FPG

Excessive reactive oxygen species (ROS) production plays a crucial role in the pathogenesis of diabetes and its associated vascular complications. This study investigates whether IH636 grape seed proanthocyanidins (GSPs) can mitigate high glucose (HG)-induced hyperproliferation of vascular smooth muscle cells (VSMCs) and elucidates the underlying molecular mechanisms. The findings demonstrate that GSPs significantly inhibit HG-induced VSMC proliferation, ROS generation, and NADPH oxidase activity. Mechanistically, HG treatment promotes phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits, leading to NADPH oxidase activation, a process effectively disrupted by GSPs. Furthermore, GSPs suppress key HG-induced signaling pathways, including ERK1/2, JNK1/2, PI3K/AKT/GSK3β, and NF-κB, which are dependent on ROS generation and Rac1 activation. Notably, PI3K subunit p110α activation is identified as a critical mediator of HG-induced VSMC proliferation and ROS overproduction. Collectively, these findings suggest that GSPs exert vascular protective effects by inhibiting PI3K-dependent pathways, highlighting their potential therapeutic role in preventing intimal hyperplasia and restenosis in diabetic vascular disease.