Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: Mechanistic role of angiotensin converting enzyme, cholinesterase and arginase activities in cyclosporine induced hypertensive rats

Background: The 2019 novel coronavirus disease (COVID-19) has caused a global health catastrophe by affecting the whole human population around the globe. Unfortunately, there is no specific medication or treatment for COVID-19 currently available. Objective: It’s extremely necessary to apply effective drug treatment in order to end the pandemic period and return daily life to normal. In terms of the urgency of treatment, rather than focusing on the discovery of novel compounds, it is critical to explore the effects of existing herbal agents with proven antiviral properties on the virus. Method: Molecular docking studies were carried out with three different methods, Glide extra precision (XP) docking, Induced Fit docking (IFD), and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA), to determine the potential effects of 58 phytochemicals in the content of Rosmarinus officinalis, Thymbra spicata, Satureja thymbra, and Stachys lavandulifolia plants -have antiviral and antibacterial effects- against Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) enzymes. Results: 7 compounds stand out among all molecules by showing very high binding affinities. According to our findings, the substances chlorogenic acid, rosmarinic acid, and rosmanol exhibit extremely significant binding affinities for both Mpro and ACE2 enzymes. Furthermore, it was discovered that carnosic acid and alpha-cadinol showed potential anti-Mpro activity, whereas caffeic acid and carvacrol had promising anti-ACE2 activity. Conclusion: Chlorogenic acid, rosmarinic acid, rosmanol, carnosic acid, alpha-cadinol, caffeic acid, and carvacrol compounds have been shown to be powerful anti-SARS-COV-2 agents in docking simulations against Mpro and ACE2 enzymes, as well as ADME investigations.

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Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1–7) in transgenic Ren-2 hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01198.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. H3019-H3024 ◽

Cited By ~ 42

Author(s):

Aaron J. Trask ◽

David B. Averill ◽

Detlev Ganten ◽

Mark C. Chappell ◽

Carlos M. Ferrario

Keyword(s):

Angiotensin Converting Enzyme ◽

Primary Role ◽

Ang Ii ◽

Converting Enzyme ◽

Sprague Dawley ◽

Hypertensive Rats ◽

Direct Role ◽

Compensatory Response ◽

Angiotensin Converting Enzyme 2

Angiotensin-converting enzyme-2 (ACE2) converts angiotensin II (ANG II) to angiotensin-(1–7) [ANG-(1–7)], and this enzyme may serve as a key regulatory juncture in various tissues. Although the heart expresses ACE2, the extent that the enzyme participates in the cardiac processing of ANG II and ANG-(1–7) is equivocal. Therefore, we utilized the Langendorff preparation to characterize the ACE2 pathway in isolated hearts from male normotensive Sprague-Dawley [Tg(−)] and hypertensive [mRen2]27 [Tg(+)] rats. During a 60-min recirculation period with 10 nM ANG II, the presence of ANG-(1–7) was assessed in the cardiac effluent. ANG-(1–7) generation from ANG II was similar in both the normal and hypertensive hearts [Tg(−): 510 ± 55 pM, n = 20 vs. Tg(+): 497 ± 63 pM, n = 14] with peak levels occurring at 30 min after administration of the peptide. ACE2 inhibition (MLN-4760, 1 μM) significantly reduced ANG-(1–7) production by 83% (57 ± 19 pM, P < 0.01, n = 7) in the Tg(+) rats, whereas the inhibitor had no significant effect in the Tg(−) rats (285 ± 53 pM, P > 0.05, n = 10). ACE2 activity was found in the effluent of perfused Tg(−) and Tg(+) hearts, and it was highly associated with ACE2 protein expression ( r = 0.78). This study is the first demonstration for a direct role of ACE2 in the metabolism of cardiac ANG II in the hypertrophic heart of hypertensive rats. We conclude that predominant expression of cardiac ACE2 activity in the Tg(+) may be a compensatory response to the extensive cardiac remodeling in this strain.

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Caffeic and chlorogenic acids modulate altered activity of key enzymes linked to hypertension in cyclosporine-induced hypertensive rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2019-0360 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Odunayo M. Agunloye ◽

Ganiyu Oboh ◽

Gbemisola T. Bello ◽

Ademola A. Oyagbemi

Keyword(s):

Blood Pressure ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Angiotensin Converting Enzyme ◽

Chlorogenic Acid ◽

Antihypertensive Effect ◽

Protective Mechanism ◽

Converting Enzyme ◽

Chlorogenic Acids ◽

Hypertensive Rats

AbstractObjectivesThis study aimed to explore the protective mechanism of caffeic acid (CAA) and chlorogenic acid (CHA) on cyclosporine (CSA) induced hypertensive rats.MethodsEffect of CAA and CHA on diastolic blood pressure (DBP), mean arterial pressure (MAP), angiotensin-converting enzyme (ACE), e-nucleotide triphosphate dephosphorylase (e-NTPDase), 5′ nucleotidase and adenosine deaminase (ADA) activity in CSA-induced hypertensive rats were determined.ResultsCAA and CHA administration stabilized hypertensive effect caused by CSA administration. Also, altered activity of ACE (lung), e-NTPDase, 5′ nucleotidase, ADA as well as elevated malondiadehyde (MDA) level was restored in all the treated hypertensive rats in comparison with the untreated hypertensive rats.ConclusionHence, these observed results could underlie some of the mechanisms through which CAA and CHA could offer antihypertensive effect.

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