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Abstract Title:

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.

Abstract Source:

Life Sci. 2017 Dec 15 ;191:115-121. Epub 2017 Oct 14. PMID: 29037842

Abstract Author(s):

Hua-Fei Deng, Xiao-Li Wang, Hui Sun, Xian-Zhong Xiao

Article Affiliation:

Hua-Fei Deng

Abstract:

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 (50mg/l) for 24h 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 (50-200μM) for 1h 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 (100μM) was abolished by LY294002 (10μM), an inhibitor of phosphoinositide 3-kinase (PI3K), or NG-nitro-L-arginine methyl ester (100μM), 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.

Study Type : Human In Vitro

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Sayer Ji
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