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


Cite item

Full Text

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.

Result: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.

About the authors

Hua Qu

Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences

Email: info@benthamscience.net

Ying Zhang

Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences

Email: info@benthamscience.net

Jun-he Shi

Xiyuan Hospital, China Heart Institute of Chinese Medicine,, China Academy of Chinese Medical Sciences

Email: info@benthamscience.net

Yi-han Zhao

Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences

Email: info@benthamscience.net

Jie Gao

Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences

Email: info@benthamscience.net

Zhu-ye Gao

Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

Da-zhuo Shi

Xiyuan Hospital, China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1254/jphs.93.381 PMID: 14737006
  26. Coccheri, S. Antiplatelet therapy: Controversial aspects. Thromb. Res., 2012, 129(3), 225-229. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1186/s40168-017-0271-9 PMID: 28506279

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers