RESUMO
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. CONCLUSION: 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.
Assuntos
Medicamentos de Ervas Chinesas , Doença de Parkinson , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/genética , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas , Medicina Tradicional Chinesa/métodos , MicroRNAs/metabolismo , MicroRNAs/genéticaRESUMO
INTRODUCTION: Functional dyspepsia (FD) is typically treated with serotonin receptor (5-HT) agonists such as cisapride, mosapride, tegaserod and tandospirone citrate. However, there are conflicting efficacy data, possibly due to significant heterogeneity between studies. In this meta-analysis, we analyzed the efficacy and safety data from studies evaluating the efficacy of serotonin receptor agonists in patients with FD. MATERIAL AND METHODS: Relevant studies were selected from the Medline, Cochrane, EMBASE, and Google Scholar databases. The meta-analysis included 10 RCTs which evaluated the efficacy of serotonin receptor agonists in patients with FD (final total of 892 patients in the serotonin receptor agonist group, and 640 participants in the placebo group). The primary outcomes were the response rates and abdominal symptoms score. The Cochrane Collaboration's tool was used to assess risk. Sensitivity analysis was carried out using the leave-one-out approach. RESULTS: Patients treated with serotonin receptor agonists had a significantly higher response rate compared to placebo-treated patients (pooled OR = 2.99; 95% CI: 1.15-7.77; p = 0.025). Patients treated with serotonin receptor agonists had a significant improvement in symptom scores compared to the placebo group (pooled standardized mean difference = -0.43; 95% CI: -0.83 to -0.04; p = 0.031). Sensitivity analysis indicated that the pooled estimates for abdominal symptom score might be affected by the Yeoh et al. (1997) study. CONCLUSIONS: Serotonin receptor agonists had a significantly higher efficacy compared to placebo in the treatment of FD.