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.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the correlation between the recurrence of cerebral infarction and aspirin resistance (AR)/Chinese medical (CM) constitutions.</p><p><b>METHODS</b>Totally 413 cerebral infarction patients took Aspirin Enteric-coated Tablet (100 mg per day) while receiving routine therapy, 5 days at least in a week. They were followed-up for 12 months. Aspirin sensitivity (AS) was determined using turbidimetry. CM constitutions among patients with different AS were compared. Ratios of AR patients and AS patients of different CM constitutions in cerebral infarction recurrent patients were compared. Platelet membrane glycoproteins (GP) II b HPA-3 gene polymorphism was detected by polymerase chain reaction (PCR) method. Correlation between recurrence of cerebral infarction and AR, bb genotypes, CM constitutions times AS were analyzed by Logistic regression.</p><p><b>RESULTS</b>Totally 11 patients dropped out, 101 (25.12%)with recurrent cerebral infarction and 301 (74.88%) without recurrent cerebral infarction. There were 152 (37.81%) AR patients and 250 (62.19%) AS patients. AR accounted for 26.6% (80/ 301) and AS accounted for 73.4% (221/301) in non-recurrent cerebral infarction patients. AR accounted for 71.3% (72/101) and AS accounted for 28.7% (29/101) in recurrent cerebral infarction patients. There was statistical difference in AR and AS ratios (χ2 = 64.287, P = 0.000). The proportion of yin deficiency constitution (YDC) was the largest [28.3% (43/152)] in AR patients. The proportion of blood stasis constitution (BSC) was the largest [23.6% (59/250)] in AS patients. There was statistical difference in CM constitutions between AR patients and AS patients (χ2 = 21.574, P < 0.01). The former 4 recurrent rates occurred in AR patients of YDC, BSC, damp-phlegm constitution (DPC), qi deficiency constitution (QDC). YDC occupied the first place [22.4% (34/152)]. The former 4 recurrent rates occurred in AS patients of BSC, QDC, DPC, damp-heat constitution (DHC). BSC occupied the first place [3.2% (2/250)]. Compared with non-recurrent cerebral infarction patients and AS patients, bb gene occurred most often, but aa gene and ab gene occurred obviously lesser in non-recurrent cerebral infarction patients and AR patients (χ2 = 20.171, χ2 = 55.139, P < 0.01). AR and bb gene were positively correlated with recurrent cerebral infarction (OR = 18.423, P = 0.000; OR = 1.304, P = 0.028). Body constitutions interacted with AS (OR = 0.707, P = 0.000).</p><p><b>CONCLUSIONS</b>Recurrent cerebral infarction was closely related to AR and constitutional types. The recurrence rate was higher in AR patients of YDC. GP I b HPA-3 bb genotype might be a risk factor for AR and recurrent cerebral infarction.</p>