Inhibitory effects of luteolin‑4'‑O‑β‑D‑glucopyranoside on P2Y12 and thromboxane A2 receptor‑mediated amplification of platelet activation in vitro

Xu,Huanjun; Lu,Hong; Zhu,Xiaocui; Wang,Wei; Zhang,Zhoumiao; Fu,Huizheng; Ma,Shuangcheng; Luo,Yuehua; Fu,Jianjiang

doi:10.3892/ijmm.2018.3634

Inhibitory effects of luteolin‑4'‑O‑β‑D‑glucopyranoside on P2Y12 and thromboxane A2 receptor‑mediated amplification of platelet activation in vitro

Authors:
- Huanjun Xu
- Hong Lu
- Xiaocui Zhu
- Wei Wang
- Zhoumiao Zhang
- Huizheng Fu
- Shuangcheng Ma
- Yuehua Luo
- Jianjiang Fu
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Affiliations: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China, Network and Educational Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China, Jiangxi Provincial Institute for Drug Control, Nanchang, Jiangxi 330029, P.R. China, National Institutes for Food and Drug Control, Beijing 100050, P.R. China
Published online on: April 19, 2018 https://doi.org/10.3892/ijmm.2018.3634
Pages: 615-624

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Abstract

Platelet activation and subsequent accumulation at sites of vascular injury are central to thrombus formation, which is considered to be a trigger of several cardiovascular diseases. Callicarpa nudiflora (C. nudiflora) Hook is a traditional Chinese medicinal herb for promoting blood circulation by removing blood stasis. In our previous study, several compounds extracted from this herb, including luteolin‑4'‑O‑β‑D‑glucopyranoside (LGP), were revealed to exert inhibitory effects on adenosine diphosphate (ADP)‑induced platelet aggregation. The aim of present study was to confirm these antiplatelet effects and elucidate the potential mechanisms. Using a platelet‑aggregation assay, it was revealed that LGP significantly inhibited platelet aggregation induced by ADP, U46619 and arachidonic acid. It was also found that LGP exhibited marked inhibitory effects on the activation of αIIbβ3 integrin, the secretion of serotonin from granules, and the synthesis of thromboxane A2. In addition, the results showed that LGP suppressed Ras homolog family member A and phosphoinositide 3‑kinase/Akt/glycogen synthase kinase 3β signal transduction. Data from a radiolabeled ligand‑binding assay indicated that LGP exhibited apparent competing effects on thromboxane receptor (TP) and P2Y12 receptors. In conclusion, the data presented here demonstrated that LGP, a natural compound from C. nudiflora Hook, inhibited the development of platelet aggregation and amplification of platelet activation. These inhibitory effects may be associated with its dual‑receptor inhibition on P2Y12 and TP receptors.

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