Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme

Author(s): Hua Qu, Ying Zhang, Jun-he Shi, Yi-han Zhao, Jie Gao, Zhu-ye Gao* and Da-zhuo Shi*

Volume 31, Issue 24, 2024

Published on: 12 July, 2023

Page: [3844 - 3856] Pages: 13

DOI: 10.2174/0929867330666230524142632

Price: $65

Abstract

Introduction: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear.

Objective: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it.

Methods: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays.

Results: The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-- choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme.

Conclusion: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

« Previous
[1]
Watts, N.; Amann, M.; Ayeb-Karlsson, S.; Belesova, K.; Bouley, T.; Boykoff, M.; Byass, P.; Cai, W.; Campbell-Lendrum, D.; Chambers, J.; Cox, P.M.; Daly, M.; Dasandi, N.; Davies, M.; Depledge, M.; Depoux, A.; Dominguez-Salas, P.; Drummond, P.; Ekins, P.; Flahault, A.; Frumkin, H.; Georgeson, L.; Ghanei, M.; Grace, D.; Graham, H.; Grojsman, R.; Haines, A.; Hamilton, I.; Hartinger, S.; Johnson, A.; Kelman, I.; Kiesewetter, G.; Kniveton, D.; Liang, L.; Lott, M.; Lowe, R.; Mace, G.; Odhiambo Sewe, M.; Maslin, M.; Mikhaylov, S.; Milner, J.; Latifi, A.M.; Moradi-Lakeh, M.; Morrissey, K.; Murray, K.; Neville, T.; Nilsson, M.; Oreszczyn, T.; Owfi, F.; Pencheon, D.; Pye, S.; Rabbaniha, M.; Robinson, E.; Rocklöv, J.; Schütte, S.; Shumake-Guillemot, J.; Steinbach, R.; Tabatabaei, M.; Wheeler, N.; Wilkinson, P.; Gong, P.; Montgomery, H.; Costello, A. The lancet countdown on health and climate change: From 25 years of inaction to a global transformation for public health. Lancet, 2018, 391(10120), 581-630.
[http://dx.doi.org/10.1016/S0140-6736(17)32464-9] [PMID: 29096948]
[2]
Al-Azzam, S.I.; Alzoubi, K.H.; Khabour, O.; Alowidi, A.; Tawalbeh, D. The prevalence and factors associated with aspirin resistance in patients premedicated with aspirin. Acta Cardiol., 2012, 67(4), 445-448.
[http://dx.doi.org/10.1080/AC.67.4.2170686] [PMID: 22997999]
[3]
Patrono, C.; Morais, J.; Baigent, C.; Collet, J.P.; Fitzgerald, D.; Halvorsen, S.; Rocca, B.; Siegbahn, A.; Storey, R.F.; Vilahur, G. Antiplatelet agents for the treatment and prevention of coronary atherothrombosis. J. Am. Coll. Cardiol., 2017, 70(14), 1760-1776.
[http://dx.doi.org/10.1016/j.jacc.2017.08.037] [PMID: 28958334]
[4]
Lincoff, A.M.; Bittl, J.A.; Harrington, R.A.; Feit, F.; Kleiman, N.S.; Jackman, J.D.; Sarembock, I.J.; Cohen, D.J.; Spriggs, D.; Ebrahimi, R.; Keren, G.; Carr, J.; Cohen, E.A.; Betriu, A.; Desmet, W.; Kereiakes, D.J.; Rutsch, W.; Wilcox, R.G.; de Feyter, P.J.; Vahanian, A.; Topol, E.J. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA, 2003, 289(7), 853-863.
[http://dx.doi.org/10.1001/jama.289.7.853] [PMID: 12588269]
[5]
Cheng, W.; Lu, J.; Li, B.; Lin, W.; Zhang, Z.; Wei, X.; Sun, C.; Chi, M.; Bi, W.; Yang, B.; Jiang, A.; Yuan, J. effect of functional oligosaccharides and ordinary dietary fiber on intestinal microbiota diversity. Front. Microbiol., 2017, 8, 1750.
[http://dx.doi.org/10.3389/fmicb.2017.01750] [PMID: 28979240]
[6]
Roberts, A.B.; Gu, X.; Buffa, J.A.; Hurd, A.G.; Wang, Z.; Zhu, W.; Gupta, N.; Skye, S.M.; Cody, D.B.; Levison, B.S.; Barrington, W.T.; Russell, M.W.; Reed, J.M.; Duzan, A.; Lang, J.M.; Fu, X.; Li, L.; Myers, A.J.; Rachakonda, S.; DiDonato, J.A.; Brown, J.M.; Gogonea, V.; Lusis, A.J.; Garcia-Garcia, J.C.; Hazen, S.L. Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med., 2018, 24(9), 1407-1417.
[http://dx.doi.org/10.1038/s41591-018-0128-1] [PMID: 30082863]
[7]
Tang, W.H.W.; Wang, Z.; Levison, B.S.; Koeth, R.A.; Britt, E.B.; Fu, X.; Wu, Y.; Hazen, S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med., 2013, 368(17), 1575-1584.
[http://dx.doi.org/10.1056/NEJMoa1109400] [PMID: 23614584]
[8]
Qi, J.; You, T.; Li, J.; Pan, T.; Xiang, L.; Han, Y.; Zhu, L. Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: A systematic review and meta-analysis of 11 prospective cohort studies. J. Cell. Mol. Med., 2018, 22(1), 185-194.
[http://dx.doi.org/10.1111/jcmm.13307] [PMID: 28782886]
[9]
Schiattarella, G.G.; Sannino, A.; Toscano, E.; Giugliano, G.; Gargiulo, G.; Franzone, A.; Trimarco, B.; Esposito, G.; Perrino, C. Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: A systematic review and dose-response meta-analysis. Eur. Heart J., 2017, 38(39), 2948-2956.
[http://dx.doi.org/10.1093/eurheartj/ehx342] [PMID: 29020409]
[10]
Zhu, W.; Gregory, J.C.; Org, E.; Buffa, J.A.; Gupta, N.; Wang, Z.; Li, L.; Fu, X.; Wu, Y.; Mehrabian, M.; Sartor, R.B.; McIntyre, T.M.; Silverstein, R.L.; Tang, W.H.W.; DiDonato, J.A.; Brown, J.M.; Lusis, A.J.; Hazen, S.L. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 2016, 165(1), 111-124.
[http://dx.doi.org/10.1016/j.cell.2016.02.011] [PMID: 26972052]
[11]
Kanitsoraphan, C.; Rattanawong, P.; Charoensri, S.; Senthong, V. Trimethylamine N-Oxide and risk of cardiovascular disease and mortality. Curr. Nutr. Rep., 2018, 7(4), 207-213.
[http://dx.doi.org/10.1007/s13668-018-0252-z] [PMID: 30362023]
[12]
Imenshahidi, M.; Hosseinzadeh, H. Berberine and barberry (Berberis vulgaris): A clinical review. Phytother. Res., 2019, 33(3), 504-523.
[http://dx.doi.org/10.1002/ptr.6252] [PMID: 30637820]
[13]
Paul, M.; Hemshekhar, M.; Kemparaju, K.; Girish, K.S. Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity. Free Radic. Biol. Med., 2019, 130, 196-205.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.453] [PMID: 30391673]
[14]
Wang, X.; Zhang, Y.; Yang, Y.; Wu, X.; Fan, H.; Qiao, Y. Identification of berberine as a direct thrombin inhibitor from traditional Chinese medicine through structural, functional and binding studies. Sci. Rep., 2017, 7(1), 44040.
[http://dx.doi.org/10.1038/srep44040] [PMID: 28276481]
[15]
Chen, K.; Febbraio, M.; Li, W.; Silverstein, R.L. A specific CD36-dependent signaling pathway is required for platelet activation by oxidized low-density lipoprotein. Circ. Res., 2008, 102(12), 1512-1519.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.172064] [PMID: 18497330]
[16]
Grüner, S.; Prostredna, M.; Aktas, B.; Moers, A.; Schulte, V.; Krieg, T.; Offermanns, S.; Eckes, B.; Nieswandt, B. Anti-glycoprotein VI treatment severely compromises hemostasis in mice with reduced alpha2beta1 levels or concomitant aspirin therapy. Circulation, 2004, 110(18), 2946-2951.
[http://dx.doi.org/10.1161/01.CIR.0000146341.63677.3C] [PMID: 15505105]
[17]
Chen, M.; Yi, L.; Zhang, Y.; Zhou, X.; Ran, L.; Yang, J.; Zhu, J.; Zhang, Q.; Mi, M. Resveratrol attenuates trimethylamine- N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. MBio, 2016, 7(2), e02210-15.
[http://dx.doi.org/10.1128/mBio.02210-15] [PMID: 27048804]
[18]
Morris, G.M.; Huey, R.; Olson, A.J. Using AutoDock for ligand-receptor docking. Curr Protoc Bioinformatics., 2008, 8(8), 14.
[http://dx.doi.org/10.1002/0471250953.bi0814s24]
[19]
Orman, M.; Bodea, S.; Funk, M.A.; Campo, A.M.; Bollenbach, M.; Drennan, C.L.; Balskus, E.P. Structure-guided identification of a small molecule that inhibits anaerobic choline metabolism by human gut bacteria. J. Am. Chem. Soc., 2019, 141(1), 33-37.
[http://dx.doi.org/10.1021/jacs.8b04883] [PMID: 30557011]
[20]
Badimon, L.; Padró, T.; Vilahur, G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur. Heart J. Acute Cardiovasc. Care, 2012, 1(1), 60-74.
[http://dx.doi.org/10.1177/2048872612441582] [PMID: 24062891]
[21]
Lievens, D.; von Hundelshausen, P. Platelets in atherosclerosis. Thromb. Haemost., 2011, 106(5), 827-838.
[PMID: 22012554]
[22]
Gum, P.A.; Kottke-Marchant, K.; Welsh, P.A.; White, J.; Topol, E.J. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J. Am. Coll. Cardiol., 2003, 41(6), 961-965.
[http://dx.doi.org/10.1016/S0735-1097(02)03014-0] [PMID: 12651041]
[23]
Breet, N.J.; van Werkum, J.W.; Bouman, H.J.; Kelder, J.C.; Ruven, H.J.; Bal, E.T.; Deneer, V.H.; Harmsze, A.M.; van der Heyden, J.A.; Rensing, B.J.; Suttorp, M.J.; Hackeng, C.M.; ten Berg, J.M. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA, 2010, 303(8), 754-762.
[http://dx.doi.org/10.1001/jama.2010.181] [PMID: 20179285]
[24]
Puurunen, M.K.; Hwang, S.J.; Larson, M.G.; Vasan, R.S.; O’Donnell, C.J.; Tofler, G.; Johnson, A.D. ADP platelet hyperreactivity predicts cardiovascular disease in the FHS (Framingham Heart Study). J. Am. Heart Assoc., 2018, 7(5), e008522.
[http://dx.doi.org/10.1161/JAHA.118.008522] [PMID: 29502103]
[25]
McNicol, A.; Israels, S.J. Platelets and anti-platelet therapy. J. Pharmacol. Sci., 2003, 93(4), 381-396.
[http://dx.doi.org/10.1254/jphs.93.381] [PMID: 14737006]
[26]
Coccheri, S. Antiplatelet therapy: Controversial aspects. Thromb. Res., 2012, 129(3), 225-229.
[http://dx.doi.org/10.1016/j.thromres.2011.10.036] [PMID: 22119155]
[27]
Jing, W.; Huang, S.; Xiang, P.; Huang, J.; Yu, H. Dietary precursors and cardiovascular disease: A mendelian randomization study. Front. Cardiovasc. Med., 2023, 10, 1061119.
[http://dx.doi.org/10.3389/fcvm.2023.1061119] [PMID: 36844729]
[28]
Meyer, K.A.; Benton, T.Z.; Bennett, B.J.; Jacobs, D.R., Jr; Lloyd-Jones, D.M.; Gross, M.D.; Carr, J.J.; Gordon-Larsen, P.; Zeisel, S.H. Microbiota‐dependent metabolite trimethylamine N-Oxide and coronary artery calcium in the coronary artery risk development in young adults study (CARDIA). J. Am. Heart Assoc., 2016, 5(10), e003970.
[http://dx.doi.org/10.1161/JAHA.116.003970] [PMID: 27792658]
[29]
Berger, M.; Kleber, M.E.; Delgado, G.E.; März, W.; Andreas, M.; Hellstern, P.; Marx, N.; Schuett, K.A. Trimethylamine N-Oxide and adenosine diphosphate–induced platelet reactivity are independent risk factors for cardiovascular and all-cause mortality. Circ. Res., 2020, 126(5), 660-662.
[http://dx.doi.org/10.1161/CIRCRESAHA.119.316214] [PMID: 31958034]
[30]
Wang, Z.; Klipfell, E.; Bennett, B.J.; Koeth, R.; Levison, B.S.; DuGar, B.; Feldstein, A.E.; Britt, E.B.; Fu, X.; Chung, Y.M.; Wu, Y.; Schauer, P.; Smith, J.D.; Allayee, H.; Tang, W.H.W.; DiDonato, J.A.; Lusis, A.J.; Hazen, S.L. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 2011, 472(7341), 57-63.
[http://dx.doi.org/10.1038/nature09922] [PMID: 21475195]
[31]
Miao, L.; Du, J.; Chen, Z.; Shi, D.; Qu, H. Effects of microbiota-driven therapy on circulating trimethylamine-N-Oxide metabolism: A systematic review and meta-analysis. Front. Cardiovasc. Med., 2021, 8, 710567.
[http://dx.doi.org/10.3389/fcvm.2021.710567] [PMID: 34552967]
[32]
Boutagy, N.E.; Neilson, A.P.; Osterberg, K.L.; Smithson, A.T.; Englund, T.R.; Davy, B.M.; Hulver, M.W.; Davy, K.P. Probiotic supplementation and trimethylamine- N -oxide production following a high-fat diet. Obesity, 2015, 23(12), 2357-2363.
[http://dx.doi.org/10.1002/oby.21212] [PMID: 26465927]
[33]
Tenore, G.C.; Caruso, D.; Buonomo, G.; D’Avino, M.; Ciampaglia, R.; Maisto, M.; Schisano, C.; Bocchino, B.; Novellino, E. Lactofermented annurca apple puree as a functional food indicated for the control of plasma lipid and oxidative amine Levels: Results from a randomised clinical trial. Nutrients, 2019, 11(1), 122.
[http://dx.doi.org/10.3390/nu11010122] [PMID: 30634393]
[34]
Nathan, A.S.; Sen, S.; Yeh, R.W. The risk of bleeding with the use of antiplatelet agents for the treatment of cardiovascular disease. Expert Opin. Drug Saf., 2017, 16(5), 561-572.
[http://dx.doi.org/10.1080/14740338.2017.1315101] [PMID: 28387542]
[35]
Krueger, S.K.; Williams, D.E. Mammalian flavin-containing monooxygenases: Structure/function, genetic polymorphisms and role in drug metabolism. Pharmacol. Ther., 2005, 106(3), 357-387.
[http://dx.doi.org/10.1016/j.pharmthera.2005.01.001] [PMID: 15922018]
[36]
Bennett, B.J.; Vallim, T.Q.A.; Wang, Z.; Shih, D.M.; Meng, Y.; Gregory, J.; Allayee, H.; Lee, R.; Graham, M.; Crooke, R.; Edwards, P.A.; Hazen, S.L.; Lusis, A.J. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab., 2013, 17(1), 49-60.
[http://dx.doi.org/10.1016/j.cmet.2012.12.011] [PMID: 23312283]
[37]
Wang, K.; Feng, X.; Chai, L.; Cao, S.; Qiu, F. The metabolism of berberine and its contribution to the pharmacological effects. Drug Metab. Rev., 2017, 49(2), 139-157.
[http://dx.doi.org/10.1080/03602532.2017.1306544] [PMID: 28290706]
[38]
de la Visitación, N.; Robles-Vera, I.; Toral, M.; Duarte, J. Protective effects of probiotic consumption in cardiovascular disease in systemic lupus erythematosus. Nutrients, 2019, 11(11), 2676.
[http://dx.doi.org/10.3390/nu11112676] [PMID: 31694260]
[39]
Malik, M.; Suboc, T.M.; Tyagi, S.; Salzman, N.; Wang, J.; Ying, R.; Tanner, M.J.; Kakarla, M.; Baker, J.E.; Widlansky, M.E. Lactobacillus plantarum 299v supplementation improves vascular endothelial function and reduces inflammatory biomarkers in men with stable coronary artery disease. Circ. Res., 2018, 123(9), 1091-1102.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313565] [PMID: 30355158]
[40]
Rath, S.; Heidrich, B.; Pieper, D.H.; Vital, M. Uncovering the trimethylamine-producing bacteria of the human gut microbiota. Microbiome, 2017, 5(1), 54.
[http://dx.doi.org/10.1186/s40168-017-0271-9] [PMID: 28506279]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy