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

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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.

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Acknowledgment

The authors would like to express their sincere gratitude and thanks to the staff of the department of pharmacognosy at the college of pharmacy at King Khalid University.

Author information

Authors and Affiliations

  1. Department of Medicine, Cardiology Section, College of Medicine, King Khalid University, Abha, 64121, Saudi Arabia

    Abdullah S. Shatoor & S. Al Humayed

  2. Department of Biology, College of Science, College of Medicine, King Khalid University, Abha, 64121, Saudi Arabia

    Ali Shati

  3. Department of Physiology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, 11481, Saudi Arabia

    Sultan AL-Qahtani & Mahmoud Alkhateeb

Authors
  1. Abdullah S. Shatoor
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  2. Ali Shati
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  3. S. Al Humayed
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  4. Sultan AL-Qahtani
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  5. Mahmoud Alkhateeb
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Contributions

Shatoor A obtained the fund. Shati A and Humayed AI designed the drafted the proposal and the experimental design. AL-Qahtani S, Shatoor A, and Shati A performed the experimental measurements with the help of the department technician. Alkhateeb M, Humayed SA, AL-Qahtani S, and Shati S analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Abdullah S. Shatoor.

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All authors have not disclosed any affiliation or financial involvement with organizations or entities with a direct financial interest in the subject matter or materials discussed in the manuscript.

Additional information

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

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Shatoor, A.S., Shati, A., Humayed, S.A. et al. Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats. Chin. J. Integr. Med. 27, 696–704 (2021). https://doi.org/10.1007/s11655-020-3187-3

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  • DOI: https://doi.org/10.1007/s11655-020-3187-3

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