Generic placeholder image

Cardiovascular & Hematological Disorders-Drug Targets


ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

Research Article

Antihypertensive and Vasorelaxant Effects of Hibiscus rosa-sinensis through Angiotensin-Converting Enzyme-2 (ACE-2), and Ca2+ Channels Pathways

Author(s): Smail Amtaghri, Ayoub Amssayef, Miloudia Slaoui and Mohamed Eddouks*

Volume 22, Issue 1, 2022

Published on: 25 March, 2022

Page: [27 - 37] Pages: 11

DOI: 10.2174/1871529X22666220329190331

Price: $65


Aims: The aim of the study was to assess the antihypertensive activity of Hibiscus rosasinensis. Background: Hibiscus rosa-sinensis is used traditionally to treat hypertension.

Objective: The goal of the study was to investigate the effect of the aqueous extract of Hibiscus rosa- sinensis flowers (AEHRS) on resting blood pressure in rats.

Methods: In the present study, AEHRS was prepared, and its antihypertensive activity was evaluated using in vivo and in vitro studies. In the in vivo study, hypertensive and normotensive rats were treated by AEHRS (100 mg/kg) orally for 6 hours in the acute treatment and for 7 days in the subchronic treatment. Systolic, diastolic, and mean arterial blood pressure values and heart rate were then recorded using a tail-cuff and a computer-assisted monitoring device. To assess the vasorelaxant activity of AEHRS, isolated thoracic aortic rings were suspended in a tissue bath, and changes in tension were recorded using a data acquisition system. Potential pathways involved in the vasorelaxant activity were evaluated using several standard pharmacological agents.

Results: The results indicated that repeated oral administration of AEHRS during 7 days lowered systolic, diastolic, and mean arterial blood pressure in hypertensive rats without affecting normotensive rats. Furthermore, the data revealed that AEHRS exerts vasorelaxant properties via an endothelium- independent pathway. More interestingly, the study demonstrates that the vasorelaxant capacity of AEHRS seems to be exerted through the stimulation of angiotensin-converting enzyme-2 (ACE-2) and the inhibition of Ca2+ channels pathway.

Conclusion: The present study revealed that aqueous extract of Hibiscus rosa-sinensis has a significant antihypertensive activity and that its vasorelaxant effect may be mediated through stimulation of ACE-2, and inhibition of the Ca2+ channels.

Keywords: Hibiscus rosa-sinensis, hypertension, l-name, vasorelaxant, angiotensin-converting enzyme-2(ACE2), calcium channels.

Graphical Abstract
Touyz, R.M.; Alves-Lopes, R.; Rios, F.J.; Camargo, L.L.; Anagnostopoulou, A.; Arner, A.; Montezano, A.C. Vascular smooth muscle contraction in hypertension. Cardiovasc. Res., 2018, 114(4), 529-539.
[] [PMID: 29394331]
Meyler, L.; Dukes, M.N.G.; Al Disi, S.S.; Anwar, M.A.; Eid, A.H. Anti-hypertensive herbs and their mechanisms of action: Part I. Front. Pharmacol., 2016, 6, 323.
[] [PMID: 26834637]
Kizhakekuttu, T.J.; Widlansky, M.E. Natural antioxidants and hypertension: Promise and challenges. Cardiovasc. Ther., 2010, 28(4), e20-e32.
[] [PMID: 20370791]
Tabassum, N.; Ahmad, F. Role of natural herbs in the treatment of hypertension. Pharmacogn. Rev., 2011, 5(9), 30-40.
[] [PMID: 22096316]
Archer, J.S. Evaluation and treatment of hypertension. Primary Care Update for OB/GYNS., 2000, 7(1), 1-6.
Weber, M.A.; Schiffrin, E.L.; White, W.B.; Mann, S.; Lindholm, L.H.; Kenerson, J.G.; Flack, J.M.; Carter, B.L.; Materson, B.J.; Ram, C.V.; Cohen, D.L.; Cadet, J.C.; Jean-Charles, R.R.; Taler, S.; Kountz, D.; Townsend, R.; Chalmers, J.; Ramirez, A.J.; Bakris, G.L.; Wang, J.; Schutte, A.E.; Bisognano, J.D.; Touyz, R.M.; Sica, D.; Harrap, S.B. Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of Hypertension. J. Hypertens., 2014, 32(1), 3-15.
[] [PMID: 24270181]
Singh, P.; Mishra, A.; Singh, P.; Goswami, S.; Singh, A. Hypertension and herbal plant for its treatment: A review. IJRPB, 2015, 3(5), 358-366.
Adhirajan, N.; Ravi Kumar, T.; Shanmugasundaram, N.; Babu, M. In vivo and in vitro evaluation of hair growth potential of Hibiscus rosa-sinensis Linn. J. Ethnopharmacol., 2003, 88(2-3), 235-239.
[] [PMID: 12963149]
Chadha, Y.R. The wealth of India: A dictionary of Indian raw materials and industrial products. Publication Information Directorate. CSIR, New Delhi, 1976, 10, 522-524.
Mhaskar, K.S.; Blatter, E.; Caius, J.F.; Ram, V.A. Kirtikar and Basu’s illustrated Indian medicinal plants: Their usage in Ayurveda and Unani medicines; Sri Satguru Publications: Delhi, 2000, Vol. 1, .
Pekamwar, S.; Kalyankar, T.M.; Jadhav, A.C. Hibiscus rosa-sinecis: A review on ornamental plant. World J. Pharm. Pharm. Sci., 2013, 4719-4727.
Sharma, K.; Shukla, S.; Chauhan, E.S. Evaluation of aegle marmelos (Bael) as hyperglycemic and hyperlipidemic diminuting agent in type ii diabetes mellitus subjects. Pharma Innov., 2016, 5(5), 43-46.
Kalpesh, G.; Kori, M.L.; Nema, R.K. Investigation of immunomodulatory potential of hydro-alcoholic extracts of Euphorbia neriifolia Linn. and Hibiscus rosa-sinensis Linn. Int J Med Sci (India), 2009, 2, 61-65.
Upadhyay, S.M.; Upadhyay, P.; Ghosh, A.K.; Singh, V.; Dixit, V.K. Effect of ethanolic extract of Hibiscus rosa-sinensis L. flowers on hair growth in female wistar rats. Pharm. Lett., 2011, 3, 258-263.
Nayak, D.; Ashe, S.; Rauta, P.R.; Nayak, B. Biosynthesis, characterisation and antimicrobial activity of silver nanoparticles using Hibiscus rosa-sinensis petals extracts. IET Nanobiotechnol., 2015, 9(5), 288-293.
[] [PMID: 26435282]
Khalid, L.; Rizwani, G.H.; Sultana, V.; Zahid, H.; Khursheed, R.; Shareef, H. Antidepressant activity of ethanolic extract of Hibiscus rosa sinenesis Linn. Pak. J. Pharm. Sci., 2014, 27(5), 1327-1331.
[PMID: 25176367]
Shewale, P.B.; Patil, R.A.; Hiray, Y.A. Antidepressant-like activity of anthocyanidins from Hibiscus rosa-sinensis flowers in tail suspension test and forced swim test. Indian J. Pharmacol., 2011, 5.
[] [PMID: 23087504]
Afiune, L.A.F.; Leal-Silva, T.; Sinzato, Y.K.; Moraes-Souza, R.Q.; Soares, T.S.; Campos, K.E.; Fujiwara, R.T.; Herrera, E.; Damasceno, D.C.; Volpato, G.T. Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes. PLoS One, 2017, 12(6), e0179785.
[] [PMID: 28644857]
Bhaskar, A.; Nithya, V. Evaluation of the wound-healing activity of Hibiscus rosa sinensis L (Malvaceae) in Wistar albino rats. Indian J. Pharmacol., 2012, 44(6), 694-698.
[] [PMID: 23248396]
Shivananda Nayak, B.; Sivachandra Raju, S.; Orette, F.A.; Chalapathi Rao, A.V. Effects of Hibiscus rosa sinensis L (Malvaceae) on wound healing activity: A preclinical study in a Sprague Dawley rat. Int. J. Low. Extrem. Wounds, 2007, 6(2), 76-81.
[] [PMID: 17558005]
Gauthaman, K.K.; Saleem, M.T.; Thanislas, P.T.; Prabhu, V.V.; Krishnamoorthy, K.K.; Devaraj, N.S.; Somasundaram, J.S. Cardioprotective effect of the Hibiscus rosa sinensis flowers in an oxidative stress model of myocardial ischemic reperfusion injury in rat. BMC Complement. Altern. Med., 2006, 6(1), 32.
[] [PMID: 16987414]
Dwivedi, R.N.; Pandey, S.P.; Tripathi, V.J. Role of Japapushpa in the treatment of arterial hypertension. A trial study. J Res Ind Med. Yoga Homeopathy, 1977, 12, 13-36.
Kate, I.E.; Lucky, O.O. The effects of aqueous extracts of the leaves of Hibiscus rosa-sinensis Linn. on renal function in hypertensive rats. Afr. J. Biochem. Res., 2010, 4(2), 43-46.
Khare, C.P. Indian medicinal plants: An illustrated dictionary; Springer Science & Business Media, 2007.
Ajebli, M.; Eddouks, M. Buxus sempervirens L improves streptozotocin-induced diabetes mellitus in rats. Cardiovasc. Hematol. Disord. Drug Targets, 2017, 17(2), 142-152.
Ajebli, M.; Eddouks, M. Antihypertensive activity of Petroselinum crispum through inhibition of vascular calcium channels in rats. J. Ethnopharmacol., 2019, 242, 112039.
[] [PMID: 31252093]
de Carvalho, E.F.; Nunes, A.F.; Silva, N.C.B.; da Silva Gomes, J.P.; de Sousa, R.P.; Silva, V.G.; Nunes, P.H.M.; Santos, R.F.; Chaves, M.H.; Oliveira, A.P.; Oliveira, R.C.M. Terminalia fagifolia Mart. & Zucc. elicits vasorelaxation of rat thoracic aorta through nitric oxide and K+ channels dependent mechanism. Biol. Open, 2019, 8(2), bio035238.
[] [PMID: 30683674]
Anwar, M.A.; Samaha, A.A.; Ballan, S.; Saleh, A.I.; Iratni, R.; Eid, A.H. Salvia fruticosa induces vasorelaxation in rat isolated thoracic aorta: Role of the PI3K/Akt/eNOS/NO/cGMP signaling pathway. Sci. Rep., 2017, 7(1), 686.
[] [PMID: 28386068]
Kopincová, J.; Púzserová, A.; Bernátová, I. L-NAME in the cardiovascular system - nitric oxide synthase activator? Pharmacol. Rep., 2012, 64(3), 511-520.
[] [PMID: 22814004]
Potue, P.; Wunpathe, C.; Maneesai, P.; Kukongviriyapan, U.; Prachaney, P.; Pakdeechote, P. Nobiletin alleviates vascular alterations through modulation of Nrf-2/HO-1 and MMP pathways in l-NAME induced hypertensive rats. Food Funct., 2019, 10(4), 1880-1892.
[] [PMID: 30864566]
Moncada, S.; Higgs, E.A. The discovery of nitric oxide and its role in vascular biology. Br. J. Pharmacol., 2006, 147(S1)(Suppl. 1), S193-S201.
[] [PMID: 16402104]
Aekthammarat, D.; Pannangpetch, P.; Tangsucharit, P. Moringa oleifera leaf extract lowers high blood pressure by alleviating vascular dysfunction and decreasing oxidative stress in L-NAME hypertensive rats. Phytomedicine, 2019, 54, 9-16.
Bilanda, D.C.; Dzeufiet, P.D.D.; Kouakep, L.; Aboubakar, B.F.O.; Tedong, L.; Kamtchouing, P.; Dimo, T. Bidens pilosa ethylene acetate extract can protect against L-NAME-induced hypertension on rats. BMC Complement. Altern. Med., 2017, 17(1), 479.
[] [PMID: 29017485]
James, P.A.; Oparil, S.; Carter, B.L.; Cushman, W.C.; Dennison-Himmelfarb, C.; Handler, J.; Lackland, D.T.; LeFevre, M.L.; MacKenzie, T.D.; Ogedegbe, O.; Smith, S.C., Jr; Svetkey, L.P.; Taler, S.J.; Townsend, R.R.; Wright, J.T., Jr; Narva, A.S.; Ortiz, E. 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), 507-520.
[] [PMID: 24352797]
Kiriyama, A.; Honbo, A.; Nishimura, A.; Shibata, N.; Iga, K. Pharmacokinetic-pharmacodynamic analyses of antihypertensive drugs, nifedipine and propranolol, in spontaneously hypertensive rats to investigate characteristics of effect and side effects. Regul. Toxicol. Pharmacol., 2016, 76, 21-29.
[] [PMID: 26773344]
Stenmark, K.R.; Rabinovitch, M. Emerging therapies for the treatment of pulmonary hypertension. Pediatr. Crit. Care Med., 2010, 11(2)(Suppl.), S85-S90.
[] [PMID: 20216170]
Herrera-Arellano, A.; Flores-Romero, S.; Chávez-Soto, M.A.; Tortoriello, J. Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: A controlled and randomized clinical trial. Phytomedicine, 2004, 11(5), 375-382.
[] [PMID: 15330492]
Mojiminiyi, F.B.O.; Dikko, M.; Muhammad, B.Y.; Ojobor, P.D.; Ajagbonna, O.P.; Okolo, R.U.; Igbokwe, U.V.; Mojiminiyi, U.E.; Fagbemi, M.A.; Bello, S.O.; Anga, T.J. Antihypertensive effect of an aqueous extract of the calyx of Hibiscus sabdariffa. Fitoterapia, 2007, 78(4), 292-297.
[] [PMID: 17482378]
Amssayef, A.; Eddouks, M. Aqueous extract of matricaria pubescens exhibits antihypertensive activity in L-NAME-induced hypertensive rats through its vasorelaxant effect. Cardiovasc. Hematol. Agents Med. Chem., 2019, 17, 135-143.
EL-Ouady. F.; Eddouks, M. Warionia saharae induces antihypertensive and vasorelaxant activities through nitric oxide and KATP channels pathways in rats. J. Complement. Integr. Med., 2019, 17(1)
Chinnadurai, S.; Fonnesbeck, C.; Snyder, K.M.; Sathe, N.A.; Morad, A.; Likis, F.E.; McPheeters, M.L. Pharmacologic interventions for infantile hemangioma: A meta-analysis. Pediatrics, 2016, 137(2), e20153896-e20153896.
[] [PMID: 26772662]
Baratam, S.R.; Janjanam, K.C. Determination of nifedipine in human plasma by high- performance liquid chromatography–tandem mass spectrometry and its validation. World J. Pharm. Pharm. Sci., 2018, 7, 15.
Gorzalczany, S.; Moscatelli, V.; Ferraro, G. Artemisia copa aqueous extract as vasorelaxant and hypotensive agent. J. Ethnopharmacol., 2013, 148(1), 56-61.
[] [PMID: 23588093]
Fraga-Silva, R.A.; Costa-Fraga, F.P.; Montecucco, F.; Sturny, M.; Faye, Y.; Mach, F.; Pelli, G.; Shenoy, V.; da Silva, R.F.; Raizada, M.K.; Santos, R.A.; Stergiopulos, N. Diminazene protects corpus cavernosum against hypercholesterolemia-induced injury. J. Sex. Med., 2015, 12(2), 289-302.
[] [PMID: 25411084]
Bavishi, C.; Maddox, T.M.; Messerli, F.H. Coronavirus disease 2019 (COVID-19) infection and renin angiotensin system blockers. JAMA Cardiol., 2020, 5(7), 745-747.
[] [PMID: 32242890]
Gosain, R.; Abdou, Y.; Singh, A.; Rana, N.; Puzanov, I.; Ernstoff, M.S. COVID-19 and cancer: A comprehensive review. Curr. Oncol. Rep., 2020, 22(5), 53.
[] [PMID: 32385672]
Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med., 2020, 14(2), 185-192.
[] [PMID: 32170560]
Bosso, M.; Thanaraj, T.A.; Abu-Farha, M.; Alanbaei, M.; Abubaker, J.; Al-Mulla, F. The two faces of ACE2: The Role of ACE2 receptor and its polymorphisms in hypertension and COVID-19. Mol. Ther. Methods Clin. Dev., 2020, 18, 321-327.
[] [PMID: 32665962]
Fang, Y.; Gao, F.; Liu, Z. Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways. QJM, 2019, 112(12), 914-924.
[] [PMID: 31393582]
Raduan, S.; Aziz, M.A.; Roslida, A.; Zakaria, Z.; Zuraini, A.; Hakim, M. Anti- inflammatory effects of Hibiscus rosa-sinensis l. and Hibiscus rosa-sinensis var. alba ethanol extracts. Int. J. Pharm. Pharm. Sci., 2013, 5(4), 10.
Gheblawi, M.; Wang, K.; Viveiros, A.; Nguyen, Q.; Zhong, J-C.; Turner, A.J.; Raizada, M.K.; Grant, M.B.; Oudit, G.Y. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: Celebrating the 20th anniversary of the discovery of ACE2. Circ. Res., 2020, 126(10), 1456-1474.
[] [PMID: 32264791]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy