Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-Hypertensive Effects of Black Raspberry (Rubus occidentalis) in Spontaneously Hypertensive Rats (SHR)

본태성 고혈압 쥐에서 복분자 완숙과 추출물의 혈압 개선 효과

  • Received : 2014.12.16
  • Accepted : 2015.02.26
  • Published : 2015.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

The purpose of this study was to investigate the effects of 50% ethanol extracts of ripe black raspberry (Rubus occidentalis, RBR) on hypertension in spontaneously hypertensive rats (SHR). The final systolic blood pressure of the group treated with RBR for 12 weeks was significantly lower than that of the SHR group. The mRNA expression level of endothelial nitric oxide synthase (eNOS) was significantly decreased in SHR. However, treatment with RBR and captopril increased the level of eNOS mRNA in SHR. Moreover, plasma levels of homocysteine and plasminogen activator inhibitor-1 were significantly reduced by RBR. Plasma total cholesterol, high-density lipoprotein, and low-density lipoprotein cholesterol levels were lower in SHR than Wistar Kyoto rats (WKY). However, there was no significant difference in plasma triglyceride level between WKY and SHR. The number of eosinophilic cardiac muscle cells was reduced in heart muscles after treatment with captopril and RBR. Therefore, this study suggests that RBR extracts may be useful for improvement of hypertension.

본 연구는 본태성 고혈압 쥐인 SHR을 이용하여 복분자 완숙과 에탄올 50% 추출물의 혈압 강하 효과 및 그와 관련된 인자들[endothelial nitric oxide synthase(eNOS), homocysteine, plasminogen activator inhibitor-1(PAI-1), albumin, creatinine, blood lipid 등]에 미치는 영향을 조사하였다. 본태성 고혈압 쥐에게 복분자 완숙과 에탄올 50% 추출물을 12주간 투여한 결과 수축기 혈압이 고혈압대조군에 비하여 약 12% 억제되었다. 또한 eNOS 유전자 발현을 유의하게 증가하였으며 혈청 homocysteine 및 PAI-1의 활성이 눈에 띄게 감소됨을 확인하였다. 또한 심근 호산성 세포수를 감소시켜 심장의 손상 및 병변을 경감시키는 효과가 있음을 확인하였다. 그러나 혈중 지질 및 혈청 albumin, creatinine의 농도에는 각 군 간의 변화가 뚜렷하게 나타나지 않았다. 본 연구 결과 복분자 완숙과 에탄올 50% 추출물은 혈관의 손상을 야기할 수 있는 homocysteine이나 PAI-1과 같은 염증성 인자로부터 혈관을 보호하고 이를 통해 eNOS의 유전자 발현을 개선시킴으로써 혈압의 조절에 영향을 미치는 것으로 나타났으며, 향후 심혈관계 질환의 개선에 도움이 되는 식품소재로서의 가능성이 있음을 확인하였다.

Keywords

References

  1. Ministry of Health and Welfare. 2006. The third Korea National Health and Nutrition Examination Survey. Sejong, Korea. p 61-66.
  2. Lee JH, Choi HR, Lee SJ, Lee MJ, Ko YJ, Kwon JW, Lee HK, Jeong JT, Lee TB. 2014. Blood pressure modulating effects of black raspberry extract in vitro and in vivo. Korean J Food Sci Technol 46: 375-383. https://doi.org/10.9721/KJFST.2014.46.3.375
  3. Gielis JF, Lin JY, Wingler K, Van Schil PE, Schmidt HH, Moens AL. 2011. Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders. Free Radic Biol Med 50: 765-776. https://doi.org/10.1016/j.freeradbiomed.2010.12.018
  4. Yoon HJ, Park SY, Oh ST, Lee KY, Yang SY. 2001. Extract of Rubus coreanus fruits increases expression and activity of endothelial nitric oxide synthase in the human umbilical vein endothelial cells. J Life Sci 21: 44-45.
  5. Faeh D, Chiolero A, Paccaud F. 2006. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about it? Swiss Med Wkly 136: 745-756.
  6. Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H. 2005. Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 66: 276-285. https://doi.org/10.1016/j.cardiores.2004.11.013
  7. Lee SW, Koo ES, Kim BS, Kang JH, Lee MH, Park JR, Shin HC, Jung HW, Lee HS. 1998. The relationships between blood pressure and serum lipids in Korean adults. Korean Circ J 28: 1552-1560. https://doi.org/10.4070/kcj.1998.28.9.1552
  8. Atlas SA. 2007. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm 13: S9-20.
  9. Lee J, Dossett M, Finn CE. 2013. Anthocyanin fingerprinting of true bokbunja (Rubus coreanus Miq.) fruit. J Funct Foods 5: 1985-1990. https://doi.org/10.1016/j.jff.2013.06.006
  10. Lee MJ, Lee SJ, Choi HR, Lee JH, Kwon JW, Chae KS, Jeong JT, Lee TB. 2014. Improvement of cholesterol and blood pressure in fruit, leaf and stem extracts from black raspberry in vitro. Korean J Medicinal Sci 22: 177-187. https://doi.org/10.7783/KJMCS.2014.22.3.177
  11. Jeong JH, Jung H, Lee SR, Lee HJ, Hwang KT, Kim TY. 2010. Anti-oxidant, anti-proliferative and anti-inflammatory activities of the extracts from black raspberry fruits and wine. Food Chem 123: 338-344. https://doi.org/10.1016/j.foodchem.2010.04.040
  12. Zhang Z, Knobloch TJ, Seamon LG, Stoner GD, Cohn DE, Paskett ED, Fowler JM, Weghorst CM. 2011. A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells. Gynecol Oncol 123: 401-406. https://doi.org/10.1016/j.ygyno.2011.07.023
  13. Wang SY, Lin HS. 2000. Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. J Agric Food Chem 48: 140-146. https://doi.org/10.1021/jf9908345
  14. Lee MJ, Lee SJ, Choi HR, Lee JH, Jeong JT, Choi KM, Cha JD, Hwang SM, Park JH, Lee JH, Lee TB. 2014. Cholesterol improvement effects of co-treatment with black raspberry and red ginseng extracts in mice fed a high cholesterol diet. J Korean Soc Food Sci Nutr 43: 1491-1499. https://doi.org/10.3746/jkfn.2014.43.10.1491
  15. Friedewald WT, Levy RI, Fredrickson DS. 1972. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499-502.
  16. Ghassibe-Sabbagh M, Platt DE, Youhanna S, Abchee AB, Stewart K, Badro DA, Haber M, Salloum AK, Douaihy B, el Bayeh H, Othman R, Shasha N, Kibbani S, Chammas E, Milane A, Nemr R, Kamatani Y, Hager J, Cazier JB, Gauguier D, Zalloua PA. 2012. Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk. Atherosclerosis 222: 180-186. https://doi.org/10.1016/j.atherosclerosis.2012.02.035
  17. Pang X, Liu J, Zhao J, Mao J, Zhang X, Feng L, Han C, Li M, Wang S, Wu D. 2014. Homocysteine induces the expression of C-reactive protein via NMDAr-ROS-MAPKNF-${\kappa}B$ signal pathway in rat vascular smooth muscle cells. Atherosclerosis 236: 73-81. https://doi.org/10.1016/j.atherosclerosis.2014.06.021
  18. Undas A, Brozek J, Szczeklik A. 2005. Homocysteine and thrombosis: from basic science to clinical evidence. Thromb Haemost 94: 907-915.
  19. Unlu Y, Keles S, Becit N, Kocogullari CU, Kocak H, Bakan E. 2005. Hyperhomocysteinaemia as a risk factor for deepvein thrombosis. Eur J Vasc Endovasc Surg 30: 315-318. https://doi.org/10.1016/j.ejvs.2005.05.002
  20. den Heijer M, Blom HJ, Gerrits WB, Rosendaal FR, Haak HL, Wijermans PW, Bos GM. 1995. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis? Lancet 345: 882-885. https://doi.org/10.1016/S0140-6736(95)90008-X
  21. Kang HJ, Han KH, Choe SC, Kim HS, Sohn DW, Oh BH, Lee MM, Park YB, Choi YS, Lee YW. 1998. 4G/5G polymorphism of plasminogen activator inhibitor-1 gene and its effects on coronary artery disease. Korean Circ J 28: 1105-1111. https://doi.org/10.4070/kcj.1998.28.7.1105
  22. Midorikawa S, Sanada H, Hashimoto S, Watanabe T. 2000. Enhancement by homocysteine of plasminogen activator inhibitor-1 gene expression and secretion from vascular endothelial and smooth muscle cells. Biochem Biophys Res Commun 272: 182-185. https://doi.org/10.1006/bbrc.2000.2753
  23. Kerins DM, Hao Q, Vaughan DE. 1995. Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest 96: 2515-2520. https://doi.org/10.1172/JCI118312
  24. Vaughan DE. 1998. Fibrinolytic balance, the renin-angiotensin system and atherosclerotic disease. Eur Heart J 19: G9-12.
  25. Nishimura H, Tsuji H, Masuda H, Kasahara T, Yoshizumi M, Sugano T, Kimura S, Kawano H, Kunieda Y, Yano S, Nakagawa K, Kitamura H, Nakahara Y, Sawada S, Nakagawa M. 1999. The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells. Thromb Haemost 82: 1516-1521.
  26. Brown NJ, Nadeau JH, Vaughan DE. 1997. Selective stimulation of tissue-type plasminogen activator (t-PA) in vivo by infusion of bradykinin. Thromb Haemost 77: 522-525.
  27. Li H, Forstermann U. 2000. Nitric oxide in the pathogenesis of vascular disease. J Pathol 190: 244-254. https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<244::AID-PATH575>3.0.CO;2-8
  28. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC. 1995. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377: 239-242. https://doi.org/10.1038/377239a0
  29. Aisaka K, Gross SS, Griffith OW, Levi R. 1989. NG-methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochem Biophys Res Commun 160: 881-886. https://doi.org/10.1016/0006-291X(89)92517-5
  30. Rees DD, Palmer RM, Moncada S. 1989. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86: 3375-3378.
  31. Park SH, Hahm TS, Han JH. 2005. Effects of ethanol-extract of lotus root in the renal function and blood pressure of fructose-induced hypertensive rats. J East Asian Soc Dietary Life 15: 165-170.
  32. Henry JB. 2001. Clinical diagnosis and management by laboratory methods. 20th ed. WB Saunders Company, Philadelphia, PA, USA. p 17-19.
  33. Pagana KD, Pagana TJ. 1998. Mosby's manual of diagnostic and laboratory test. Mosby Inc., St. Louis, MO, USA. p 97-100.
  34. Glodny B, Unterholzner V, Taferner B, Hofmann KJ, Rehder P, Strasak A, Petersen J. 2009. Normal kidney size and its influencing factors: a 64-slice MDCT study of 1.040 asymptomatic patients. BMC Urol 9: 19. https://doi.org/10.1186/1471-2490-9-19
  35. Høstmark AT, Tomten SE, Berg JE. 2005. Serum albumin and blood pressure: a population-based, cross-sectional study. J Hypertens 23: 725-730. https://doi.org/10.1097/01.hjh.0000163139.44094.1d
  36. Menne J, Chatzikyrkou C, Haller H. 2010. Microalbuminuria as a risk factor: the influence of renin-angiotensin system blockade. J Hypertens 28: 1983-1994. https://doi.org/10.1097/HJH.0b013e32833c206d
  37. Hu H, Sparrow D, Weiss S. 1992. Association of serum albumin with blood pressure in the normative aging study. Am J Epidemiol 136: 1465-1473. https://doi.org/10.1093/oxfordjournals.aje.a116467
  38. Jung YS, Kim IS, Park SJ, Kim KM, Lee KJ, Kwak MH, Kim TH, Kim CJ, Ryu WS, Ryoo UH, Song KY, Cho SH. 1997. Ultrastructural changes of the aorta in spontaneously hypertensive rats and the effect of high cholesterol diet. Korean Circ J 27: 633-643. https://doi.org/10.4070/kcj.1997.27.6.633