色谱测定法,比较当归炮制前后有效成分的变化。方法利用HPLC-DAD方法,梯度洗脱,测定了生当归及其炮制品中藁本内酯、阿魏酸的含量。色谱条件为:色谱柱Zorbax SB-C18柱(4.6mm×250mm,5μm);柱温25℃,以乙腈-0.01%磷酸水溶液为流动相,进行梯度洗脱,分析时间为60min。流速为0.8mL·min-1,检测波长220nm。结果当归经不同方法炮制后,其所含成分发生了变化。实验证明,该方法简便、可靠、重现性好。结论本方法可用于当归药材及其炮制品中藁本内酯及阿魏酸的含量测定,并为其全面质量控制提供参考;为探讨当归炮制意义,提供了一定的实验依据。

不同产地当归药材及其土壤无机元素的关联分析与探讨

目的:通过对不同产地当归药材及其土壤无机元素类成分的关联分析,以评价该类成分与药材地道性和功效间的关系。方法:采用微波消解法-电感耦合等离子体发射法,测定了我国4个主产区40余份当归药材及其土壤中14种无机元素的含量。结果:当归药材与土壤中Ca、Na、Ni显著相关;当归可能对Mg元素具有富集作用;Zn、Cu、Mn、Mg等元素可能是影响当归地道性最为显著的无机元素。实验结果从无机元素的角度支持岷归为道地药材。结论:当归药材所含无机元素类成分可能与其地道性呈现一定的相关性,为从认识当归的地道性成因及其药材功效物质基础提供参考。

当归多糖AP-0对小鼠移植性肿瘤的抑制作用

目的 观察当归总多糖AP 0对于 3种小鼠移植性肿瘤的抑制作用。方法 小鼠肉瘤S180模型建立 :二级昆明种小鼠 ,每只鼠鼷部接种 5× 10 6瘤细胞。接种次日起 ,每日 1次定时ipAP 0 30mg·kg-1,10 0mg·kg-1和 30 0mg·kg-1,阳性对照组ip环磷酰胺 (Cy) 30mg·kg-1,共 10d ,第 11天活杀小鼠 ,称瘤质量、体质量、胸腺和脾质量 ,统计结果。小鼠Ehrlich腹水癌 (EAC)模型建立 :二级昆明种小鼠 ,每鼠ip接种 2 .5× 10 6瘤细胞。接种后次日起 ,每日 1次定时ipAP 0 30mg·kg-1,10 0mg·kg-1和 30 0mg·kg-1,阳性对照组ip氟尿嘧啶 ( 5 FU) 2 0mg·kg-1,共 10d ,观察各组 6 0d平均存活天数 ,计算生命延长率。小鼠白血病L12 10模型建立 :二级DBA/2小鼠 ,每鼠ip接种 1× 10 5瘤细胞。接种后次日起 ,每日 1次定时ipAP 0 30mg·kg-1,10 0mg·kg-1和 30 0mg·kg-1,阳性对照组ip环磷酰胺 (Cy) 30mg·kg-1,共 10d ;第 30天处死 ,计算生命延长率。结果 小鼠肉瘤 180实验结果 :瘤质量指标 :NS组和各治疗组瘤质量均大于Cy组 (P <0 .0 1) ;胸腺质量指标 :10 0mg·kg-1组胸腺质量小于NS组 (P <0 .0 5 ) ,30mg·kg-1和 30 0mg·kg-1组胸腺质量明显小于NS组 (P <0 .0 1) ,但 30mg·kg-1组胸腺质量大于Cy组 (P <0 .0 5 ) ,10 0mg·

当归不同药用部位水煎液指纹图谱及成分分析

目的建立当归Angelica sinensis(Oliv.)Diels不同药用部位水煎液HPLC指纹图谱,并分析其化学成分。方法全当归、当归头、当归身、当归尾水煎液的分析采用Ultimate XB-C18色谱柱(4.6 mm×250 mm,5μm);以0.1%甲酸-乙腈为流动相,梯度洗脱;柱温25℃;体积流量1 m L/min;检测波长280 nm。采用HPLC-MS联用技术分析其所含化学成分。结果以阿魏酸为参比峰,标定了24个特征峰,聚类分析表明全归和归身聚为一类,归头和归尾为一类。定性鉴定出8种化学成分,分别为色氨酸、绿原酸、阿魏酸、洋川芎内酯I、洋川芎内酯H、丁基苯酞、E-藁本内酯、Z-藁本内酯。结论该方法准确稳定,重复性好,可用于当归的质量控制。