Extract from the leaf of nucifera reduced the development of atherosclerosis via inhibition of vascular smooth muscle cell proliferation and migration.
Nelumbo 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.
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, South District, Taichung City 402, Taiwan, ROC.
Hsieh-Hsun
HH
Ho
Li-Sung
LS
Hsu
Kuei-Chuan
KC
Chan
Hsiang-Mei
HM
Chen
Cheng-Hsun
CH
Wu
Chau-Jong
CJ
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D028023:Arecaceae / Q000737:chemistry*; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D007211:Indoles; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D004396:Coloring Agents; D005456:Fluorescent Dyes; D007211:Indoles; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C007293:DAPI; C022616:thiazolyl blue