Abstract：
BACKGROUND: Parkinson\'s disease (PD) is the fastest growing neurological disease. Currently, there is no disease-modifying therapy to slow the progression of the disease. Danggui buxue decoction (DBD) is widely used in the clinic because of its therapeutic effect. However, little is known about the molecular mechanism of DBD against PD. This study intends to explore the possible molecular mechanisms involved in DBD treatment of PD based on network pharmacology, and provide potential research directions for future research.
METHODS: Firstly, the active components and target genes of DBD were screened from the traditional Chinese medicine systems pharmacology (TCMSP), DrugBank and UniProt database. Secondly, target genes of PD were identified from the (GEO) dataset, followed by identification of common target genes of DBD and PD. Thirdly, analysis of protein-protein interaction (PPI), functional enrichment and diagnosis was performed on common target genes, followed by correlation analysis between core target genes, immune cell, miRNAs, and transcription factors (TFs). Finally, molecular docking between core target genes and active components, and real-time PCR were performed.
RESULTS: A total of 72 common target genes were identified between target genes of DBD and target genes of PD. Among which, 11 target genes with potential diagnostic value were further identified, including TP53, AKT1, IL1B, MMP9, NOS3, RELA, MAPK14, HMOX1, TGFB1, NOS2, and ERBB2. The combinations with the best docking binding were identified, including kaempferol-AKT1/HMOX1/NOS2/NOS3, quercetin-AKT1/ERBB2/IL1B/HMOX1/MMP9/TP53/NOS3/TGFB1. Moreover, IL1B and NOS2 respectively positively and negatively correlated with neutrophil and Type 1 T helper cell. Some miRNA-core target gene regulatory pairs were identified, such as hsa-miR-185-5p-TP53/TGFB1/RELA/MAPK14/IL1B/ERBB2/AKT1 and hsa-miR-214-3p-NOS3. These core target genes were significantly enriched in focal adhesion, TNF, HIF-1, and ErbB signaling pathway.
CONCLUSIONS: Diagnostic TP53, AKT1, IL1B, MMP9, NOS3, RELA, MAPK14, HMOX1, TGFB1, NOS2, and ERBB2 may be considered as potential therapeutic targets of DBD in the treatment of PD.
METHODS: Firstly, the active components and target genes of DBD were screened from the traditional Chinese medicine systems pharmacology (TCMSP), DrugBank and UniProt database. Secondly, target genes of PD were identified from the (GEO) dataset, followed by identification of common target genes of DBD and PD. Thirdly, analysis of protein-protein interaction (PPI), functional enrichment and diagnosis was performed on common target genes, followed by correlation analysis between core target genes, immune cell, miRNAs, and transcription factors (TFs). Finally, molecular docking between core target genes and active components, and real-time PCR were performed.
RESULTS: A total of 72 common target genes were identified between target genes of DBD and target genes of PD. Among which, 11 target genes with potential diagnostic value were further identified, including TP53, AKT1, IL1B, MMP9, NOS3, RELA, MAPK14, HMOX1, TGFB1, NOS2, and ERBB2. The combinations with the best docking binding were identified, including kaempferol-AKT1/HMOX1/NOS2/NOS3, quercetin-AKT1/ERBB2/IL1B/HMOX1/MMP9/TP53/NOS3/TGFB1. Moreover, IL1B and NOS2 respectively positively and negatively correlated with neutrophil and Type 1 T helper cell. Some miRNA-core target gene regulatory pairs were identified, such as hsa-miR-185-5p-TP53/TGFB1/RELA/MAPK14/IL1B/ERBB2/AKT1 and hsa-miR-214-3p-NOS3. These core target genes were significantly enriched in focal adhesion, TNF, HIF-1, and ErbB signaling pathway.
CONCLUSIONS: Diagnostic TP53, AKT1, IL1B, MMP9, NOS3, RELA, MAPK14, HMOX1, TGFB1, NOS2, and ERBB2 may be considered as potential therapeutic targets of DBD in the treatment of PD.
摘要：
背景：帕金森病（PD）是发展最快的神经系统疾病。目前,没有疾病改善疗法来减缓疾病的进展。当归补血汤(DBD)因其治疗作用而被广泛应用于临床。然而,关于DBD抗PD的分子机制知之甚少。本研究拟基于网络药理学探讨DBD治疗PD的可能分子机制,为今后的研究提供潜在的研究方向。
方法：首先，从中药系统药理学(TCMSP)中筛选DBD的活性成分和靶基因,DrugBank和UniProt数据库。其次,从(GEO)数据集中鉴定PD的靶基因，然后鉴定DBD和PD的共同靶基因。第三，蛋白质-蛋白质相互作用(PPI)分析，对常见的靶基因进行功能富集和诊断，其次是核心靶基因之间的相关性分析，免疫细胞，miRNA,和转录因子(TFs)。最后,核心靶基因和活性成分之间的分子对接，并进行实时PCR。
结果：在DBD的靶基因和PD的靶基因之间共鉴定出72个共同的靶基因。其中,进一步鉴定了11个具有潜在诊断价值的靶基因，包括TP53、AKT1、IL1B、MMP9,NOS3,RELA,MAPK14、HMOX1、TGFB1、NOS2和ERBB2。确定了具有最佳对接结合的组合，包括山奈酚-AKT1/HMOX1/NOS2/NOS3、槲皮素-AKT1/ERBB2/IL1B/HMOX1/MMP9/TP53/NOS3/TGFB1。此外，IL1B和NOS2分别与中性粒细胞和1型T辅助细胞呈正相关和负相关。鉴定了一些miRNA-核心靶基因调控对,例如hsa-miR-185-5p-TP53/TGFB1/RELA/MAPK14/IL1B/ERBB2/AKT1和hsa-miR-214-3p-NOS3。这些核心靶基因在粘着斑显著富集，TNF,HIF-1和ErbB信号通路。
结论：诊断TP53，AKT1，IL1B，MMP9,NOS3,RELA,MAPK14、HMOX1、TGFB1、NOS2和ERBB2可能被认为是DBD治疗PD的潜在治疗靶点。
方法：首先，从中药系统药理学(TCMSP)中筛选DBD的活性成分和靶基因,DrugBank和UniProt数据库。其次,从(GEO)数据集中鉴定PD的靶基因，然后鉴定DBD和PD的共同靶基因。第三，蛋白质-蛋白质相互作用(PPI)分析，对常见的靶基因进行功能富集和诊断，其次是核心靶基因之间的相关性分析，免疫细胞，miRNA,和转录因子(TFs)。最后,核心靶基因和活性成分之间的分子对接，并进行实时PCR。
结果：在DBD的靶基因和PD的靶基因之间共鉴定出72个共同的靶基因。其中,进一步鉴定了11个具有潜在诊断价值的靶基因，包括TP53、AKT1、IL1B、MMP9,NOS3,RELA,MAPK14、HMOX1、TGFB1、NOS2和ERBB2。确定了具有最佳对接结合的组合，包括山奈酚-AKT1/HMOX1/NOS2/NOS3、槲皮素-AKT1/ERBB2/IL1B/HMOX1/MMP9/TP53/NOS3/TGFB1。此外，IL1B和NOS2分别与中性粒细胞和1型T辅助细胞呈正相关和负相关。鉴定了一些miRNA-核心靶基因调控对,例如hsa-miR-185-5p-TP53/TGFB1/RELA/MAPK14/IL1B/ERBB2/AKT1和hsa-miR-214-3p-NOS3。这些核心靶基因在粘着斑显著富集，TNF,HIF-1和ErbB信号通路。
结论：诊断TP53，AKT1，IL1B，MMP9,NOS3,RELA,MAPK14、HMOX1、TGFB1、NOS2和ERBB2可能被认为是DBD治疗PD的潜在治疗靶点。
