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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Zhilong Huoxue Tongyu Capsule Ameliorates Platelet Aggregation and Thrombus Induced by Aspirin in Rats by Regulating Lipid Metabolism and MicroRNA Pathway

Author(s): Li Qiuyue, Deng Gulin, Xu Hong, Yin Jiazhen, Yuan Rukui, Huang Xinwu and Li Guochun*

Volume 27, Issue 6, 2024

Published on: 03 August, 2023

Page: [854 - 862] Pages: 9

DOI: 10.2174/1386207326666230712110103

Price: $65

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Abstract

Introduction: Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported.

Objectives: This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats.

Methods: An AR model was established through treatment with a high-fat, high-sugar, and highsalt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6- keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA- 126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction.

Results: Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p.

Conclusion: This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.

Keywords: Zhilong huoxue tongyu capsule, aspirin resistance, ELISA, lipid metabolism, miRNA, cardiovascular disease.

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[1]
Robert, M.; Miossec, P. Effects of Interleukin 17 on the cardiovascular system. Autoimmun. Rev., 2017, 16(9), 984-991.
[http://dx.doi.org/10.1016/j.autrev.2017.07.009] [PMID: 28705781]
[2]
Chinese cardiovascular health and disease report 2019. JJ Cardiovasc. Dis. Res., 2020, 39, 1145-1156.
[3]
Stark, K.; Massberg, S. Interplay between inflammation and thrombosis in cardiovascular pathology. Nat. Rev. Cardiol., 2021, 18(9), 666-682.
[http://dx.doi.org/10.1038/s41569-021-00552-1] [PMID: 33958774]
[4]
Sun, T.; Yu, J.S. Research progress of aspirin resistance. Medical Recapitulate., 2018, 24, 853-857.
[5]
Ge, Y.R.; Huan, N.; Wang, C.L.; Wang, P.L. Application Progress and prospect of herbal and western medicine combined with antiplatelet therapy for cardiovascular events. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-7.
[http://dx.doi.org/10.1155/2021/5563987] [PMID: 34367302]
[6]
Powers, W.J.; Rabinstein, A.A. Response by powers and rabinstein to letter regarding article, “2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association”. Stroke, 2019, 50(9), e277-e278.
[http://dx.doi.org/10.1161/STROKEAHA.119.026917] [PMID: 31390963]
[7]
McCullough, P.A.; Vasudevan, A.; Sathyamoorthy, M.; Schussler, J.M.; Velasco, C.E.; Lopez, L.R.; Swift, C.; Peterson, M.; Bennett-Firmin, J.; Schiffmann, R.; Bottiglieri, T. Urinary 11-Dehydro-Thromboxane B 2 and mortality in patients with stable coronary artery disease. Am. J. Cardiol., 2017, 119(7), 972-977.
[http://dx.doi.org/10.1016/j.amjcard.2016.12.004] [PMID: 28139223]
[8]
Navaratnam, K.; Alfirevic, A.; Alfirevic, Z. Low dose aspirin and pregnancy: How important is aspirin resistance? BJOG, 2016, 123(9), 1481-1487.
[http://dx.doi.org/10.1111/1471-0528.13914] [PMID: 26929162]
[9]
FitzGerald, R.; Pirmohamed, M. Aspirin resistance: Effect of clinical, biochemical and genetic factors. Pharmacol. Ther., 2011, 130(2), 213-225.
[http://dx.doi.org/10.1016/j.pharmthera.2011.01.011] [PMID: 21295071]
[10]
Du, G.; Lin, Q.; Wang, J. A brief review on the mechanisms of aspirin resistance. Int. J. Cardiol., 2016, 220, 21-26.
[http://dx.doi.org/10.1016/j.ijcard.2016.06.104] [PMID: 27372038]
[11]
Hao, P.; Jiang, F.; Cheng, J.; Ma, L.; Zhang, Y.; Zhao, Y. Traditional chinese medicine for cardiovascular disease. J. Am. Coll. Cardiol., 2017, 69(24), 2952-2966.
[http://dx.doi.org/10.1016/j.jacc.2017.04.041] [PMID: 28619197]
[12]
Liang, B.; Gu, N. Traditional chinese medicine for coronary artery disease treatment: Clinical evidence from randomized controlled trials. Front. Cardiovasc. Med., 2021, 8, 702110.
[http://dx.doi.org/10.3389/fcvm.2021.702110] [PMID: 34422929]
[13]
Chao, J.; Dai, Y.; Verpoorte, R.; Lam, W.; Cheng, Y.C.; Pao, L.H.; Zhang, W.; Chen, S. Major achievements of evidence-based traditional Chinese medicine in treating major diseases. Biochem. Pharmacol., 2017, 139, 94-104.
[http://dx.doi.org/10.1016/j.bcp.2017.06.123] [PMID: 28636884]
[14]
Xiao, H.Q.; Bai, X.; Yang, S.J. Clinical application of Zhilong Huoxue Tongyu Capsule. World Latest Med. Inform., 2016, 16, 81-82.
[15]
Lu, W.L. Clinical efficacy of Xue sai tong capsule combined with aspirin in the treatment of aspirin resistant coronary heart disease. Modern Med. J. China, 2017, 19, 50-52.
[16]
Liu, T.T.; Yao, K.; Duan, J.L. Research progress on pharmacological mechanism of Xuefu Zhuyu Decoction in treating cardiovascular disease. Ji lin. J. Chin. Med., 2019, 39, 1397-1400.
[17]
Xie, S.Q.; Tan, H.; Chen, C.X. Evalue of Tong xin luo Capsule on clopidogrel resistance in patients with acute coronary syndrome. Chinese J. Integr. Medic. Cardio. Cerebrovasc. Dis., 2015, 13, 1571-1573.
[18]
Luo, G.; Chen, H.; Yang, S.J. Intervention of Zhilong Huoxue Tongyu Capsule on Senile dementia model rats with Qi deficiency and blood stasis. World Latest Med. Info., 2019, 19, 44-46.
[19]
Wang, W.; Du, Y.; Bai, X. Analysis of research status of Zhilong Huoxue Tongyu Capsule in treating cerebrovascular diseases. J Lu zhou Med. Coll., 2016, 39, 91-93.
[20]
Luo, G.; Chen, H.; Bai, X. Clinical trial and mechanism of Zhilong Huoxue Tongyu Capsule on aspirin resistance. J. Lu. Zhou Med. Coll., 2012, 35, 50-52.
[21]
Chen, H.; Yang, S.J.; Luo, G. Preparation and evaluation of aspirin resistance animal models. J. Lu. Zhou. Med. Coll., 2012, 35, 35-37.
[22]
Wang, G.G.; Li, Q.; Wang, S.; Ni, C.; Xu, J.M.; Zhang, L.H. Dynamic changes of thromboelastography and coagulation function parameters before and after liver transplantation and its significance for guidance of blood transfusion. Shiyong Ganzangbing Zazhi, 2020, 23, 901-904.
[23]
Wang, J.; Liu, J.; Zhou, Y.; Wang, F.; Xu, K.; Kong, D.; Bai, J.; Chen, J.; Gong, X.; Meng, H.; Li, C. Association among PlA1/A2 gene polymorphism, laboratory aspirin resistance and clinical outcomes in patients with coronary artery disease: An updated meta-analysis. Sci. Rep., 2019, 9(1), 13177.
[http://dx.doi.org/10.1038/s41598-019-49123-y] [PMID: 31511539]
[24]
Floyd, C.N.; Ferro, A. Mechanisms of aspirin resistance. Pharmacol. Ther., 2014, 141(1), 69-78.
[http://dx.doi.org/10.1016/j.pharmthera.2013.08.005] [PMID: 23993980]
[25]
Wu, W. The clinical factors of aspirin resistance and the association of the cyclooxygenase-2 gene polymorphism with aspirin resistance; Tianjin Medical University, 2006.
[26]
Gao, H.; Long, Y.; Jiang, X.; Liu, Z.; Wang, D.; Zhao, Y.; Li, D.; Sun, B. Beneficial effects of Yerba Mate tea (Ilex paraguariensis) on hyperlipidemia in high-fat-fed hamsters. Exp. Gerontol., 2013, 48(6), 572-578.
[http://dx.doi.org/10.1016/j.exger.2013.03.008] [PMID: 23562841]
[27]
Reimann, M.; Rüdiger, H.; Weiss, N.; Ziemssen, T. Acute hyperlipidemia but not hyperhomocysteinemia impairs reflex regulation of the cardiovascular system. Atheroscler. Suppl., 2015, 18, 8-15.
[http://dx.doi.org/10.1016/j.atherosclerosissup.2015.02.004] [PMID: 25936298]
[28]
Yang, H.Y.; Zhang, X.D.; Liu, K.Y.; Du, Z.H.; Bai, X.J. Effect of Hirudo on blood metabolism and its related gene expression in blood stasis syndrome rabbits. Chin. J. Mod. Appl. Pharm., 2013, 30, 959.
[29]
Cipollone, F.; Prontera, C.; Pini, B.; Marini, M.; Fazia, M.; De Cesare, D.; Iezzi, A.; Ucchino, S.; Boccoli, G.; Saba, V.; Chiarelli, F.; Cuccurullo, F.; Mezzetti, A. Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation, 2001, 104(8), 921-927.
[http://dx.doi.org/10.1161/hc3401.093152] [PMID: 11514380]
[30]
Li, J.; Liu, W.X. Status and prospect of aspirin resistance. J Cardiovasc. Pulmonary Dis., 2009, 28, 61-63.
[31]
Müller, B. Pharmacology of thromboxane A2, prostacyclin and other eicosanoids in the cardiovascular system. Therapie, 1991, 46(3), 217-221.
[PMID: 1792655]
[32]
Woulfe, D.S. Platelet G protein-coupled receptors in hemostasis and thrombosis. J. Thromb. Haemost., 2005, 3(10), 2193-2200.
[http://dx.doi.org/10.1111/j.1538-7836.2005.01338.x] [PMID: 16194198]
[33]
Sakata, C.; Kawasaki, T.; Kato, Y.; Abe, M.; Suzuki, K.; Ohmiya, M.; Funatsu, T.; Morita, Y.; Okada, M. ASP6537, a novel highly selective cyclooxygenase-1 inhibitor, exerts potent antithrombotic effect without “aspirin dilemma”. Thromb. Res., 2013, 132(1), 56-62.
[http://dx.doi.org/10.1016/j.thromres.2013.03.005] [PMID: 23522855]
[34]
Fang, W.; Wei, J.; Han, D.; Chen, X.; He, G.; Wu, Q.; Chu, S.; Li, Y. MC-002 exhibits positive effects against platelets aggregation and endothelial dysfunction through thromboxane A 2 inhibition. Thromb. Res., 2014, 133(4), 610-615.
[http://dx.doi.org/10.1016/j.thromres.2014.01.029] [PMID: 24525312]
[35]
Ai, J.; Zhang, R.; Li, Y.; Pu, J.; Lu, Y.; Jiao, J.; Li, K.; Yu, B.; Li, Z.; Wang, R.; Wang, L.; Li, Q.; Wang, N.; Shan, H.; Li, Z.; Yang, B. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem. Biophys. Res. Commun., 2010, 391(1), 73-77.
[http://dx.doi.org/10.1016/j.bbrc.2009.11.005] [PMID: 19896465]
[36]
Luo, X.; Pan, Z.; Shan, H.; Xiao, J.; Sun, X.; Wang, N.; Lin, H.; Xiao, L.; Maguy, A.; Qi, X.Y.; Li, Y.; Gao, X.; Dong, D.; Zhang, Y.; Bai, Y.; Ai, J.; Sun, L.; Lu, H.; Luo, X.Y.; Wang, Z.; Lu, Y.; Yang, B.; Nattel, S. MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. J. Clin. Invest., 2013, 123(5), 1939-1951.
[http://dx.doi.org/10.1172/JCI62185] [PMID: 23543060]
[37]
Seok, H.Y.; Chen, J.; Kataoka, M.; Huang, Z.P.; Ding, J.; Yan, J.; Hu, X.; Wang, D.Z. Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. Circ. Res., 2014, 114(10), 1585-1595.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.303784] [PMID: 24657879]
[38]
Du, W.; Pan, Z.; Chen, X.; Wang, L.; Zhang, Y.; Li, S.; Liang, H.; Xu, C.; Zhang, Y.; Wu, Y.; Shan, H.; Lu, Y. By targeting Stat3 microRNA-17-5p promotes cardiomyocyte apoptosis in response to ischemia followed by reperfusion. Cell. Physiol. Biochem., 2014, 34(3), 955-965.
[http://dx.doi.org/10.1159/000366312] [PMID: 25200830]
[39]
Pan, Z.; Sun, X.; Shan, H.; Wang, N.; Wang, J.; Ren, J.; Feng, S.; Xie, L.; Lu, C.; Yuan, Y.; Zhang, Y.; Wang, Y.; Lu, Y.; Yang, B. MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene/transforming growth factor-β1 pathway. Circulation, 2012, 126(7), 840-850.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.094524] [PMID: 22811578]
[40]
Dangwal, S.; Thum, T. MicroRNAs in platelet biogenesis and function. Thromb. Haemost., 2012, 108(10), 599-604.
[http://dx.doi.org/10.1160/TH12-03-0211] [PMID: 22782083]
[41]
Liu, W.W.; Wang, H.; Chen, X.H.; Fu, S.W.; Liu, M.L. miR-34b-3p may promote antiplatelet efficiency of aspirin by inhibiting thromboxane synthase expression. Thromb. Haemost., 2019, 119(9), 1451-1460.
[http://dx.doi.org/10.1055/s-0039-1692681] [PMID: 31266078]
[42]
Czajka, P.; Fitas, A.; Jakubik, D.; Eyileten, C.; Gasecka, A.; Wicik, Z.; Siller-Matula, J.M.; Filipiak, K.J.; Postula, M. MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review. Front. Physiol., 2021, 12, 652579.
[http://dx.doi.org/10.3389/fphys.2021.652579] [PMID: 33935804]
[43]
Hromadka, M.; Motovska, Z.; Hlinomaz, O.; Kala, P.; Tousek, F.; Jarkovsky, J.; Beranova, M.; Jansky, P.; Svoboda, M.; Krepelkova, I.; Rokyta, R.; Widimsky, P.; Karpisek, M. MiR-126-3p and MiR-223-3p as biomarkers for prediction of thrombotic risk in patients with acute myocardial infarction and primary angioplasty. J. Pers. Med., 2021, 11(6), 508.
[http://dx.doi.org/10.3390/jpm11060508] [PMID: 34199723]
[44]
Cavarretta, E.; Chiariello, G.A.; Condorelli, G. Platelets, endothelium, and circulating microRNA-126 as a prognostic biomarker in cardiovascular diseases: Per aspirin ad astra. Eur. Heart J., 2013, 34(44), 3400-3402.
[http://dx.doi.org/10.1093/eurheartj/eht032] [PMID: 23391580]
[45]
Akbar, N.; Digby, J.E.; Cahill, T.J.; Tavare, A.N.; Corbin, A.L.; Saluja, S.; Dawkins, S.; Edgar, L.; Rawlings, N.; Ziberna, K.; McNeill, E.; Johnson, E.; Aljabali, A.A.; Dragovic, R.A.; Rohling, M.; Belgard, T.G.; Udalova, I.A.; Greaves, D.R.; Channon, K.M.; Riley, P.R.; Anthony, D.C.; Choudhury, R.P. Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction. JCI Insight, 2017, 2(17), e93344.
[http://dx.doi.org/10.1172/jci.insight.93344]
[46]
Schober, A.; Nazari-Jahantigh, M.; Wei, Y.; Bidzhekov, K.; Gremse, F.; Grommes, J.; Megens, R.T.A.; Heyll, K.; Noels, H.; Hristov, M.; Wang, S.; Kiessling, F.; Olson, E.N.; Weber, C. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat. Med., 2014, 20(4), 368-376.
[http://dx.doi.org/10.1038/nm.3487] [PMID: 24584117]

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