Supplementing Quercetin for Neurotrophic and Senolytic Effects
Updated: Nov 3
Click here to watch the companion video to this blog post.
My favorite quercetin supplements:
Thorne Research's Phytosomal Quercetin, which you can find here.
Double Wood's very cheap product, which you can find here.
BulkSupplements' product, which you can find here.
A comparison of these products' prices per mg of quercetin can be found at this end of this blog post.
1. Flavonoids are categorized into flavonols, flavones, flavanones, catechins, and anthocyanidins.
a. Flavonols include quercetin, fisetin, galangin, kaempferol, myricetin, quercitrin, and rutin.
2. Quercetin (3,3’,4’,5,7-pentahydroxylflavone) is the most prevalent flavonoid in food, followed by kaempferol.
3. Quercetin is found as quercetin aglycone in food and quercetin rutinoside (also called rutin) in tea, where aglycone is absorbed more quickly and uniformly by people.
4. The richest quercetin containing foods in descending order are elderberries, red onions, white onions, cranberries, green hot peppers, kale, blueberries, and red apples.
1. Quercetin’s various metabolites have differential ability to scavenge free radicals.
2. Using human leukemia cells stimulated by lipopolysaccharides, quercetin was shown to inhibit reactive oxygen and nitrogen species with a higher reduction potential than curcumin at three different PHs and a total antioxidant capacity (TAC) 3.5x more powerful than curcumin.
3. On the DPPH assay, quercetin’s ability to scavenge free radicals is worse than EGCG and tied with epicatechin gallate (ECG), though it is superior to myricetin and kaempferol.
4. Quercetin’s ORAC score is lower than kaempferol and myricetin (and all of the catechins, which are led by epicatechin).
5. In the FRAP and ABTS assays, quercetin is a better free radical scavenger than alpha-tocopherol.
6. It is less effective than epigallocatechin gallate (EGCG) at inhibiting DNA damage but more capable at producing DNA damage (at high concentrations).
1. Nanoparticles have been developed to deliver quercetin.
2. Quercetin reduced oxidative stress by inhibiting inducible nitric oxide synthase protein expression and mitochondrial superoxide radicals and reduced the expression of IL-6, IL-1beta, and TNF-alpha in microglia treated with the Parkinsonian toxin MPP.
3. In rodent models of cerebral ischemia (hypoxic brain), quercetin protects neurons from apoptosis likely via upregulated of TrkB and BDNF.
4. Higher doses of quercetin increase BDNF mRNA in the rodent hippocampus.
5. In a model of polychlorinated biphenyl (PCBs) toxicity, PCB-induced suppression of rodent steroidogenesis was attenuated by quercetin. Quercetin also attenuated reductions on estrogen receptors in the hippocampus and BDNF signaling.
6. In a model of dimethylhydrazine-induced colorectal cancer, quercetin (with exercise) reduced tumor incidence, improved depressive symptoms, and upregulated BDNF.
7. In a model of lipopolysaccharide-induced rodent depression (and anxiety), quercetin could attenuated LPS-induced downregulation of BDNF.
8. In a rodent model of oxidative injury to a mother, quercetin given to the mother improved BDNF signaling in offspring.
9. In rodents, quercetin can prophylactically protect rodents from memory impairments due to hypoxia.
10. In a rodent model of transgenic Parkinsonian mice, it appears that quercetin attenuates the progression of the disease.
11. Pre-treatment with quercetin limits dopaminergic neuron loss from the MPP toxin.
12. Quercetin improved BDNF expression after a spinal chord injury to rodents.
13. In a transgenic rodent model of Alzheimer’s, quercetin was more effective at attenuating the pathology of beta amyloid plaques when the rodents were given less vitamin D.
14. Quercetin’s neuroprotective element may require greater concentrations of the flavonoid than myricetin.
15. Chronic unpredicted stress (CUS) produces cognitive dysfunction and insulin resistance in rodents. Quercetin upregulates GLUT4 expression in the hippocampus and alleviates memory dysfunction.
16. Quercetin protects against dopaminergic dysfunction due to cadmium toxicity in a rodent model.
17. Quercetin and its glucosides (including rutin) affect alpha7 nicotinic cholinergic receptor ion currents. Quercetin increases them and rutin most potently decreases them.
18. Quercetin can attenuate GABA-A alpha5 receptor downregulation due to glutamate excitotoxicity (as seen here in a mouse seizure model with kainic acid).
1. Quercetin is selectively cytotoxic against cancers cells of blood, brain, lung, uterine, skin, and salivary glands.
a. It is compared to other flavonoids in this paper.
2. Quercetin aglycone interacts with the aryl hydrocarbon receptor and modulates MEK/ERK and Nrf2/keap1 pathways.
3. Quercetin is also thought to reduce the phosphorylation of activated heat shock protein transcription factor (HSF), allowing it to experience proteolytic degradation, thereby reducing heat shock protein expression. Heat shock proteins are overexpressed in tumors.
4. Quercetin inhibits breast cancer stem cell development.
5. Quercetin’s cytotoxicity to human prostate and skin cancer cell lines is enhanced with ultrasound use.
6. Quercetin sensitizes prostate cancer cells to chemotherapeutic medicines, such as docetaxel.
7. Quercetin improves apoptosis in human pancreatic cancer cell lines.
8. Quercetin suppresses the development of metastatic osteosarcoma cancer cells.
9. Quercetin nanoparticles exert an anti-tumor effect on hepatocellular carcinoma cells by inhibiting NFkB, COX-2, and Akt signalling.
a. Quercetin is also being investigated as a treatment for primary liver tumors (PLTs), due to its competitive inhibition of the glucose transporter 1 (GLUT1), which is upregulated in PLT.
1. Quercetin upregulates the expression of metallothioneins, which in turn may phosphorylate JNK, p38, and PI3K/Akt, and may enhance Nrf2 activity. This produces a protective effect over hepatocytes.
2. In a rodent model of T2D-induced NAFLD, quercetin improved inflammatory measures, bile acid measures, and reduced fat retention in the liver.
3. Quercetin has improved measures of hepatic function in a rodent model of liver fibrosis.
4. Quercetin protects the liver from damage due to hyperthyroidism by upregulating the Nrf2 pathway.
5. Quercetin can protect the liver from damage due to T1D by inhibiting the CYP2E1 protein, as seen in a mouse model.
6. Quercetin protects rodents’ livers from ethanol-induced injury by inhibiting the Akt, NFkB, and STAT3 pathways.
7. In a rodent model of ethanol-induced liver steatosis, quercetin encouraged lipolysis in the liver and attenuated the inhibition of AMPK due to the chronic ethanol intake.
8. Quercetin is antifibrotic in rodents’ livers (tested with carbon tetrachloride).
9. In a rodent model of lipopolysaccharide-induced liver injury, quercetin was hepatoprotective. It inhibited NFkB and MAPK signaling and limited hepatocyte apoptosis.
10. Quercetin aglycone appears more hepatoprotective than quercetin glucosides (the glycosylated forms).
11. Liposomal nanoparticles of quercetin have also been used to protect rodent livers from acute injury.
12. The combination of fish oil and quercetin produced synergistic protection of rodent livers from oxidative stress due to Western diet.
1. Rutin, the quercetin glycoside, protected rodent kidneys from nephrotoxic effects of lipopolysaccharides.
2. Quercetin protects from acute kidney injury due to the chemotherapeutic drug, cisplatin.
3. Quercetin inhibits the iron-dependent necrosis of kidneys called ferroptosis.
4. Quercetin protects rodent kidneys from cadmium toxicity.
5. Quercetin combined with N-acetylglucosamine at a 1:1 ratio protected rodent kidneys from acute kidney injury synergistically.
6. In a rodent model of chronic kidney disease, quercetin appears to slightly improve kidney health metrics and reduce fibrosis.
7. In rodents with obstructive nephropathy, quercetin reduced fibrosis by suppressing mTORC1 and mTORC2.
8. It also reduces fibrosis by reducing renal tubular epithelial cell senescence via SIRT1.
1. In a mouse model of lung fibrosis due to senescent idiopathic fibroblasts, quercetin attenuated pulmonary fibrosis.
1. In rodents, quercetin attenuated gains in bodyweight, as well as dyslipidemia, due to a high-fat diet in rodents by regulating the transcription of genes involved in lipogenesis.
2. At serum concentrations, quercetin can inhibit adipogenesis. At higher concentrations, it can reduce fat accumulation in mature adipocytes.
3. In combination with resveratrol, quercetin increases MUFA and PUFA levels, PPAR-alpha expression, and UCP2 expression in WAT.
4. In high-fat diet fed rodents, quercetin decreases inflammation in subcutaneous and visceral fat while red onion extract did so only for subcutaneous fat and instead increased inflammation in visceral fat. It also remodeled white adipose tissue and reduced circulation adipokines.
5. In rodents, quercetin appears to promote the browning of fat via activation of AMPK, or via the sympathetic nervous system, through which it upregulates both AMPK and PPAR-gamma, and, consequently, UCP1.
1. In vitro, quercetin prevents the oxidation of LDL by macrophages, though it does this less effectively than fellow flavonoids morin and fisetin.
2. In rodents, quercetin attenuates left ventricular hypertrophy due to hypertension, likely by upregulating PPAR-gamma and downregulating AP-1 signaling.
3. In humans, quercetin supplementation (730 mg) reduced blood pressure only in hypertensives and despite a lack of improvement in markers of oxidative stress.
4. In rodents fed a methionine-rich diet, quercetin reduced homocysteine. It also elevated ALT and AST levels at higher doses.
5. Quercetin’s effect on hypertension and lipids varies significantly depending on whether people carry ApoE3 or ApoE4 genes.
a. Quercetin only decreased systolic blood pressure in ApoE3 carriers.
b. Quercetin worsened lipid ratios among ApoE4 carriers.
i. This is similar to how fish oil was observed to raise HDL levels in ApoE4 carriers.
6. Quercetin protects against myocardial ischemia-reperfusion injury by activating PPAR-gamma which in turn inhibits the NFkB pathway.
1. Quercetin supplementation prolonged the lifespans of C. elegans by 15% due to the modulation of four genes and not caloric restriction/sirtuin effects.
2. Quercetin, to a lesser extent than resveratrol, is an indirect activator of SIRT1.
3. The major human quercetin metabolite quercetin-3-O-glucuronide weakly inhibits SIRT1 in human cell lines.
4. Supplementation with quercetin (0.1% of diets) significantly reduced the lifespans of mice.
5. Quercetin (in combination with the chemotherapeutic drug dasatinib) significantly decreased senescent cells in humans.
1. Quercetin can transactivate both alpha and beta estrogen receptors.
1. Quercetin can inhibit the growth of some bacteria.
2. Quercetin improves atherogenic metrics in rodents by modulating the microbiome and causing less synthesis of the atherogenic lysophosphatidylcholine.
3. Quercetin improves the diversity of the microbiome and attenuates disease pathology in a rodent model of colitis.
4. Quercetin attenuates dysbiosis due to antibiotics in rodents.
1. Unlike the catechins, it appears that quercetin may stimulate melanin synthesis.
2. Quercetin may protect against the progression of arthritis. 500 mg of quercetin taken daily improved the symptoms of arthritis in a controlled human study in Iran.
3. Quercetin binds to the vitamin D receptor and is consequently being studied as a first molecule on which to build an allosteric modulator of the vitamin D receptor.
4. There is evidence that quercetin may produce an antiviral outcome in upper respiratory tract infections.
5. Quercetin has been shown to improve symptoms of prostatitis in human trials.
1. Safety of dietary supplementation with quercetin:
a. Intakes of 3-40 mg of quercetin aglycone are common in Western diets, with hyperconsumers of fruits and vegetables consuming about 250 mg, while dietary supplements recommend 500-1000mg.
b. When metabolized, quercetin is mostly glucuronidated, sulfated, or methylated, though it may also be oxidized.
c. Quercetin is mostly found in the liver and kidneys, and to a lesser degree, in the brain, heart, and spleen.
d. Quercetin may worsen kidney function in those with impaired kidneys.
e. Quercetin has been shown to be mutagenic in smaller organisms (bacteria and yeast), possibly via its oxidation into o-quinone and quinone methide, though this was not shown in animal studies.
f. Chronic consumption of quercetin appears to decrease CYP1A2 and increase CYP2A6, CYP3A, and CYP3A5.
g. Quercetin can modulate steroidogenesis in some species and in some contexts (this has not been observed in humans).
h. It can alter the bioavailability of angiotensin receptor blockers, calcium channel blockers, PPAR agonists, statins, antipsychotics, and immunosuppressive drugs.
a. Quercetin Phytosome, a branded formulation of quercetin delivered with lecithin, is up to 20x more bioavailable.
b. Quercetin is better absorbed when taken with glucose.
c. Quercetin is more bioavailable when consumed with fats, and it is more bioavailable from onions than apples.
3. Questionable effectiveness:
a. In a randomized, double-blind, controlled trial of humans, quercetin supplementation (500 mg or 1000 mg) did not affect measures of oxidative stress.
b. Supplemental quercetin dose-dependently raises plasma quercetin levels but does not influence measures of oxidative stress.
a. Cheapest reviewed source: BulkSupplements.com is $0.11/500 mg of quercetin.
b. The least expensive tested capsule is Solaray Quercetin, which is $0.17/500 mg, though Double Wood’s contains bromelain and costs less than $0.07/500 mg.
c. Now brand is similarly cheap.
d. Thorne Research carries the Quercetin Phytosome which costs $.60/250 mg capsule made from sunflower lecithin.
 Kuhnau, J. (1976). Flavonoids. A class of semi-essential food components: Their role in human nutrition. World review of nutrition and dietetics.  Hertog, M. G., Hollman, P. C., Katan, M. B., & Kromhout, D. (1993). Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands.  Erlund, I., Kosonen, T., Alfthan, G., Mäenpää, J., Perttunen, K., Kenraali, J., ... & Aro, A. (2000). Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. European journal of clinical pharmacology, 56(8), 545-553.  Deng, Q., Li, X. X., Fang, Y., Chen, X., & Xue, J. (2020). Therapeutic Potential of Quercetin as an Antiatherosclerotic Agent in Atherosclerotic Cardiovascular Disease: A Review. Evidence-Based Complementary and Alternative Medicine, 2020.  Dueñas, M., Surco-Laos, F., González-Manzano, S., González-Paramás, A. M., & Santos-Buelga, C. (2011). Antioxidant properties of major metabolites of quercetin. European Food Research and Technology, 232(1), 103-111.  Lesjak, M., Beara, I., Simin, N., Pintać, D., Majkić, T., Bekvalac, K., ... & Mimica-Dukić, N. (2018). Antioxidant and anti-inflammatory activities of quercetin and its derivatives. Journal of Functional Foods, 40, 68-75.  Zhang, M., Swarts, S. G., Yin, L., Liu, C., Tian, Y., Cao, Y., ... & Ju, S. (2011). Antioxidant properties of quercetin. In Oxygen transport to tissue XXXII (pp. 283-289). Springer, Boston, MA.  Hirano, R., Sasamoto, W., Matsumoto, A., Itakura, H., Igarashi, O., & Kondo, K. (2001). Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation. Journal of nutritional science and vitaminology, 47(5), 357-362.  Ishimoto, H., Tai, A., Yoshimura, M., Amakura, Y., Yoshida, T., Hatano, T., & Ito, H. (2012). Antioxidative properties of functional polyphenols and their metabolites assessed by an ORAC assay. Bioscience, biotechnology, and biochemistry, 1201312797-1201312797.  Dueñas, M., González-Manzano, S., González-Paramás, A., & Santos-Buelga, C. (2010). Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin. Journal of Pharmaceutical and Biomedical Analysis, 51(2), 443-449.  Johnson, M. K., & Loo, G. (2000). Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA. Mutation Research/DNA Repair, 459(3), 211-218.  Kumari, A., Yadav, S. K., Pakade, Y. B., Singh, B., & Yadav, S. C. (2010). Development of biodegradable nanoparticles for delivery of quercetin. Colloids and Surfaces B: Biointerfaces, 80(2), 184-192.  Das, S. S., Verma, P. R. P., & Singh, S. K. (2020). Quercetin-Loaded Nanomedicine as Nutritional Application. In Nanomedicine for Bioactives (pp. 259-301). Springer, Singapore.  Bournival, J., Plouffe, M., Renaud, J., Provencher, C., & Martinoli, M. G. (2012). Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system. Oxidative medicine and cellular longevity, 2012.  Yao, R. Q., Qi, D. S., Yu, H. L., Liu, J., Yang, L. H., & Wu, X. X. (2012). Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF–TrkB–PI3K/Akt signaling pathway. Neurochemical research, 37(12), 2777-2786.  Rahvar, M., Owji, A. A., & Mashayekhi, F. J. (2018). Effect of quercetin on the brain-derived neurotrophic factor gene expression in the rat brain. Bratislavske lekarske listy, 119(1), 28-31.   Sadighparvar, S., Darband, S. G., Yousefi, B., Kaviani, M., Ghaderi‐Pakdel, F., Mihanfar, A., ... & Majidinia, M. (2020). Combination of quercetin and exercise training attenuates depression in rats with 1, 2‐dimethylhydrazine‐induced colorectal cancer: Possible involvement of inflammation and BDNF signalling. Experimental Physiology, 105(9), 1598-1609.  Lee, B., Yeom, M., Shim, I., Lee, H., & Hahm, D. H. (2020). Protective Effects of Quercetin on Anxiety-Like Symptoms and Neuroinflammation Induced by Lipopolysaccharide in Rats. Evidence-Based Complementary and Alternative Medicine, 2020.  Ke, F., Li, H., Chen, X., Gao, X., Huang, L., Du, A., ... & Ge, J. (2019). Quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of Copine 6 and TREM1/2 in the hippocampus and PFC. Frontiers in pharmacology, 10, 1544.  Zhang, M., Liu, W., Zhou, Y., Li, Y., Qin, Y., & Xu, Y. (2018). Neurodevelopmental toxicity induced by maternal PM2. 5 exposure and protective effects of quercetin and Vitamin C. Chemosphere, 213, 182-196.  Liu, P., Zou, D., Yi, L., Chen, M., Gao, Y., Zhou, R., ... & Mi, M. (2015). Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1α pathway. Restorative neurology and neuroscience, 33(2), 143-157.  Ay, M., Luo, J., Langley, M., Jin, H., Anantharam, V., Kanthasamy, A., & Kanthasamy, A. G. (2017). Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's Disease. Journal of neurochemistry, 141(5), 766-782.  Bournival, J., Quessy, P., & Martinoli, M. G. (2009). Protective effects of resveratrol and quercetin against MPP+-induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cellular and molecular neurobiology, 29(8), 1169-1180.  Wang, Y., Li, W., Wang, M., Lin, C., Li, G., Zhou, X., ... & Jin, D. (2018). Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats. Journal of Cellular Biochemistry, 119(2), 2298-2306.  Lv, M., Yang, S., Cai, L., Qin, L. Q., Li, B. Y., & Wan, Z. (2018). Effects of quercetin intervention on cognition function in APP/PS1 mice was affected by vitamin D status. Molecular nutrition & food research, 62(24), 1800621.  Oyama, Y., Fuchs, P. A., Katayama, N., & Noda, K. (1994). Myricetin and quercetin, the flavonoid constituents ofGinkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+-loaded brain neurons. Brain research, 635(1-2), 125-129.  Mehta, V., Parashar, A., Sharma, A., Singh, T. R., & Udayabanu, M. (2017). Quercetin ameliorates chronic unpredicted stress-mediated memory dysfunction in male Swiss albino mice by attenuating insulin resistance and elevating hippocampal GLUT4 levels independent of insulin receptor expression. Hormones and behavior, 89, 13-22.  Gupta, R., Shukla, R. K., Pandey, A., Sharma, T., Dhuriya, Y. K., Srivastava, P., ... & Khanna, V. K. (2018). Involvement of PKA/DARPP-32/PP1α and β-arrestin/Akt/GSK-3β Signaling in Cadmium-Induced DA-D2 Receptor-Mediated Motor Dysfunctions: Protective Role of Quercetin. Scientific reports, 8(1), 1-18.  Lee, B. H., Choi, S. H., Kim, H. J., Jung, S. W., Hwang, S. H., Pyo, M. K., ... & Nah, S. Y. (2016). Differential effects of quercetin and quercetin glycosides on human α7 nicotinic acetylcholine receptor-mediated ion currents. Biomolecules & therapeutics, 24(4), 410.  Moghbelinejad, S., Alizadeh, S., Mohammadi, G., Khodabandehloo, F., Rashvand, Z., Najafipour, R., & Nassiri-Asl, M. (2017). The effects of quercetin on the gene expression of the GABA A receptor α5 subunit gene in a mouse model of kainic acid-induced seizure. The Journal of Physiological Sciences, 67(2), 339-343.  Sak, K. (2014). Site-specific anticancer effects of dietary flavonoid quercetin. Nutrition and cancer, 66(2), 177-193.  Sak, K. (2014). Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacognosy reviews, 8(16), 122.  Murakami, A., Ashida, H., & Terao, J. (2008). Multitargeted cancer prevention by quercetin. Cancer letters, 269(2), 315-325.  Nagai, N., Nakai, A., & Nagata, K. (1995). Quercetin suppresses heat shock response by down-regulation of HSF1. Biochemical and biophysical research communications, 208(3), 1099-1105.  Li, D. P., Calzi, S. L., & Sánchez, E. R. (1999). Inhibition of heat shock factor activity prevents heat shock potentiation of glucocorticoid receptor-mediated gene expression. Cell stress & chaperones, 4(4), 223.  Jäättelä, M. (1999). Escaping cell death: survival proteins in cancer. Experimental cell research, 248(1), 30-43.  Wang, R., Yang, L., Li, S., Ye, D., Yang, L., Liu, Q., ... & Li, X. (2018). Quercetin inhibits breast cancer stem cells via downregulation of aldehyde dehydrogenase 1A1 (ALDH1A1), chemokine receptor type 4 (CXCR4), mucin 1 (MUC1), and epithelial cell adhesion molecule (EpCAM). Medical Science Monitor: international medical journal of experimental and clinical research, 24, 412.  Paliwal, S., Sundaram, J., & Mitragotri, S. (2005). Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound. British journal of cancer, 92(3), 499-502.  Lu, X., Yang, F., Chen, D., Zhao, Q., Chen, D., Ping, H., & Xing, N. (2020). Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. International Journal of Biological Sciences, 16(7), 1121.  Lan, C. Y., Chen, S. Y., Kuo, C. W., Lu, C. C., & Yen, G. C. (2019). Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells. Journal of food and drug analysis, 27(4), 887-896.  Li, S., Pei, Y., Wang, W., Liu, F., Zheng, K., & Zhang, X. (2019). Quercetin suppresses the proliferation and metastasis of metastatic osteosarcoma cells by inhibiting parathyroid hormone receptor 1. Biomedicine & Pharmacotherapy, 114, 108839.  Zhao, P., Hu, Z., Ma, W., Zang, L., Tian, Z., & Hou, Q. (2020). Quercetin alleviates hyperthyroidism‐induced liver damage via Nrf2 Signaling pathway. BioFactors.  Brito, A. F., Ribeiro, M., Abrantes, A. M., Mamede, A. C., Laranjo, M., Casalta-Lopes, J. E., ... & Botelho, M. F. (2016). New approach for treatment of primary liver tumors: the role of quercetin. Nutrition and Cancer, 68(2), 250-266.  Weng, C. J., Chen, M. J., Yeh, C. T., & Yen, G. C. (2011). Hepatoprotection of quercetin against oxidative stress by induction of metallothionein expression through activating MAPK and PI3K pathways and enhancing Nrf2 DNA-binding activity. New biotechnology, 28(6), 767-777.  Yang, H., Yang, T., Heng, C., Zhou, Y., Jiang, Z., Qian, X., ... & Lu, Q. (2019). Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice. Phytotherapy Research, 33(12), 3140-3152.  Li, X., Jin, Q., Yao, Q., Xu, B., Li, L., Zhang, S., & Tu, C. (2018). The flavonoid quercetin ameliorates liver inflammation and fibrosis by regulating hepatic macrophages activation and polarization in mice. Frontiers in Pharmacology, 9, 72.  Zhao, P., Hu, Z., Ma, W., Zang, L., Tian, Z., & Hou, Q. (2020). Quercetin alleviates hyperthyroidism‐induced liver damage via Nrf2 Signaling pathway. BioFactors.  Maksymchuk, O., Shysh, A., Rosohatska, I., & Chashchyn, M. (2017). Quercetin prevents type 1 diabetic liver damage through inhibition of CYP2E1. Pharmacological Reports, 69(6), 1386-1392.  Zhu, M., Zhou, X., & Zhao, J. (2017). Quercetin prevents alcohol‑induced liver injury through targeting of PI3K/Akt/nuclear factor‑κB and STAT3 signaling pathway. Experimental and therapeutic medicine, 14(6), 6169-6175.  Zeng, H., Guo, X., Zhou, F., Xiao, L., Liu, J., Jiang, C., ... & Yao, P. (2019). Quercetin alleviates ethanol-induced liver steatosis associated with improvement of lipophagy. Food and chemical toxicology, 125, 21-28.  Wang, R., Zhang, H., Wang, Y., Song, F., & Yuan, Y. (2017). Inhibitory effects of quercetin on the progression of liver fibrosis through the regulation of NF-кB/IкBα, p38 MAPK, and Bcl-2/Bax signaling. International immunopharmacology, 47, 126-133.  Peng, Z., Gong, X., Yang, Y., Huang, L., Zhang, Q., Zhang, P., ... & Zhang, B. (2017). Hepatoprotective effect of quercetin against LPS/d-GalN induced acute liver injury in mice by inhibiting the IKK/NF-κB and MAPK signal pathways. International immunopharmacology, 52, 281-289.  Lee, S., Lee, J., Lee, H., & Sung, J. (2019). Relative protective activities of quercetin, quercetin‐3‐glucoside, and rutin in alcohol‐induced liver injury. Journal of food biochemistry, 43(11), e13002.  Liu, X., Zhang, Y., Liu, L., Pan, Y., Hu, Y., Yang, P., & Liao, M. (2020). Protective and therapeutic effects of nanoliposomal quercetin on acute liver injury in rats. BMC Pharmacology and Toxicology, 21(1), 1-7.  Kobori, M., Akimoto, Y., Takahashi, Y., & Kimura, T. (2020). Combined Effect of Quercetin and Fish Oil on Oxidative Stress in the Liver of Mice fed a Western-style diet. Journal of Agricultural and Food Chemistry.  Khajevand-Khazaei, M. R., Mohseni-Moghaddam, P., Hosseini, M., Gholami, L., Baluchnejadmojarad, T., & Roghani, M. (2018). Rutin, a quercetin glycoside, alleviates acute endotoxemic kidney injury in C57BL/6 mice via suppression of inflammation and up-regulation of antioxidants and SIRT1. European journal of pharmacology, 833, 307-313.  Tan, R. Z., Wang, C., Deng, C., Zhong, X., Yan, Y., Luo, Y., ... & Wang, L. (2020). Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation. Phytotherapy Research, 34(1), 139-152.  Wang, Y., Quan, F., Cao, Q., Lin, Y., Yue, C., Bi, R., ... & Li, X. (2020). Quercetin alleviates acute kidney injury by inhibiting ferroptosis. Journal of Advanced Research.  Yuan, Y., Ma, S., Qi, Y., Wei, X., Cai, H., Dong, L., ... & Guo, Q. (2016). Quercetin inhibited cadmium-induced autophagy in the mouse kidney via inhibition of oxidative stress. Journal of toxicologic pathology.  Shebeko, S. K., Zupanets, I. A., & Propisnova, V. V. (2020). N-acetylglucosamine increases the efficacy of quercetin in the treatment of experimental acute kidney injury.  Layal, K., Perdhana, I. S., Louisa, M., Estuningtyas, A., & Soetikno, V. (2017). The effects of quercetin on oxidative stress and fibrosis markers in chronic kidney disease rat model. Medical Journal of Indonesia, 26(3), 169-77.  Ren, J., Li, J., Liu, X., Feng, Y., Gui, Y., Yang, J., ... & Dai, C. (2016). Quercetin inhibits fibroblast activation and kidney fibrosis involving the suppression of mammalian target of rapamycin and β-catenin signaling. Scientific reports, 6, 23968.  Kim, S. R., Jiang, K., Ogrodnik, M., Chen, X., Zhu, X. Y., Lohmeier, H., ... & Kirkland, J. L. (2019). Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin. Translational Research, 213, 112-123.  Liu, T., Yang, Q., Zhang, X., Qin, R., Shan, W., Zhang, H., & Chen, X. (2020). Quercetin alleviates kidney fibrosis by reducing renal tubular epithelial cell senescence through the SIRT1/PINK1/mitophagy axis. Life Sciences, 257, 118116.  Hohmann, M. S., Habiel, D. M., Coelho, A. L., Verri Jr, W. A., & Hogaboam, C. M. (2019). Quercetin enhances ligand-induced apoptosis in senescent idiopathic pulmonary fibrosis fibroblasts and reduces lung fibrosis in vivo. American Journal of Respiratory Cell and Molecular Biology, 60(1), 28-40.  Jung, C. H., Cho, I., Ahn, J., Jeon, T. I., & Ha, T. Y. (2013). Quercetin reduces high‐fat diet‐induced fat accumulation in the liver by regulating lipid metabolism genes. Phytotherapy Research, 27(1), 139-143.  Eseberri, I., Miranda, J., Lasa, A., Churruca, I., & Portillo, M. P. (2015). Doses of quercetin in the range of serum concentrations exert delipidating effects in 3T3-L1 preadipocytes by acting on different stages of adipogenesis, but not in mature adipocytes. Oxidative Medicine and Cellular Longevity, 2015.  Castrejón-Tellez, V., Rodríguez-Pérez, J. M., Pérez-Torres, I., Pérez-Hernández, N., Cruz-Lagunas, A., Guarner-Lans, V., ... & Rubio-Ruiz, M. E. (2016). The effect of resveratrol and quercetin treatment on PPAR mediated uncoupling protein (UCP-) 1, 2, and 3 expression in visceral white adipose tissue from metabolic syndrome rats. International Journal of Molecular Sciences, 17(7), 1069.  Forney, L. A., Lenard, N. R., Stewart, L. K., & Henagan, T. M. (2018). Dietary quercetin attenuates adipose tissue expansion and inflammation and alters adipocyte morphology in a tissue-specific manner. International journal of molecular sciences, 19(3), 895.  Lee, S. G., Parks, J. S., & Kang, H. W. (2017). Quercetin, a functional compound of onion peel, remodels white adipocytes to brown-like adipocytes. The Journal of Nutritional Biochemistry, 42, 62-71.  Choi, H., Kim, C. S., & Yu, R. (2018). Quercetin upregulates uncoupling protein 1 in white/brown adipose tissues through sympathetic stimulation. Journal of obesity & metabolic syndrome, 27(2), 102.  de Whalley, C. V., Rankin, S. M., Hoult, J. R. S., Jessup, W., & Leake, D. S. (1990). Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages. Biochemical pharmacology, 39(11), 1743-1750.  Yan, L., Zhang, J. D., Wang, B., Lv, Y. J., Jiang, H., Liu, G. L., ... & Guo, X. F. (2013). Quercetin inhibits left ventricular hypertrophy in spontaneously hypertensive rats and inhibits angiotensin II-induced H9C2 cells hypertrophy by enhancing PPAR-γ expression and suppressing AP-1 activity. PLoS One, 8(9), e72548.  Edwards, R. L., Lyon, T., Litwin, S. E., Rabovsky, A., Symons, J. D., & Jalili, T. (2007). Quercetin reduces blood pressure in hypertensive subjects. The Journal of nutrition, 137(11), 2405-2411.  Meng, B., Gao, W., Wei, J., Yang, J., Wu, J., Pu, L., & Guo, C. (2013). Quercetin reduces serum homocysteine level in rats fed a methionine-enriched diet. Nutrition, 29(4), 661-666.  Egert, S., Boesch-Saadatmandi, C., Wolffram, S., Rimbach, G., & Müller, M. J. (2010). Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. The Journal of nutrition, 140(2), 278-284.  Minihane, A. M., Khan, S., Leigh-Firbank, E. C., Talmud, P., Wright, J. W., Murphy, M. C., ... & Williams, C. M. (2000). ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arteriosclerosis, thrombosis, and vascular biology, 20(8), 1990-1997.  Liu, X., Yu, Z., Huang, X., Gao, Y., Wang, X., Gu, J., & Xue, S. (2016). Peroxisome proliferator-activated receptor γ (PPARγ) mediates the protective effect of quercetin against myocardial ischemia-reperfusion injury via suppressing the NF-κB pathway. American journal of translational research, 8(12), 5169.  Kampkötter, A., Timpel, C., Zurawski, R. F., Ruhl, S., Chovolou, Y., Proksch, P., & Wätjen, W. (2008). Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 149(2), 314-323.  Pietsch, K., Saul, N., Menzel, R., Stürzenbaum, S. R., & Steinberg, C. E. (2009). Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43. Biogerontology, 10(5), 565-578.  Suchankova, G., Nelson, L. E., Gerhart-Hines, Z., Kelly, M., Gauthier, M. S., Saha, A. K., ... & Ruderman, N. B. (2009). Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. Biochemical and biophysical research communications, 378(4), 836-841.  de Boer, V. C., de Goffau, M. C., Arts, I. C., Hollman, P. C., & Keijer, J. (2006). SIRT1 stimulation by polyphenols is affected by their stability and metabolism. Mechanisms of ageing and development, 127(7), 618-627.  Jones, E., & Hughes, R. E. (1982). Quercetin, flavonoids and the life-span of mice. Experimental gerontology, 17(3), 213-217.  Hickson, L. J., Prata, L. G. L., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., ... & Kellogg, T. A. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47, 446-456.  Maggiolini, M., Bonofiglio, D., Marsico, S., Panno, M. L., Cenni, B., Picard, D., & Andò, S. (2001). Estrogen receptor α mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Molecular pharmacology, 60(3), 595-602.  Jaisinghani, R. N. (2017). Antibacterial properties of quercetin. Microbiology Research, 8(1).  Nie, J., Zhang, L., Zhao, G., & Du, X. (2019). Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites. Journal of applied microbiology, 127(6), 1824-1834.  Lin, R., Piao, M., & Song, Y. (2019). Dietary quercetin increases colonic microbial diversity and attenuates colitis severity in citrobacter rodentium-infected mice. Frontiers in microbiology, 10, 1092.  Shi, T., Bian, X., Yao, Z., Wang, Y., Gao, W., & Guo, C. (2020). Quercetin improves gut dysbiosis in antibiotic-treated mice. Food & Function.  Liu‐Smith, F., & Meyskens, F. L. (2016). Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma. Molecular nutrition & food research, 60(6), 1264-1274.  Haleagrahara, N., Miranda-Hernandez, S., Alim, M. A., Hayes, L., Bird, G., & Ketheesan, N. (2017). Therapeutic effect of quercetin in collagen-induced arthritis. Biomedicine & pharmacotherapy, 90, 38-46.  Javadi, F., Ahmadzadeh, A., Eghtesadi, S., Aryaeian, N., Zabihiyeganeh, M., Rahimi Foroushani, A., & Jazayeri, S. (2017). The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: a double-blind, randomized controlled trial. Journal of the American College of Nutrition, 36(1), 9-15.  Lee, K. Y., Choi, H. S., Choi, H. S., Chung, K. Y., Lee, B. J., Maeng, H. J., & Seo, M. D. (2016). Quercetin directly interacts with vitamin D Receptor (VDR): Structural implication of VDR activation by quercetin. Biomolecules & therapeutics, 24(2), 191.  Somerville, V. S., Braakhuis, A. J., & Hopkins, W. G. (2016). Effect of flavonoids on upper respiratory tract infections and immune function: A systematic review and meta-analysis. Advances in nutrition, 7(3), 488-497.  Shoskes, D. A., Zeitlin, S. I., Shahed, A., & Rajfer, J. (1999). Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology, 54(6), 960-963.  Andres, S., Pevny, S., Ziegenhagen, R., Bakhiya, N., Schäfer, B., Hirsch‐Ernst, K. I., & Lampen, A. (2018). Safety aspects of the use of quercetin as a dietary supplement. Molecular Nutrition & Food Research, 62(1), 1700447.  Riva, A., Ronchi, M., Petrangolini, G., Bosisio, S., & Allegrini, P. (2019). Improved oral absorption of quercetin from quercetin phytosome®, a new delivery system based on food grade lecithin. European journal of drug metabolism and pharmacokinetics, 44(2), 169-177.  Hollman, P. C., de Vries, J. H., van Leeuwen, S. D., Mengelers, M. J., & Katan, M. B. (1995). Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. The American journal of clinical nutrition, 62(6), 1276-1282.  Kaşıkcı, M. B., & Bağdatlıoğlu, N. (2016). Bioavailability of quercetin. Current research in nutrition and food science journal, 4(Special Issue Nutrition in Conference October 2016), 146-151.  Shanely, R. A., Knab, A. M., Nieman, D. C., Jin, F., McAnulty, S. R., & Landram, M. J. (2010). Quercetin supplementation does not alter antioxidant status in humans. Free radical research, 44(2), 224-231.  Egert, S., Wolffram, S., Bosy-Westphal, A., Boesch-Saadatmandi, C., Wagner, A. E., Frank, J., ... & Mueller, M. J. (2008). Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. The Journal of nutrition, 138(9), 1615-1621.