Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats.
Chin J Integr Med
; 27(9): 696-704, 2021 Sep.
Article
in En
| MEDLINE
| ID: mdl-32418179
ABSTRACT
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 P2Y12 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 P2Y12, p-Akt, cyclic adenosine monophosphate (cAMP), phosphorylated vasodilator-stimulated-phosphoprotein (p-VASP), nuclear factor κB (NF-κB), P-selectin, and etc. in platelets were determined by Western blot; mRNA expressions of P2Y12 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 P2Y12 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 P2Y12 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 cAMP and Akt signaling through two major mechanisms including downregulation of P2Y12 and inhibition of ROS-induced activation of NF-κB, an effect that is observed to be in the opposite direction with its high dose.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Platelet Aggregation Inhibitors
/
Plant Extracts
/
Crataegus
Limits:
Animals
Language:
En
Journal:
Chin J Integr Med
Journal subject:
TERAPIAS COMPLEMENTARES
Year:
2021
Document type:
Article
Affiliation country:
Saudi Arabia
Publication country:
CHINA
/
CN
/
REPUBLIC OF CHINA