Quercetin in the quantity of 400 mg (2 tablets with 200 mg each) per day during 3 months, provided 4 times less COVID-19 infection rate vs. the control group, according to the clinical study diclosed in Mariangela Rondanelli et al., “Promising effects of 3-month period of Quercetin Phytosome® supplementation in the prevention of symptomatic COVID-19 disease in healthcare workers: A pilot study,” Life 2022, 4 January 2022, 12(1), 66, https://doi.org/10.3390/life12010066, JIF 3.253 (top 42% journals in Biology).
Quercetin in the quantity of 600 mg (3 tablets with 200 mg each) per day in the first week and 400 mg (2 tablets of 200 mg) per day in the second week completely eliminated deaths from COVID-19 to 0.0% vs. 4.8% in the control group; completely eliminated the progression to intensive care units (ICU) to 0.0% vs. 4.8% in the control group; and completely eliminated hospitalizations to 0.0% vs. 4.8% in the control group, according to the clinical study disclosed in Francesco Di Pierro et al., “Potential clinical benefits of quercetin in the early stage of COVID-19: Results of a second, pilot, randomized, controlled and open-label clinical trial,” International Journal of General Medicine, 24 June 2021, 14, 2807-2816, https://doi.org/10.2147/IJGM.S318949, JIF 2.145 (top 66% journals in Medicine, General & Internal).
Quercetin in the quantity of 400 mg (2 tablets with 200 mg each) per day during 30 days completely eliminated deaths from COVID-19 to 0.0% vs. 3.9% deaths in the control group, and completely eliminated the progression to intensive care units (ICU) to 0.0% vs. 10.5% in the control group, according to the clinical study disclosed in Francesco Di Pierro et al., “Possible therapeutic effects of adjuvant quercetin supplementation against early-stage COVID-19 infection: A prospective, randomized, controlled, and open-label study,” International Journal of General Medicine, 8 June 2021, 14, 2359-2366, https://doi.org/10.2147/ijgm.s318720, JIF 2.145 (top 66% journals in Medicine, General & Internal).
Flavonoids have been proven to be active against hypertension, inflammation, diabetes and vascular diseases. Quercetin protects against atherosclerosis, oxidative stress, cardiotoxicity, endothelial cell dysfunction, heart failure etc., according to Rahul V. Patel et al., “Therapeutic potential of quercetin as a cardiovascular agent,” European Journal of Medicinal Chemistry, 15 July 2018, 155, 889-904, https://doi.org/10.1016/j.ejmech.2018.06.053, JIF 7.088 (top 8% journals in Chemistry, Medicinal).
Quercetin is a naturally-occurring flavonol (a member of the flavonoid family of compounds) that has a long history of consumption as part of the normal human diet. Because a number of biological properties of quercetin may be beneficial to human health, interest in the addition of this flavonol to various traditional food products has been increasing. Prior to the use of quercetin in food applications that would increase intake beyond that from naturally-occurring levels of the flavonol in the typical Western diet, its safety needs to be established or confirmed. This review provides a critical examination of the scientific literature associated with the safety of quercetin. Results of numerous genotoxicity and mutagenicity, short- and long-term animal, and human studies are reviewed in the context of quercetin exposure in vivo. To reconcile results of in vitro studies, which consistently demonstrated quercetin-related mutagenicity to the absence of carcinogenicity in vivo, the mechanisms that lead to the apparent in vitro mutagenicity, and those that ensure absence of quercetin toxicity in vivo are discussed. The weight of the available evidence supports the safety of quercetin for addition to food, according to M. Harwood et al., “A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties,” Food and Chemical Toxicology 2007;45(11):2179–205, https://doi.org/10.1016/j.fct.2007.05.015, JIF 5.572 (top 16% journals in Toxicology, top 24% journals in Food Science & Technology).
High levels of cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6, are associated with chronic diseases like rheumatoid arthritis, asthma, atherosclerosis, Alzheimer's disease and cancer; therefore cytokine inhibition might be an important target for the treatment of these diseases. Most drugs used to alleviate some inflammation-related symptoms act by inhibiting cyclooxygenases activity or by blocking cytokine receptors. Nevertheless, these drugs have secondary effects when used on a long-term basis. It has been mentioned that flavonoids, namely quercetin, apigenin and luteolin, reduce cytokine expression and secretion. In this regard, flavonoids may have therapeutical potential in the treatment of inflammation-related diseases as cytokine modulators. This review is focused on current research about the effect of flavonoids on cytokine modulation and the description of the way these compounds exert their effect, according to Nayely Leyva-Lopez et al. “Flavonoids as cytokine modulators: a possible therapy for inflammation-related diseases,” International Journal of Molecular Sciences 2016;17(6):921. https://doi.org/10.3390/ijms17060921, JIF 6.208 (top 24% journals in Biochemistry & Molecular Biology and top 28% journals in Chemistry, Multidisciplinary).
Quercetin as a member of flavonoids, has emerged as a potential therapeutic agent in cardiovascular diseases (CVDs) in recent decades. Experimental studies including both in vitro methods and in vivo animal models mainly outline the following effects of quercetin: (1) antihypertensive, (2) hypolipidemic, (3) hypoglycemic, (4) anti-atherosclerotic, and (5) cardioprotective (suppressed cardiotoxicity), according to Paraskevi Papakyriakopoulou et al., “Potential pharmaceutical applications of quercetin in cardiovascular diseases,” Pharmaceuticals, 2022, 15, 1019, https://doi.org/10.3390/ph15081019, JIF 5.125 (top 25% journals in Pharmacology & Pharmacy).
Research in animals and humans has indicated that polyphenols can delay the age-related decline in learning, memory and neurodegenerative diseases. Among the polyphenols, berry phenolics have extensive beneficial effects because of their antioxidant and anti-inflammatory properties. Long-term consumption of grapes results in accumulation of polyphenols in the brain, which modulates cell-signalling pathways and neutralises the redox imbalance in the aging brain. Here we review the in vivo and in vitro evidence for considering grape-derived polyphenolics, the flavonoids- catechins, epicatechin, anthocyanidin, and quercetin, and non-flavonoids-gallic acid and resveratrol, as effective dietary sources to facilitate cognition in adults and lessen the decline in the old and pathogenic states, Alzheimer's and Parkinson's disease. Furthermore, a combined intervention of polyphenols along with regular physical exercise provides cognitive benefits for the aging brain and holds promising venues for preclinical and clinical studies in formulating neuro-nutraceuticals as functional foods for a healthy brain, according to S. Asha Devi et al., “Polyphenols as an effective therapeutic intervention against cognitive decline during normal and pathological brain aging,” Advances in Experimental Medicine and Biology 2020;1260:159–74, https://doi.org/10.1007/978-3-030-42667-5_7, JIF 3.650 (top 35% journals in Biology and top 60% journals in Medicine, Research & Experimental).
Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucosidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson's patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood, according to Anna K. Jager AK, “Flavonoids and the CNS,” Molecules 2011;16(2):1471–85, https://doi.org/10.3390/molecules16021471, JIF 4.927 (top 37% journals in Chemistry, Multidisciplinary and top 39% journals in Biochemistry & Molecular biology).
Quercetin is the major flavonoid involved in vegetables and fruits. Quercetin is ingested from the daily diet, but in 1970s it was reported as mutagenic. Quercetin possesses a variety of pharmacological activities, and in order for further clinical application, it is important to evaluate its safety. In Ames test, quercetin is regarded as mutagenic. However, recent in vitro studies indicate that quercetin is protective against genotoxicants, and regarded as antimutagenic. Some in vivo studies including National Toxicology Program reported carcinogenic effect of quercetin in F344 rats. However, the method used in the study was unusual and the result was not reproduced. Most of the results of in vivo studies indicate that quercetin is not carcinogenic. Since 1969, the International Agency for Research on Cancer (IARC) has undertaken a program to evaluate the carcinogenic risk of chemicals. In 1999, IARC concluded that quercetin is not classified carcinogenic to humans. In the U.S. and Europe, supplements of quercetin is commercially available, and beneficial effects of quercetin supplements were reported in clinical trials. Overall, quercetin is genotoxic to salmonella, but its safety upon human application is approved, according to Toshihiro Okamoto et al., “Safety of quercetin for clinical application (review),” International Journal of Molecular Medicine 2005;16(2):275–8, https://doi.org/10.3892/ijmm.16.2.275, JIF 5.314 (top 38% journals in Medicine, Research & Experimental).
The inflammatory process in the human body is a physiological response involving many cellular types and mediators. It results in scar formation to separate the damaged area from the surrounding healthy tissue. Because of increased blood-brain barrier permeability following inflammation, leukocytes infiltrate the central nervous system (CNS) and are also supplemented by proinflammatory mediators. However, an acute inflammatory process after cerebral trauma or stroke may also result in a prolonged lesion formation, leading to a severe neuronal loss. The prolonged inflammatory process in the CNS may cause serious damage to the neuronal system. It may lead to CNS damage in such a way that endangers functional integration and proinflammatory system balance. Effects of different flavonoid species on ischemia-reperfusion injury and cognition and function have also been shown in experimental studies. Flavonoids are presented broadly in plants and diets. They are believed to have various bioactive effects including anti-viral, anti-inflammatory, cardioprotective, anti-diabetic, anti-cancer, anti-aging, etc. Quercetine is the predominant dietary flavonoid. Main sources are tea, onion, and apple. It is demonstrated that the frequently consumed food like soybean, peanut, mustard, rice, sesame, olive, potatoes, onion, and oats contain flavonoids, according to Zehra Calis et al., “The roles of flavonoles/flavonoids in neurodegeneration and neuroinflammation,” Mini-Reviews in Medicinal Chemistry 2020;20(15):1475–88, http://doi.org/10.2174/1389557519666190617150051, JIF 3.737 (top 50% journals in Chemistry, Medicinal).