LI-SUNG HSUKUEI-CHUAN CHAN2026-10-162026-10-162010-01-01Pure ID: 15282566Pure UUID: bc3eb7e6-3f3e-4928-949d-8fef68c9c58c10.1016/j.fct.2009.09.033https://www.scopus.com/pages/publications/72149093504https://scholars.csmu.edu.tw/handle/123456789/27816Nelumbo nucifera GAERTN, a perennial aquatic plant, has been used as a medicinal herb in China and India. We have previously reported that consumption of nucifera leaf extract (NLE) reduced the development of atherosclerosis in cholesterol-fed rabbits; however, the molecular mechanisms involved were unclear. Atherosclerotic plaque is generated partly by proliferation and migration of vascular smooth muscle cells (VSMC). Herein, we demonstrated that VSMC treated with NLE-triggered apoptosis and affected the JNK and p38 Mitogen-Activated Protein Kinase (MAPK) pathways. Pre-treating VSMC with inhibitors of JNK, p38, and p53 reduced NLE-induced apoptosis. Non-cytotoxic doses of NLE also abolished secretion of MMP-2/9 and inhibited cell migration via restraining the FAK/PI 3-kinase/small G protein pathway. Histopathological examination showed that 1.0% of NLE reduced neointima formation conspicuously and inhibited smooth muscle cell proliferation and MMP-2 secretion in the blood vessel of rabbits fed with a high cholesterol diet (HCD). We also verified that the extract's total phenolic acids and the total flavonoids were approximately about 70%. In conclusion, our results shed light on the molecular mechanisms whereby the polyphenol-rich water extract of nucifera leaves could inhibit both proliferation and migration of VSMC, and it might serve as a potential anti-atherogenic agent.10enjournal article