Original ArticleCelastrol, a Triterpene Extracted From Tripterygium wilfordii Hook F, Inhibits Platelet ActivationHu, Houyuan MD, PhD*†; Straub, Andreas MD†; Tian, Zhuo MS*; Bassler, Nicole BA†; Cheng, Jun MS*; Peter, Karlheinz MD, PhD†Author Information From the *Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China; and †Centre for Thrombosis and Myocardial Infarction, Baker IDI Heart and Diabetes Institute, Melbourne, Australia. Received for publication January 3, 2009; accepted May 26, 2009. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jcvp.org). The authors report no conflicts of interest. Reprints: Houyuan Hu, MD, PhD, Department of Cardiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: September 2009 - Volume 54 - Issue 3 - p 240-245 doi: 10.1097/FJC.0b013e3181b21472 Buy SDC Metrics Abstract Celastrol is an active ingredient of the traditional Chinese medicinal plant, Tripterygium wilfordii Hook F, which is known especially for its anti-inflammatory effects. However, on the cellular and molecular levels, celastrol's mechanism of action is only poorly understood. Because platelets contribute to inflammatory events, this study investigates the effects of celastrol on platelet function using flow cytometry, aggregometry, and adhesion assays. In in vitro experiments with human platelets, celastrol inhibits adenosine-5-diphosphate (ADP)-induced expression of the platelet activation marker P-selectin and glycoprotein IIb/IIIa activation with 50% inhibition values of 1.62 and 1.86 μM, respectively. Celastrol also inhibits thrombin-stimulated and phorbol 12-myristate 13-acetate-stimulated P-selectin expression on platelets. Furthermore, ADP-stimulated platelet adhesion on fibrinogen is partially prevented by 5 μM celastrol. In platelet aggregometry, celastrol (0.05-0.5 mM) inhibits ADP-induced aggregation of platelet-rich plasma. Moreover, 12 male C57BL/6J mice were randomly grouped to receive intraperitoneal treatment with either celastrol (2 mg·kg−1·day−1) or vehicle. After 4 weeks of the respective treatment, celastrol inhibited 2 and 20 μM ADP-stimulated platelet fibrinogen binding by 34.5% (P < 0.01) and 28.9% (P < 0.05), respectively, compared with controls. In conclusion, these results indicate that celastrol exerts inhibitory effects on platelets. This new finding contributes to the understanding of antithrombotic and also anti-inflammatory effects of celastrol. © 2009 Lippincott Williams & Wilkins, Inc.