FOLLOWUS
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
Prof. Abdullah S. Shatoor, E-mail:asshalghamdi@yahoo.com
纸质出版日期:2021-09-01,
网络出版日期:2020-05-16,
录用日期:2019-05-13
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Abdullah S. Shatoor, Ali Shati, S. Al Humayed, 等. Opposite Modulatory Effects of
Abdullah S. Shatoor, Ali Shati, S. Al Humayed, et al. Opposite Modulatory Effects of
Abdullah S. Shatoor, Ali Shati, S. Al Humayed, 等. Opposite Modulatory Effects of
Abdullah S. Shatoor, Ali Shati, S. Al Humayed, et al. Opposite Modulatory Effects of
Objectives:
2
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:
2
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 (cAMP)
phosphorylated vasodilator-stimulated-phosphoprotein (p-VASP)
nuclear factor κB (NF-κB)
P-selectin
etc. in platelets were determined by Western blot; mRNA expressions of P
2
Y
12
and some inflammatory markers were determined by real-time polymerase chain reaction.
Results:
2
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:
2
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 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.
Crataegus aroniaplateletsaggregationP2Y12Intracellular cyclic adenosine monophosphatereactive oxygen speciesnuclear factor κB
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