DOI QR코드

DOI QR Code

Cucumber (Cucumis sativus L.) Fruit and Combination with Losartan Attenuate the Elevation of Blood Pressure in Hypertensive Rats Induced by Angiotensin II

  • Tomi Hendrayana (Pharmacology and Clinical Pharmacy Research Group, School of Pharmacy, Bandung Institute of Technology) ;
  • Klaudia Yoana (Pharmacology and Clinical Pharmacy Research Group, School of Pharmacy, Bandung Institute of Technology) ;
  • I Ketut Adnyana (Pharmacology and Clinical Pharmacy Research Group, School of Pharmacy, Bandung Institute of Technology) ;
  • Elin Yulinah Sukandar (Faculty of Pharmacy, General Achmad Yani University)
  • Received : 2023.05.08
  • Accepted : 2023.09.12
  • Published : 2023.12.31

Abstract

Objectives: Cucumis sativus L. (C. sativus) is vegetable commonly used for managing blood pressure and often consumed in combination with standard antihypertensive therapy, despite lack of scientific evidence supporting their use. Combination of herbs and standard medication could have positive or negative effects. Therefore, this study aimed to evaluate the antihypertensive activity of C. sativus and the combined effect with losartan in the hypertensive rat model induced by angiotensin II. Angiotensin II is a component of the renin-angiotensin-aldosterone system that, upon binding to its receptor, constricts blood vessels leading to elevation of blood pressure. Methods: In an antihypertensive study, rats received C. sativus orally at doses of 9, 18, 27, and 36 mg/kg (full dose); while in a combination study, animals received losartan 2.25 mg/kg combined by either with C. sativus 9 or 18 mg/kg. The standards group received losartan 2.25 mg/kg or 4.5 mg/kg (full dose). Results: Blood pressure was measured using the tail-cuff method. C. sativus significantly attenuated angiotensin II-induced hypertension as observed in groups receiving C. sativus at 9, 18, 27, and 36 mg/kg at 30 minutes after induction showed the average change (Δ) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with respect to time zero were 28.8/18.3, 24.8/15.8, 22.8/15.5, and 11.5/9.0 mmHg, respectively. Whereas the average change (Δ) of SBP and DBP in the rats receiving the combination of half doses of C. sativus and losartan were 8.8/9.0 mmHg, respectively. These diminished effects were better than a full dose of C. sativus and comparable with a full dose of losartan (6.5/7.8 mmHg). Conclusion: The present findings indicate that C. sativus dose-dependently blocks blood pressure elevation induced by angiotensin II. The combination of half dose of C. sativus and losartan has an additive effect in lowering blood pressure.

Keywords

Acknowledgement

The authors would like to thank Kusnandar Anggadiredja for critically reading the manuscript and all members of the Pharmacology lab for fruitful discussions. We highly appreciate the kind assistance of staff at the School of Pharmacy ITB in conducting the research.

References

  1. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-324. Erratum in: Hypertension. 2018;71(6):e136-9. Erratum in: Hypertension. 2018;72(3):e33.
  2. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217-23. https://doi.org/10.1016/S0140-6736(05)17741-1
  3. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet. 2017;389(10064):37-55. Erratum in: Lancet. 2020;396(10255):886.
  4. Feng XL, Pang M, Beard J. Health system strengthening and hypertension awareness, treatment and control: data from the China Health and Retirement Longitudinal Study. Bull World Health Organ. 2014;92(1):29-41. https://doi.org/10.2471/BLT.13.124495
  5. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-20. Erratum in: JAMA. 2014;311(17):1809.
  6. Tabassum N, Ahmad F. Role of natural herbs in the treatment of hypertension. Pharmacogn Rev. 2011;5(9):30-40. https://doi.org/10.4103/0973-7847.79097
  7. Mansoor GA. Herbs and alternative therapies in the hypertension clinic. Am J Hypertens. 2001;14(9 Pt 1):971-5. https://doi.org/10.1016/S0895-7061(01)02172-0
  8. Kamyab R, Namdar H, Torbati M, Ghojazadeh M, Araj-Khodaei M, Fazljou SMB. Medicinal plants in the treatment of hypertension: a review. Adv Pharm Bull. 2021;11(4):601-17. https://doi.org/10.34172/apb.2021.090
  9. Al Disi SS, Anwar MA, Eid AH. Anti-hypertensive herbs and their mechanisms of action: part I. Front Pharmacol. 2016;6:323.
  10. Yuan RQ, Qian L, Yun WJ, Cui XH, Lv GX, Tang WQ, et al. Cucurbitacins extracted from Cucumis melo L. (CuEC) exert a hypotensive effect via regulating vascular tone. Hypertens Res. 2019;42(8):1152-61. https://doi.org/10.1038/s41440-019-0258-y
  11. Mali VR, Mohan V, Bodhankar SL. Antihypertensive and cardioprotective effects of the Lagenaria siceraria fruit in NG-nitroL-arginine methyl ester (L-NAME) induced hypertensive rats. Pharm Biol. 2012;50(11):1428-35. https://doi.org/10.3109/13880209.2012.684064
  12. Trejo-Moreno C, Mendez-Martinez M, Zamilpa A, JimenezFerrer E, Perez-Garcia MD, Medina-Campos ON, et al. Cucumis sativus aqueous fraction inhibits angiotensin ii-induced inflammation and oxidative stress in vitro. Nutrients. 2018;10(3):276.
  13. Palanisamy V, Shanmugam S, Balakrishnan S. Evaluation of diuretic activity of polyherbal formulation. Int J Pharm. 2015;5(1):244-7.
  14. Teixeira K, dos Santos P, Citadini-Zanette V, DalBo S, de Aguiar Amaral P. Medicinal plants that can cause changes in blood pressure and interactions with antihypertensive agents. Am J Ethnomed. 2017;4(1):1-8. https://doi.org/10.21767/2348-9502.100002
  15. Nana FW, Hilou A, Millogo JF, Nacoulma OG. Phytochemical composition, antioxidant and xanthine oxidase inhibitory activities of Amaranthus cruentus L. and Amaranthus hybridus L. extracts. Pharmaceuticals (Basel). 2012;5(6):613-28. https://doi.org/10.3390/ph5060613
  16. Kamkar-Del Y, Mohebbati R, Hosseini M, Khajavirad A, Shafei MN, Rakhshandeh H. Ethyl acetate and aqueous fractions of Ziziphus jujuba prevent acute hypertension induced by angiotensin II in rats. Cardiovasc Hematol Disord Drug Targets. 2020;20(2):108-15. https://doi.org/10.2174/1871529X19666191119141400
  17. Kazemi F, Mohebbati R, Niazmand S, Shafei MN. Antihypertensive effects of standardized asafoetida: effect on hypertension induced by angiotensin II. Adv Biomed Res. 2020;9:77.
  18. Luft FC, Wilcox CS, Unger T, Kuhn R, Demmert G, Rohmeiss P, et al. Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins. Hypertension. 1989;14(4):396-403. https://doi.org/10.1161/01.HYP.14.4.396
  19. Diz DI, Baer PG, Nasjletti A. Angiotensin II-induced hypertension in the rat. Effects on the plasma concentration, renal excretion, and tissue release of prostaglandins. J Clin Invest. 1983; 72(2):466-77. https://doi.org/10.1172/JCI110994
  20. Loiola RA, Fernandes L, Eichler R, Passaglia Rde C, Fortes ZB, de Carvalho MH. Vascular mechanisms involved in angiotensin II-induced venoconstriction in hypertensive rats. Peptides. 2011;32(10):2116-21. https://doi.org/10.1016/j.peptides.2011.09.011
  21. Zhang F, Tang H, Sun S, Luo Y, Ren X, Chen A, et al. Angiotensin-(1-7) induced vascular relaxation in spontaneously hypertensive rats. Nitric Oxide. 2019;88:1-9. https://doi.org/10.1016/j.niox.2019.03.007
  22. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest. 1996;97(8):1916-23. https://doi.org/10.1172/JCI118623
  23. Lever AF. Slow pressor mechanisms in hypertension: a role for hypertrophy of resistance vessels? J Hypertens. 1986;4(5):515-24. https://doi.org/10.1097/00004872-198610000-00001
  24. Kumar D, Kumar S, Singh J, Narender, Rashmi, Vashistha B, et al. Free radical scavenging and analgesic activities of Cucumis sativus L. fruit extract. J Young Pharm. 2010;2(4):365-8. https://doi.org/10.4103/0975-1483.71627
  25. Tuama AA, Mohammed AA. Phytochemical screening and in vitro antibacterial and anticancer activities of the aqueous extract of Cucumis sativus. Saudi J Biol Sci. 2019;26(3):600-4. https://doi.org/10.1016/j.sjbs.2018.07.012
  26. Liang J, Chen D. Advances in research on the anticancer mechanism of the natural compound cucurbitacin from Cucurbitaceae plants: a review. Tradit Med Res. 2019;4(2):68-81. https://doi.org/10.53388/TMR20190225102
  27. Krauze-Baranowska M, Cisowski W. Flavonoids from some species of the genus Cucumis. Biochem Syst Ecol. 2001;29(3):321-4. https://doi.org/10.1016/S0305-1978(00)00053-3
  28. Clark JL, Zahradka P, Taylor CG. Efficacy of flavonoids in the management of high blood pressure. Nutr Rev. 2015;73(12):799-822. https://doi.org/10.1093/nutrit/nuv048
  29. Ciumarnean L, Milaciu MV, Runcan O, Vesa sC, Rachisan AL, Negrean V, et al. The effects of flavonoids in cardiovascular diseases. Molecules. 2020;25(18):4320.
  30. Tettey CO, Yang IJ, Shin HM. Vasodilatory effect of kaempferol7-O-α-L-rhamnopyranoside via NO-cGMP-PKG signaling. Arch Biochem Biophys. 2019;667:1-5. https://doi.org/10.1016/j.abb.2019.04.001
  31. Serban MC, Sahebkar A, Zanchetti A, Mikhailidis DP, Howard G, Antal D, et al. Effects of quercetin on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5(7):e002713.
  32. Karmazyn M, Gan XT. Chemical components of ginseng, their biotransformation products and their potential as treatment of hypertension. Mol Cell Biochem. 2021;476(1):333-47. https://doi.org/10.1007/s11010-020-03910-8
  33. Niyi O, Jonathan A, Ibukun A. Comparative assessment of the proximate, mineral composition and mineral safety index of peel, pulp and seeds of cucumber (Cucumis sativus). Open J Appl Sci. 2019;9(9):691-701. https://doi.org/10.4236/ojapps.2019.99056
  34. Houston MC, Harper KJ. Potassium, magnesium, and calcium: their role in both the cause and treatment of hypertension. J Clin Hypertens (Greenwich). 2008;10(7 Suppl 2):3-11. https://doi.org/10.1111/j.1751-7176.2008.08575.x
  35. Mousavi SM, Mofrad MD, do Nascimento IJB, Milajerdi A, Mokhtari T, Esmaillzadeh A. The effect of zinc supplementation on blood pressure: a systematic review and dose-response meta-analysis of randomized-controlled trials. Eur J Nutr. 2020;59(5):1815-27. Erratum in: Eur J Nutr. 2020;59(5):1829.
  36. Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci. 2018;68(1):19-31. https://doi.org/10.1007/s12576-017-0571-7
  37. Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829-37, 837a-837d.
  38. Benjamin N, Vane J. Nitric oxide and hypertension. Circulation. 1996;94(6):1197-8. https://doi.org/10.1161/01.CIR.94.6.1197
  39. Roell KR, Reif DM, Motsinger-Reif AA. An introduction to terminology and methodology of chemical synergy-perspectives from across disciplines. Front Pharmacol. 2017;8:158.