大蒜具有抗氧化抗腫瘤抗血小板凝集以及血脂等功效﹐一直受到許多學者廣泛研究。本研究以初代肝細胞模式探討大蒜有機成分(DASDADSDATS)對於調控解毒酵素
Uptake of oxidized LDL (ox-LDL) by vascular endothelial cells is a critical step in the initiation and development of
atherosclerosis. Adhesion molecules are upregulated by ox-LDL and numerous inflammatory cytokines and play a pivotal
role in atherogenesis. In this study, we examined whether diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide
(DATS), 3 major organosulfur compounds of garlic oil, reduce adhesion molecule expression induced by ox-LDL and, if so,
through what mechanism. Human umbilical vein endothelial cells were preincubated with 1 mmol/L DAS, 200 mmol/L
DADS, or 100 mmol/L DATS for 16 h and then with 40 mg/L ox-LDL for an additional 24 h. ox-LDL induction of cellular and
cell surface expression of E-selectin and vascular cell adhesion molecule (VCAM)-1 was suppressed by garlic allyl sulfides
in the order DATS . DADS . DAS. The adhesion of HL-60 cells to endothelial cells was inhibited 27 and 33% and the
production of cellular peroxides was inhibited 43 and 50% by DADS and DATS, respectively (P , 0.05). ox-LDL alone
dephosphorylated protein kinase B (PKB) and cAMP responsive element binding protein (CREB); such deactivation
was reversed by DADS and DATS. Electrophoretic mobility shift assay showed that the activation of CREB binding to
DNA was consistent with changes in CREB phosphorylation. The protein kinase A (PKA) inhibitor H89 reversed
the suppression of VCAM-1 by DADS and DATS, but the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin had
no effect. In contrast, wortmannin abolished DADS- and DATS-induced suppression of ox-LDL–induced E-selectin
expression. These results suggest that the suppression of ox-LDL–induced E-selectin and VCAM-1 expression by DADS
and DATS and, thus,monocyte adhesion to endothelial cells is likely dependent on the PI3K/PKB or PKA/CREB signaling
pathway in an adhesion molecule-specific manner. To our knowledge, this is the first report that garlic modulates ox-
LDL–mediated leukocyte adhesion to human endothelial cells through the PKB and PKA pathways. J. Nutr. 138: 996–1003,
2008.
