Login Register Cart 0
Generic placeholder image

Cardiovascular & Hematological Disorders-Drug Targets

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Vitamin C Inhibits Angiotensin-Converting Enzyme-2 in Isolated Rat Aortic Ring

Author(s): Ayoub Amssayef, Ismail Bouadid and Mohamed Eddouks*

Volume 21, Issue 4, 2021

Published on: 28 December, 2021

Page: [235 - 242] Pages: 8

DOI: 10.2174/1871529X21666211214153308

Price: $65

Abstract

Aims: The study aimed to assess the inhibitory effect of Vitamin C on angiotensin-converting enzyme 2.

Background: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses angiotensin-converting enzyme 2 (ACE-II) as the first route to infect human cells. Accordingly, agents with potential inhibition of ACE-II receptors might be effective in the prevention and management of COVID-19.

Objective: The goal of this work was to assess the possible inhibitory effect of ACE-II on ascorbic acid using an ex vivo approach based on the inhibition of diminazene-induced vasorelaxation.

Materials and Methods: In the present study, diminazene was used as a known specific inhibitor of ACE-II. Then, the vasorelaxant effect of ascorbic acid on diminazene-induced relaxation was examined using isolated aortic rings. All experiments of this study were evaluated on isolated aortic rings precontracted by epinephrine.

Results: The results confirmed that diminazene-induced vasorelaxation in a dose-dependent manner. More interestingly, ascorbic acid inhibited diminazene-induced vasorelaxation in a dose-dependent manner.

Conclusion: This investigation provides valuable experimental proof of the efficacy of ascorbic acid (Vitamin C) on inhibiting ex vivo vascular angiotensin-converting enzyme II, which is known among the pharmacological targets of anti-COVID-19 drugs.

Keywords: Ascorbic acid, ACE-II, COVID-19, diminazene, inhibition, aortic rings.

« Previous Next »
Graphical Abstract

[1]
Chhikara, B.S.; Rathi, B.; Singh, J.; Poonam, F. Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics. Chem. Biol. Lett, 2020, 7, 63-72.
[2]
Patel, B.; Sharma, S.; Nair, N.; Majeed, J.; Goyal, R.K.; Dhobi, M. Therapeutic opportunities of edible antiviral plants for COVID-19. Mol. Cell. Biochem., 2021, 476(6), 2345-2364.
[http://dx.doi.org/10.1007/s11010-021-04084-7] [PMID: 33587232]
[3]
World health organization. WHO Coronavirus (COVID-19) Dashboard. Available from: https://covid19.who.int/ (accessed on 23 April 2020)
[4]
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[5]
Monpara, J.D.; Sodha, S.J.; Gupta, P.K. COVID-19 associated complications and potential therapeutic targets. Eur. J. Pharmacol., 2020, 886, 173548.
[http://dx.doi.org/10.1016/j.ejphar.2020.173548] [PMID: 32926918]
[6]
Forni, G.; Mantovani, A. COVID-19 vaccines: where we stand and challenges ahead. Cell Death Differ., 2021, 28(2), 626-639.
[http://dx.doi.org/10.1038/s41418-020-00720-9] [PMID: 33479399]
[7]
Awadasseid, A.; Wu, Y.; Tanaka, Y.; Zhang, W. Current advances in the development of SARS-CoV-2 vaccines. Int. J. Biol. Sci., 2021, 17(1), 8-19.
[http://dx.doi.org/10.7150/ijbs.52569] [PMID: 33390829]
[8]
Abdool Karim, S.S.; de Oliveira, T. New SARS-CoV-2 variants-clinical, public health, and vaccine implications. N. Engl. J. Med., 2021, 384(19), 1866-1868.
[http://dx.doi.org/10.1056/NEJMc2100362]
[9]
Muchtaridi, M.; Fauzi, M.; Khairul Ikram, N.K.; Mohd Gazzali, A.; Wahab, H.A. Natural flavonoids as potential angiotensin-converting enzyme 2 inhibitors for anti-SARS-CoV-2. Molecules, 2020, 25(17), 3980.
[http://dx.doi.org/10.3390/molecules25173980] [PMID: 32882868]
[10]
Chen, Y.; Guo, Y.; Pan, Y.; Zhao, Z.J. Structure analysis of thereceptor binding of 2019-nCoV. Biochem. Biophys. Res. Commun., 2020, 525, 135-140.
[http://dx.doi.org/10.1016/j.bbrc.2020.02.071]
[11]
Jovic, T.H.; Ali, S.R.; Ibrahim, N.; Jessop, Z.M.; Tarassoli, S.P.; Dobbs, T.D.; Holford, P.; Thornton, C.A.; Whitaker, I.S. Could vitamins help in the fight against COVID-19? Nutrients, 2020, 12(9), 2550.
[http://dx.doi.org/10.3390/nu12092550] [PMID: 32842513]
[12]
JamaliMoghadamSiahkali, S.; Zarezade, S.; Koolaji, S.; SeyedAlinaghi, S.; Zendehdel, A.; Tabarestani, M.; Moghadam, ES.; Abbasian, L.; Manshadi, SA.; Salehi, M.; Hasannezhad, M. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: A randomized open-label clinical trial. Eur. J. Med. Res., 2021, 26(1), 1-9.
[PMID: 33388089]
[13]
Ivanov, V.; Goc, A.; Ivanova, S.; Niedzwiecki, A.; Rath, M. Inhibition of ace2 expression by ascorbic acid alone and its combinations with other natural compounds. Infect. Dis. (Auckl.), 2021, 14, 1178633721994605-, 1178633721994605.
[http://dx.doi.org/10.1177/1178633721994605] [PMID: 33642866]
[14]
Behl, T.; Kaur, I.; Bungau, S.; Kumar, A.; Uddin, M.S.; Kumar, C.; Pal, G.; Sahil, ; Shrivastava, K.; Zengin, G.; Arora, S. The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions. Life Sci., 2020, 257, 118075.
[http://dx.doi.org/10.1016/j.lfs.2020.118075] [PMID: 32653522]
[15]
Sartório, C.L.; Pimentel, E.B.; Dos Santos, R.L.; Rouver, W.N.; Mill, J.G. Acute hypotensive effect of diminazene aceturate in spontaneously hypertensive rats: role of NO and Mas receptor. Clin. Exp. Pharmacol. Physiol., 2020, 47(10), 1723-1730.
[http://dx.doi.org/10.1111/1440-1681.13368] [PMID: 32603499]
[16]
Amssayef, A.; Ajebli, M.; Eddouks, M. Aqueous extract of oakmoss produces antihypertensive activity in L-NAME-induced hypertensive rats through sGC-cGMP pathway. Clin. Exp. Hypertens., 2021, 43(1), 49-55.
[http://dx.doi.org/10.1080/10641963.2020.1797087] [PMID: 32706597]
[17]
Ajebli, M.; Eddouks, M. Eucalyptus globulus possesses antihypertensive activity in L-NAME- induced hypertensive rats and relaxes isolated rat thoracic aorta through nitric oxide pathway. Nat. Prod. Res., 2019, 8, 1-3.
[PMID: 30966776]
[18]
Ajebli, M.; Eddouks, M. Antihypertensive activity of Petroselinum crispum through inhibition of vascular calcium channels in rats. J. Ethnopharmacol., 2019, 242, 112039.
[http://dx.doi.org/10.1016/j.jep.2019.112039] [PMID: 31252093]
[19]
Dabaghian, F.; Khanavi, M.; Zarshenas, M.M. Bioactive compounds with possible inhibitory activity of Angiotensin-Converting Enzyme-II; a gate to manage and prevent COVID-19. Med. Hypotheses, 2020, 143, 109841.
[http://dx.doi.org/10.1016/j.mehy.2020.109841] [PMID: 32425303]
[20]
Zheng, Y-Y.; Ma, Y-T.; Zhang, J-Y.; Xie, X. COVID-19 and the cardiovascular system. Nat. Rev. Cardiol., 2020, 17(5), 259-260.
[http://dx.doi.org/10.1038/s41569-020-0360-5] [PMID: 32139904]
[21]
Teli, D.M.; Shah, M.B.; Chhabria, M.T. In silico screening of natural compounds as potential inhibitors of sars-cov-2 main protease and spike rbd: targets for COVID-19. Front. Mol. Biosci., 2021, 7, 599079.
[http://dx.doi.org/10.3389/fmolb.2020.599079] [PMID: 33542917]
[22]
Yang, J.; Petitjean, S.J.L.; Koehler, M.; Zhang, Q.; Dumitru, A.C.; Chen, W.; Derclaye, S.; Vincent, S.P.; Soumillion, P.; Alsteens, D. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat. Commun., 2020, 11(1), 4541.
[http://dx.doi.org/10.1038/s41467-020-18319-6] [PMID: 32917884]
[23]
Kaur, U.; Acharya, K.; Mondal, R.; Singh, A.; Saso, L.; Chakrabarti, S.; Chakrabarti, S.S. Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2. Eur. J. Pharmacol., 2020, 887, 173545.
[http://dx.doi.org/10.1016/j.ejphar.2020.173545] [PMID: 32926917]
[24]
De Maria, M.L.; Araújo, L.D.; Fraga-Silva, R.A.; Pereira, L.A.; Ribeiro, H.J.; Menezes, G.B.; Shenoy, V.; Raizada, M.K.; Ferreira, A.J. Anti-hypertensive effects of diminazene aceturate: An angiotensin- converting enzyme 2 activator in rats. Protein Pept. Lett., 2016, 23(1), 9-16.
[http://dx.doi.org/10.2174/0929866522666151013130550] [PMID: 26458404]
[25]
Zhang, J.; Rao, X.; Li, Y.; Zhu, Y.; Liu, F.; Guo, G.; Luo, G.; Meng, Z.; De Backer, D.; Xiang, H.; Peng, Z. Pilot trial of high- dose vitamin C in critically ill COVID-19 patients. Ann. Intensive Care, 2021, 11(1), 5.
[http://dx.doi.org/10.1186/s13613-020-00792-3] [PMID: 33420963]
[26]
Waqas Khan, H.M.; Parikh, N.; Megala, S.M.; Predeteanu, G.S. Unusual early recovery of a critical COVID-19 patient after administration of intravenous vitamin C. Am. J. Case Rep., 2020, 21, e925521.
[http://dx.doi.org/10.12659/AJCR.925521] [PMID: 32709838]
[27]
Name, J.J.; Souza, A.C.R.; Vasconcelos, A.R.; Prado, P.S.; Pereira, C.P.M. Zinc, vitamin D and vitamin C: Perspectives for COVID-19 with a focus on physical tissue barrier integrity. Front. Nutr., 2020, 7, 606398.
[http://dx.doi.org/10.3389/fnut.2020.606398] [PMID: 33365326]
[28]
Carr, A.C.; Maggini, S. Vitamin C and immune function. Nutrients, 2017, 9(11), 1211.
[http://dx.doi.org/10.3390/nu9111211] [PMID: 29099763]

Rights & Permissions Print Cite
Article Metrics
25
1
© 2024 Bentham Science Publishers | Privacy Policy