Mechanisms of Forsythia suspensa Extract Against IgA Nephropathy through Network Pharmacology and Experimental Validation

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

CRediT Authorship Contribution Statement

Yali Xi: Investigation, methodology, data curation, writing–original draft, and writing–review and editing. Yawen Bai: Conceptualization, funding acquisition, project administration, and supervision.

Publikationsverlauf

Eingereicht: 21. April 2025

Angenommen: 27. Juli 2025

Artikel online veröffentlicht:
30. September 2025

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