Skip to main navigation menu Skip to main content Skip to site footer

Research Articles

Vol. 13 No. 3 (2026)

Antihypertensive and vasorelaxant activities of flavonoid glycosides from Ruta montana (L.) L. in rat

DOI
https://doi.org/10.14719/pst.9762
Submitted
1 June 2025
Published
31-07-2026 — Updated on 10-08-2026
Versions

Abstract

Species of the genus Ruta have attracted attention as a source of various classes of natural products with biological activities. This study aimed to evaluate the antihypertensive property of Ruta montana (L.) L. Flavonoid-glycosides enriched extract (RMFEE) in the Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Each treated group received, the RMFEE (150 and 400 mg/kg), orally and the blood pressure (BP) parameters were measured. Additionally, the vasorelaxant activity of RMFEE (0.75, 1.50, 2.25 and 3.75 mg/mL) was evaluated in isolated thoracic aortic rings previously contracted with epinephrine (EP; 10-5 M) or potassium chloride (KCl; 80 mM). Moreover, to investigate the signalling pathways involved in RMFEE-induced vascular relaxation of aortic rings, we employed specific pathway inhibitors. The involvement of calcium channels in the vasodilator activity of plant RMFEE (0.50 and 1 mg/mL) was also assessed using a calcium-free Krebs-Henseleit (KH) buffer. In this investigation, a sub-chronic oral administration of RMFEE (400 mg/kg body weight) demonstrated a significant systolic blood pressure-lowering effect in L-NAME-induced hypertensive rats on the 4th and 7th days (p < 0.05 and p < 0.0001 respectively). Furthermore, aortic rings pre-contracted with PE or KCl were significantly relaxed by RMFEE (p < 0.0001 and p < 0.01 respectively). The present study demonstrates that RMFEE exhibits significant antihypertensive and vasorelaxant activities via the involvement of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and vascular prostaglandin pathways. Also, the inhibition of the receptor-operated calcium channels (ROCCs) may be implicated in this pharmacological effect.

References

  1. 1. Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957-80. https://doi.org/10.1016/S0140-6736(21)01330-1
  2. 2. Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The global burden of cardiovascular diseases and risk: a compass for future health. J Am Coll Cardiol. 2022;80(25):2361-71. https://doi.org/10.1016/j.jacc.2022.11.005
  3. 3. Lee HH, Crawford EB, Cho SMJ, Krawisz AK, Juraschek SP, Cluett JL, et al. Trends in prevalence, treatment and control of cardiometabolic risk factors among adults with hypertension in the United States, 1999-2023. J Am Coll Cardiol. 2025;86(25):2577-93. https://doi.org/10.1016/j.jacc.2025.09.1607
  4. 4. Balasuriya BN, Rupasinghe HV. Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Funct Foods Health Dis. 2011;1(5):172-88. https://doi.org/10.31989/ffhd.v1i5.132
  5. 5. Kim B, Jo C, Choi HY, Lee K. Prunetin relaxed isolated rat aortic rings by blocking calcium channels. Molecules. 2018;23(9):2372. https://doi.org/10.3390/molecules23092372
  6. 6. Xu JF, Xia J, Wan Y, Yang Y, Wu JJ, Peng C, et al. Vasorelaxant activities and its underlying mechanisms of magnolia volatile oil on rat thoracic aorta based on network pharmacology. Front Pharmacol. 2022;13:812716. https://doi.org/10.3389/fphar.2022.812716
  7. 7. Paredes MD, Romecín P, Atucha NM, O'Valle F, Castillo J, Ortiz MC, et al. Beneficial effects of different flavonoids on vascular and renal function in L-NAME hypertensive rats. Nutrients. 2018;10(4):484. https://doi.org/10.3390/nu10040484
  8. 8. El-Akhal J, Oliveira AP, Bencheikh R, Valentão P, Andrade PB, Morato M. Vasorelaxant mechanism of herbal extracts from Mentha suaveolens, Conyza canadensis, Teucrium polium and Salvia verbenaca in the aorta of Wistar rats. Molecules. 2022;27(24):8752. https://doi.org/10.3390/molecules27248752
  9. 9. Abdallah HM, Hassan NA, El-Halawany AM, Mohamed GA, Safo MK, Hany El-Bassossy M. Major flavonoids from Psiadia punctulata produce vasodilation via activation of endothelial dependent NO signaling. J Adv Res. 2020;24:273-79. https://doi.org/10.1016/j.jare.2020.01.002
  10. 10. Luna-Vázquez FJ, Ibarra-Alvarado C, Rojas-Molina A, Rojas-Molina I, Zavala-Sánchez MÁ. Vasodilator compounds derived from plants and their mechanisms of action. Molecules. 2013;18(5):5814-57. https://doi.org/10.3390/molecules18055814
  11. 11. Eddouks M, Maghrani M, Lemhadri A, Ouahidi ML, Jouad H. Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). J Ethnopharmacol. 2002;82:97-103. https://doi.org/10.1016/S0378-8741(02)00164-2
  12. 12. Farid O, Hebi M, Ajebli M, El Hidani A, Eddouks M. Antidiabetic effect of Ruta montana L. in streptozotocin-induced diabetic rats. J Basic Clin Physiol Pharmacol. 2017;28(3):275-82. https://doi.org/10.1515/jbcpp-2016-0030
  13. 13. El-Ouady F, Eddouks M. Ruta montana evokes antihypertensive activity through an increase of prostaglandins release in L-NAME-induced hypertensive rats. Endocr Metab Immune Disord Drug Targets. 2021;21(2):305-14. https://doi.org/10.2174/1871530320666200628025430
  14. 14. Merghem M, Dahamna S. In-vitro antioxidant activity and total phenolic content of Ruta montana L. extracts. J Drug Deliv Ther. 2020;10(2):69-75. https://doi.org/10.22270/jddt.v10i2.3919
  15. 15. De Sa RZ, Rey A, Arganaraz E, Bindstein E. Perinatal toxicology of Ruta chalepensis (Rutaceae) in mice. J Ethnopharmacol. 2000;69(2):93-98. https://doi.org/10.1016/S0378-8741(98)00232-3
  16. 16. Raghav SK, Gupta B, Agrawal C, Goswami K, Das HR. Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells. J Ethnopharmacol. 2006;108:104-24. https://doi.org/10.1016/j.jep.2005.09.008
  17. 17. Clark JL, Zahradka P, Taylor CG. Efficacy of flavonoids in the management of high blood pressure. Nutr Rev. 2015;73:799-822. https://doi.org/10.1093/nutrit/nuv048
  18. 18. Li H, Zhang Q. Research progress of flavonoids regulating endothelial function. Pharmaceuticals (Basel). 2023;16(9):1201. https://doi.org/10.3390/ph16091201
  19. 19. Bouadid I, Amssayef A, Eddouks M. Study of the antihypertensive effect of Laurus nobilis in rats. Cardiovasc Hematol Agents Med Chem. 2023;21(1):42-54. https://doi.org/10.2174/1871525720666220512154041
  20. 20. Evans WC. Trease and Evans Pharmacognosy. 14th ed. Singapore: Harcourt Brace and Company Asia Pvt Ltd; 1997. p. 12-68.
  21. 21. Bouadid I, Akdad M, Eddouks M. Antihypertensive activity of Prunus armeniaca in hypertensive rats. Cardiovasc Hematol Agents Med Chem. 2023;21(1):20-30. https://doi.org/10.2174/1871525720666220613164559
  22. 22. Farid O, Bouadid I, Qabouche A, Azzane A, Elaydy S, Eddouks M. The acute toxicity, antioxidant and antihyperlipidemic activity of flavonoid glycosides from Ruta montana in female rats with hyperlipidemia induced by Triton WR-1339. Plant Sci Today. 2025;12(4):1-8. https://doi.org/10.14719/pst.7863
  23. 23. Ajebli M, Eddouks M. Antihypertensive activity of Petroselinum crispum through inhibition of vascular calcium channels in rats. J Ethnopharmacol. 2019;242:112039. https://doi.org/10.1016/j.jep.2019.112039
  24. 24. Amssayef A, Bouadid I, Eddouks M. Vitamin C inhibits angiotensin-converting enzyme-2 in isolated rat aortic ring. Cardiovasc Hematol Disord Drug Targets. 2021;21(4):235-42. https://doi.org/10.2174/1871529X21666211214153308
  25. 25. Damiani CE, Rossoni LV, Vassallo DV. Vasodilation effects of eugenol on rat thoracic aorta. Vasc Pharmacol. 2003;40:59-66. https://doi.org/10.1016/S1537-1891(02)00311-7
  26. 26. Wu XL, Wang YY, Cheng J, Zhao YY. Calcium channel blocking activity of calycosin, a major active component of Astragali radix, on rat aorta. Acta Pharmacol Sin. 2006;27(8):1007-12. https://doi.org/10.1111/j.1745-7254.2006.00349.x
  27. 27. Gao Y, Chen T, Raj JU. Endothelial and smooth muscle cell interactions in the pathobiology of pulmonary hypertension. Am J Respir Cell Mol Biol. 2016;54(4):451-60. https://doi.org/10.1165/rcmb.2015-0323TR
  28. 28. Puzserova A, Bernatova I. Blood pressure regulation in stress: focus on nitric oxide-dependent mechanisms. Physiol Res. 2016;65 Suppl 3:S309-42. https://doi.org/10.33549/physiolres.933442
  29. 29. Mallat RK, John CM, Kendrick DJ, Braun AP. The vascular endothelium: A regulator of arterial tone and interface for the immune system. Crit Rev Clin Lab Sci. 2017;54(7-8):458-70. https://doi.org/10.1080/10408363.2017.1394267
  30. 30. Benali T, Chtibi H, El Yamani M, Marmouzi I, Khabbach A, Achbani EH, et al. Effect of extraction solvent on total phenol content, total flavonoids content, antioxidant and antimicrobial activities against phytopathogenic and foodborne pathogens bacteria of Ruta montana extracts. Mor J Chem. 2020;8(2):552–9.
  31. 31. Maaliki D, Shaito AA, Pintus G, El-Yazbi A, Eid AH. Flavonoids in hypertension: a brief review of the underlying mechanisms. Curr Opin Pharmacol. 2019;45:57-65. https://doi.org/10.1016/j.coph.2019.04.014
  32. 32. Juma BF, Midiwo JO, Yenesew A, Waterman PG, Heydenreich M, Peter MG. Three ent-trachylobane diterpenes from the leaf exudates of Psiadia punctulata. Phytochemistry. 2006;67(13):1322-25. https://doi.org/10.1016/j.phytochem.2006.04.007
  33. 33. Xu Y, Leung S, Yeung D, Hu L, Chen GH, Che CM, et al. Structure-activity relationships of flavonoids for vascular relaxation in porcine coronary artery. Phytochemistry. 2007;68(8):1179-88. https://doi.org/10.1016/j.phytochem.2007.02.013
  34. 34. Vukics V, Guttman A. Structural characterization of flavonoid glycosides by multi-stage mass spectrometry. Mass Spectrom Rev. 2010;29(1):1-16. https://doi.org/10.1002/mas.20212
  35. 35. Johnson J, Mani J, Broszczak D, Prasad SS, Ekanayake CP, et al. Hitting the sweet spot: A systematic review of the bioactivity and health benefits of phenolic glycosides from medicinally used plants. Phytother Res. 2021;35(7):3484-508. https://doi.org/10.1002/ptr.7042
  36. 36. Oyagbemi AA, Omobowale TO, Adejumobi OA, Owolabi AM, Ogunpolu BS, et al. Antihypertensive power of naringenin is mediated via attenuation of mineralocorticoid receptor (MCR)/angiotensin converting enzyme (ACE)/kidney injury molecule (Kim-1) signaling pathway. Eur J Pharmacol. 2020;880:173142. https://doi.org/10.1016/j.ejphar.2020.173142
  37. 37. Leeya Y, Mulvany MJ, Queiroz EF, Marston A, Hostettmann K, Jansakul C. Hypotensive activity of an n-butanol extract and their purified compounds from leaves of Phyllanthus acidus (L.) Skeels in rats. Eur J Pharmacol. 2010;649(1-3):301-13. https://doi.org/10.1016/j.ejphar.2010.09.038
  38. 38. Guerrero L, Castillo J, Quinones M, Garcia-Vallve S, Arola L, et al. Inhibition of angiotensin-converting enzyme activity by flavonoids: structure-activity relationship studies. PLoS One. 2012;7(11):e49493. https://doi.org/10.1371/journal.pone.0049493
  39. 39. Ikemura M, Sasaki Y, Giddings JC, Yamamoto J. Preventive effects of hesperidin, glucosyl hesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats. Phytother Res. 2012;26(9):1272-77. https://doi.org/10.1002/ptr.3724
  40. 40. Si H, Wyeth RP, Liu D. The flavonoid luteolin induces nitric oxide production and arterial relaxation. Eur J Nutr. 2014;53:269-75. https://doi.org/10.1007/s00394-013-0525-7
  41. 41. Calderone V, Chericoni S, Martinelli C, Testai L, Nardi A, et al. Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 2004;370:290-98. https://doi.org/10.1007/s00210-004-0964-z
  42. 42. Liu D, Homan LL, Dillon JS. Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5'-monophosphate-dependent mechanism. Endocrinology. 2004;145(12):5532-39. https://doi.org/10.1210/en.2004-0102
  43. 43. Larson AJ, Symons JD, Jalili T. Quercetin: A treatment for hypertension? A review of efficacy and mechanisms. Pharmaceuticals (Basel). 2010;3(1):237-50. https://doi.org/10.3390/ph3010237
  44. 44. Zhang W, Zheng Y, Yan F, Dong M, Ren Y. Research progress of quercetin in cardiovascular disease. Front Cardiovasc Med. 2023;10:1203713. https://doi.org/10.3389/fcvm.2023.1203713
  45. 45. Kunasegaran T, Mustafa MR, Achike FI, Murugan DD. Quercetin and pioglitazone synergistically reverse endothelial dysfunction in isolated aorta from fructose-streptozotocin (F-STZ)-induced diabetic rats. Eur J Pharmacol. 2017;799:160-70. https://doi.org/10.1016/j.ejphar.2017.02.022
  46. 46. Xin M, Xu A, Tian J, Wang L, He Y, et al. Anthocyanins as natural bioactives with anti-hypertensive and atherosclerotic potential: health benefits and recent advances. Phytomedicine. 2024;132:155889. https://doi.org/10.1016/j.phymed.2024.155889
  47. 47. Liu ZM, Ho SC, Chen YM, Tomlinson B, Ho S, To K, et al. Effect of whole soy and purified daidzein on ambulatory blood pressure and endothelial function-a 6-month double-blind, randomized controlled trial among Chinese postmenopausal women with prehypertension. Eur J Clin Nutr. 2015;69(10):1161-68. https://doi.org/10.1038/ejcn.2015.24
  48. 48. Sun MY, Ye Y, Xiao L, Rahman K, Xia W, Zhang H. Daidzein: A review of pharmacological effects. Afr J Tradit Complement Altern Med. 2016;13(3):117-32. https://doi.org/10.21010/ajtcam.v13i3.15

Downloads

Download data is not yet available.