Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Cardioprotective Potential of Gracilaria Verrucosa Extract in Myocardial Infarction-Induced Heart Failure Model

심근 경색 유발 심부전 모델에서 강리 추출물의 심장 보호 가능성

  • Youn Jae Jang (Hanbang Cardio-Renal Syndrome Research Center, Wonkwnag University) ;
  • Hye Yoom Kim (Hanbang Cardio-Renal Syndrome Research Center, Wonkwnag University) ;
  • Jung Joo Yoon (Hanbang Cardio-Renal Syndrome Research Center, Wonkwnag University) ;
  • Byung Hyuk Han (Hanbang Cardio-Renal Syndrome Research Center, Wonkwnag University) ;
  • Je Kuk Yu (Professional Graduate School of Korean Medicine, Wonkwang University) ;
  • Nam Geun Cho (Professional Graduate School of Korean Medicine, Wonkwang University) ;
  • Ho Sub Lee (Hanbang Cardio-Renal Syndrome Research Center, Wonkwnag University) ;
  • Dae Gill Kang (Hanbang Cardio-Renal Syndrome Research Center, Wonkwnag University)
  • 장윤재 (원광대학교 한방심신증후군연구센터) ;
  • 김혜윰 (원광대학교 한방심신증후군연구센터) ;
  • 윤정주 (원광대학교 한방심신증후군연구센터) ;
  • 한병혁 (원광대학교 한방심신증후군연구센터) ;
  • 유제국 (원광대학교 한의학전문대학원) ;
  • 조남근 (원광대학교 한의학전문대학원) ;
  • 이호섭 (원광대학교 한방심신증후군연구센터) ;
  • 강대길 (원광대학교 한방심신증후군연구센터)
  • Received : 2023.07.11
  • Accepted : 2023.08.18
  • Published : 2023.08.31
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Abstract

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

Keywords

Acknowledgement

본 논문의 연구는 원광대학교 (2023)의 지원을 받아 수행되었으며 이에 감사드립니다.

References

  1. Minicucci MF, Azevedo PS, Polegato BF, Paiva SAR, Zornoff AML. Heart Failure after Myocardial Infarction: Clinical Implications and Treatment. Clin Cardiol. 2011;34:410-414.  https://doi.org/10.1002/clc.20922
  2. Velagaleti R, Vasan RS. Heart Failure in the 21st Century: Is it a Coronary Artery Disease Problem or Hypertension Problem? Cardiol Clin. 2007;25:487-495.  https://doi.org/10.1016/j.ccl.2007.08.010
  3. Schirone L, Forte M, Palmerio S, Yee D, Nocella C, Angelini F, et al. A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling. Oxid Med Cell Longev. 2017;2017:3920195. 
  4. Martin GS, John S, Norman S. Left Ventricular Remodeling After Myocardial Infarction. Circulation. 2000;101(25):2981-2988.  https://doi.org/10.1161/01.CIR.101.25.2981
  5. Ilayaraja M, Marleen L, Frank J, Bart DG. Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Postmyocardial Infarction Remodeling and Heart Failure. J Vis Exp. 2014;(94):52206. 
  6. Michael LH, Entman ML, Hartley CJ, Youker KA, Zhu J, Hall SR, Hawkins HK, Berens K, Ballantyne CM. Myocardial Ischemia and Reperfusion: A Murine Model. Am J Physiol. 1995;269(6 Pt 2):H2147-H2154.  https://doi.org/10.1152/ajpheart.1995.269.6.H2147
  7. Feng Y, Hemmeryckx B, Frederix L, Lox M, Wu J, Heggermont W, et al. Monitoring Reperfused Myocardial Infarction with Delayed Left Ventricular Systolic Dysfunction in Rabbits by Longitudinal Imaging. Imaging Med Surg. 2018;8:754-769.  https://doi.org/10.21037/qims.2018.09.05
  8. Gheorghiad M, Fonarow GC. Management of Post-Myocardial Infarction Patients with Left Ventricular Systolic Dysfunction. Am J Med. 2007;120:109-120.  https://doi.org/10.1016/j.amjmed.2005.08.010
  9. Brienesse SC, Davies AJ, Khan A, Boyle AJ. Prognostic Value of LVEDP in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis. J Cardiovasc Transl Res. 2018;11:33-35.  https://doi.org/10.1007/s12265-017-9776-7
  10. Sjblom J, Muhrbeck J, Witt N, Alam M, Frykman-Kull V. Evolution of Left Ventricular Ejection Fraction After Acute Myocardial Infarction. Circulation. 2014;130:743-748.  https://doi.org/10.1161/CIRCULATIONAHA.114.009924
  11. Ishikawa K, Chemaly RE, Tilemann L, Fish K, Ladage D, Aguero J, et al. Assessing Left Ventricular Systolic Dysfunction After Myocardial Infarction: Are Ejection Fraction and dP/dtmax Complementary or Redundant? Am J Physiol Heart Circ Physiol. 2012;302:H1423-H1428.  https://doi.org/10.1152/ajpheart.01211.2011
  12. French BA, Kramer MC. Mechanisms of Post-Infarct Left Ventricular Remodeling. Today Dis Mech. 2007;4:185-196.  https://doi.org/10.1016/j.ddmec.2007.12.006
  13. de Jong S, van Veen TA, de Bakker JM, van Rijen HV. Monitoring cardiac fibrosis: a technical challenge. Neth Heart J. 2012, 20(1):44-8.  https://doi.org/10.1007/s12471-011-0226-x
  14. Khan R, Sheppard R. Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia. Immunology. 2006, 118(1):10-24.  https://doi.org/10.1111/j.1365-2567.2006.02336.x
  15. Hata A, Chen YG. TGF-β Signaling from Receptors to Smads. Cold Spring Harb Perspect Biol. 2016, 8(9):a022061. 
  16. Buwaneka P, Ralko A, Gorai S, Pham H, Cho W. Phosphoinositide-binding activity of Smad2 is essential for its function in TGF-β signaling. J Biol Chem. 2021, 297(5):101303. 
  17. Goumans MJ, Ten Dijke P. TGF-β Signaling in Control of Cardiovascular Function. Cold Spring Harb Perspect Biol. 2018, 10(2):a022210. 
  18. Jeon US, Jeong JG. A Herbological Study on the Phaeophyta Growing in the Korean Coastal Waters. Kor J Herbol. 2021；36(4):9-22. 
  19. Ryu DH, Roh SS. A Systematic Review of Clinical Researches of Korean Medicine for Alopecia. J Korean Med Ophthalmol Otolaryngol Dermatol 2017;30(2):1-18. 
  20. Park EK, Kim HW, Ji YH, Park SH. Moisturizing and Skin Improvement Effect of Polysaccharides from Gracilariopsis sp. J Mar Biosci Biotechnol. 2017:58-64. 
  21. Choi MH, Kim YW, Kim MS, Shin HJ. Development of Cosmetic Emulsion Using Blueberry Fruit Extract and Agarose from Gracilaria verrucosa. KSBB J. 2016; 31(4):256-262.  https://doi.org/10.7841/ksbbj.2016.31.4.256
  22. Hong SM, Cho HD, Kim JH, Lee JH, Song WS, Lee ST, Lee MK, Seo KI. Anti-proliferative Effects of Acid Extract of Gracilaria Verrucosa on Primary Human Prostate Cancer Cells. J Life Sci. 2016;26(10):1130-1136.  https://doi.org/10.5352/JLS.2016.26.10.1130
  23. Dang HT, Lee HJ, Yoo ES, Shinde PB, Lee YB, Hong JK, Kim DH, Jung JH. Anti-inflammatory constituents of the red alga Gracilaria verrucosa and their synthetic analogues. J Nat Prod. 2008;72:232-240.  https://doi.org/10.1021/np070452q
  24. Imbs AB, Bologodskaya AA, Nevshupova NV, Kho-timchenko SV, Titlyanov EA. Response of prostaglandin content in the red alga Gracilaria verrucosa to season and solar irradiance. Phytochemistry. 2001;58:1067-1072.  https://doi.org/10.1016/S0031-9422(01)00321-1
  25. Shin JH, Choi DJ, Lim HC, Seo JK, Lee SJ, Choi SY, Sung NJ. Nutrients and antioxidant activity of red seaweeds. J Life Sci. 2006;16:400-408.  https://doi.org/10.5352/JLS.2006.16.3.400
  26. JX LIU, Z YU, XZ LI, JJ FU, XH SHANG, AG YAN, Y SHI, YL MA. Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine. Acta Pharmacol Sin. 2007;28(1):52-57.  https://doi.org/10.1111/j.1745-7254.2007.00464.x
  27. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, et al. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022;145(8):e153-e639. 
  28. Mann DL, Bristow MR. Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation. 2005;111(21): 2837-2849.  https://doi.org/10.1161/CIRCULATIONAHA.104.500546
  29. Wu Y, Yin X, Wijaya C, Huang MH, McConnell BK. Acute Myocardial Infarction in Rats. J Vis Exp. 2011;(48):2464. 
  30. Johns TN, Olson BJ. Experimental myocardial infarction. I.A method of coronary occlusion in small animals. Ann Surg. 1954;140(5):675-682.  https://doi.org/10.1097/00000658-195411000-00006
  31. Kogan ME, Belov LN, Leont'eva TA, Zolotareva AG. Modeling of myocardial pathology in mice with the surgical methods. Kardiologiia. 1977;17(6):125-128. 
  32. Zolotareva AG, Kogan ME. Production of experimental occlusive myocardial infarction in mice. Cor Vasa. 1978;20(4):308-314. 
  33. Frangogiannis NG. The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol. 2014;11(5):255-265.  https://doi.org/10.1038/nrcardio.2014.28
  34. Kirkpatrick JN, Vannan MA, Narula J, Lang RM. Echocardiography in Heart Failure: Applications, Utility, and New Horizons. J Am Coll Cardiol. 2007;50:381-396.  https://doi.org/10.1016/j.jacc.2007.03.048
  35. Degabriele NM, Griesenbach U, Sato K, Post MJ, Zhu J, et al. Critical Appraisal of the Mouse Model of Myocardial Infarction. Exp Physiol. 2004;89:497-505.  https://doi.org/10.1113/expphysiol.2004.027276
  36. Shioura KM, Geenen DL, Goldspink PH. Assessment of Cardiac Function with the Pressure-Volume Conductance System Following Myocardial Infarction in Mice. Heart Circ Physiol. 2007;293:H2870-H2877.  https://doi.org/10.1152/ajpheart.00585.2007
  37. Bastos MB, Burkhoff D, Maly J, Daemen J, den Uil CA, et al. Invasive Left Ventricle Pressure-Volume Analysis: Overview and Practical Clinical Implications. Eur Heart J. 2020;41:1286-1297.  https://doi.org/10.1093/eurheartj/ehz552
  38. Bodor GS. Biochemical Markers of Myocardial Damage. Int EJIFCC. 2016;27:95-111. 
  39. Khalil ML, Ahmmed I, Ahmed R, Tanvir EM, Afroz R, Paul S, et al. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania Somnifera Leaf Extract. Biomed Res Int. 2015;624159. 
  40. Zong J, Zhang H, Li FF, Liang K, Liu JL, Xu LH, Qian WH. NLRP1 promotes TGF-β 1-induced myofibroblast differentiation in neonatal rat cardiac fibroblasts. J Mol Histol. 2018;49(5):509-518.  https://doi.org/10.1007/s10735-018-9789-9
  41. McCurdy S, Baicu CF, Heymans S, Bradshaw AD. Cardiac extracellular matrix remodeling: fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC). J Mol Cell Cardiol. 2010;48(3):544-549.  https://doi.org/10.1016/j.yjmcc.2009.06.018
  42. Frangogiannis NG. Transforming growth factor-β in myocardial disease. Nat Rev Cardiol. 2022;19(7):435-455. https://doi.org/10.1038/s41569-021-00646-w