TẠP CHÍ KHOA HỌC YERSIN

YERSIN JOURNAL OF SCIENCE

ISSN: 2525 - 2372

Nghiên cứu tính chất bảo vệ tim mạch và khả năng gây độc của (-)-Epicatechin trên tế bào cơ tim chuột H9c2 thông qua vai trò của ERK1/2.

  • File: Tải bài viết
  • Title: Investigation cardiotoxicity and cardioprotection of (-)-epicatechin in green tea via the role of erk1/2.
  • Ngày nhận bài: 01/01/2022
  • Ngày xét duyệt: 01/02/2022
  • Ngày xuất bản: 01/03/2022
  • Tác giả: Huỳnh Hồng Đào
  • Trang: 88 - 100

Tóm tắt

Bệnh tim mạch được Tổ chức Y tế Thế giới nhận định là một trong những nguyên nhân gây tử vong hàng đầu hiện nay nếu không được phát hiện và điều trị kịp thời. Flavoids chứa trong các thực phẩm hằng ngày có liên quan chặt chẽ đến sự điều hoà huyết áp của cơ thể và giảm các nguy cơ về tim mạch. Trong nghiên cứu này, (-)-Epicatechin – một dạng flavonoid trong trà xanh được khảo sát tác dụng gây độc cho tim thông qua mô hình stress do H2O2 trong khi các đặc tính bảo vệ tim được chứng minh bằng thử nghiệm MTT và lactate dehydrogenase trên tế bào cơ tim đã biệt hóa H9c2 của chuột. Kết quả cho thấy, sau 48 giờ (-)-Epicatechin có thể gây tổn thương tế bào từ 10 µM. Tuy nhiên, khi điều trị trước với 10, 30 hoặc 100 µM (-)-Epicatechin trong 24 giờ có thể bảo vệ các tế bào H9c2 đã biệt hóa chống lại sự chết tế bào do H2O2.

Abstract

Cardiovascular disease is considered by the World Health Organization as a silent killer, which is the leading cause of death globally if it is not detected and treated promptly. Flavonoids contained in daily foods are closely related to the regulation of body blood pressure and the reduction of cardiovascular risks. In this paper, flavonoid (-)-epicatechin extracted from green tea was investigated for the cardiotoxic effects, through H2O2-induced oxidative stress modeling, while cardioprotective properties were demonstrated by MTT and lactate dehydrogenase assays on rat differentiated H9c2 cardio myoblasts with various time prolonged. Results show that after 48 hours (-)-Epicatechin can cause cell damage from 10 µM. However, pre-treatment with 10, 30, or 100 µM (-)-Epicatechin in 24 hours could protect differentiated H9c2 cells from H2O2-induced cell death.

Từ khóa

flavonoids, catechin, (-)-Epicatechin, bảo vệ tim mạch, độc tính trên tim tế bào H9c2, extracellular signal-regulated kinases, con đường tín hiệu protein kinase ERK1/2.

Tài liệu tham khảo

Bueno, O. F., 2000. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. The EMBO Journal, 19(23), 6341–6350.

Bueno, O. F., 2002. Involvement of Extracellular Signal-Regulated Kinases 1/2 in Cardiac Hypertrophy and Cell Death. Circulation Research, 91(9), 776–781.

Chen, Y., Ba, L., Huang, W., Liu, Y., Pan, H., Mingyao, E., … Cao, Y., 2017. Role of carvacrol in cardioprotection against myocardial ischemia/reperfusion injury in rats through activation of MAPK/ERK and Akt/eNOS signaling pathways. European Journal of Pharmacology, 796, 90–100. 

Daubney, J. (2015) The Cardioprotective Mechanisms of Dietary Flavonoids. Nottingham Trent University, Doctorate Dissertation.

Drouin A., Bolduc V., ThorinTrescases N., Bélanger É., Fernandes P., Baraghis E., Lesage F., Gillis M. A., Villeneuve L., Hamel E., et al., 2011. Catechin treatment improves cerebrovascular flowmediated dilation and learning abilities in atherosclerotic mice. Am J Physiol Heart Circ Physiol, 300, 10321043.

Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J., & Saltiel, A. R., 1995. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proceedings of the National Academy of Sciences, 92(17), 7686–7689.

Germack, R., & Dickenson, J. M., 2004. Characterization of ERK1/2 signalling pathways induced by adenosine receptor subtypes in newborn rat cardiomyocytes. British journal of pharmacology141(2), 329–339. 

Goldsmith, C. S., & Bell-Pedersen, D., 2013. Diverse Roles for MAPK Signaling in Circadian Clocks. Advances in Genetics, 1–39. 

Granado-Serrano, A. B., Martín, M. A., Haegeman, G., Goya, L., Bravo, L., & Ramos, S., 2010. Epicatechin induces NF-kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells. The British journal of nutrition103(2), 168–179. 

Hausenloy, D. J., & Yellon, D. M., 2007. Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection. Heart Failure Reviews, 12(3-4), 217–234.

Hu, J., Webster, D., Cao, J., & Shao, A., 2018. The safety of green tea and green tea extract consumption in adults – Results of a systematic review. Regulatory Toxicology and Pharmacology, 95, 412–433.

Janszky, I., Mukamal, K.J., Ljung, R., Ahnve, S., Ahlbom, A., Hallqvist, J., 2009. Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program. J. Intern. Med. 266, 248–257.

Li, JiaWen & Wang, XiaoYun & Zhang, Xin & Gao, Lei & Wang, LiFeng & Yin, XinHua., 2018. Epicatechin protects against myocardial ischemiainduced cardiac injury via activation of the PTEN/PI3K/AKT pathway. Molecular Medicine Reports. 17(6), 8300-8308

Liu, F., Yang, X., Geng, M., & Huang, M., 2018. Targeting ERK, an Achilles’ Heel of the MAPK pathway, in cancer therapy. Acta Pharmaceutica Sinica B, 8(4), 552–562.

Lv, L., Yao, Y., Zhao, G., & Zhu, G., 2018. Rutin inhibits coronary heart disease through ERK1/2 and Akt signaling in a porcine model. Experimental and Therapeutic Medicine, 15, 506-512. 

Mak, J. C., 2012. Potential role of green tea catechins in various disease therapies: Progress and promise. Clinical and Experimental Pharmacology and Physiology, 39(3), 265–273.

Mutlak, M., & Kehat, I., 2015. Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy. Frontiers in Pharmacology, 6.

Ortiz-Vilchis, P., Yamazaki, K. G., Rubio-Gayosso, I., Ramirez-Sanchez, I., Calzada, C., Romero-Perez, D., ... & Ceballos, G., 2014. Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling. European journal of pharmacology, 744, 76-82.

Reygaert, W. C., 2018. Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases. BioMed Research International, 2018, 1–9.

Schroeter, H., Bahia, P., Spencer, J. P., Sheppard, O., Rattray, M., Cadenas, E., Rice-Evans, C., & Williams, R. J. (2007). (-)Epicatechin stimulates ERK-dependent cyclic AMP response element activity and up-regulates GluR2 in cortical neurons. Journal of neurochemistry101(6), 1596–1606. 

Schroeter, H., Heiss, C., Balzer, J., Kleinbongard, P., Keen, C. L., Hollenberg, N. K., … Kelm, M. (2006). (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proceedings of the National Academy of Sciences, 103(4), 1024–1029.

Shaul, Y. D., & Seger, R., 2007. The MEK/ERK cascade: From signaling specificity to diverse functions. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1773(8), 1213–1226.

Sun-Mi, W., Youn-Hee, P., Hee-Jung, K., Kwon-Moo, P. and Won-Jung, L. (2006) Catechins inhibit angiotensin II-induced vascular smooth muscle cell proliferation via mitogen-activated protein kinase pathway. Experimental and molecular medicine. 38(5), 525-534.

Sun, B., Sun, G.-B., Xiao, J., Chen, R.-C., Wang, X., Wu, Y., … Sun, X.-B., 2012. Isorhamnetin inhibits H2O2-induced activation of the intrinsic apoptotic pathway in H9c2 cardiomyocytes through scavenging reactive oxygen species and ERK inactivation. Journal of Cellular Biochemistry, 113(2), 473–485.

Testai, L., Martelli, A., Cristofaro, M., Breschi, M. C., & Calderone, V., 2013. Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts. Journal of Pharmacy and Pharmacology, 65(5), 750–756.

Xu, T., Wu, X., Chen, Q., Zhu, S., Liu, Y., Pan, D., … Li, D., 2014. The Anti-Apoptotic and Cardioprotective Effects of Salvianolic Acid A on Rat Cardiomyocytes following Ischemia/Reperfusion by DUSP-Mediated Regulation of the ERK1/2/JNK Pathway. PLoS ONE, 9(7), e102292.

Yamazaki, K. G., Andreyev, A. Y., Ortiz-Vilchis, P., Petrosyan, S., Divakaruni, A. S., Wiley, S. E., … Murphy, A. N., 2014. Intravenous (−)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function. International Journal of Cardiology, 175(2), 297–306.

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