Abstract
Objective
Forsythia suspensa has long been utilized in traditional Chinese medicine (TCM) for the treatment of
IgA nephropathy (IgAN), the most prevalent form of primary glomerular disease. However,
the precise mechanisms remain inadequately understood. This study seeks to elucidate
the underlying mechanisms of Forsythia suspensa extract (FSE) in the treatment of IgAN by employing an integrated approach that combines
network pharmacology with in vivo experimental validation.
Methods
The chemical components of FSE were identified using high-performance liquid chromatography-mass
spectrometry (HPLC–MS/MS). Additional chemical components and targets were determined
through the Traditional Chinese Medicine Systems Pharmacology database. Potential
therapeutic targets for IgAN were sourced from GeneCards and the Comparative Toxicogenomics
Database. Subsequently, the enrichment analyses were conducted to evaluate the biological
functions and pathways associated with the core targets. Finally, a mouse model of
IgAN was developed to validate the findings of the network pharmacology analysis.
Results
Through network analysis and HPLC–MS/MS, 31 chemical components of FSE were identified.
A total of 99 common targets were discovered between FSE and IgAN. The enrichment
analyses suggested that FSE may mitigate IgAN primarily by inhibiting the TLR and
NF-κB signaling pathways. In vivo experiments demonstrated that FSE reduced inflammation
and preserved renal function in mice with IgAN through the Toll-like receptor 9 (TLR9)/NF-κB
pathway.
Conclusion
The integration of network pharmacology and animal experiments suggests that FSE alleviates
renal inflammation and damage in IgAN through the TLR9/NF-κB signaling pathway.
Keywords
Forsythia suspensa extract - IgA nephropathy - TLR9/NF-κB signaling pathway - network pharmacology -
experimental validation
