Abstract:
OBJECTIVE To identify the chemical composition of Qingzi mixture, and to explore and verify its mechanism in treating Henoch Schönlein purpura (HSP) through network pharmacology.
METHODS UPLC-Q-TOF-MSE technology was combined with UNIFI analysis software to quickly identify the components in Qingzi mixture. Seaware and SwissTargetPrediction database were used to predict the targets of the identified compounds. GeneCards and Disgenet database were used to screen the disease targets of HSP. Target protein-protein interactions were analyzed using the STRING database, GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using the Metascape database. Molecular docking analysis was conducted by SYBYL-X 1.2 software to verify the binding activity between active ingredients and targets. Western blotting was used to detect the effect of Qingzi mixture on key pathways in HSP model rats induced by heat syndrome combined with ovalbumin.
RESULTS A total of 150 compounds were identified in Qingzi mixture. Sixty-two intersection of component targets and disease targets were screened. The results of GO function annotation and KEGG signaling pathway analysis showed that PI3K/Akt, MAPK, HIF1A pathway were the key pathways, among which STAT3, EGFR, CXCL8 were the key targets. Molecular docking showed that the 5 active ingredients of Qingzi mixture had robust binding activities with the core targets. Animal experiments showed that Qingzi mixture significantly improved skin damage in HSP rats, reduced the serum levels of abnormal IgA1 and inflammatory factors, and inhibited the protein expression of the PI3K/Akt pathway in skin tissues.
CONCLUSION Quercetin, ferulic acid, homovanillic acid, isoferulic acid, protocatechuic acid might be the main substances for treating HSP, which may play a role in regulating PI3K/Akt signaling pathway.