Ginkgo biloba extract inhibits the expressions of cell adhesion molecules and nuclear factor-kappa B in arterial endothelial cells

Hai PENG; Ying LI; Xiangjun LIU

ABSTRACT

BACKGROUND:

Previous studies have indicated that hyperhomocysteinemia can induce atherosclerosis by enhancing oxidative stress, whereas Ginkgo biloba extract (GbE) can scavenge oxygen-derived free radicals.

OBJECTIVE:

To observe the role of reactive oxygen species (ROS) and nuclear factor-kappa B (NF-κB) in the expression of cell adhesion molecules (CAMs) induced by homocysteine (Hcy), and investigate the effect of GbE.

DESIGN:

A randomized controlled animal trial.

SETTING:

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.MATERrALS Twenty-four healthy male rabbits of 6 months old. Dl-methionine (Sigma Chemical, Co.,Ltd.); GbE (Guizhou Yibai Pharmaceutical Company; powder).

METHODS:

The experiment was accomplished in the Laboratory of Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2003 to April 2004. ① After adaptive feeding for 2 weeks, the rabbits were randomly divided into three groups Model group (n =12) The rabbits were treated with subcutaneous injection of dl-methionine (80 mg/kg per day); GbE group (n =8) The rabbits were administrated with GbE (mixed with feed, 50 m/kg per day) at 1 hour before the subcutaneous injection of dl-methionine; Control group (n=4) The rabbits were injected with equivalent sodium chloride. They were administrated for 7 weeks continuously. ②Histological changes were observed under light and electron microscopes ROS level was determined with colorimetries (721 visible spectrophotometer); The expressions of CAMs and NF-κB in endothelial cells were detected with immunohistochemical methods; The concentration of plasma Hcy was measured with high-performance liquid chromatography.MAIN OUTCOME

MEASURES:

Histological changes, ROS level and expressions of CAMs and NF-κB in endothelial cells.

RESULTS:

All the 24 rabbits were involved in the analysis of results. ① ROS level After administration, the ROS level in the model group was obviously increased (2.92±0.20,2.48±0.26, P ＜ 0.05), whereas those in the GbE group and control group (2.41±0.23, 2.43±0.20) had no obvious differences as compared with those before administration (2.31±0.27,2.47±0.32, P ＞ 0.05). ② Histological changes Aortas of rabbits in the model group presented initial changes of atherosclerosis, including shedding or necrosis of endothelial cells and nuclear pyknosis or standing in a clutter of smooth muscle cells. There were scarcely any changes in the GbE group and control group. ③ Expressions of CAMs and NF-κB in endothelial cells After treatments, the expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and NF-κB in the model group were obviously higher than those in the control group (P ＜0.05), and there were no significant differences between the GbE group and control group (P ＞ 0.05). ④ Concentration of plasma Hcy After 7 weeks, the concentration of plasma Hcy was higher in the model group and GbE group than in the control group [(25.01±6.80), (26.71±2.36), (16.85± 1.64) μmol/L, P ＜ 0.05].

CONCLUSION:

Hcy-induced oxidative stress plays an important role in NF-κB activation. GbE might suppress the activation of NF-κB and expression of CAMs by reducing ROS.