Study on Mechanism and Validation of Effect of Astragali Radix in Treatment of Parkinson's Disease by Network Pharmacology / 中国实验方剂学杂志

ABSTRACT

Objective:To analyze the mechanism of Astragali Radix in the treatment of Parkinson's disease by network pharmacology and PC-12 extracellular model. Method:Traditional Chinese medicines systems pharmacology platform （TCMSP） and CD-HIT databases were used to screen out active components and targets of Astragali Radix， GENECARDS and Online Mendelian Inheritance in Man （OMIM） databases were used to screen out targets relating to Parkinson's disease and draw component-target network， STRING database was used to build the protein-protein interaction network， Bioconductor Cluster Profiler was applied in Gene Ontology （GO） enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. PC-12 cells were pretreated with water extract of Astragali Radix， and Western blot was used to assess the expression of phosphorylation extracellular regulatory protein kinase 1/2（p-ERK1/2）， ERK1/2， B cell lymphoma -2 （Bcl-2） associated X protein （Bax）， Bcl-2， cysteine aspartic acid protease -3 （Caspase-3） and cleaved-Caspase3 （c-Caspase-3）. The levels of interleukin-6 （IL-6）， IL-10 and tumor necrosis factor-α（TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA） interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α（TNF-α）. Result:Network pharmacology showed that 14 compounds in Astragali Radix， including emodin and quercetin， played a role through multi-target and multi-channel synergy， involving ERK signal pathway， Bax， Bcl-2， Caspase-3， IL-6， IL-10， TNF-α and other target proteins. Western blot showed that the expressions of Bax， p-ERK1/2， c-Caspase-3 and Bcl-2 in Astragali Radix Extract group decreased， while the expressions of Bcl-2 in Astragali Radix Extract group was significantly higher than that in model group （P<0.05）. There were statistical differences between the two groups. ELISA showed that Astragali Radix water extract could reduce the expressions of IL-6， TNF-α， but increase the expression of IL-10， with statistical differences from the model group （P<0.05）. Conclusion:This study shows that Astragali Radix can affect the expressions of these proteins， and verify the results of network pharmacology， so as to provide a basis for further study of Astragali Radix in the treatment of Parkinson's disease.