Jianpi Huazhuo Formula Suppresses Choroidal Neovascularization by Modulating the AKT1/MAPK3/IL6 Axis

This study elucidates the therapeutic mechanisms of Jianpi Huazhuo formula (JHF) in suppressing laser-induced choroidal neovascularization (CNV) through the modulation of the AKT1/MAPK3/IL6 signaling pathway. Utilizing a murine CNV model, JHF administration markedly attenuated vascular leakage, as evidenced by fluorescein angiography, optical coherence tomography, and fundus imaging. Integrated network pharmacology pinpointed AKT1, MAPK3, and IL6 as pivotal targets, with functional enrichment analyses highlighting their roles in key processes such as reactive oxygen species response and inflammatory regulation, particularly within the PI3K-Akt and IL-17 pathways. Molecular docking validated robust interactions between JHF-derived compounds (e.g., luteolin and quercetin) and these targets, exhibiting binding energies ranging from -4.0 to -7.41 kcal/mol. Subsequent molecular assays confirmed that JHF significantly reduced AKT1, MAPK3, and IL6 expression at transcriptional and translational levels in RPE-choroid tissues. Time-dependent expression profiling further revealed sustained suppression of these targets throughout CNV progression, and in vitro validation in an oxidative stress-induced ARPE-19 cell model confirmed the direct regulatory effect of JHF on this signaling axis. These findings demonstrate that JHF exerts its antiangiogenic effects via a multitarget network centered on the AKT1/MAPK3/IL6 axis. The study innovatively delineates JHF's polypharmacological mode of action, offering novel insights for leveraging traditional Chinese medicine in managing neovascular ocular diseases.