Celastrol inhibits platelet function and thrombus formation.
Celastrol inhibits platelet function and thrombus formation.
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DOI：
10.1016/j.bbrc.2023.149366
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发表时间：
2023-12
影响因子：
3.1
通讯作者：
Xiaoqian Li;Jie Zhang;Yingying Li;Yue Dai;Hui Zhu;Huimin Jiang;Yiran Han;Xiang Chu;Yueyue Sun;Wen Ju;Zhenyu Li;L. Zeng;Kailin Xu;J. Qiao
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文献类型：
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作者：
Xiaoqian Li;Jie Zhang;Yingying Li;Yue Dai;Hui Zhu;Huimin Jiang;Yiran Han;Xiang Chu;Yueyue Sun;Wen Ju;Zhenyu Li;L. Zeng;Kailin Xu;J. Qiao
雷公藤红素是从雷公藤中提取的一种活性五环三萜类化合物，具有抗炎和抗肿瘤作用。雷公藤红素是否调节血小板功能仍不清楚。我们的研究探讨了其在血小板功能和thrombosis.Methodshuman platelets分离和孵育Celastrol（0，1，3和5 μM）在37 °C为1小时，以测量血小板聚集，颗粒释放，蔓延，凝血酶诱导的凝块收缩和细胞内钙动员。此外，雷公藤红素（2 mg/kg）腹腔注射到小鼠体内，以评估止血和血栓形成invivo.ResultsCelastrol治疗显着降低血小板聚集和分泌致密或α颗粒诱导的胶原相关肽（CRP）或凝血酶的剂量依赖性方式。此外，雷公藤红素处理的血小板显示出显著降低的扩散活性和减少的凝块收缩。此外，雷公藤红素给药延长尾部出血时间，抑制动脉/静脉血栓形成。此外，雷公藤红素显着降低钙mobility.ConclusionCelastrol抑制血小板功能和静脉/动脉血栓形成，这意味着它可能被用于治疗血栓性疾病。
IntroductionCelastrol is an active pentacyclic triterpenoid extracted from Tripterygium wilfordii and has anti-inflammatory and anti-tumor properties. Whether Celastrol modulates platelet function remains unknown. Our study investigated its role in platelet function and thrombosis.MethodsHuman platelets were isolated and incubated with Celastrol (0, 1, 3 and 5 μM) at 37 °C for 1 h to measure platelet aggregation, granules release, spreading, thrombin-induced clot retraction and intracellular calcium mobilization. Additionally, Celastrol (2 mg/kg) was intraperitoneally administrated into mice to evaluate hemostasis and thrombosis in vivo.ResultsCelastrol treatment significantly decreased platelet aggregation and secretion of dense or alpha granules induced by collagen-related peptide (CRP) or thrombin in a dose-dependent manner. Additionally, Celastrol-treated platelets showed a dramatically reduced spreading activity and decreased clot retraction. Moreover, Celastrol administration prolonged tail bleeding time and inhibited formation of arterial/venous thrombosis. Furthermore, Celastrol significantly reduced calcium mobilization.ConclusionCelastrol inhibits platelet function and venous/arterial thrombosis, implying that it might be utilized for treating thrombotic diseases.