Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity

Liu, Xiaocao; Raghuvanshi, Ruma; Ceylan, Fatma Duygu; Bolling, Bradley W.

doi:10.1021/acs.jafc.0c05064

Cited by 79 publications

(83 citation statements)

References 47 publications

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“…Additional recent studies report that early, but not late phase ( Mongardon et al, 2020 ), low-dose corticosteroids decrease mortality and improve COVID-19 clinical outcomes ( Ji et al, 2020 ). However, another recent study indicates that corticosteroid use is associated with increased mortality and delayed SARS–CoV-2 coronavirus RNA clearance in 409 COVID-19 patients ( J. Liu et al, 2020 ). While some of the meta-analyses conclude that the use of corticosteroids is associated with a higher rate of ARDS in COVID-19 patients ( Z. Yang et al, 2020 ; J. J. Y. Zhang, Lee, Ang, Leo, & Young, 2020 ), a recent randomized study of several thousands of hospitalized COVID-19 patients reports that dexamethasone reduces the mortality among those receiving invasive mechanical ventilation or oxygen ( Horby et al, 2020 ).…”

Section: Corticosteroids Non-steroid Anti-inflammatory Drugs and Acmentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

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The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

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Section: Corticosteroids Non-steroid Anti-inflammatory Drugs and Acmentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

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“…Conversely, a computational investigation evidenced it as able to bind at S protein: ACE2 receptor interface [ 73 ]. In vitro studies demonstrated that quercetin inhibited recombinant human (rh) ACE2 activity [ 74 , 75 ]. More recently, the clinical trials (NCT04468139 and NCT04377789) including quercetin, were involved in both prophylaxis and treatment of COVID-19 [ 76 , 77 , 78 ].…”

Section: Resultsmentioning

confidence: 99%

Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

et al. 2021

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified in China as the etiologic agent of the recent COVID-19 pandemic outbreak. Due to its high transmissibility, this virus quickly spread throughout the world, causing considerable health issues. The scientific community exerted noteworthy efforts to obtain therapeutic solutions for COVID-19, and new scientific networks were constituted. No certified drugs to efficiently inhibit the virus were identified, and the development of de-novo medicines requires approximately ten years of research. Therefore, the repurposing of natural products could be an effective strategy to handle SARS-CoV-2 infection. This review aims to update on current status of the natural occurring compounds recognizing SARS-CoV-2 druggable targets. Among the clinical trials actually recruited, some natural compounds are ongoing to examine their potential role to prevent and to treat the COVID-19 infection. Many natural scaffolds, including alkaloids, terpenes, flavonoids, and benzoquinones, were investigated by in-silico, in-vitro, and in-vivo approaches. Despite the large data set obtained by a computational approach, experimental evidences in most cases are not available. To fill this gap, further efforts to validate these results are required. We believe that an accurate investigation of naturally occurring compounds may provide insights for the potential treatment of COVID-19 patients.

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“…For example, free quercetin was found to have the strongest antioxidant activity, confirming the important contribution of unbound hydroxyl groups ( 49 ). Among its metabolites, free quercetin was also the most effective recombinant human angiotensin-converting enzyme (ACE) 2 inhibitor ( 50 ). Tamarixetin and isorhamnetin demonstrated a stronger inhibition of lipid peroxidation compared to quercetin ( 49 , 51 ).…”

Section: Quercetinmentioning

confidence: 99%

Therapeutic Potential of Quercetin to Alleviate Endothelial Dysfunction in Age-Related Cardiovascular Diseases

Dagher

Mury

Thorin‐Trescases

et al. 2021

Front. Cardiovasc. Med.

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The vascular endothelium occupies a catalog of functions that contribute to the homeostasis of the cardiovascular system. It is a physically active barrier between circulating blood and tissue, a regulator of the vascular tone, a biochemical processor and a modulator of coagulation, inflammation, and immunity. Given these essential roles, it comes to no surprise that endothelial dysfunction is prodromal to chronic age-related diseases of the heart and arteries, globally termed cardiovascular diseases (CVD). An example would be ischemic heart disease (IHD), which is the main cause of death from CVD. We have made phenomenal advances in treating CVD, but the aging endothelium, as it senesces, always seems to out-run the benefits of medical and surgical therapies. Remarkably, many epidemiological studies have detected a correlation between a flavonoid-rich diet and a lower incidence of mortality from CVD. Quercetin, a member of the flavonoid class, is a natural compound ubiquitously found in various food sources such as fruits, vegetables, seeds, nuts, and wine. It has been reported to have a wide range of health promoting effects and has gained significant attention over the years. A growing body of evidence suggests quercetin could lower the risk of IHD by mitigating endothelial dysfunction and its risk factors, such as hypertension, atherosclerosis, accumulation of senescent endothelial cells, and endothelial-mesenchymal transition (EndoMT). In this review, we will explore these pathophysiological cascades and their interrelation with endothelial dysfunction. We will then present the scientific evidence to quercetin's anti-atherosclerotic, anti-hypertensive, senolytic, and anti-EndoMT effects. Finally, we will discuss the prospect for its clinical use in alleviating myocardial ischemic injuries in IHD.

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Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity

Cited by 79 publications

References 47 publications

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

Therapeutic Potential of Quercetin to Alleviate Endothelial Dysfunction in Age-Related Cardiovascular Diseases

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