Isorhyncophylline Targets <scp>PP2AC</scp> to Modulate <scp>YAP</scp> to Inhibit Endothelial Cell Inflammation

Atherosclerosis (AS) constitutes the pathological basis of multiple cardiovascular diseases, predisposing to severe clinical complications. Isorhynchophylline (IRN), a principal bioactive alkaloid derived from Uncaria rhynchophylla, exhibits anti-inflammatory properties, yet its therapeutic potential and molecular mechanisms in AS remain unexplored. Scratch wound healing and Transwell migration assays were conducted to evaluate the effects of monomer compounds on cellular migratory and invasive capabilities. The changes in mRNA and protein expression levels of inflammation genes were determined using RT-PCR and western blot analyses, respectively. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRN and PP2AC. Our findings demonstrate that IRN treatment effectively ameliorates atherosclerotic plaque progression and mitigates endothelial inflammation. The underlying mechanism involves the binding of IRN to PP2AC and the subsequent regulation of YAP activity. This study underscores the therapeutic potential of IRN in alleviating inflammation and its promise as a treatment for AS.