Utilizing network pharmacology to explore the scientific connotation of processing technology about Rehmanniae Radix Praeparata

Objective: Network pharmacology method was adopted in this study to establish differential component-target network of Rehmanniae Radix Praeparata before and after "steamed for nine times and dried for nine times", explore the mechanism of the difference of pharmacological effect, reveal the scientific connotation of the processing method. Methods: The different components of Rehmanniae Radix Praeparata before and after "steamed for nine times and dried for nine times" were detected by consulting and screening the literature. PubChem database was used to convert all compounds to standard Canonical SMILES format. SMILES format files were imported into Swiss Target Prediction platform to predict potential targets for different components (possibility > 0). Targets with the highest confidence (score 0.900) were screened from STRING database to construct protein-protein interaction network. GO enrichment and KEGG pathway enrichment were analyzed by ClusterProfiler package in R language. Results: A total of 12 different components (catalpol, ajugol, Rehmannioside A, Acteoside, 5-hydroxymethy lfurfural, Isoacteoside, stachyose, D(+)-Sucrose, raffinose, fructose, glucose and Manninotriose) were screened through literature review, and 101 potential targets were predicted. The GO analysis contained a total of 113 enrichment results. A total of 15 pathways were enriched by KEGG. Conclusion: The changes of glucoses (stachyose, raffinose and Manninotriose) in Rehmanniae Radix Praeparata may be the main reason for the enhancement of the tonifying effect (such as Notch signaling pathway, neuroactive ligand receptor interaction, etc.) after "steamed for nine times and dried for nine times". The changes of iridoid terpenoids (catalpol, ajugol, rehmannin A, etc.) and carbohydrates (D(+)-Sucrose, raffinose, glucose, Manninotriose, etc.) may be the reasons for the loss of the hypoglycemic effect of Rehmanniae Radix Praeparata after "steamed for nine times and dried for nine times". The change of pharmacological action is the result from chemical composition interaction of Rehmanniae Radix Praeparata.