Chrysanthemum morifolium Ramat. reduces the oxidized LDL-induced expression of intercellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells.
BACKGROUND
The flower of Chrysanthemum morifolium Ramat. (CM) with antioxidant, cardiovascular protective and anti-inflammatory functions, has been widely used in China for hundreds of years as a healthy beverage and medicine.


OBJECTIVE
The purpose of the present study is to investigate the effects of HCM (a hot water extract of the flower of Chrysanthemum morifolium Ramat. [CM]), ECM (an ethanol extract of CM), and the abundant flavonoids apigenin and luteolin in CM on the oxidized LDL (oxLDL)-induced expression of ICAM-1 and E-selectin in human umbilical vein endothelial cells (HUVECs). The possible mechanism of these effects was also determined.


METHODS
MTT assay was for cell viability. Western blot was used for ICAM-1 and E-selection protein expression, and for activation of protein kinase B (PKB) and cAMP responsive element binding protein (CREB) proteins. Fluorescence flow cytometry was for ICAM-1 and E-selectin expression on cell surface. DCF-DA flow cytometric assay was used for reactive oxygen species (ROS) production.


RESULTS
HCM, ECM, apigenin, and luteolin dose-dependently inhibited ICAM-1 and E-selectin expression and adhesion of HL-60 by oxLDL. HCM, ECM, apigenin, and luteolin reversed the inhibition of phosphorylation of Akt and CREB by oxLDL; however, this reversion was abolished by wortmannin. In addition, wortmannin abrogated the inhibitory effects of CM extracts, apigenin and luteolin on adhesion molecule expression. The ROS scavenging capability of HCM, ECM, apigenin, and luteolin proceeded dose-dependently in the presence of oxLDL.


CONCLUSIONS
CM is a plant with cardiovascular-protective potential and the inhibitory effects of CM on ICAM-1 and E-selectin expression are, at least partially, attributed to its antioxidant activity and modulation of the PI3K/Akt signaling pathway.
Lii
Chong-Kuei
CK
Department of Nutrition, China Medical University, No.91 Hsueh-Shih Road, Taichung 404, Taiwan.
Lei
Yen-Ping
YP
Yao
Hsien-Tsung
HT
Hsieh
Yun-Sheng
YS
Tsai
Chia-Wen
CW
Liu
Kai-Li
KL
Chen
Haw-Wen
HW
D000730:Androstadienes / Q000494:pharmacology; D002478:Cells, Cultured; D031202:Chrysanthemum / Q000737:chemistry*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D017362:Cyclic AMP Response Element-Binding Protein; D019040:E-Selectin; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin