Xiaoliang Wang,Yiying Li,Hongyan Yang,Jiang Li,Shaofeng Xu, Ling Wang

Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050

Study on the targets and mechanisms of traditional Chinese medicine in inhibiting platelet aggregation

Xiaoliang Wang*,Yiying Li,Hongyan Yang,Jiang Li,Shaofeng Xu, Ling Wang

Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050

A R T I C L E I N F O

Article history:

Available online 23 November 2015

Platelet aggregation

Traditional Chinese medicine

ADP

P2Y1

P2Y12

Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases. To develop novel,effective and safe agents for inhibiting platelet aggregation and preventing above diseases is urgently needed.Some traditional Chinese medicines for“Houxue Huayu”have been shown to inhibit platelet aggregation potently.They are used frequently in China and also in Asian countries.Recently,the major effective components of Pueraria lobata,Salvia miltiorrhiza Bunge, Apium graveolens L.and so on were studied.The mechanisms and the molecular targets of puerarin,salvianolic acid B and the analogue of 3-n-butylphthalide,dl-PHPB were investigated.Four platelet aggregation inducers,ADP,arachidonic acid(AA),collagen(Col)and thrombin,were used in the study.

It was found that these compounds inhibited platelet aggregation induced by differentinducers in vitro and ex vivo obviously.The inhibiting potency for puerarin is ADP>>Col>Thrombin=AA.For dl-PHPB is: ADP>AA>Col>thrombin.However,the order of inhibiting potency for salvianolic acid B is:ADP≥Col>Thrombin>AA. The data showed that all compounds inhibited ADP-induced platelet aggregation signifcantly.Due to existing two ADP receptor subtypes response to platelet aggregation,P2Y1and P2Y12, we further studied the action of the above compounds on the receptors and the signaling pathways.

It was known that ADP acts on P2Y1and subsequently activates PLC through Gq protein,and produces IP3;andADP binds to P2Y12,and attenuates cAMP by inhibiting adenylyl cyclase through Gi protein.It was found that puerarin and dl-PHPB decreased PI turnover(IP1accumulation)produced by ADP,but had no effect on IP1level induced by m-3M3FBS,an activator of PLC.M-3M3FBS might attenuate the inhibitory effect of dl-PHPB on ADP-induced platelet aggregation.But salvianolic acid B showed no signifcant effect on PI turnover.In addition, puerarin and dl-PHPB did not affect cAMP formation in platelets stimulated by ADP,which is different from P2Y12antagonist ticlopidine.Puerarin showed the similar effects of dl-PHPB.

Therefore,the actions of dl-PHPB and puerarin might be through P2Y1receptor-PLC-β pathway.Salvianolic acid B might act more specifc on the receptor subtype P2Y12.All the information suggested that components of Chinese herb medicine might be a good resource for development of novel and safe anti-platelet agents.Actually they have been used frequently for prevention and treatment of ischemic stroke and heart attack.

*E-mail address:wangxl@imm.ac.cn.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.018

1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).