Hydroxysafflor yellow A attenuates oxLDL-induced tissue factor in monocytes and reduces thrombosis in dyslipidemic rats

Safflower, a traditional Chinese herbal medicine, has been approved in China for the treatment of patients with thrombotic cardiovascular events.However, the exact mechanisms by which this herbal medicine protects against these diseases remain elusive.Hydroxysafflor yellow A (HSYA) is a major component of Safflower.Tissue factor (TF) plays a pivotal role in thrombosis formation and propagation.In this study, oxidized low-density lipoprotein (oxLDL)-challenged monocytic THP-1 cells were pretreated with HSYA alone or in combination with 2-chloro-5-nitro-N-phenylbenzamide (GW9662), a peroxisome proliferator-activated receptor- (PPAR) antagonist.Then, TF, PPAR and phospho-p38 MAPK levels were assessed by real-time PCR and Western blot.In addition, HSYA or HSYA plus GW9662 were administered to rats fed a high-fat diet (HFD) for 4 weeks, and TF, PPAR and phospho-p38 MAPK levels in peripheral blood mononuclear cells (PBMCs) were evaluated, as well as plasma lipids and thrombus formation were measured.The results showed that HSYA pretreatment reversed oxLDL-induced TF expression and p38 MAPK phosphorylation, and promoted PPAR expression and activity in THP-1 cells.Plasma lipid and oxLDL amounts were elevated in HFD-fed rats.Although failing to change lipid profile, HSYA reduced TF expression, p38 MAPK phosphorylation, thrombus formation, and promoted PPAR expression and activity in dyslipidemic rats.GW9662 abolished the effects of HSYA in monocytes.The results indicated that HSYA attenuates oxLDL-induced TF expression in monocytes, and reduces arterial and venous thrombus formation in dyslipidemic rats.These effects of HSYA are likely dependent on PPAR upregulation and subsequent p38 MAPK inhibition.