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Open AccessArticle

Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation

1
College of Pharmacy, Seoul National University, Seoul 08826, Korea
2
College of Pharmacy, Ewha Womans University, Seoul 03760, Korea
3
College of Pharmacy, Hanyang University, Ansan 15588, Korea
4
Faculty of Pharmacy, Thai Binh University of Medicine and Pharmacy, Thai Binh city 410000, Vietnam
5
School of Public Health, China Medical University, Shenyang 110122, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5040; https://doi.org/10.3390/ijms20205040
Received: 24 July 2019 / Revised: 30 September 2019 / Accepted: 9 October 2019 / Published: 11 October 2019
Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agents selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets. The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented arterial thrombosis in vivo from the dose of 10 mg/kg without prolonging bleeding time or blood clotting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile. View Full-Text
Keywords: paeoniflorin; Paeonia suffruticosa; shear stress; antiplatelet; antithrombotic paeoniflorin; Paeonia suffruticosa; shear stress; antiplatelet; antithrombotic
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MDPI and ACS Style

Ngo, T.; Kim, K.; Bian, Y.; Noh, H.; Lim, K.-M.; Chung, J.-H.; Bae, O.-N. Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation. Int. J. Mol. Sci. 2019, 20, 5040.

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