DOI QR코드

DOI QR Code

Blood Pressure Modulating Effects of Black Raspberry Extracts in vitro and in vivo

복분자 추출물의 항고혈압 활성

  • Received : 2014.01.16
  • Accepted : 2014.03.19
  • Published : 2014.06.30

Abstract

This study aimed to investigate the effects of 50% ethanol extract of ripe black raspberry (Rubus occidentalis, RBR) on hypertension in human umbilical vein endothelial cells (HUVECs) and in spontaneously hypertensive rats (SHR). Angiotensin converting enzyme (ACE) inhibition and activation of nitric oxide production by endothelial nitric oxide synthase were significantly regulated by RBR in HUVEC cells. Moreover, the SHR showed significantly higher levels of blood pressure, ACE, renin, endothelin-1, and interleukin-6 than Wistar Kyoto rats (WKY). However, treatment with captopril and RBR decreased the levels of these hypertension-related events in the SHR. The renal arteriole showed greater media thickness/lumen diameter (%) in the SHR than in the WKY. However, media thickness/lumen diameter (%) was reduced in SHR by treatment with captopril and RBR. In addition, the number of eosinophilic cardiac muscle cells was decreased in the heart muscles after treatment with captopril and RBR. Therefore, this study suggests that 50% ethanol extract of RBR may be useful for the prevention and treatment of high blood pressure.

본 연구는 복분자 완숙과 50% 에탄올 추출물을 이용하여 인간제대정맥내피세포주(HUVEC)에서 복분자 추출물이 NO의 생성에 미치는 영향과 ACE 단백질 발현을 조사하였으며, 본태성 고혈압 흰쥐(SHR)에서 혈압강하 효과 및 혈압의 조절과 관련 깊은 인자들(renin, AT1-R, ET-1, IL-6)의 유전자 발현 그리고 혈관조직의 변화를 조사하였다. 그 결과 복분자 완숙과 50% 에탄올 추출물은 HUVEC 세포주에서 NO의 생성을 촉진하였으며 혈관수축활성을 가지는 ACE 단백질의 발현을 억제하였고 본태성 고혈압 흰쥐에게 복분자 완숙과 에탄올 50% 추출물을 8주간 투여한 결과 혈액 내 ACE의 활성이 억제되었으며 renin 및 혈관 수축인자인 ET-1 유전자의 발현이 억제되고 염증관련 유전자인 IL-6의 발현이 억제됨을 확인하였다. 그리고 신세동맥의 두께 및 심근 호산성세포수를 감소시켜 혈관내피세포의 손상을 보호하며 심장의 병변을 경감시키는 효과가 있음을 확인하였다. 본 연구 결과 복분자 완숙과 추출물은 혈압 조절과 연관된 단백질 및 유전자의 발현과 활성을 조절하고, 혈관의 두께 및 심근의 변성을 감소시켜 혈압 강하에 도움이 되는 것으로 나타났으며 향후 심혈관계 질환을 개선시킬 수 있는 식품소재로서의 가능성이 있음을 확인하였다.

Keywords

References

  1. Kim EJ, Kim HY, Lee JY, Lee JK, Kim SJ, Choi KM, Kang DG. Effect of samhwangsasim-tang, samigangap-tang and bangtan-tang on blood pressure in stroke prone spontaneously hypertensive rats. Korean J. Herbology 26: 75-80 (2011)
  2. Kim JS, Kim MJ, Park MH, Ryu BM, Moon GS. Angiotensin converting enzyme inhibition and antihypertensive effects of Phyllostachys pubescens culm extracts in spontaneously hypertensive rats. J. Korean Soc. Food Sci. Nutr. 37: 27-34 (2008) https://doi.org/10.3746/jkfn.2008.37.1.27
  3. Korea National Statistics Office. Death statistics in 2012. Korea National Statistical Office, Daejeon, Korea. pp. 3-4 (2012)
  4. Ministry of Health and Welfare. The third korea national health and nutrition examination survey; health examination. Ministry of Health and Welfare, Sejong, Korea. pp. 61-66 (2005)
  5. Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J. Manag. Care Pharm. 13: S9-20 (2007)
  6. Dhaun N, Goddard J, Kohan DE, Pollock DM, Schiffrin EL, Webb DJ. Role of endothelin-1 in clinical hypertension: 20 years on. Hypertension. 52: 452-459 (2008) https://doi.org/10.1161/HYPERTENSIONAHA.108.117366
  7. Cho HS. Effect of regular swimming training on myocardium eNOS, iNOS gene expression & elasticity of aorta in hypertensive rats. Korean J. Sport Sci. 16: 21-33 (2005)
  8. Imai T, Hirata Y, Emori T, Yanagisawa M, Masaki T, Marumo F. Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension 19: 753-757 (1996)
  9. Barton M, Cosentino F, Brandes RP, Moreau P, Shaw S, Luscher TF. Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin. Hypertension 30: 817-824 (1997) https://doi.org/10.1161/01.HYP.30.4.817
  10. Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. Renin-angiotensin system and cardiovascular risk. Lancet 369: 1208-1219 (2007) https://doi.org/10.1016/S0140-6736(07)60242-6
  11. Kang SY, Kim ND. The antihypertensive effect of red ginseng saponin and the endothelium-derived vascular relaxation. Korean J. Ginseng Sci. 16: 175-182 (1992)
  12. Choi HD, Kim YS, Choi IW, Park YK, Park YD. Hypotensive effect of germinated brown rice on spontaneously hypertensive rats. Korean J. Food Sci. Technol. 38: 448-451 (2006)
  13. Son HS, Kim HS, Kwon TB, Ju JS. Isolation, purification and hypotensive effect of bioflavonoids in Citrus sinensis. J. Korean Soc. Food Nutr. 21: 136-142 (1992)
  14. Eu GS, Chung BY, Bandopadhyay R, Yoo NH, Choi DG, Yun SJ. Phylogenic relationships of Rubus species revealed by randomly amplified polymorphic DNA markers. J. Crop Sci. Biotech. 11: 39-44 (2008)
  15. Jeong JH, Jung HN, Lee SR, Lee HJ, Hwang KT, Kim TY. Anti-oxidant, anti-proliferative and anti-inflammatory activities of the extracts from black raspberry fruits and wine. Food Chem. 123: 338-344 (2010) https://doi.org/10.1016/j.foodchem.2010.04.040
  16. Zhang Z, Knobloch TJ, Seamon LG, Stoner GD, Cohn DE, Paskett ED, Fowler JM, Weghorst CM. A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells. Gynecol. Oncol. 123: 401-406 (2011) https://doi.org/10.1016/j.ygyno.2011.07.023
  17. Wnag SY, Lin HS. Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. J. Agr. Food Chem. 48: 140-146 (2000) https://doi.org/10.1021/jf9908345
  18. Amerine MA, Ough CS. Methods for Analysis of Musts and Win. Wiley. New York, NY, USA. pp. 176-180 (1980)
  19. Chang CC, Yang MH, Wen HM, Chern JC. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J. Food Drug Anal. 10: 178-182 (2002)
  20. Ojeda D, Jimenez-Ferrer E, Zamilpa A, Herrera-Arellano A, Tortoriello J, Alvarez L. Inhibition of angiotensin converting enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. J. Ethnopharmacol. 127: 7-10 (2010) https://doi.org/10.1016/j.jep.2009.09.059
  21. Ahmed F, Siddesha JM, Urooj A, Vishwanath BS. Radical scavenging and angiotensin converting enzyme inhibitory activities of standardized extracts of Ficus racemosa stem bark. Phytother. Res. 24: 1839-1843 (2010) https://doi.org/10.1002/ptr.3205
  22. Pintoa Mda S, Kwon YI, Apostolidis E, Lajoloa FM, Genovesea MI, Shetty K. Potential of Ginkgo biloba L. leaves in the management of hyperglycemia and hypertension using in vitro models. Bioresource Technol. 100: 6599-6609 (2009) https://doi.org/10.1016/j.biortech.2009.07.021
  23. Godse S, Mohan M, Kasture V, Kasture S. Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats. Pharm. Biol. 48: 494-498 (2010) https://doi.org/10.3109/13880200903188526
  24. Song YW, Moon KS, Cho SK. Antioxidant activity and nutrient content of ethanol and hot-water extracts of Citrus unshiu pomace. J. Korean Soc. Food Sci. Nutr. 42: 1345-1350 (2013) https://doi.org/10.3746/jkfn.2013.42.9.1345
  25. Murad F. Cyclic guanosine monophosphate as a mediator of vasodilation. J. Clin. Invest. 78: 1-5 (1986) https://doi.org/10.1172/JCI112536
  26. Yoon HJ, Park SY, Oh ST, Lee KY, Yang S. 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: 44-55 (2011) https://doi.org/10.5352/JLS.2011.21.1.44
  27. Friederich JA, Butterworth JF 4th. Sodium nitroprusside: twenty years and counting. Anesth. Analg. 81: 152-162 (1995)
  28. Kim BR, Park JH, Kim SH, Cho KJ, Chang MJ. Antihypertensive properties of dried radish leaves powder in spontaneously hypertensive rats. Korean J. Nutr. 43: 561-569 (2010) https://doi.org/10.4163/kjn.2010.43.6.561
  29. Na CS, Yun H, Choi DH, Kim JS, Jo CH, Eun JB. Effects of pear phenolic compound on blood pressure, plasma renin, ANP and cardiac hypertophy in hypertensive rat induced by 2K1C. Korean J. Orient. Physiol. Pathol. 17: 363-367 (2003)
  30. Bautista LE, Vera LM, Arenas IA, Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-${\alpha}$) and essential hypertension. J. Hum. Hypertens. 19: 149-154 (2005) https://doi.org/10.1038/sj.jhh.1001785
  31. Park EJ, Kim YA, Lim DS, Gee MS, You SW, Woo HY. Comparison of hs-CRP and lipid values between hypertensive and normotensive groups. Korean J. Clin. Lab. Sci. 37: 185-189 (2005)
  32. Hong YM, Lee HR, Kim KC. Effect of small hairpin RNA molecules targeting angiotensin-converting enzyme gene in spontaneously hypertensive rats. J. Korean Soc. Hypertens. 18: 105-116 (2012) https://doi.org/10.5646/jksh.2012.18.3.105
  33. Kang CS, Jeon SY, Hong S. Effect of hyeonsamdansameum on hypertension rat induced monocrotaline. Korean J. Orient. Physiol. Pathol. 22: 1223-1235 (2008)

Cited by

  1. Screening of Biogenic Amine Non-Producing Yeast and Optimization of Culture Conditions Using Statistical Method for Manufacturing Black Raspberry Wine vol.44, pp.4, 2015, https://doi.org/10.3746/jkfn.2015.44.4.592
  2. Anti-microbial, Anti-oxidant, and Anti-thrombosis Activities of the Lees of Bokbunja Wine (Rubus coreanus Miquel) vol.25, pp.7, 2015, https://doi.org/10.5352/JLS.2015.25.7.757
  3. Effects of Rubus occidentalis extract on blood pressure in patients with prehypertension: Randomized, double-blinded, placebo-controlled clinical trial vol.32, pp.4, 2016, https://doi.org/10.1016/j.nut.2015.10.014
  4. Anti-Hypertensive Effects of Black Raspberry (Rubus occidentalis) in Spontaneously Hypertensive Rats (SHR) vol.44, pp.4, 2015, https://doi.org/10.3746/jkfn.2015.44.4.483
  5. Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial vol.19, pp.4, 2016, https://doi.org/10.1089/jmf.2015.3563
  6. Freeze-thawing Conditions to Produce High Quality Bokbunja (Rubus occidentalis) vol.46, pp.6, 2014, https://doi.org/10.9721/KJFST.2014.46.6.710
  7. Characteristics of Lactic Acid Fermentation of Black Raspberry Juice Using the Lactobacillus plantarum GBL17 Strain vol.31, pp.6, 2015, https://doi.org/10.9724/kfcs.2015.31.6.773