PMID- 31132460 OWN - NLM STAT- MEDLINE DCOM- 20200513 LR - 20200513 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 241 DP - 2019 Sep 15 TI - The antithrombotic activity of the active fractions from the fruits of Celastrus orbiculatus Thunb through the anti-coagulation, anti-platelet activation and anti-fibrinolysis pathways. PG - 111974 LID - S0378-8741(18)34718-4 [pii] LID - 10.1016/j.jep.2019.111974 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Celastrus orbiculatus Thunb (C. orbiculatus) with peel and seeds is mainly composed of flavonoids, sesquiterpenes and tripenes. According to the Traditional Chinese medicine standard of Liaoning province (2009), it has been long used to invigorate blood circulation. AIM OF THE STUDY: To identify the antithrombus fraction and components of C. orbiculatus, and to investigate the underlying mechanisms. MATERIALS AND METHODS: The antithrombus effects of C. orbiculatus fractions were evaluated in vitro by plasma recalcification time (PRT). The antithrombus effect of NST-50, the most effective fraction, was further investigated in acute pulmonary embolism (APE) mice and FeCl(3)-induced carotid arterial thrombus rats. Bleeding assessment was also carried out to assess the side effects of NST-50. In addition, the content of total flavonoids and active components of NST-50 was also quantified. RESULTS: Nine flavonoids were detected in NST-50 as main components with the content of 44.70%. Next, NST-50 was found with significant anticoagulation activity by prolonging the plasma recalcification time (PRT), activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) and decreasing the content of fibrinogen (FIB). Furthermore, NST-50 administration markedly suppressed the level of TXB(2) and PAI-1, while significantly up-regulated the level of 6-keto-PGF(1a) and t-PA (p < 0.05). CONCLUSION: The results demonstrated that NST-50 could be valuable in clinical application against acute coronary syndrome, venous thromboembolisms and cerebrovascular thrombosis. It was possible that the anticoagulation action of NST-50 could be related to the regulation of TXA(2) - PGI(2) and t-PA - PAI-1 pairs. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Zhou, Jingjing AU - Zhou J AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zhoujingjing8338@163.com. FAU - Zhai, JianXiu AU - Zhai J AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: lookingformilk@163.com. FAU - Zheng, Wenlin AU - Zheng W AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 1373984922@qq.com. FAU - Han, Na AU - Han N AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: hanna82@163.com. FAU - Liu, Zhihui AU - Liu Z AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 48867414@qq.com. FAU - Lv, Guanghui AU - Lv G AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 1018594714@qq.com. FAU - Zheng, Xiaojiao AU - Zheng X AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 826781537@qq.com. FAU - Chang, Sheng AU - Chang S AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: 987758836@qq.com. FAU - Yin, Jun AU - Yin J AD - Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: yinjun2002@yahoo.com. LA - eng PT - Journal Article DEP - 20190524 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anticoagulants) RN - 0 (Fibrinolytic Agents) RN - 0 (Flavonoids) RN - 0 (Plant Extracts) RN - 0 (Platelet Aggregation Inhibitors) SB - IM MH - Animals MH - Anticoagulants/pharmacology/*therapeutic use MH - Blood Coagulation/drug effects MH - Blood Coagulation Tests MH - Carotid Arteries/drug effects/pathology MH - *Celastrus MH - Fibrinolytic Agents/pharmacology/*therapeutic use MH - Flavonoids/pharmacology/therapeutic use MH - Fruit MH - Lung/drug effects/pathology MH - Male MH - Mice MH - Plant Extracts/pharmacology/*therapeutic use MH - Platelet Activation/drug effects MH - Platelet Aggregation Inhibitors/pharmacology/therapeutic use MH - Pulmonary Embolism/*drug therapy/pathology MH - Rabbits MH - Rats, Sprague-Dawley MH - Thrombosis/*drug therapy/pathology OTO - NOTNLM OT - Antithrombotic activity OT - Celastrus orbiculatus Thunb OT - Flavonoids OT - Thrombosis EDAT- 2019/05/28 06:00 MHDA- 2020/05/14 06:00 CRDT- 2019/05/28 06:00 PHST- 2018/12/10 00:00 [received] PHST- 2019/05/09 00:00 [revised] PHST- 2019/05/23 00:00 [accepted] PHST- 2019/05/28 06:00 [pubmed] PHST- 2020/05/14 06:00 [medline] PHST- 2019/05/28 06:00 [entrez] AID - S0378-8741(18)34718-4 [pii] AID - 10.1016/j.jep.2019.111974 [doi] PST - ppublish SO - J Ethnopharmacol. 2019 Sep 15;241:111974. doi: 10.1016/j.jep.2019.111974. Epub 2019 May 24.