Nobiletin Inhibits PDGF-BB-Induced Vascular Smooth Muscle Cell Proliferation and Migration and Attenuates Neointimal Hyperplasia in a Rat Carotid Artery Injury Model

Preclinical Research The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti‐inflammatory and anti‐oxidative activities. The present study evalutaed whether nobiletin could inhibit platelet‐derived growth factor (PDGF)‐BB‐ stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with nobiletin before being stimulated with 20 ng/ml PDGF‐BB, and rats were subjected to carotid artery injury. Nobiletin inhibited PDGF‐BB‐induced VSMC proliferation and migration, attenuated reactive oxygen species (ROS) production and reduced phosphorylation of ERK1/2 and the expression of nuclear NF‐κB p65 in PDGF‐BB‐stimulated VSMCs. Nobiletin decreased the intima area and the ratio of neointima to media in balloon‐injured rat carotid arteries. Serum levels of TNF‐α and IL‐6 in nobiletin‐treated rats were decreased. These results indicated that nobiletin could be a potential protective agent for the prevention and treatment of restenosis after angioplasty.