Journal of Industrial Convergence (산업융합연구)

DAEHAN Society of Industrial Management (대한산업경영학회)
권호 표지
DOI QR코드

DOI QR Code

The Effect of Silymarin and Ethanol Intake on Vascular Contractility

엉겅퀴 유래 Silymarin의 단독 및 알코올 병용 시 혈압 조절 효과

  • Je, Hyun Dong (Dept. of Pharmacology, College of Pharmacy, Daegu Catholic University) ;
  • Min, Young Sil (Dept. of Pharmaceutical Science, Jungwon University)
  • 제현동 (대구가톨릭대학교 약학대학) ;
  • 민영실 (중원대학교 의약바이오학과)
  • Received : 2022.05.09
  • Accepted : 2022.07.20
  • Published : 2022.07.28
Download PDF
⟨ Previous Next ⟩

Abstract

In the study, we endeavored to assess the convergence effect of Silybum marianum-derived silymarin and epidemiologically-correlated alcohol intake on vascular contractility and to determine the mechanism involved. There were few reports addressing the question whether thin or thick filament modulation is included in ethanol and silymarin-induced regulation. We hypothesized that ethanol at a low concentration and silymarin play a role in agonist-dependent regulation of vascular contractility. Denuded arterial muscles of Sprague-Dawley male rats were suspended in organ baths and isometric tensions were transduced and recorded using isometric transducers and an automatic data acquisition system. Interestingly, both silymarin and ethanol didn't encourage silymarin alone-induced inhibition in agonists-induced contraction suggesting that endothelial nitric oxide synthesis might be involved in ethanol or silymarin-induced modulation of vascular contractility and additional pathways besides endothelial nitric oxide synthesis such as ROCK inactivation might be involved in the silymarin-induced modulation of vascular contractility.

역학 조사에서 알코올 섭취와 고혈압 증가 사이에 인과관계가 있어서 이번 연구에서 엉겅퀴 유래 silymarin의 단독 및 알코올 병용 투여에서 혈관수축 억제능을 관찰하였고 아직 불분명한 수축성 조절 기전에 대해 효능제 선택적 조절 가설을 수립하여 조사하였다. 내피가 손상된 혈관이 수조 내 현수되었고 혈관에 의한 기계적 신호가 등장력 변환기에서 전기적 신호로 변환되어 생리측정기에 표시되었다. 저농도의 ethanol과 silymarin은 혈관 내피에서 산화질소 생성 작용 외에 평활근에 대한 직접 작용으로 동맥의 수축성을 감소시킬 것으로 추측되었는데 인위적으로 내피가 손상된 동맥에서 ethanol과 병용된 silymarin이 silymarin 단독에 비해 굵은 미세섬유성 조절성 수축약 (fluoride, thromboxane mimetic)에 의한 혈관 수축 억제에 차이가 없었고 silymarin 단독에 비해 가는 미세섬유성 조절성 phorbol ester에 의한 혈관 수축억제에 차이가 없었다. 따라서 silymarin 단독은 내피 의존성 산화질소 생성과 내피에 비의존적으로 평활근에서 주로 ROCK 활성 감소에 참여하여 결과적으로 평활근에서 악틴-미오신 상호작용을 억제하여 혈관을 이완시키고 ethanol은 내피 의존성 산화질소 생성 외에 평활근에 대한 작용이 없는 것으로 생각된다.

Keywords

References

  1. L. J. Appel et al. (2003). Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA, 289(16), 2083-2093. DOI: 10.1001/jama.289.16.2083.
  2. P. J. Elmer et al. (2006). Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial. Ann Intern Med., 144(7), 485-495. DOI: 10.7326/0003-4819-144-7-200604040-00007
  3. J. R. Emberson, A. G. Shaper, S. G. Wannamethee, R. W. Morris & P. H. Whincup. (2005). Alcohol intake in middle age and risk of cardiovascular disease and mortality: accounting for intake variation over time. Am J Epidemiol, 161(9), 856-863. DOI: 10.1093/aje/kwi111
  4. H. Lee et al. (2010). Factors associated with control of blood pressure among elderly people diagnosed with hypertension in a rural area of South Korea: the Chungju Metabolic Disease Cohort Study (CMC study). Blood Press, 19(1), 31-39. DOI: 10.3109/08037050903424117
  5. W. Motz & B. E. Strauer. (1994). Benefits and risks of hypertension therapy from the cardiac viewpoint. Review Z Kardiol, 83(3), 179-187.
  6. L. Abenavoli, R. Capasso, N. Milic & Capasso, F. (2010). Milk thistle in liver diseases: past, present, future. Phytotherapy Research, 24, 1423-1432. DOI: 10.1002/ptr.3207
  7. S. Cufi et al. (2013). Silibinin meglumine, a water-soluble form of milk thistle silymarin, is an orally active anti-cancer agent that impedes the epithelial-to-mesenchymal transition (EMT) in EGFR-mutant non-small-cell lung carcinoma cells. Food and Chemical Toxicology, 60, 360-368. DOI: 10.1016/j.fct.2013.07.063
  8. A. P. Somlyo & A. V. Somlyo. (1994). Signal transduction and regulation in smooth muscle. Nature, 372, 231-236. DOI: 10.1038/372231a0
  9. A. P. Somlyo & A. V. Somlyo. (1998). From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiologica Scandinavica, 164, 437-448. DOI: 10.1046/j.1365-201X.1998.00454.x
  10. M. Uehata et al. (1997). Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature, 389, 990-994. DOI: 10.1038/40187
  11. S. Sakurada et al. (2003). Ca2+-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circulation Research, 93, 548-556. DOI : 10.1161/01.RES.0000090998.08629.60
  12. T. Kitazawa, M. Masuo & A. P. Somlyo. (1991). G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proceedings of National Academy of Sciences of USA, 88, 9307-9310.
  13. A. Gohla, G. Schultz & S. Offermanns. (2000). Roles for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction. Circulation Research, 87, 221-227. DOI : 10.1161/01.res.87.3.221
  14. T. Leung, E. Manser, L. Tan & L. Lim. (1995). A novel serine/threonine kinase binding the Rasrelated RhoA GTPase which translocates the kinase to peripheral membranes. The Journal of Biological Chemistry, 270(49), 29051-29054. DOI : 10.1074/jbc.270.49.29051
  15. T. Matsui et al. (1996). Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. The EMBO Journal, 15, 2208-2216. PMID: 8641286 https://doi.org/10.1002/j.1460-2075.1996.tb00574.x
  16. W. G. Wier & K. G. Morgan. (2003). Alpha1- adrenergic signaling mechanisms in contraction of resistance arteries. Reviews of Physiology, Biochemistry and Pharmacology, 150, 91-139. DOI : 10.1007/s10254-003-0019-8
  17. J. D. Clark et al (1997). The 1996 guide for the care and use of laboratory animals. ILAR journal, 38(1), 41-48. DOI : 10.1093/ilar.38.1.41
  18. S. Cufi et al. (2013). Silibinin meglumine, a water-soluble form of milk thistle silymarin, is an orally active anti-cancer agent that impedes the epithelial-to-mesenchymal transition (EMT) in EGFR-mutant non-small-cell lung carcinoma cells. Food Chem Toxicol, 60, 360-368. DOI : 10.1016/j.fct.2013.07.063
  19. S. B. Jeon et al (2006). A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochemical and Biophysical Research Communications, 343(1), 27-33. PMID: 16527249 https://doi.org/10.1016/j.bbrc.2006.02.120