Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats  

作　　者：Abdullah S.Shatoor Ali Shati S.Al Humayed Sultan AL-Qahtani Mahmoud Alkhateeb 

机构地区：[1]Department of Medicine,Cardiology Section,College of Medicine,King Khalid University,Abha(64121),Saudi Arabia [2]Department of Biology,College of Science,College of Medicine,King Khalid University,Abha(64121),Saudi Arabia [3]Department of Physiology,College of Medicine,King Saud bin Abdulaziz University for Health Sciences,Riyadh(11481),Saudi Arabia

出　　处：《Chinese Journal of Integrative Medicine》2021年第9期696-704,共9页中国结合医学杂志（英文版）

基　　金：Supported by the Deanship of Scientific Research at King Khalid University,Saudi Arabia (No. R.G.P.1/41/39)。

摘　　要：Objectives:To reveal the mechanisms behind the dual effects of Crataegus aronia(C.aronia)aqueous extract on platelet aggregation by focusing on function,regulation,expression,and signaling of platelets P_(2)Y_(12)receptors.Methods:Adult male Wistar rats(120±10 g)were classified as control received the vehicle,C.aronia(200 mg/kg),and C.aronia(2,000 mg/kg)-treated rats.After treatments for consecutive 7 days,hematological and molecular experiments were conducted to detect alterations in platelet aggregation,thromboxane B2(THXB2)and intracellular reactive oxygen species(ROS)content;protein levels of P_(2)Y_(12),p-Akt,cyclic adenosine monophosphate(c AMP),phosphorylated vasodilator-stimulated-phosphoprotein(p-VASP),nuclear factorκB(NF-κB),P-selectin,etc.in platelets were determined by Western blot;m RNA expressions of P_(2)Y_(12)and some inflammatory markers were determined by real-time polymerase chain reaction.Results:At a concentration of 200 mg/kg,C.aronia inhibited platelet aggregation through multiple interconnected mechanisms including downregulation P_(2)Y_(12)synthesis and expression,stimulating intracellular cAMP levels and protein levels of p-VASP,inhibiting platelets THXB2 release and protein levels of P-selectin.Also,it inhibited platelets level of ROS and of NF-κB,a major signaling pathway that stimulates the expression of P_(2)Y_(12)and THXA2 synthesis.Opposite findings were seen in platelets of rats received C.aronia at a concentration of 2,000 mg/kg.Interestingly,co-administration of N-acetylcysteine prevented all hematological and molecular alterations exerted by the high dose of the extract and inhibited platelet aggregation.Conclusion:Oral administration of C.aronia at low dose inhibits platelet aggregation by reducing THXB2 release,expression of P-selectin and activating c AMP and Akt signaling through two major mechanisms including downregulation of P_(2)Y_(12)and inhibition of ROS-induced activation of NF-κB,an effect that is observed to be in the opposite direction with its high dose.

关 键 词：Crataegus aronia PLATELETS AGGREGATION P_(2)Y_(12) Intracellular cyclic adenosine monophosphate reactive oxygen species nuclear factorκB 

分 类 号：R285.5[医药卫生—中药学]