Exploring the molecular mechanism of Tripterygium Wilfordii Hook F in treating systemic lupus erythematosus via network pharmacology and molecular docking.

Background: Tripterygium wilfordii Hook F (TwHF) is a prominent Chinese herbal formula. It exhibits significant clinical efficacy in treating systemic lupus erythematosus (SLE), though its mechanisms remain unclear. Our study employs network pharmacology and molecular docking to explore active compounds of TwHF and their associated targets for SLE treatment.

Methods: Primary active compounds of TwHF and their targets were sourced from the TCMSP, SwissTargetPrediction, and UniProt databases. SLE-relevant target proteins were identified from the OMIM and GeneCards databases. Enrichment analyses were conducted to reveal results of common TwHF-SLE targets. STRING and Cytoscape software were used to systematically analyze and construct protein-protein interaction (PPI) networks, compound-target-pathway, and target-organ networks. Molecular docking was utilized to confirm the binding of key targets to the top active compounds.

Results: A total of 14 active compounds and 300 overlapping targets between TwHF and SLE were identified. PPI network analysis revealed 29 core targets. Several pathways were found to contribute to the potential therapeutic effects of TwHF in SLE, including PI3K-Akt signaling pathway, Th17 cell differentiation, chemokine signaling, and T cell receptor signaling. Disease Ontology (DO) analysis highlighted the involvement of TwHF in genes associated with myocardial infarction (MI), atherosclerosis (AS), breast carcinoma, and ischemia. Molecular docking results demonstrated strong binding affinities, with 37 signal molecule-receptor interactions in SLE and 97 interactions in SLE-related MI and AS showing binding energies lower than -7 kJ/mol.

Conclusions: This research effectively anticipates the potent constituents, probable targets, and pathways implicated in treating SLE with TwHF, specifically addressing complications such as MI and AS. Comprehending the precise molecular mechanism targeting SLE of TwHF and its efficacious bioactive components furnishes a theoretical groundwork for enhancing its clinical utilization. Key Points •SLE is characterized by aberrant immune activation and persistent inflammation. •TwHF exerts immunomodulatory and anti-inflammatory effects. •TwHF exhibits prospects in the treatment of SLE with unknown molecular mechanisms. •Network pharmacology and molecular docking reveal promise in the mechanism of TwHF.