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Life
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Quercetin and Its Complexes for Medicinal Applications
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Quercetin and Its Complexes for Medicinal Applications

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Plant Science".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 54077

Special Issue Editors

Dr. Luiz Leonardo Saldanha

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Guest Editor
Swiss Federal Research Station Agroscope, 1964 Conthey, Switzerland
Interests: mass spectrometry; metabolomics; natural products; phytochemistry
Special Issues, Collections and Topics in MDPI journals
Dr. Thais Fernanda de Campos Fraga-Silva

E-Mail Website
Guest Editor
Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto14049-900, Brazil
Interests: natural products; complary and alternative medicine; immune response; immunomodulationement

Special Issue Information

Dear Colleagues,

With various pharmacological effects and biological functions, flavonoids are effective active natural products in the prevention and treatment of various diseases. Quercetin is one of the most abundant and frequently studied flavonoids in nature. Flavonoids are ubiquitously distributed in plants and represent an important class of natural products from the specialized metabolism of plants. Quercetin (5,7,3′,4′-tetrahydroxyflavonol, C15H10O7) is commonly found in seeds, barks, flowers, and leaves. It is frequently studied in dietary products and in many medicinal plants. Quercetin frequently occurs in the form of glycosides where polyhydroxyl substitution appears in its structure. This compound has attracted extensive interest due to typical effects of flavonoids such as anti-inflammatory, analgesic, anti-rheumatic, antioxidant, and anti-tumor which gives it a wide potential for use in the treatment of several diseases. Despite its wide pharmacological effects, the real-life medicinal application of quercetin is still limited. Low aqueous solubility, poor permeability, instability in physiological medium, and short biological half-life result in low oral bioavailability and are some of the barriers that must be overcome to enable the use of quercetin as a pharmaceutical product. Sustainable and comprehensible approaches to its extraction and purification, as well as analysis that links quercetin in complex mixtures to specific pharmacological effects, also still face issues. Despite many advances in our understanding and use of this compound, to date, many of the pharmacological effects and medicinal properties of quercetin have not been fully unraveled. In this Special Issue, we focus on the most recent advances in our understanding of the role and mechanism of action of quercetin from medicinal plants and dietary products using innovative techniques and approaches that can relate quercetin to a medicinal property or improvement of bioavailability which increases the medicinal applicability of this compound.

Dr. Luiz Leonardo Saldanha
Dr. Thais Fernanda de Campos Fraga-Silva
Guest Editors

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Published Papers (8 papers)

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Research

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14 pages, 1670 KiB  
Article
Enzymatic Hydrolysis of Rutin: Evaluation of Kinetic Parameters and Anti-Proliferative, Mutagenic and Anti-Mutagenic Effects
by Mariana Alves Sobreiro, Adriana Della Torre, Maria Elisa Melo Branco de Araújo, Paula Renata Bueno Campos Canella, João Ernesto de Carvalho, Patrícia de Oliveira Carvalho and Ana Lucia Tasca Gois Ruiz
Life 2023, 13(2), 549; https://doi.org/10.3390/life13020549 - 16 Feb 2023
Cited by 6 | Viewed by 1979
Abstract
The bioavailability of glucoside flavonoids is influenced by the nature of the sugar, glucosides being absorbed faster than rhamnoglucosides, for example. One strategy to enhance the bioavailability is enzymatic hydrolysis. In this study, some kinetic parameters of hesperidinase-mediated hydrolysis of rutin were evaluated [...] Read more.
The bioavailability of glucoside flavonoids is influenced by the nature of the sugar, glucosides being absorbed faster than rhamnoglucosides, for example. One strategy to enhance the bioavailability is enzymatic hydrolysis. In this study, some kinetic parameters of hesperidinase-mediated hydrolysis of rutin were evaluated using an UHPLC/QTOF-MSE analysis of the products of a bioconversion reaction. The resulting hydrolyzed rutins (after 4, 8 and 12 h of reaction) were submitted to anti-proliferative and Cytokinesis-Block Micronucleus (CBMN) assays in CHO-K1 cells. In the hesperidinase-mediated hydrolysis, the final concentration of quercetin-3-O-glucoside (Q3G) was directly proportional to the rutin concentration and inversely proportional to the reaction time. At an anti-proliferative concentration (2.5 μg/mL), hydrolyzed rutin derivatives did not show a mutagenic effect, except for the sample with a higher content of Q3G (after 4 h of the enzymatic hydrolysis of rutin). Moreover, the higher Q3G content in hydrolyzed rutin protected the CHO-K1 cells 92% of the time against methyl methanesulfonate-induced mutagenic damage. These results suggested that the anti-mutagenic effect of hydrolyzed rutin might be related to antioxidant and cell death induction. Presenting a good lipophilicity/hydrophilicity ratio, together with antioxidant and anti-mutagenic activities, the hesperidinase-mediated hydrolyzed rutin seemed to be a promisor raw material for the development of food supplements. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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14 pages, 2414 KiB  
Article
Cryopreservation of Pig Semen Using a Quercetin-Supplemented Freezing Extender
by Seonggyu Bang, Bereket Molla Tanga, Xun Fang, Gyeonghwan Seong, Islam M. Saadeldin, Ahmad Yar Qamar, Sanghoon Lee, Keun-Jung Kim, Yun-Jae Park, Abdelbagi Hamad Talha Nabeel, Il-jeoung Yu, Akila Cooray, Kyu Pil Lee and Jongki Cho
Life 2022, 12(8), 1155; https://doi.org/10.3390/life12081155 - 29 Jul 2022
Cited by 10 | Viewed by 3060
Abstract
Reactive oxygen species (ROS) produced during freeze–thaw procedures cause oxidative damage to the sperm, reducing fertility. We aimed to improve the post-thaw quality of pig sperm by quercetin (QRN) supplementation to reduce the cryodamage associated with the freeze–thaw procedure. Four equal aliquots of [...] Read more.
Reactive oxygen species (ROS) produced during freeze–thaw procedures cause oxidative damage to the sperm, reducing fertility. We aimed to improve the post-thaw quality of pig sperm by quercetin (QRN) supplementation to reduce the cryodamage associated with the freeze–thaw procedure. Four equal aliquots of pooled boar semen were diluted with a freezing extender supplemented with different concentrations of QRN (0, 25, 50, and 100 µM) and then were subjected to cryopreservation in liquid nitrogen. Semen analysis was performed following 7 days of cryopreservation. Results demonstrated that the semen samples supplemented with 50 µM QRN significantly improved the post-thaw sperm quality than those subjected to other supplementations (p < 0.05). Semen samples supplemented with 50 µM QRN showed significantly improved plasma membrane functional integrity (47.5 ± 1.4 vs. 43.1 ± 4.1, 45.3 ± 1.7, and 44.1 ± 1.4) and acrosome integrity (73.6 ± 3.4 vs. 66.3 ± 2.4, 66.7 ± 3.6, and 68.3 ± 32.9) as compared to the control, 25 µM, and 100 µM QRN groups, respectively. The mitochondrial activity of the 50 µM QRN group was greater than control and 25 µM QRN groups (43.0 ± 1.0 vs. 39.1 ± 0.9 and 41.9 ± 1.0) but showed no difference with the 100 µM QRN group. Moreover, the 50 µM QRN group showed a higher sperm number displaced to 1 cm and 3 cm points in the artificial mucus than other groups. Therefore, supplementing the freezing extender with QRN can serve as an effective tool to reduce the magnitude of oxidative damage associated with sperm freezing. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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18 pages, 4002 KiB  
Article
Quercetin Abrogates Oxidative Neurotoxicity Induced by Silver Nanoparticles in Wistar Rats
by Samar S. Elblehi, Eman M. Abd El-Maksoud, Adil Aldhahrani, Saqer S. Alotaibi, Heba I. Ghamry, Salwa A. Elgendy, Mohamed Mohamed Soliman and Mustafa Shukry
Life 2022, 12(4), 578; https://doi.org/10.3390/life12040578 - 13 Apr 2022
Cited by 13 | Viewed by 2953
Abstract
This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and [...] Read more.
This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1β, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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11 pages, 1337 KiB  
Article
Promising Effects of 3-Month Period of Quercetin Phytosome® Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study
by Mariangela Rondanelli, Simone Perna, Clara Gasparri, Giovanna Petrangolini, Pietro Allegrini, Alessandro Cavioni, Milena Anna Faliva, Francesca Mansueto, Zaira Patelli, Gabriella Peroni, Alice Tartara and Antonella Riva
Life 2022, 12(1), 66; https://doi.org/10.3390/life12010066 - 4 Jan 2022
Cited by 27 | Viewed by 21529
Abstract
Quercetin, for its crucial properties, fulfills the need for a multifactor action that is useful for the potential counterbalance of a COVID-19 infection. Given this background, the aim of the study was to evaluate the potential effect of 3 months’ supplementation with Quercetin [...] Read more.
Quercetin, for its crucial properties, fulfills the need for a multifactor action that is useful for the potential counterbalance of a COVID-19 infection. Given this background, the aim of the study was to evaluate the potential effect of 3 months’ supplementation with Quercetin Phytosome® (250 mg twice a day) as prevention against symptomatic COVID-19. In total, 120 subjects were enrolled (males, 63; females, 57; age 49 ± 12), with 60 in the supplementation group and 60 in the placebo group. No significant differences were detected between groups in terms of gender, smoking, and chronic disease. Subjects underwent rapid COVID-19 diagnostic tests every 3 weeks. During our study, 5 subjects had COVID-19, 1 out of 60 subjects in the quercetin group and 4 out of 60 in the control group. Complete clinical remission was recorded at 7 and 15 days in the quercetin and placebo groups, respectively. Analysis showed that, at 5 months, the COVID free survival function (risk of infection) was 99.8% in subjects under quercetin supplementation and 96.5% in control group. As shown by the value of EXP(B), those who had taken the supplement had a protection factor of 14% more to not contract the COVID-19 infection than that of those who had taken a placebo. Obtained results are encouraging, but further studies are required to add quercetin as regular prophylaxis. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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15 pages, 2850 KiB  
Article
Effect of Quercetin on Injury to Indomethacin-Treated Human Embryonic Kidney 293 Cells
by Chun Chen, Jai-Sing Yang, Chi-Cheng Lu, Yu-Tse Wu and Fu-An Chen
Life 2021, 11(11), 1134; https://doi.org/10.3390/life11111134 - 25 Oct 2021
Cited by 5 | Viewed by 4336
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammation and pain and even to prevent the progression of cardiovascular disease. They have become widely used because of their effectiveness, especially among athletes performing high-intensity training. Indomethacin is used for pain management in sports [...] Read more.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammation and pain and even to prevent the progression of cardiovascular disease. They have become widely used because of their effectiveness, especially among athletes performing high-intensity training. Indomethacin is used for pain management in sports medicine and is highly effective and versatile. However, several clinical studies have reported that indomethacin induces acute renal damage. In the present study, we determined that indomethacin reduced human embryonic kidney 293 (HEK293) cell viability in a concentration-dependent manner by triggering apoptosis. In addition, we demonstrated the effect of quercetin on indomethacin-treated HEK293 cells by inactivating the caspase-3 and caspase-9 signals. Furthermore, quercetin reduced ROS production and increased mitochondrial membrane potential (ΔΨm) in indomethacin-treated HEK293 cells. Our results indicate that quercetin can interrupt the activated caspase and mitochondrial pathway induced by indomethacin in HEK293 cells and affect apoptotic mRNA expression. Quercetin can protect against indomethacin-induced HEK293 cell apoptosis by regulating abnormal ΔΨm and apoptotic mRNA expression. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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Review

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15 pages, 1507 KiB  
Review
Quercetin Derivatives in Combating Spinal Cord Injury: A Mechanistic and Systematic Review
by Sajad Fakhri, Mohammad Mehdi Gravandi, Sadaf Abdian, Seyed Zachariah Moradi and Javier Echeverría
Life 2022, 12(12), 1960; https://doi.org/10.3390/life12121960 - 23 Nov 2022
Cited by 9 | Viewed by 2601
Abstract
Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing symptoms. During SCI, inflammation, oxidative stress, apoptosis, and autophagy are behind the secondary phase of SCI and cause serious [...] Read more.
Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing symptoms. During SCI, inflammation, oxidative stress, apoptosis, and autophagy are behind the secondary phase of SCI and cause serious consequences. It urges the need for providing multi-targeting agents, that possess lower side effects and higher efficacy. The plant secondary metabolites are multi-targeting agents and seem to provide new roads in combating diseases. Flavonoids are phytochemicals of continual interest to scientists in combating neurodegenerative diseases (NDDs). Flavonoids are being studied for their biological and pharmacological effects, particularly as antioxidants, anti-inflammatory agents, anti-apoptotic, and autophagy regulators. Quercetin is one of the most well-known flavonols known for its preventative and therapeutic properties. It is a naturally occurring bioactive flavonoid that has recently received a lot of attention for its beneficial effects on NDDs. Several preclinical evidence demonstrated its neuroprotective effects. In this systematic review, we aimed at providing the biological activities of quercetin and related derivatives against SCI. Detailed neuroprotective mechanisms of quercetin derivatives are also highlighted in combating SCI. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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18 pages, 1002 KiB  
Review
Therapeutic Potential of Quercetin in the Management of Type-2 Diabetes Mellitus
by Prawej Ansari, Samara T. Choudhury, Veronique Seidel, Akib Bin Rahman, Md. Abdul Aziz, Anika E. Richi, Ayesha Rahman, Umme H. Jafrin, J. M. A. Hannan and Yasser H. A. Abdel-Wahab
Life 2022, 12(8), 1146; https://doi.org/10.3390/life12081146 - 28 Jul 2022
Cited by 55 | Viewed by 5719
Abstract
Diabetes Mellitus (DM) is a metabolic disorder that is spreading alarmingly around the globe. Type-2 DM (T2DM) is characterized by low-grade inflammation and insulin resistance and is closely linked to obesity. T2DM is mainly controlled by lifestyle/dietary changes and oral antidiabetic drugs but [...] Read more.
Diabetes Mellitus (DM) is a metabolic disorder that is spreading alarmingly around the globe. Type-2 DM (T2DM) is characterized by low-grade inflammation and insulin resistance and is closely linked to obesity. T2DM is mainly controlled by lifestyle/dietary changes and oral antidiabetic drugs but requires insulin in severe cases. Many of the drugs that are currently used to treat DM are costly and present adverse side effects. Several cellular, animal, and clinical studies have provided compelling evidence that flavonoids have therapeutic potential in the management of diabetes and its complications. Quercetin is a flavonoid, present in various natural sources, which has demonstrated in vitro and in vivo antidiabetic properties. It improves oral glucose tolerance, as well as pancreatic β-cell function to secrete insulin. It inhibits the α-glucosidase and DPP-IV enzymes, which prolong the half-life of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Quercetin also suppresses the release of pro-inflammatory markers such as IL-1β, IL-4, IL-6, and TNF-α. Further studies are warranted to elucidate the mode(s) of action of quercetin at the molecular level. This review demonstrates the therapeutic potential of quercetin in the management of T2DM. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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28 pages, 1329 KiB  
Review
A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders
by Dagmara Wróbel-Biedrawa, Karolina Grabowska, Agnieszka Galanty, Danuta Sobolewska and Irma Podolak
Life 2022, 12(4), 591; https://doi.org/10.3390/life12040591 - 15 Apr 2022
Cited by 43 | Viewed by 10529
Abstract
Quercetin is one of the most common, naturally occurring flavonoids, structurally classified to the flavonol subfamily. This compound, found in many edible and medicinal plants either as a free or glycosidated form, has been scientifically exploited for many years, and one could hardly [...] Read more.
Quercetin is one of the most common, naturally occurring flavonoids, structurally classified to the flavonol subfamily. This compound, found in many edible and medicinal plants either as a free or glycosidated form, has been scientifically exploited for many years, and one could hardly expect it could be a hero of some additional story. Commonly recognized as an anti-inflammatory agent, quercetin not only limits capillary vessel permeability by inhibiting hyaluronidase but also blocks cyclooxygenases and lipoxygenases. As a typical flavonoid, it is also known for its antioxidant effect, which was confirmed by many in vitro and in vivo studies. Throughout the years, numerous other activities were reported for quercetin, including antidiabetic, anti-proliferative, or anti-viral. Of note, recent data have revealed its potential role as a therapeutic agent for several central nervous system disorders. This review provides an overview of available experimental data on quercetin and its complexes with respect to central nervous system diseases, with a main focus on some aspects that were not discussed previously, such as anti-anxiolytic effects, anti-Huntington’s disease activity, or therapeutic potential in brain cancer. Moreover, quercetin’s protective role in some of these diseases is discussed, especially as an anti-neuroinflammatory agent. Bearing in mind the poor bioavailability of this compound, possible options that would enhance its delivery to the site of action are also presented. Full article
(This article belongs to the Special Issue Quercetin and Its Complexes for Medicinal Applications)
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