Department of Pharmacology, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea.
Korean J Physiol Pharmacol. 2013 Apr;17(2):133-7. doi: 10.4196/kjpp.2013.17.2.133. Epub 2013 Apr 10.
Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-κB) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaBα (IκBα) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of IκBα expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.
血管细胞黏附分子 1（VCAM-1）、细胞间黏附分子 1（ICAM-1）、P-选择素和 E-选择素在动脉粥样硬化的发生中起着关键作用。人参皂苷是一类甾体糖苷，在人参根中含量丰富，在韩国一直被用于预防疾病。在这项研究中，我们研究了人参皂苷 Rg2 可能通过何种机制抑制脂多糖（LPS）刺激的人脐静脉内皮细胞（HUVEC）中 VCAM-1 和 ICAM-1 的表达。LPS 增加了 VCAM-1 和 ICAM-1 的表达。人参皂苷 Rg2 阻止了 LPS 介导的 VCAM-1 和 ICAM-1 表达的增加。另一方面，核因子 kappa B（NF-κB）抑制剂 JSH 降低了 LPS 刺激的 VCAM-1 和 ICAM-1 的表达。p38 丝裂原活化蛋白激酶（p38 MAPK）抑制剂 SB202190 和磷脂酰肌醇 3-激酶（PI3-kinase）抑制剂wortmannin 降低了 LPS 介导的 VCAM-1 但不降低 ICAM-1 的表达。丝裂原活化蛋白激酶激酶/细胞外信号调节激酶（MEK/ERK）抑制剂 PD98059 不影响 LPS 刺激的 VCAM-1 和 ICAM-1 的表达。c-Jun N-末端激酶（JNK）抑制剂 SP600125 降低了 LPS 介导的 ICAM-1 但不降低 VCAM-1 的表达。LPS 以时间依赖的方式在 1 小时内降低 IkappaBα（IκBα）的表达。人参皂苷 Rg2 阻止了 LPS 刺激的 IκBα 表达的减少。此外，人参皂苷 Rg2 以浓度依赖的方式降低了 LPS 介导的 THP-1 单核细胞与 HUVEC 的黏附。这些数据提供了一种新的机制，即人参皂苷 Rg2 可能通过抑制白细胞黏附到血管壁来提供直接的血管益处，从而提供对血管炎症性疾病的保护。
