Puerarin inhibits expression of tissue factor induced by oxidative low-density lipoprotein through activating the PI3K/Akt/eNOS pathway and inhibiting activation of ERK1/2 and NF-κB

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Aims:The present study aimed to investigate whether puerarin regulated tissue factor (TF) expression induced by oxidative low-density lipoprotein (ox-LDL), an independent risk factor for atherosclerosis, and its mechanisms.Main methods:TF expression at the mRNA level was determined by reverse transcription-quantitative polymerase chain reaction, and its expression at the protein level, as well as other target proteins, was assessed by western blotting. Nitric oxide (NO) production was measured by a nitrate reduction method.Key findings:Results demonstrated that treatment with ox-LDL (50 mg/l) for 24 h significantly increased (P < 0.01) TF expression at the mRNA and protein levels in human umbilical vein endothelial cells (HUVECs). Such an ox-LDL exposure also triggered the dephosphorylation of Akt, resulting in a reduction of NO production and activated the extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)-κB signaling pathways. Pre-treatment with puerarin (50–200 μM) for 1 h significantly attenuated the ox-LDL-induced TF expression, augmented the phosphorylation of Akt, with a resultant increase of the NO production, and inhibited the activation of ERK1/2 and NF-κB (P < 0.01). However, this beneficial effect of puerarin (100 μM) was abolished by LY294002 (10 μM), an inhibitor of phosphoinositide 3-kinase (PI3K), or NG-nitro-L-arginine methyl ester (100 μM), an inhibitor of NO synthase.Significance:These results suggested that puerarin suppressed TF expression in HUVECs through activating the PI3K/Akt/endothelial nitric oxide synthase signaling pathway and inhibiting the activation of ERK1/2 and NF-κB. These findings suggested that puerarin possessed certain anticoagulation and may be a potential novel therapeutic drug for thrombosis in coronary artery disease.

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