Inhibitory effect and mechanism of Adina rubella flavonoids on platelet aggregation and thrombosis

doi:10.12092/j.issn.1009-2501.2018.06.007

Abstract

Abstract:

AIM: To investigate the effect and mechanism of Adina rubella flavonoids (ARF) on platelet aggregation and activation. METHODS: Different stimulus［adenosine 5'diphosphate (ADP)，arachidonic acid (AA), platelet activating factor (PAF)］were used to induce platelet aggregation in vitro. A rat model of acute pulmonary embolism caused by ADP, a mouse model of bleeding time and a rat model of arteriovenous shunt thrombosis were established to observe the inhibitory effect of ARF on platelet aggregation and thrombosis. The expression of CD41 and the activation of PI3K/Akt signal pathway were illustrated by Western blot. RESULTS: Compared with the control group, all ARF groups of the low-dose, middle-dose and high-dose significantly improved the survival rates of acute pulmonary embolism rats, prolonged the bleeding time and inhibited arteriovenous shunt thrombosis formation. ARF also inhibited platelet aggregation, and up-regulated expression of CD41 and the activation of PI3K/Akt signal pathway induced by ADP. CONCLUSION: ARF significantly inhibits the platelet aggregation and thrombosis, the mechanism may be related to CD41/PI3K/Akt signaling pathway.

Key words: Adina rubella, flavonoids, platelet aggregation, thrombus, signaling pathway

CLC Number:

R965.2

FANG Qingxia，ZOU Xiaozhou，YU Wenying，FANG Jie，MO Li，YU Chenhuan. Inhibitory effect and mechanism of Adina rubella flavonoids on platelet aggregation and thrombosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 640-645.

References

［1］Sharma D, BrummelZiedins KE, Bouchard BA, et al. Platelets in tumor progression: a host factor that offers multiple potential targets in the treatment of cancer［J］. J Cell Physiol, 2014, 229(8): 1005-1015.
［2］Mezouar S, Frère C, Darbousset R, et al. Role of platelets in cancer and cancerassociated thrombosis: Experimental and clinical evidences［J］. Thromb Res, 2016, 139: 65-76.
［3］Bambace NM, Holmes CE. The platelet contribution to cancer progression［J］. J Thromb Haemost, 2011, 9(2): 237-249.
［4］Wojtukiewicz MZ, Sierko E, Hempel D, et al. Platelets and cancer angiogenesis nexus［J］. Cancer Metastasis Rev, 2017, 36(22): 249-262.
［5］费鲜明, 陈艳, 吴万飞，等. 仙鹤草水提物体外对血小板聚集、凝血功能及血液流变学的影响［J］. 中国临床药理学与治疗学, 2013, 18(1): 10-16.
［6］Metharom P, Berndt MC, Baker RI, et al.Current state and novel approaches of antiplatelet therapy［J］. Arterioscler Thromb Vasc Biol, 2015, 35(6): 1327-1338.
［7］Kamada H, Imai Y, Nakamura M, et al.Computational study on thrombus formation regulated by platelet glycoprotein and blood flow shear［J］. Microvasc Res，2013, 89: 95-106.
［8］Kamata T，Takada Y.Platelet integrin alpha IIb beta3ligand interactions: what we learn from the structure ［J］?Int J Hematol, 2001, 74: 382-389.
［9］张磊, 高颖, 蒋云涛，等.水杨梅根的化学成分［J］.中国药科大学学报, 2015, 46(5): 556-560.
［10］阮善明，沈敏鹤，林红,等.解毒三根汤干预肿瘤相关成纤维细胞及抑制结肠癌侵袭转移的实验研究［J］.中国中西医结合杂志, 2013, 33(9): 1242-1246.
［11］吴秋玲, 卢宏达, 郭继龙，等.活血化瘀中药治疗恶性肿瘤的探讨［J］.世界中西医结合杂志, 2010, 5(6): 530-531.
［12］陈程，冯锁民，罗国平，等. BoxBehnken 设计响应面法优选水杨梅总黄酮提取工艺研究［J］.中国药师, 2016, 19(2): 241-244.
［13］轻曼古丽·阿吉，马虎，美合热阿依·伊萨克,等.榅桲总黄酮对血栓形成和血小板聚集作用的影响［J］.中成药, 2015, 37(7): 1589-1592.
［14］吴曙光，钱宁.速眠新在实验动物麻醉中的应用［J］.贵阳中医学院学报, 2007, 29(1): 28-60.
［15］Fei YX, Wang SQ, Yang LJ, et al.Salvia miltiorrhiza Bunge (Danshen) extract attenuates permanent cerebral ischemia through inhibiting platelet activation in rats ［J］.J Ethnopharmacol,2017, 207: 57-66.
［16］Nieswandt B, Pleines I, Bender M, et al.Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke［J］. J Thromb Haemost, 2011, 9(2): 92-104.
［17］Ortel Jiang W, Boyle SH, Ortel TL, et al.Platelet aggregation and mental stress induced myocardial ischemia: results from the REMIT study［J］. Am Heart J, 2015, 169(4): 496-507.
［18］包文龙. 活血化瘀中药在肿瘤治疗中应用浅析［J］.浙江中医杂志, 2013, 48(5): 388-389.
［19］Xiang BG, Zhang GY, Ren HM, et al.The P2Y12 Antagonists, 2MeSAMP and Cangrelor, Inhibit Platelet Activation through P2Y12/Gi-Dependent Mechanism［J］. PLoS One, 2012, 7(12): e51037.
［20］吴雅凝, 赵娣, 李宁,等.二磷酸腺苷受体拮抗剂类抗血小板药物研究进展［J］.中国临床药理学与治疗学, 2010, 15(12): 1434-1440.

[1]	QIN Wenxiu, XU Junfeng, YANG Ting, WANG Pingfei. Research progress on signaling pathway of tanshinoneIIA in treatment of nerve injury after ischemic stroke [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(6): 705-713.
[2]	CHEN Manxin, ZHANG Bingyu, DAI Min. Clinical efficacy of intracoronally targeted recombinant human urokinase combined with percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) with high thrombus burden [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(5): 544-549.
[3]	HOU Ruiying, GUO Lige, JIAO Weijie, DU Lei, WU Guiyue, ZHAO Xu. Effects of Xiaokeshu recipe on levels of serum inflammatory factors in type2 diabetic rats and its mechanism [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(4): 377-382.
[4]	LI Ruoning, GUO Zhanli, WANG Yuan, SUN Jianjun. Platelet-endothelial aggregation receptor 1 and its mediated signalling pathway Advances in the study of the role of platelets and endothelial cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(4): 438-444.
[5]	LI Junmin, NIU Hengli, XIE Mingquan, SU Jinlong. Effects of hawthorn flavonoids on atherosclerotic and hyperlipidemia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(3): 276-282.
[6]	ZHU Ruifang, GUO Dongkai, ZHI Hui, JIANG Yiguo, ZHANG Yueling, QIAN Xiaoping, JI Shiliang. Exploring the mechanism of elemene synergistic bortezomib against multiple myeloma by ROS-NF-κB-p38MAPK pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(11): 1219-1226.
[7]	CHEN Yulin, JIANG Hugang, WANG Xinqiang, LIU Kai, LI Yingdong, AN Tao, ZHAO Xinke. Effects and mechanism of Ginseng Yixin granules (QSYXG) for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(10): 1081-1092.
[8]	ZHOU Huan, XU Ming, LI Bo, LIU Chunying, WANG Chun. PI3K/Akt/FOXO3a signaling pathway inducing protective autophagy promotes acquired lung adenocarcinoma resistance remodeling to DDP [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(9): 961-970.
[9]	HE Xudong, FU Zhongyu, HUANG Ying, HE Jinbiao, PU Xuemei, LI Jie, LI Yanjuan, YU Jie, YANG Xingxin. Research progress on chemistry and bioactivity of isopentenyl flavonoids from Sophora flavescens [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(8): 899-907.
[10]	YAO Qian, CHEN Yun, SHANG Juan, XI Xiaoyun, CHEN Ying, GU Xiao, JU Wenzheng, ZOU Jiandong, LU Su, XU Meijuan. Investigation of potential pharmacodynamic substances and mechanism of Qingxin-zishen prescription decoction in treatment of menopause syndrome based on HPLC-Q-TOF-MS/MS and network pharmacology [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(5): 481-497.
[11]	CHEN Shengfu, LI Xiaolin, WANG Weigang, DU Weize, LI Maoxing. Research progress on antipyretic effect of Chinese medicine [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(3): 334-344.
[12]	NIU Pilian, FAN Yongxin, LU Furui, ZHOU Xuezhang, BAI Mingsheng. Effects of liquorice extract on cardiac fibroblasts fibrosis induced by TGF-β1 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(2): 129-135.
[13]	PAN Rongrong, ZHI Yinghao, JIN Yongxi, ZHOU Xiahui. Influences of theaflavins on neuronal apoptosis and blood-brain barrier in rats with cerebral hemorrhage by regulating CaMKK2/AMPK signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(11): 1240-1246.
[14]	LIU Peng, WANG Chen, WANG Yun, QIU Xinping. Dioscin attenuates inflammatory injury in uric acid-induced renal tubular epithelial cells by suppression of NF-κB signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(10): 1099-1105.
[15]	LIU Xiaoping, LAI Xiangmao, OUYANG Zizhang, JIANG Sheng, ZHANG Ying. Nobiletin inhibits neonatal rat cardiomyocytes hypertrophy induced by high glucose [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(7): 753-759.