A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders

Wróbel-Biedrawa, Dagmara; Grabowska, Karolina; Galanty, Agnieszka; Sobolewska, Danuta; Podolak, Irma

doi:10.3390/life12040591

Cited by 95Flavonoids in Medical ResearchPhytochemicals and Antioxidant ActivitiesMedicinal plant effects and applications

A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders

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Wróbel-Biedrawa, Dagmara, Grabowska, Karolina, Galanty, Agnieszka, Sobolewska, Danuta, Podolak, Irma·2022·Life

DOI 10.3390/life12040591PMC PMC9027262

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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 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.

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Quercetin alleviates chronic unpredictable mild stress-induced depressive-like behaviors by promoting adult hippocampal neurogenesis via FoxG1/CREB/ BDNF signaling pathway
Ma, Z., Zhang, R., Rui, W., Wang, Z.-Q., & Feng, X. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113245 · Cited by 91 · see citing works
Neuroprotective effect of quercetin nanoparticles: A possible prophylactic and therapeutic role in alzheimer’s disease
Rifaai, R. A., Mokhemer, S. A., Saber, E. A., El‐Aleem, S. A. A., & El‐Tahawy, N. F. G. (2020) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2020.101795 · Cited by 88 · see citing works
Pharmacokinetics and antitumor efficacy of DSPE-PEG2000 polymeric liposomes loaded with quercetin and temozolomide: Analysis of their effectiveness in enhancing the chemosensitization of drug-resistant glioma cells
Hu, J. X., Wang, J., Wang, G., Yao, Z., & Dang, X. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2458 · Cited by 87 · see citing works
Using superparamagnetic iron oxide nanoparticles to enhance bioavailability of quercetin in the intact rat brain
Najafabadi, R. E., Kazemipour, N., Esmaeili, A., Beheshti, S., & Nazıfı, S. (2018) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-018-0249-7 · Cited by 87 · see citing works
Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.
Maciel, R. M., Carvalho, F., Olabiyi, A., Schmatz, R., Gutierres, J., Stefanello, N., Zanini, D., Rosa, M. M., Andrade, C. M., Rubin, M., et al. (2016) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2016.09.069 · Cited by 86 · see citing works
Astrocytic control of neural circuit formation: Highlights on TGF-beta signaling
Diniz, L. P., Matias, I. C. P., Garcia, M. N., & Gomes, F. C. A. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.07.008 · Cited by 84 · see citing works
The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases
Tarek, B., Soleti, R., & Porro, C. (2021) · Nutrients · doi:10.3390/nu13041318 · Cited by 84 · see citing works
Quercetin ameliorates diabetic encephalopathy through SIRT1/ER stress pathway in db/db mice
Tian, H., Shi, J., Fang, J., Wang, Q., Chen, Y., & Zhang, S. (2020) · Aging · doi:10.18632/aging.103059 · Cited by 76 · see citing works
Quercetin mitigates anxiety-like behavior and normalizes hypothalamus–pituitary–adrenal axis function in a mouse model of mild traumatic brain injury
Kosari‐Nasab, M., Shokouhi, G., Ghorbanihaghjo, A., Abbasi, M. M., & Salari, A. (2019) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000480 · Cited by 71 · see citing works
Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line
Jakubowicz-Gil, J., Langner, E., Wertel, I., Piersiak, T., & Rzeski, W. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.07.015 · Cited by 70 · see citing works
Inhibition of autophagy induced by quercetin at a late stage enhances cytotoxic effects on glioma cells
Bi, Y., Shen, C., Li, C., Liu, Y., Gao, D., Chen, S., Peng, F., Liu, Z., Zhao, B., Zheng, Z., et al. (2015) · Tumor Biology · doi:10.1007/s13277-015-4125-4 · Cited by 70 · see citing works
Protective Effects of Quercetin on Anxiety‐Like Symptoms and Neuroinflammation Induced by Lipopolysaccharide in Rats
Lee, B., Yeom, M., Shim, I., Lee, H., & Hahm, D. (2020) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2020/4892415 · Cited by 69 · see citing works
Protective Role of Quercetin in Cadmium-Induced Cholinergic Dysfunctions in Rat Brain by Modulating Mitochondrial Integrity and MAP Kinase Signaling
Gupta, R., Shukla, R. K., Chandravanshi, L. P., Srivastava, P., Dhuriya, Y. K., Shanker, J., Singh, M. P., Pant, A. B., & Khanna, V. K. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9950-y · Cited by 67 · see citing works
Neuroprotective effect of quercetin in ectoenzymes and acetylcholinesterase activities in cerebral cortex synaptosomes of cadmium-exposed rats
Abdalla, F. H., Cardoso, A. M., Pereira, L. B., Schmatz, R., Gonçalves, J. F., Stefanello, N., Fiorenza, A. M., Gutierres, J. M., Serres, J. D. D. S., Zanini, D., et al. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1659-x · Cited by 67 · see citing works
Quercetin and Baicalein Act as Potent Antiamyloidogenic and Fibril Destabilizing Agents for SOD1 Fibrils
Bhatia, N. K., Modi, P., Sharma, S., & Deep, S. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00677 · Cited by 66 · see citing works
Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme
Barbarisi, M., Iaffaioli, R. V., Armenia, E., Schiavo, L., Sena, G. D., Tafuto, S., Barbarisi, A., & Quagliariello, V. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26238 · Cited by 64 · see citing works
Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity
Han, Q., Wang, X., Cai, S., Liu, X., Zhang, Y., Yang, L., Wang, C., & Yang, R. (2018) · Journal of Materials Chemistry B · doi:10.1039/c7tb03053c · Cited by 62 · see citing works
Curcumin Downregulates GSK3 and Cdk5 in Scopolamine-Induced Alzheimer’s Disease Rats Abrogating Aβ 40/42 and Tau Hyperphosphorylation
Das, T. K., Jana, P., Chakrabarti, S. K., & Hamid, M. R. W. A. (2019) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-190135 · Cited by 60 · see citing works
Fast-Dissolving Core-Shell Composite Microparticles of Quercetin Fabricated Using a Coaxial Electrospray Process
Li, C., Yu, D., Williams, G. R., & Wang, Z. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092106 · Cited by 59 · see citing works
Quercetin and Sodium Butyrate Synergistically Increase Apoptosis in Rat C6 and Human T98G Glioblastoma Cells Through Inhibition of Autophagy
Taylor, M. A., Khathayer, F. H., & Ray, S. K. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02802-8 · Cited by 58 · see citing works
Anticancer activity of flavonoids isolated from Achyrocline satureioides in gliomas cell lines
de Souza, P. O., Bianchi, S. E., Figueiró, F., Heimfarth, L., Moresco, K. S., Gonçalves, R. M., Hoppe, J. B., Klein, C. P., Salbego, C. G., Gelain, D. P., et al. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.04.013 · Cited by 58 · see citing works
Low concentration of quercetin antagonizes the invasion and angiogenesis of human glioblastoma U251 cells
Liu, Y., Tang, Z., Yang, J., Zhou, Y. F., Meng, L., Wang, H., & Li, C.-L. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s136821 · Cited by 56 · see citing works
Potential Therapeutic Targets of Quercetin and Its Derivatives: Its Role in the Therapy of Cognitive Impairment
Jakaria, M., Azam, S., Jo, S.-H., Kim, I., Dash, R., & Choi, D. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8111789 · Cited by 56 · see citing works
Optimized liposomes with transactivator of transcription peptide and anti-apoptotic drugs to target hippocampal neurons and prevent tau-hyperphosphorylated neurodegeneration
Kuo, Y., Chen, C.-L., & Rajesh, R. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.01.065 · Cited by 54 · see citing works
A Preliminary Study of the Effect of Quercetin on Cytotoxicity, Apoptosis, and Stress Responses in Glioblastoma Cell Lines
Kusaczuk, M., Krętowski, R., Naumowicz, M., Stypułkowska, A., & Cechowska‐Pasko, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031345 · Cited by 54 · see citing works
Quercetin and Sorafenib as a Novel and Effective Couple in Programmed Cell Death Induction in Human Gliomas
Jakubowicz-Gil, J., Langner, E., Bądziul, D., Wertel, I., & Rzeski, W. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9452-x · Cited by 52 · see citing works
The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial
Broman‐Fulks, J. J., Canu, W. H., Trout, K. L., & Nieman, D. C. (2012) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125312445894 · Cited by 51 · see citing works
Combination of lycopene, quercetin and poloxamer188 alleviates anxiety and depression in 3-nitropropionic acid-induced Huntingtons disease in rats
Jain, D. P., & Gangshettiwar, A. (2014) · Journal of Intercultural Ethnopharmacology · doi:10.5455/jice.20140903012921 · Cited by 50 · see citing works
Anti-cancer activity of quercetin in neuroblastoma: an in vitro approach
Priya, E. S., Selvakumar, K., Bavithra, S., Perumal, E., Arunkumar, R. S., Singh, P., Mercy, A. B., & Arunakaran, J. (2013) · Neurological Sciences · doi:10.1007/s10072-013-1462-1 · Cited by 50 · see citing works
Quercetin-loaded selenium nanoparticles inhibit amyloid-β aggregation and exhibit antioxidant activity
Qi, Y., Yi, P., He, T., Song, X., Liu, Y., Li, Q., Zheng, J., Song, R., Liu, C., Zhang, Z., et al. (2020) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2020.125058 · Cited by 49 · see citing works
Quercetin affects shoaling and anxiety behaviors in zebrafish: Involvement of neuroinflammation and neuron apoptosis
Zhang, J., Liu, M., Cui, W., Yang, L., & Zhang, C. (2020) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2020.06.058 · Cited by 48 · see citing works
Quercetin Protects Mouse Brain against Lead-Induced Neurotoxicity
Liu, C., Zheng, G., Cheng, C., & Sun, J.-M. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf303387d · Cited by 47 · see citing works
Role of Quercetin in Depressive-Like Behaviors: Findings from Animal Models
Silvestro, S., Bramanti, P., & Mazzon, E. (2021) · Applied Sciences · doi:10.3390/app11157116 · Cited by 46 · see citing works
The therapeutic potential of quercetin in Parkinson's disease: Insights into its molecular and cellular regulation.
Tamtaji, O., Hadinezhad, T., Fallah, M., Shahmirzadi, A., Taghizadeh, M., Behnam, M., & Asemi, Z. (2019) · Current Drug Targets · doi:10.2174/1389450120666191112155654 · Cited by 45 · see citing works
Effects of quercetin-conjugated with superparamagnetic iron oxide nanoparticles on learning and memory improvement through targeting microRNAs/NF-κB pathway
Ebrahimpour, S., Esmaeili, A., Dehghanian, F., & Beheshti, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-71678-4 · Cited by 45 · see citing works
Quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo
Li, J., Tang, C., Li, L., Li, R., & Fan, Y. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0331-1 · Cited by 44 · see citing works
Quercetin Regulates the Integrated Stress Response to Improve Memory
Nakagawa, T., & Ohta, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112761 · Cited by 43 · see citing works
Quercetin Increases the Efficacy of Glioblastoma Treatment Compared to Standard Chemoradiotherapy by the Suppression of PI-3-Kinase-Akt Pathway
Pozsgai, É., Bellyei, S., Cseh, A. M., Boronkai, Á., Rácz, B., Szabó, A., Sümegi, B., & Hocsák, E. (2013) · Nutrition and Cancer · doi:10.1080/01635581.2013.810291 · Cited by 43 · see citing works
Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats
Ebrahimpour, S., Shahidi, S. B., Abbasi, M., Tavakoli, Z., & Esmaeili, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-71971-2 · Cited by 42 · see citing works
Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro
Li, J., Tang, C., Li, L., Li, R., & Fan, Y. (2016) · Journal of Neuro-Oncology · doi:10.1007/s11060-016-2149-2 · Cited by 42 · see citing works
Neuroprotective Effects of Quercetin in Pediatric Neurological Diseases
Álvarez‐Arellano, L., Salazar–García, M., & Corona, J. C. (2020) · Molecules · doi:10.3390/molecules25235597 · Cited by 42 · see citing works
Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in an animal model of Alzheimer's disease
Molaei, A., Hatami, H., Dehghan, G., Sadeghian, R., & Khajehnasiri, N. (2020) · IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund · doi:10.17179/excli2019-2082 · Cited by 41 · see citing works
Effects of 2 Adenosine Antagonists, Quercetin and Caffeine, on Vigilance and Mood
Olson, C. A., Thornton, J. A., Adam, G. E., & Lieberman, H. R. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181ee0f79 · Cited by 37 · see citing works
Quercetin alleviates predator stress-induced anxiety-like and brain oxidative signs in pregnant rats and immune count disturbance in their offspring
Toumi, M. L., Merzoug, S., Baudin, B., & Tahraoui, A. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.03.009 · Cited by 35 · see citing works
Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin
Halder, S., Kar, R., Galav, V., Mehta, A. K., Bhattacharya, S. K., Mediratta, P. K., & Banerjee, B. D. (2015) · Drug and Chemical Toxicology · doi:10.3109/01480545.2015.1092042 · Cited by 33 · see citing works
Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid
Tsiailanis, A. D., Renziehausen, A., Kiriakidi, S., Vrettos, E. I., Markopoulos, G. S., Sayyad, N., Hirmiz, B., Aguilar, M., Borgo, M. P. D., Kolettas, E., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.08.007 · Cited by 32 · see citing works
Electrospun Nanofibers Loaded with Quercetin Promote the Recovery of Focal Entrapment Neuropathy in a Rat Model of Streptozotocin-Induced Diabetes
Thipkaew, C., Wattanathorn, J., & Muchimapura, S. (2017) · BioMed Research International · doi:10.1155/2017/2017493 · Cited by 32 · see citing works
Effect of quercetin on the brain-derived neurotrophic factor gene expression in the rat brain
Rahvar, M., Owji, A. A., & Mashayekhi, F. J. (2018) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2018_006 · Cited by 31 · see citing works
Quercetin and chloroquine synergistically kill glioma cells by inducing organelle stress and disrupting Ca2+ homeostasis
Jang, E., Kim, I. Y., Kim, H., Lee, D. M., Seo, D. Y., Lee, J. A., Choi, K. S., & Kim, E. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114098 · Cited by 29 · see citing works
Long-term memory of configural learning is enhanced via CREB upregulation by the flavonoid quercetin inLymnaea stagnalis
Batabyal, A., Rivi, V., Benatti, C., Blom, J. M. C., & Lukowiak, K. D. (2021) · Journal of Experimental Biology · doi:10.1242/jeb.242761 · Cited by 28 · see citing works
Role of Astrocytes, Soluble Factors, Cells Adhesion Molecules and Neurotrophins in Functional Synapse Formation: Implications for Human Embryonic Stem Cell Derived Neurons
Dodla, M. C., Mumaw, J. L., & Stice, S. L. (2010) · Current Stem Cell Research & Therapy · doi:10.2174/157488810791824520 · Cited by 27 · see citing works
Impact of quercetin on tight junctional proteins and BDNF signaling molecules in hippocampus of PCBs-exposed rats
Selvakumar, K., Bavithra, S., Krishnamoorthy, G., & Arunakaran, J. (2018) · Interdisciplinary Toxicology · doi:10.2478/intox-2018-0029 · Cited by 27 · see citing works
Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats
Braun, J. B. S., Ruchel, J. B., Adefegha, S. A., Coelho, A. P. V., Trelles, K. B., Signor, C., Rubin, M. A., de Oliveira, J. S., Dornelles, G. L., de Andrade, C. M., et al. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.01.134 · Cited by 25 · see citing works
Effects of quercetin on the neuromotor function and behavioral responses of Wistar and Zucker rats fed a high-fat and high-carbohydrate diet
Mzhelskaya, K. V., Shipelin, V. A., Shumakova, A. A., Musaeva, A. D., Soto, J. S., Riger, N. A., Trusov, N. V., Kirbaeva, N. V., Apryatin, S. A., & Gmoshinski, I. V. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112270 · Cited by 24 · see citing works
A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer
Lagerweij, T., Hiddingh, L., Biesmans, D., Crommentuijn, M. H. W., Cloos, J. J., Li, X., Kogiso, M., Tannous, B. A., Vandertop, W. P., Noske, D. P., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7980 · Cited by 21 · see citing works
A novel acylated flavonol tetraglycoside and rare oleanane saponins with a unique acetal-linked dicarboxylic acid substituent from the xero-halophyte Bassia indica
Othman, A., Amen, Y. M., & Shimizu, K. (2021) · Fitoterapia · doi:10.1016/j.fitote.2021.104907 · Cited by 17 · see citing works
Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6-OHDA in rats
Mu, X. L., Yuan, X., Du, L.-D., He, G., & Du, G. (2015) · Journal of Asian Natural Products Research · doi:10.1080/10286020.2015.1057576 · Cited by 17 · see citing works
Quercetin improves the impairment in memory function and attenuates hippocampal damage in cadmium chloride-intoxicated male rats by suppressing acetylcholinesterase and concomitant activation of SIRT1 signaling
Alshammari, G. M., Al-Qahtani, W. H., Alshuniaber, M. A., Yagoub, A. E. A., Al-Khalifah, A. S., Al‐Harbi, L. N., Alhussain, M. H., AlSedairy, S. A., & Yahya, M. A. (2021) · Journal of Functional Foods · doi:10.1016/j.jff.2021.104675 · Cited by 16 · see citing works
Anxiolytic Effects of Quercetin: Involvement of GABAergic System
Jung, J. W., & Lee, S. (2014) · Journal of Life Science · doi:10.5352/jls.2014.24.3.290 · Cited by 16 · see citing works
Quercetin‐loaded platelets as a potential targeted therapy for glioblastoma multiforme cell line U373‐MG
Bhandarkar, S., Prabhakar, B. R., & Shende, P. K. (2021) · Biotechnology Journal · doi:10.1002/biot.202100271 · Cited by 14 · see citing works
Effects of Quercetin on Improving the Damage Caused by Free Radicals in the Rat Models of Multiple Sclerosis
Mirzazadeh, E., Khezri, S., & Froushani, S. M. A. (2019) · Iranian South Medical Journal · doi:10.29252/ismj.22.1.1 · Cited by 11 · see citing works
Molecular docking and dynamic simulation study to explore quercetin as a multi-potent candidate against gliomas
Rizvi, S. M. D., Hussain, T., Mehmood, K., Moin, A., Alanazi, A. S., & Subaiea, G. M. (2022) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v20i4.23 · Cited by 10 · see citing works
Proof of Concept in a Case Study of Glioblastoma Multiforme Successfully Treated with IV Quercetin in Combination with Leading Edge Gamma Knife and Standard Treatments
Nezami, M. A., & Duma, C. (2018) · Journal of Cancer Therapy · doi:10.4236/jct.2018.96043 · Cited by 9 · see citing works
Dietary Quercetin Ameliorates Memory Impairment in a Murine Model of Alzheimer’s Disease with Obesity and Diabetes, Suppressing ATF4 Expression
Nakagawa, K., Ueda, M., Itoh, M., Islam, S., Tana, T., & Nakagawa, T. (2017) · Journal of Neurology and Neuroscience · doi:10.21767/2171-6625.1000234 · Cited by 6 · see citing works
The Neuro-Protective effects of Quercetin
Samini, M. (2019) · Research Journal of Pharmacy and Technology · doi:10.5958/0974-360x.2019.00100.8 · Cited by 6 · see citing works
The In Vitro Anti-Proliferative Interaction of Flavonoid Quercetin and Toxic Metal Cadmium in the 1321N1 Human Astrocytoma Cell Line
Al-Hasawi, N. A., Amine, S. A., & Novotný, L. (2018) · Scientia Pharmaceutica · doi:10.3390/scipharm86030036 · Cited by 5 · see citing works
The study of attenuating effects of quercetin on spatial memory impairment and degenerative changes in hippocampus of lead exposed rats
Iliyasu, M. O., Musa, S. A., Oladele, S. B., & Iliya, I. A. (2021) · African Journal of Cellular Pathology · doi:10.5897/ajcpath2021.0034 · Cited by 3 · see citing works
Adaptogenic Potential of Triethylene Glycol and Quercetin in Stressed Mice
Kumar, V. (2015) · Pharmacy & Pharmacology International Journal · doi:10.15406/ppij.2015.02.00041 · Cited by 2 · see citing works

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Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial
Gonzales, M. M., Garbarino, V. R., Kautz, T. F., Palavicini, J. P., Lopez-Cruzan, M., Dehkordi, S. K., Mathews, J. J., Zare, H., Xu, P., Zhang, B., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02543-w · Cited by 310 · see citing works
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Flavonoids as Promising Neuroprotectants and Their Therapeutic Potential against Alzheimer’s Disease
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Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases
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A critical review on quercetin bioflavonoid and its derivatives: Scope, synthesis, and biological applications with future prospects
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Therapeutic targeting of senescent cells in the CNS
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Quercetin-functionalized nanomaterials: Innovative therapeutic avenues for Alzheimer's disease management
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Role of Plant Phytochemicals: Resveratrol, Curcumin, Luteolin and Quercetin in Demyelination, Neurodegeneration, and Epilepsy
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Neuropharmacological interventions of quercetin and its derivatives in neurological and psychological disorders
Agrawal, K., Chakraborty, P., Dewanjee, S., Arfin, S., Das, S. S., Dey, A., Moustafa, M., Mishra, P. C., Jafari, S. M., Jha, N. K., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104955 · Cited by 60 · see citing works
Quercetin Nanoemulsion Ameliorates Neuronal Dysfunction in Experimental Alzheimer’s Disease Model
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A Dual Synergetic Nanoreactor for Managing Parkinson's Disease by Regulating Inflammation and Mitigating Oxidative Damage
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Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine
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Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway
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Critical Review of the Cross-Links Between Dietary Components, the Gut Microbiome, and Depression
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Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases
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Targeting Autophagy, Ferroptosis, and Neuroinflammation: Polyphenol-Mediated Modulation of Emerging Signaling Pathways in Neurodegeneration
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The medicinal chemistry of Urtica dioica L.: from preliminary evidence to clinical studies supporting its neuroprotective activity
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Quercetin and Its Nano-Formulations for Brain Tumor Therapy—Current Developments and Future Perspectives for Paediatric Studies
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Comparative Serum and Brain Pharmacokinetics of Quercetin after Oral and Nasal Administration to Rats as Lyophilized Complexes with β-Cyclodextrin Derivatives and Their Blends with Mannitol/Lecithin Microparticles
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Enhanced bioavailability of Quercetin-loaded niosomal in situ gel for the management of Parkinson’s disease
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Update on Therapeutic potential of emerging nanoformulations of phytocompounds in Alzheimer's and Parkinson's disease
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Biflavonoid quercetin protects against cyclophosphamide–induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity
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Impact of Light and Dark Treatment on Phenylpropanoid Pathway Genes, Primary and Secondary Metabolites in Agastache rugosa Transgenic Hairy Root Cultures by Overexpressing Arabidopsis Transcription Factor AtMYB12
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Quercetin attenuates cyclophosphamide induced‐immunosuppressive indoleamine 2,3‐dioxygenase in the hippocampus and cerebral cortex of male Wister rats
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Quercetin as a Multi‐Target Natural Therapeutic in Aging‐Related Diseases: Systemic Molecular and Cellular Mechanisms
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Antihyaluronidase and Antioxidant Potential of Atriplex sagittata Borkh. in Relation to Phenolic Compounds and Triterpene Saponins
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Nanoparticle-based flavonoid therapeutics: Pioneering biomedical applications in antioxidants, cancer treatment, cardiovascular health, neuroprotection, and cosmeceuticals
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Protective Effect of Urtica dioica Extract against Oxidative Stress in Human Skin Fibroblasts
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Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer’s disease
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Optimization of the Extraction Procedure for the Phenolic-Rich Glechoma hederacea L. Herb and Evaluation of Its Cytotoxic and Antioxidant Potential
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Tetrastigma hemsleyanum suppresses neuroinflammation in febrile seizures rats via regulating PKC-δ/caspase-1 signaling pathway
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Investigating the Antioxidant Properties of Quercetin
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Natural products targeting cellular processes common in Parkinson's disease and multiple sclerosis
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Polyphenols of the Inuleae-Inulinae and Their Biological Activities: A Review
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Investigating the Tumor-Suppressive, Antioxidant Effects and Molecular Binding Affinity of Quercetin-Loaded Selenium Nanoparticles in Breast Cancer Cells
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Protective Effect of Field Horsetail Polyphenolic Extract on Erythrocytes and Their Membranes
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Unveiling the Potential of Quercetin: Chemistry, Health Benefits, Toxicity, and Cutting-Edge Advances
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Neuroprotective Effects of Myrtle Berry By-Product Extracts on 6-OHDA-Induced Cytotoxicity in PC12 Cells
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Formation and bioaccessibility of complexes of a quercetin-loaded preheated whey protein concentrate
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Potential Benefits of Quercetin through P2X7 Modulation against Neuroinflammation in Alzheimer's Disease
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Harnessing potential of liposomal drug carriers for enhanced pharmacokinetic profile of flavonoids
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Evaluation of the Neurotherapeutic Effect of Quercetin on Neuronal miR‐124 and β‐Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) in an Experimental Alzheimer's Disease Model
Al‐Sawasany, A. S., Fayed, H. M., Mahmoud, B. F., Elblehi, S. S., & Ghazal, N. A. (2025) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70290 · Cited by 8 · see citing works
Achyranthes Bidentata Radix mitigates neuronal apoptosis via regulation of JUN and CREB in the cAMP signaling pathway
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Secondary Metabolite Profiling of Satureja aintabensis P.H. Davis and Satureja spicigera (K. Koch) Boiss. by LC-HRMS and Evaluation of Antioxidant and Anticholinergic Activities
Yıldız, A. N., Çarıkçı, S., Di̇rmenci̇, T., Kartal, M., Gülçın, İ., & Gören, A. C. (2025) · Life · doi:10.3390/life15081272 · Cited by 8 · see citing works
Protective Effect of Polyphenolic Extracts from Hippophae rhamnoides L. and Reynoutria japonica Houtt. on Erythrocyte Membrane
Kaźmierczak, T., Męczarska, K., Lachowicz, S., Cyboran-Mikołajczyk, S., Oszmiański, J., & Bonarska‐Kujawa, D. (2024) · Molecules · doi:10.3390/molecules29133090 · Cited by 7 · see citing works
Chitosan‐based spray‐dried solid dispersions of apigenin in a 3D printable drug delivery system
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Nature's tool kit: Designing biocompatible and affordable NADES for sustainable extraction of plant bioactives
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Quercetin alleviates depression in CUMS rats via modulating immune plasticity in the choroid plexus to inhibit hippocampal microglial activation
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Lutein derived from Xenostegia tridentata exhibits anticancer activities against A549 lung cancer cells via hyaluronidase inhibition
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pH-responsive self-assembly of quercetin-loaded zein-sodium caseinate-fucoidan hybrid nanoparticles: nanostructure, stability and in vitro digestive behavior
Yong, F., Deng, J.-X., Wang, Z., Zhao, Q.-L., Liu, X.-F., Zhong, S., & Li, R. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1727771 · Cited by 6 · see citing works
Post-traumatic stress disorder and metabolic syndrome: the role of some antioxidants in treatment
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Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets
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Continuous intake of quercetin-rich onion powder may improve emotion but not regional cerebral blood flow in subjects with cognitive impairment
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Dynamic pH‐Responsive Release and Biological Impact of In Situ Quercetin‐Modified MIL‐101(Fe)‐NH2
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Mitochondria Modulating Therapeutic Approaches in the Management of Huntington’s Disease
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A review of natural products and small‐molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges
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Quercetin Targets HSP90α and Regulates Keap1/Nrf2 Pathway to Inhibit Crosstalk between Apoptosis and Ferroptosis in Oxidatively Stressed Neurons
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Amnesiac (AMN) gene and cnc/Nrf2-redox responses in fruit fly model of memory impairment co-administered Solanum leaves and donepezil
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Ameliorative properties of quercetin in the treatment of traumatic brain injury: a mechanistic review based on underlying mechanisms
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Co-Delivery of Temozolomide and Quercetin via Nanoemulsion for Glioblastoma Therapy: From In-Silico to In-Vivo Evaluation
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Neuroprotective Effect of Chitosan Nanoparticle–Delivered Orientin Against Hypoxia-Induced Brain Injury in Rats
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Natural polyphenols as therapeutic candidates for mitigating neuropsychiatric symptoms in post-traumatic stress disorder: Evidence from preclinical studies
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Protecting vascular health: the role of flavonoids during pregnancy complications in mitigating the risk of vascular dementia later in life
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Neuroprotective effects of cerebroprotein hydrolysate and its combination with antioxidants against oxidative stress-induced HT22 cell death
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Inhibitory effects of extracts from Eucalyptus gunnii on α-synuclein amyloid fibrils
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Kaempferol ameliorated levodopa-induced dyskinesia in experimental rats: A role of brain monoamines, cFOS, FosB, Parkin, Pdyn, TH, and p-JNK
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Low-dose quercetin at 25 mg/kg ameliorates dolutegravir-lamivudine-tenofovirdisoproxilfumarate-inducedcardio-hepato-renal toxicities in Wistar rats
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Development and Characterization of Chitosan-Based Spray-Dried Solid Dispersions of Apigenin: 3D Printed Shell-Pill for Improved Efficacy of Model FlavonoidPreprint
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Amplifying therapeutic potential through optimization of bioavailability of poorly soluble flavonols via albumin-based nanoparticles
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Investigating the pharmacodynamic mechanism of Erxian decoction to alleviate sarcopenia generated by ovarian aging through the ER-mediated estrogen signaling pathway
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The quercetin-serotonin transporter (SERT) connection: a new hope for depression therapy?
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Nutraceuticals and the Microbiota–Gut–Brain Axis: A Pathway for Preventing Cognitive Decline
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Medicinal Herbs Against Central Nervous System Disorders
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Especial diseño 2007: 5 claves para el diseño español
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Repurposing Quercetin In Treating Parkinson’s Disease With Network Based Protein-Protein Interactions And Molecular Docking Studies
Madhuri, J. V. (2024) · doi:10.48047/afjbs.6.10.2024.590-597
Developing multifaceted drug synergistic therapeutic strategy against neurological disorders
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Onion Peel Powder’s Impact on the Leptin Receptors in the Hippocampus of Obese Rats
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Mechanisms of Neuronal Damage and Dysfunction
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The association between dietary quercetin intake and risk of depressive symptoms: the TCLSIH cohort study
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Biochemical and mechanistic insights into the potential anti-neuroinflammatory and neuroprotective effect of Zombi pea (Vigna vexillata (L.) A. Rich.) by regulating NF-κB and PI3K-Akt signaling pathways
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Neuroprotective Potential of Flavonoids
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Neonatal quercetin exposure reduces motor impairments and cerebellar damage in cerebral palsy rats, with different effects on males and females
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Authors: Wróbel-Biedrawa, D., Grabowska, K., Galanty, A., Sobolewska, D., & Podolak, I.
Affiliations: Department of Pharmacognosy, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Krakow, Poland
Jagiellonian University (PL)
Corresponding author: Grabowska, Karolina
ORCID: Grabowska, Karolina
Galanty, Agnieszka
Sobolewska, Danuta
Podolak, Irma
Venue: Life
Publisher: MDPI AG
Published: 2022-04-15
Volume: 12
Issue: 4
Pages: 591
ISSN: 2075-1729 (ISSN-L)
DOI: 10.3390/life12040591
PMC: PMC9027262
OpenAlex: W4224118676
Cited by: 95
References: 147
Citations by year: 2026: 13 · 2025: 24 · 2024: 28 · 2023: 19 · 2022: 10
FWCI: 2.91
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Life (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
Keywords: quercetin, flavonoids, flavonols, central nervous system disorders, neuroprotection, neuroinflammation, Huntington's disease, brain cancer, antioxidant activity, anti-inflammatory activity, bioavailability, drug delivery, capillary permeability, cyclooxygenase inhibition

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A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders

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