Ten actinomycete strains isolated from the Yellow Sea off China＇s coasts were identified as belonging to two genera by 16S rDNA phylogenetic analysis： Streptomyces and Nocardiopsis. Six Streptomyces strains （MA10, ...Ten actinomycete strains isolated from the Yellow Sea off China＇s coasts were identified as belonging to two genera by 16S rDNA phylogenetic analysis： Streptomyces and Nocardiopsis. Six Streptomyces strains （MA10, 2SHXF01-3, MA35, MA05-2, MA05-2-1 and MA08-1） and one Nocardiopsis strain （MA03） were predicted to have the potential to produce aromatic polyketides based on the analysis of the KSa （ketoacyl-synthase） gene in the type II PKS （polyketides synthase） gene cluster. Four strains （MA03, MA01, MA10 and MA05-2） exhibited significant inhibitory effects on mycelia growth （inhibition rate 〉50%） and subsequent aria- toxin production （inhibition rate 〉75%） of the mutant aflatoxigenic Aspergillus parasiticus NFRI-95. The ethyl acetate extracts of the broth of these four strains displayed significant inhibitory effects on mycelia growth, and the IC50 values were calculated （MA03： 0.275 mg mL-1, MA01：0.106 mg mL-1, MA10：1.345 mg mL-1 and MA05-2：1.362 mg mL-1）. Five strains （2SHXF01-3, MA03, MA05-2, MA01 and MA08-1） were selected based on their high cytotoxic activities. The ethyl acetate extract of the Nocardiopsis strain MA03 was particularly noted for its high antitumor activity against human carcinomas of the cervix （HeLa）, lung （A549）, kidney （Caki-1） and liver （HepG2） （IC50： 2.890, 1.981, 3.032 and 2.603 μgmL-1, respectively）. The extract also remarkably inhibited colony formation of HeLa cells at an extremely low concentration （0.5μgmL 1）. This study highlights that marine-derived actinomycetes are a huge resource of compounds for the biological control of aflatoxin contamination and the development of novel drugs for human carcinomas.展开更多
目的基于网络药理学方法预测甘松Nardostachys jatamansi治疗帕金森病伴发焦虑(Parkinson’s disease with anxiety,PDA)的作用靶点和信号通路,并通过PDA模型大鼠进行药效学和关键靶点的验证。方法通过中药系统药理学数据库分析平台(TCM...目的基于网络药理学方法预测甘松Nardostachys jatamansi治疗帕金森病伴发焦虑(Parkinson’s disease with anxiety,PDA)的作用靶点和信号通路,并通过PDA模型大鼠进行药效学和关键靶点的验证。方法通过中药系统药理学数据库分析平台(TCMSP)和文献挖掘获得甘松主要化学成分,利用SwissTargetPrediction、GeneCards数据库获得甘松化学成分治疗PDA的潜在靶点,对其进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,利用Cytoscape 3.7.2构建"成分-靶点-通路"网络。大鼠采用颈背部sc鱼藤酮制备PD模型,并通过旷场实验筛选出PDA模型大鼠;设置对照组、模型组、甘松(620 mg/kg)组、左旋多巴(49 mg/kg)组,利用转棒实验、旷场实验和免疫组化法对甘松治疗PDA的药效学进行评价;并对关键蛋白和大鼠脑内神经递质含量进行测定。结果 "成分-靶点-通路"网络中包含甘松抗PDA的12个有效成分如甘松新酮、诺卡酮、金合欢素、β-谷甾醇等,丝裂原活化蛋白激酶3(mitogen-activated protein kinases 3,MAPK3)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)等99个靶点,主要涉及神经活性配体-受体相互作用、雌激素、FoxO、TNF等信号通路。实验结果显示,甘松延长了PDA大鼠在转棒上的停留时间,增加了其在旷场的总活动距离及在中央区的活动时间和距离,提高了黑质区酪氨酸羟化酶阳性表达(P<0.05);甘松显著降低大鼠纹状体MAPK3、TNF-α含量以及STAT3蛋白表达水平(P<0.05、0.01),提高了多巴胺、3,4-二羟基苯乙酸、高香草酸、5-羟色胺和5-羟吲哚乙酸水平(P<0.01、0.001)。结论甘松中的有效成分可能是通过MAPK3、TNF-α、STAT3等靶点调控多条信号通路来抑制神经炎症反应,提高神经递质水平以治疗PDA疾病。展开更多
基金supported by the COMRA project (No. DY125-15-R-01)
文摘Ten actinomycete strains isolated from the Yellow Sea off China＇s coasts were identified as belonging to two genera by 16S rDNA phylogenetic analysis： Streptomyces and Nocardiopsis. Six Streptomyces strains （MA10, 2SHXF01-3, MA35, MA05-2, MA05-2-1 and MA08-1） and one Nocardiopsis strain （MA03） were predicted to have the potential to produce aromatic polyketides based on the analysis of the KSa （ketoacyl-synthase） gene in the type II PKS （polyketides synthase） gene cluster. Four strains （MA03, MA01, MA10 and MA05-2） exhibited significant inhibitory effects on mycelia growth （inhibition rate 〉50%） and subsequent aria- toxin production （inhibition rate 〉75%） of the mutant aflatoxigenic Aspergillus parasiticus NFRI-95. The ethyl acetate extracts of the broth of these four strains displayed significant inhibitory effects on mycelia growth, and the IC50 values were calculated （MA03： 0.275 mg mL-1, MA01：0.106 mg mL-1, MA10：1.345 mg mL-1 and MA05-2：1.362 mg mL-1）. Five strains （2SHXF01-3, MA03, MA05-2, MA01 and MA08-1） were selected based on their high cytotoxic activities. The ethyl acetate extract of the Nocardiopsis strain MA03 was particularly noted for its high antitumor activity against human carcinomas of the cervix （HeLa）, lung （A549）, kidney （Caki-1） and liver （HepG2） （IC50： 2.890, 1.981, 3.032 and 2.603 μgmL-1, respectively）. The extract also remarkably inhibited colony formation of HeLa cells at an extremely low concentration （0.5μgmL 1）. This study highlights that marine-derived actinomycetes are a huge resource of compounds for the biological control of aflatoxin contamination and the development of novel drugs for human carcinomas.
文摘目的基于网络药理学方法预测甘松Nardostachys jatamansi治疗帕金森病伴发焦虑(Parkinson’s disease with anxiety,PDA)的作用靶点和信号通路,并通过PDA模型大鼠进行药效学和关键靶点的验证。方法通过中药系统药理学数据库分析平台(TCMSP)和文献挖掘获得甘松主要化学成分,利用SwissTargetPrediction、GeneCards数据库获得甘松化学成分治疗PDA的潜在靶点,对其进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,利用Cytoscape 3.7.2构建"成分-靶点-通路"网络。大鼠采用颈背部sc鱼藤酮制备PD模型,并通过旷场实验筛选出PDA模型大鼠;设置对照组、模型组、甘松(620 mg/kg)组、左旋多巴(49 mg/kg)组,利用转棒实验、旷场实验和免疫组化法对甘松治疗PDA的药效学进行评价;并对关键蛋白和大鼠脑内神经递质含量进行测定。结果 "成分-靶点-通路"网络中包含甘松抗PDA的12个有效成分如甘松新酮、诺卡酮、金合欢素、β-谷甾醇等,丝裂原活化蛋白激酶3(mitogen-activated protein kinases 3,MAPK3)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)等99个靶点,主要涉及神经活性配体-受体相互作用、雌激素、FoxO、TNF等信号通路。实验结果显示,甘松延长了PDA大鼠在转棒上的停留时间,增加了其在旷场的总活动距离及在中央区的活动时间和距离,提高了黑质区酪氨酸羟化酶阳性表达(P<0.05);甘松显著降低大鼠纹状体MAPK3、TNF-α含量以及STAT3蛋白表达水平(P<0.05、0.01),提高了多巴胺、3,4-二羟基苯乙酸、高香草酸、5-羟色胺和5-羟吲哚乙酸水平(P<0.01、0.001)。结论甘松中的有效成分可能是通过MAPK3、TNF-α、STAT3等靶点调控多条信号通路来抑制神经炎症反应,提高神经递质水平以治疗PDA疾病。
