Background: Immunoglobulin A nephropathy (IgAN) is a common primary glomerular disease characterized by the deposition of IgA or its complexes in the renal mesangium. Despite the availability of medications for treating IgAN, finding more effective treatment methods remains a critical need. Angelicin has shown potential therapeutic effects on IgAN due to its unique anti-inflammatory and antioxidative properties.

Methods: Immunofluorescence, Western blotting and enzyme-linked immunosorbent assay (ELISA) approaches were employed to investigate the therapeutic efficacy of angelicin in a rat model with IgAN. The hTFtarget database was used to predict estrogen receptor 1 (ESR1) targets, while analysis of the GSE35489 dataset through the Gene Expression Omnibus (GEO) database was conducted to identify the role of Fos proto-oncogene (FOS) in fibrosis regulation.

Results: Treatment with angelicin significantly reduced IgA deposition, improved kidney tissue structure, decreased the rate of cell apoptosis, alleviated renal fibrosis (p < 0.01), and suppressed the expression of inflammation markers interleukin (IL)-1β, IL-6, and IL-18 (p < 0.001). Moreover, the expression of ESR1, FOS, phosphorylated c-Jun (p-c-Jun) and phosphorylated mitogen-activated protein kinase (p-MAPK) was downregulated by angelicin in a dose-dependent manner (p < 0.05).

Conclusions: Angelicin can effectively mitigate renal fibrosis and inflammation in IgAN via the ESR1-FOS signaling pathway, highlighting its potential as a viable therapeutic agent for IgAN. This discovery provides new molecular targets and a theoretical basis for the pharmacological treatment of IgAN.