Target Prediction Of Sijunzi Decoction Based On Systems Pharmacology And Experimental Study

Objective: The study aims to provide target and experimental data for a comprehensive study on the mechanism of Sijunzi decoction.Based on formulaology, the active ingredients and targets of Sijunzi decoction were predicted by systems pharmacology; the effects of Sijunzi decoction on the gene expression of predicted targets were detected by an animal model of spleen qi deficiency syndrome.Methods: The molecular databases of Sijunzi decoction were established by integrating public resource databases. The active ingredients of Sijunzi decoction were detected by prediction of oral bioavailability and evaluation of drug-likeness. The targets of active ingredients were predicted by chemical genomics technology, computer simulation models and public network resources query. Molecule-Target-Disease(C-T-D) network was constructed.40 SD rats, three months old, in a SPF grade were used in the animal model of spleen qi deficiency syndrome, which was established by the compound factors of overstrain and improper diet. The modeled rats were divided into model group, high dose of Sijunzi decoction group and low dose of Sijunzi decoction group. The model and control groups were given distilled water, while the high dose and low dose of Sijunzi decoction groups were given the respective medicines 1ml/l00 g by gavage. After the administration, the gastric tissues and serum were extracted to determine the relevant indicators and pharmacological effects of Sijunzi decoction on rats with spleen qi deficiency syndrome and the gene expression of some targets.Results: 52 active ingredients were screened; 143 targets were obtained; 168 nodes composed of 25 candidate molecules and 143 targets, a drug-target network chart of 507 sides and a target-disease network chart from 64 targets to 56 diseases were built.The animal modeling was evaluated by fuzzy maths. The successfully modeled rats were administrated Sijunzi decoction and the relevant indicators were detected. The results showed that Sijunzi decoction has obvious effects on the repair of gastric mucosal injury of spleen qi deficiency rat model, has significant moderating effect on changes of serum cytokines such as IL-2, gastrin, SOD and other antioxidant indexes and can regulate the expression of PPARG, MAPK1, TP53 gene.Conclusion: In this study, the active ingredients and targets of Sijunzi decoction were screened and predicted by systems pharmacology, Molecule-Target-Disease network diagram was constructed and the interrelationship among drug, target and disease was systematically analyzed, which provided a precise target basis for further study on the mechanism of the Sijunzi decoction. The experimental study proved that Sijunzi decoction was effective on the animal model of spleen qi deficiency syndrome, and tested the effects of Sijunzi decoction on mRNA expression by fluorescence quantitative PCR method. The results showed that Sijunzi decoction can adjust mRNA expression of forecast targets PPARG, MAPK1, TP53.