Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health

Salehi, Bahare; Machín, Laura; Monzote, Lianet; Sharifi‐Rad, Javad; Ezzat, Shahira M.; Salem, Mohamed A.; Merghany, Rana M.; Mahdy, Nihal M. El; Kılıç, Ceyda Sibel; Sytar, Oksana; Sharifi‐Rad, Mehdi; Sharopov, Farukh; Martins, Natália; Martorell, Miquel; Cho, William C.

doi:10.1021/acsomega.0c01818

Cited by 440 publications

(283 citation statements)

References 279 publications

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“…Quercetin is a commonly occurring flavonol with anti-inflammatory and antioxidant properties. Quercetin exerts promising anti-tumor effects via the regulation of various cancer signaling pathways [ 118 ], including effect on activity of HIF-1. Quercetin inhibited HIF-1 transcriptional activity in the HCT116 colon cancer cell line.…”

Section: Beneficial Effects Of Flavonoids In the Regulation Of Hypmentioning

confidence: 99%

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Samec

Líšková

Koklesová

et al. 2021

Cancers

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Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.

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Section: Beneficial Effects Of Flavonoids In the Regulation Of Hypmentioning

confidence: 99%

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Samec

Líšková

Koklesová

et al. 2021

Cancers

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“…Fruits (such as apple, raspberries, cherries, and red grapes), leafy green vegetables and some herbs are major natural sources of quercetin and can be easily exploited for its extraction. Being a natural compound, it shows least toxicity in vivo compared to the till date known synthetic antiviral compounds (Panche et al 2016 ; Salehi et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Factual insights of the allosteric inhibition mechanism of SARS-CoV-2 main protease by quercetin: an in silico analysis

Verma

Pandey

2021

3 Biotech

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SARS-CoV-2 main protease (M pro ) cleaves the viral polypeptide 1a and 1ab in a site-specific ((L-Q|(S, A, G)) manner and produce functional enzymes for mediating viral replication. Numerous studies have reported synthetic competitive inhibitors against this target enzyme but increase in substrate concentration often reduces the effectiveness of such inhibitors. Allosteric inhibition by natural compound can provide safe and effective treatment by alleviating this limitation. Present study deals with in silico allosteric inhibition analysis of quercetin, against SARS-CoV-2-M pro . Molecular docking of quercetin with M pro revealed consistent binding of quercetin at a site other than active site in multiple runs, with the highest binding energy of − 8.31 kcal/mol, forming 6 H-bonds with residues Gln127, Cys128, Lys137, Asp289 and Glu290. Molecular dynamic simulation of 50 ns revealed high stability of M pro -quercetin complex with RMSD values ranging from 0.1 to 0.25 nm. Moreover, native-M pro and M pro -quercetin complex conformations extracted at different time points from simulation trajectories were subjected to active site-specific docking with modelled substrate peptide (AVLQSGFR) by ZDOCK server. Results displayed site-specific cleavage of peptide when docked with native-M pro . While substrate peptide remained intact when docked with M pro -quercetin complex, also the binding energy of peptide reduced from 785 to 86 from 1 to 50 ns as quercetin induced alterations in the active site cavity reducing its affinity for the substrate. Further, no interactions were noticed between peptide and active site residues of M pro -quercetin complex conformations at 40 and 50 ns. Hence, quercetin displayed effective allosteric inhibition potential against SARS-CoV-2 M pro , and can be developed into an efficient treatment for COVID-19.

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“…Quercetin is widely contained in grapes, berries, apples, cherries, citrus fruit, red wine, black tea, onions, and tomatoes. Concentrations of quercetin may vary depending on the plant or even on the parts of the same plant [ 107 ]. Like other polyphenols, quercetin has limited water solubility.…”

Section: Therapeutic Effects Of Polyphenols-loaded Polymeric Nanopmentioning

confidence: 99%

“…The bioavailability of the water-soluble derivative of quercetin is only 20% [ 108 ]. However, quercetin glycoside has a higher bioavailability than quercetin rhamnoside or quercetin galactoside [ 107 ].…”

Section: Therapeutic Effects Of Polyphenols-loaded Polymeric Nanopmentioning

confidence: 99%

“…The use of quercetin as a therapeutic target is, however, limited considering its poor aqueous solubility, instability in the physiological medium, and low bioavailability [ 107 , 118 ]. Therefore, polymeric nanoparticles are a good tool to increase bioavailability and reduce degradation of this flavonoid.…”

Section: Therapeutic Effects Of Polyphenols-loaded Polymeric Nanopmentioning

confidence: 99%

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Therapeutic Potential of Polyphenols-Loaded Polymeric Nanoparticles in Cardiovascular System

2020

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Numerous studies document an increased production of reactive oxygen species (ROS) with a subsequent decrease in nitric oxide (NO) bioavailability in different cardiovascular diseases, including hypertension, atherosclerosis, and heart failure. Many natural polyphenols have been demonstrated to decrease ROS generation and/or to induce the endogenous antioxidant enzymatic defense system. Moreover, different polyphenolic compounds have the ability to increase the activity/expression of endothelial nitric oxide synthase (eNOS) with a subsequent enhancement of NO generation. However, as a result of low absorption and bioavailability of natural polyphenols, the beneficial effects of these substances are very limited. Recent progress in delivering polyphenols to the targeted tissues revealed new possibilities for the use of polymeric nanoparticles in increasing the efficiency and reducing the degradability of natural polyphenols. This review focuses on the effects of different natural polyphenolic substances, especially resveratrol, quercetin, curcumin, and cherry extracts, and their ability to bind to polymeric nanoparticles, and summarizes the effects of polyphenol-loaded nanoparticles, mainly in the cardiovascular system.

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Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health

Cited by 440 publications

References 279 publications

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Factual insights of the allosteric inhibition mechanism of SARS-CoV-2 main protease by quercetin: an in silico analysis

Therapeutic Potential of Polyphenols-Loaded Polymeric Nanoparticles in Cardiovascular System

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