Objectives:To investigate acute toxicity of Bajitian(Morinda officinalis)in zebrafish embryos.Methods:Zebrafish embryos at 48-h post fertilization(hpf)were exposed to Bajitian ethanol extract for72 h.The causative act...Objectives:To investigate acute toxicity of Bajitian(Morinda officinalis)in zebrafish embryos.Methods:Zebrafish embryos at 48-h post fertilization(hpf)were exposed to Bajitian ethanol extract for72 h.The causative action of a delay in yolk sac absorption by Bajitian was investigated by RT-PCR analysis of lipid metabolism-related microsomal triglyceride transfer protein(MTP),apolipoprotein CII(ApoC2)and lipogenesis-related liver x receptor(LXR)genes.The effect of Bajitian eliciting an inflammatory response was studied by exposing 72 hpf myeloperoxidase(MPO):GFP transgenic zebrafish embryos to Bajitian extract for 4 h.Assessment was done by TUNEL,caspase-3/7,and RT-PCR analysis of the apoptosis related pathway B-cell lymphoma 2 associated X protein(Bax),Nuclear factor kappa-lightchain-enhancer of activated B cells(NF-k B)genes,neutrophil development-related stem cell leukaemia(SCL)and transcription factor PU.1 genes,to reveal the causative action of Bajitian reducing neutrophils.Results:RT-PCR analysis found that Bajitian extract had no effect on the expression of MTP or ApoC2 genes,but upregulated LXR gene,which might explain the delay in yolk sac absorption.Analysis of the inflammatory response showed that compared with negative controls,Bajitian extract significantly(P<.05)reduced the number of neutrophils in MPO:GFP embryos.TUNEL,caspase-3/7,and RT-PCR analysis of Bax and NF-k B genes found that Bajitian extract did not trigger the cell apoptosis.Further RT-PCR analysis found that Bajitian extract did not affect SCL expression,but did lead to down-regulation of PU.1.The inhibition of neutrophil development/differentiation may explain the decline in the total number of neutrophils following Bajitian treatment,which could be attributed to the anti-inflammatory effects found clinically for this drug.Conclusions:This study demonstrated that Bajitian caused a delay in yolk sac absorption and a decrease neutrophil in zebrafish embryos,which may be related to the inhibition of neutrophil development.展开更多
目的:运用网络药理学方法和技术研究“巴戟天-续断-益母草”组药治疗多囊卵巢综合征(polycystic ovarian syndrome,PCOS)的主要活性成分、靶点、通路等药理学作用机制。方法:通过数据挖掘获得PCOS肾虚血瘀型核心组药巴戟天-续断-益母草...目的:运用网络药理学方法和技术研究“巴戟天-续断-益母草”组药治疗多囊卵巢综合征(polycystic ovarian syndrome,PCOS)的主要活性成分、靶点、通路等药理学作用机制。方法:通过数据挖掘获得PCOS肾虚血瘀型核心组药巴戟天-续断-益母草;检索中药系统药理学数据库分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP),筛选出巴戟天-续断-益母草的活性成分和潜在靶点;查询NCBI数据库获得PCOS疾病靶点,找到药物和疾病的共靶点;通过DAVID数据库对共靶点进行基因功能GO富集分析和KEGG富集分析;采用Cytoscape软件构建成分-靶标、靶标-通路网络。结果:从“巴戟天-续断-益母草”组药中筛选得到26个候选活性分子,作用于719个靶点,找到PCOS疾病靶点228个,两者共有靶点22个,主要涉及炎性反应、细胞因子、雌激素、胰岛素抵抗等生物学过程中的多条信号通路。结论:本研究初步揭示“巴戟天-续断-益母草”组药的主要活性成分、靶点及协同作用机制,为进一步深入探讨其药理学作用提供了参考。展开更多
基金Infinitus(China)Company Ltd.internal research funding。
文摘Objectives:To investigate acute toxicity of Bajitian(Morinda officinalis)in zebrafish embryos.Methods:Zebrafish embryos at 48-h post fertilization(hpf)were exposed to Bajitian ethanol extract for72 h.The causative action of a delay in yolk sac absorption by Bajitian was investigated by RT-PCR analysis of lipid metabolism-related microsomal triglyceride transfer protein(MTP),apolipoprotein CII(ApoC2)and lipogenesis-related liver x receptor(LXR)genes.The effect of Bajitian eliciting an inflammatory response was studied by exposing 72 hpf myeloperoxidase(MPO):GFP transgenic zebrafish embryos to Bajitian extract for 4 h.Assessment was done by TUNEL,caspase-3/7,and RT-PCR analysis of the apoptosis related pathway B-cell lymphoma 2 associated X protein(Bax),Nuclear factor kappa-lightchain-enhancer of activated B cells(NF-k B)genes,neutrophil development-related stem cell leukaemia(SCL)and transcription factor PU.1 genes,to reveal the causative action of Bajitian reducing neutrophils.Results:RT-PCR analysis found that Bajitian extract had no effect on the expression of MTP or ApoC2 genes,but upregulated LXR gene,which might explain the delay in yolk sac absorption.Analysis of the inflammatory response showed that compared with negative controls,Bajitian extract significantly(P<.05)reduced the number of neutrophils in MPO:GFP embryos.TUNEL,caspase-3/7,and RT-PCR analysis of Bax and NF-k B genes found that Bajitian extract did not trigger the cell apoptosis.Further RT-PCR analysis found that Bajitian extract did not affect SCL expression,but did lead to down-regulation of PU.1.The inhibition of neutrophil development/differentiation may explain the decline in the total number of neutrophils following Bajitian treatment,which could be attributed to the anti-inflammatory effects found clinically for this drug.Conclusions:This study demonstrated that Bajitian caused a delay in yolk sac absorption and a decrease neutrophil in zebrafish embryos,which may be related to the inhibition of neutrophil development.
文摘目的:运用网络药理学方法和技术研究“巴戟天-续断-益母草”组药治疗多囊卵巢综合征(polycystic ovarian syndrome,PCOS)的主要活性成分、靶点、通路等药理学作用机制。方法:通过数据挖掘获得PCOS肾虚血瘀型核心组药巴戟天-续断-益母草;检索中药系统药理学数据库分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP),筛选出巴戟天-续断-益母草的活性成分和潜在靶点;查询NCBI数据库获得PCOS疾病靶点,找到药物和疾病的共靶点;通过DAVID数据库对共靶点进行基因功能GO富集分析和KEGG富集分析;采用Cytoscape软件构建成分-靶标、靶标-通路网络。结果:从“巴戟天-续断-益母草”组药中筛选得到26个候选活性分子,作用于719个靶点,找到PCOS疾病靶点228个,两者共有靶点22个,主要涉及炎性反应、细胞因子、雌激素、胰岛素抵抗等生物学过程中的多条信号通路。结论:本研究初步揭示“巴戟天-续断-益母草”组药的主要活性成分、靶点及协同作用机制,为进一步深入探讨其药理学作用提供了参考。
