Potential Mechanisms of White Peony against Primary Sjögren's Syndrome Based on Network Pharmacology and Molecular...

Multiple system and organ damage occurs with the continuous progression of primary Sjögren's syndrome (pSS), and the lack of specific drugs against this disease is a huge challenge. White peony (WP), a widely used traditional Chinese herb, has been confirmed to have a therapeutic value in pSS. However, the specific mechanisms of WP in the treatment of pSS are unknown.

The active ingredients and their targets in WP were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and disease-related targets were collected from GeneCards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). The overlapping targets were acquired by taking the intersection. A protein-protein interaction (PPI) network was structured using the STRING database. A disease-drug-ingredient-target (D-D-I-T) network was built using Cytoscape software. By filtering twice, core targets were acquired. Gene Ontology (GO) and Kyoto Encyclopedia Gene and Genome (KEGG) pathway enrichment analysis were accompanied by R packages. Finally, molecular docking was used to verify the abovementioned results.

In total, we screened 88 WP-related targets, 1480 pSS-related targets, and 32 overlapping targets. D-D-I-T Network analysis displayed six main active ingredients of WP, which played a significant therapeutic role in pSS. Further topological analysis selected seven core target genes, including IL-6, TNF, PPARγ, AKT1, CASP3, NOS3, and JUN. GO and KEGG analysis were used to elucidate pharmacological mechanisms, mainly acting in the AGE-RAGE signaling pathway. Molecular docking proved that paeoniflorin bound well with core targets.

Our study revealed that IL-6, TNF, AKT1, CASP3, NOS3, and JUN may be pathogenic target genes, and PPARγ may be a protective target gene. The main active ingredients of WP mainly played a therapeutic role via the AGE-RAGE signaling pathway. These findings provide a fundamental and theoretical basis for the clinical application of WP.