Baicalin prevents experimental autoimmune uveitis by promoting macrophage polarization balance through inhibiting the HIF-1α signaling pathway.

Uveitis is a series of autoimmune eye diseases that can seriously damage people's eyesight. This study aimed to explore the therapeutic potential of baicalin in treating uveitis, focusing on its modulation of HIF-1α expression and macrophage polarization. Using an experimental autoimmune uveitis (EAU) rat model, we found that baicalin can significantly reduce fundus inflammation in EAU rats. Spectral-domain optical coherence tomography revealed retinal vascular thickening in the EAU group, indicating severe inflammation, which baicalin effectively mitigated. Histopathological analysis confirmed reduced inflammatory cell infiltration in the ciliary body and retina. Co-immunoprecipitation analyses showed that HIF-1αinteracted with macrophage-related factors, including iNOS and ARG1. Baicalin downregulated HIF-1α and iNOS while upregulating ARG1, balancing pro-inflammatory M1 and anti-inflammatory M2 macrophage polarization. Flow cytometry demonstrated a reversal of M1/M2 macrophage ratios in the EAU group after baicalin treatment. Additionally, baicalin improved macrophage mitochondrial membrane potential and decreased reactive oxygen species (ROS) levels, shifting macrophage polarization toward an anti-inflammatory state. These findings confirm that baicalin can effectively reduce inflammation and restore immune balance by orchestrating the HIF-1α pathway, establishing a promising therapeutic candidate for uveitis and highlighting the potential of natural bioactive compounds in treating and preventing inflammatory diseases through targeted immune modulation.