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

**Authors:** Dagmara Wróbel-Biedrawa, Karolina Grabowska, Agnieszka Galanty, Danuta Sobolewska, Irma Podolak

PMC · DOI: 10.3390/life12040591 · Life · 2022-04-15

## TL;DR

This review explores quercetin's potential as a treatment for brain disorders, highlighting its anti-inflammatory and antioxidant properties.

## Contribution

The paper introduces new insights into quercetin's anti-anxiolytic, anti-Huntington’s disease, and brain cancer therapeutic potential.

## Key findings

- Quercetin shows anti-neuroinflammatory effects relevant to central nervous system disorders.
- It exhibits potential as an anti-anxiolytic and anti-Huntington’s disease agent.
- The compound may have therapeutic value in brain cancer treatment.

## 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.

## Linked entities

- **Chemicals:** quercetin (PubChem CID 5280343)
- **Diseases:** Huntington’s disease (MONDO:0007739), brain cancer (MONDO:0001657)

## Full-text entities

- **Genes:** Nos2 (nitric oxide synthase 2) [NCBI Gene 24599] {aka Nos2a, iNos}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, Sod1 (superoxide dismutase 1) [NCBI Gene 24786] {aka CuZnSOD}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Epha2 (Eph receptor A2) [NCBI Gene 366492], Foxg1 (forkhead box G1) [NCBI Gene 24370] {aka BF1A, Fkhl1, RATBF1A}, Acot12 (acyl-CoA thioesterase 12) [NCBI Gene 170570] {aka Cach, rACH}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, COX2 (COXII) [NCBI Gene 26198] {aka COII}, Epha2 (Eph receptor A2) [NCBI Gene 13836] {aka Eck, Myk2, Sek-2, Sek2}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 84027], Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 81687], Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Mmp2 (matrix metallopeptidase 2) [NCBI Gene 81686], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Lepr (leptin receptor) [NCBI Gene 24536] {aka Fa}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Ccnd1 (cyclin D1) [NCBI Gene 58919], Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], BACE1 (beta-secretase 1) [NCBI Gene 23621] {aka ASP2, BACE, HSPC104}, MAPK10 (mitogen-activated protein kinase 10) [NCBI Gene 5602] {aka JNK3, JNK3A, PRKM10, SAPK1b, p493F12, p54bSAPK}, Htr2a (5-hydroxytryptamine receptor 2A) [NCBI Gene 29595] {aka 5-HT2A, 5Ht-2}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, SLC60A2 (solute carrier family 60 member 2) [NCBI Gene 91749] {aka KIAA1919, MFSD4B, NaGLT1}, Mir27a (microRNA 27a) [NCBI Gene 100314006] {aka rno-mir-27a}, Igf1 (insulin-like growth factor 1) [NCBI Gene 24482] {aka IGF}, Insr (insulin receptor) [NCBI Gene 24954], Cdk5 (cyclin dependent kinase 5) [NCBI Gene 12568] {aka Crk6}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, EPHA2 (EPH receptor A2) [NCBI Gene 1969] {aka ARCC2, CTPA, CTPP1, CTRCT6, ECK}, Nampt (nicotinamide phosphoribosyltransferase) [NCBI Gene 59027] {aka 1110035O14Rik, NAmPRTase, Pbef, Pbef1, Visfatin}, Il18 (interleukin 18) [NCBI Gene 29197] {aka IL-1 gamma, IL-18}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Slc5a1 (solute carrier family 5 (sodium/glucose cotransporter), member 1) [NCBI Gene 20537] {aka Sglt1}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, MAOB (monoamine oxidase B) [NCBI Gene 4129], Serpine1 (serpin family E member 1) [NCBI Gene 24617] {aka PAI1A, Pai1, Pai1aa, Planh, RATPAI1A}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 287362] {aka Cias1}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, PON2 (paraoxonase 2) [NCBI Gene 5445], Ache (acetylcholinesterase) [NCBI Gene 83817]
- **Diseases:** neuron degeneration (MESH:D009410), crush injury (MESH:D000071576), demyelination (MESH:D003711), OCD (MESH:D009771), postural instability (MESH:D054972), chorea (MESH:D002819), plaques (MESH:D003773), striatal neuronal lesion (MESH:C537500), tauopathy (MESH:D024801), resting tremor (MESH:D014202), colon adenocarcinoma (MESH:D003110), nerve (MESH:C537568), Mental Disorders (MESH:D001523), MS (MESH:D009103), Cytotoxicity (MESH:D064420), behavioral deterioration (MESH:D002653), sexual disorders (MESH:D012734), slowness of movements (MESH:D020754), memory loss (MESH:D008569), diabetic (MESH:D003920), weight loss (MESH:D015431), AD (MESH:D000544), Neuroinflammation (MESH:D000090862), muscular rigidity (MESH:D009127), cancer (MESH:D009369), muscle relaxant (MESH:D019042), Neurotoxic Protein (MESH:D020258), GAD (MESH:C000726808), motor deficits (MESH:D009461), difficulty in concentration (MESH:C567712), ALS (MESH:D000690), NFTs (MESH:D055956), hyperkinetic dysfunction (MESH:D006948), neuropathic injury (MESH:D009437), cognitive decline symptoms (MESH:D019954), axis (MESH:C566610), cognitive decline (MESH:D003072), Depression (MESH:D003866), executive dysfunction (MESH:D006331), PD (MESH:D010300), PTSD (MESH:D013313), astrocytoma (MESH:D001254), cholinergic transmission deficiency (MESH:C535672), necrosis (MESH:D009336), Anxiety (MESH:D001007), mitochondrial suppression of respiratory chain complex (MESH:D028361), nausea (MESH:D009325), dizziness (MESH:D004244), Neurodegenerative Diseases (MESH:D019636), Glioblastoma (MESH:D005909), mental disturbances (MESH:D008607), panic disorder (MESH:D016584), neuroblastoma (MESH:D009447), Hypokinetic disorder (MESH:D004401), CNS Diseases (MESH:D002493), Neurotrophic (MESH:D009133), Dementia (MESH:D003704), SAD (MESH:D000072861), medulloblastoma (MESH:D008527), Anxiety Disorders (MESH:D001008)
- **Chemicals:** glucose (MESH:D005947), DMSO (MESH:D004121), ibuprofen (MESH:D007052), reactive nitrogen species (MESH:D026361), galactoside (MESH:D005697), apomorphine (MESH:D001058), 5-HT (MESH:D012701), oxygen (MESH:D010100), tocopherols (MESH:D024505), rivastigmine (MESH:D000068836), ADR (MESH:D004317), phospholipids (MESH:D010743), desipramine (MESH:D003891), tocopherol acetate (MESH:D024502), dopamine (MESH:D004298), iron (MESH:D007501), quercetin 3-O-rhamnoside (MESH:C012526), CMC-Na (-), dasatinib (MESH:D000069439), steroids (MESH:D013256), triethylene glycol (MESH:C028914), isoquercitrin (MESH:C016527), DA (MESH:C025953), quercetin 4'-O-glucoside (MESH:C080613), unsaturated fatty acids (MESH:D005231), sulfur (MESH:D013455), flavonol (MESH:C041477), imipramine (MESH:D007099), polyphenols (MESH:D059808), ATP (MESH:D000255), PBS (MESH:D007854), cortisol (MESH:D006854), isorhamnetin (MESH:C047368), diazepam (MESH:D003975), 6-OHDA (MESH:D016627), sodium carboxymethyl cellulose (MESH:D002266), H2O2 (MESH:D006861), water (MESH:D014867), hydrogen (MESH:D006859), CD (MESH:D002104), acetylcholine (MESH:D000109), LPS (MESH:D008070), TEG (MESH:C000619859), buspirone (MESH:D002065), Que (MESH:D011794), Aluminum (MESH:D000535), lycopene (MESH:D000077276), GSH (MESH:D005978), AMPA (MESH:D018350), rutoside (MESH:D012431), GABA (MESH:D005680), RNS (MESH:D011886), pyran (MESH:D011714), noradrenaline (MESH:D009638), glucuronide (MESH:D020719), ruthenium (MESH:D012428), MTT (MESH:C070243), okadaic-acid (MESH:D019319), selenium (MESH:D012643), sodium butyrate (MESH:D020148)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Styphnolobium japonicum (Japanese pagoda tree, species) [taxon 3897], Homo sapiens (human, species) [taxon 9606], Arthrobacter sp. TF4 (species) [taxon 1748362], Danio rerio (leopard danio, species) [taxon 7955], Allium cepa (onion, species) [taxon 4679], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** A1 adenosine
- **Cell lines:** PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), -2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628), U87 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), U-251 glioblastoma — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_0021), U97 glioma — Homo sapiens (Human), Ataxia telangiectasia syndrome, Finite cell line (CVCL_WX49), 1321N1 — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_0110), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), DBTRG-05 — Homo sapiens (Human), Anaplastic astrocytoma, Cancer cell line (CVCL_1169), C6 — Rattus norvegicus (Rat), Rat malignant glioma, Cancer cell line (CVCL_0194), MOGGCCM — Homo sapiens (Human), Anaplastic astrocytoma, Cancer cell line (CVCL_2613), C6 glioma — Rattus norvegicus (Rat), Rat malignant glioma, Cancer cell line (CVCL_3581), U373-MG — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_2818), T98G — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0556)

## Full text

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## Figures

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## References

146 references — full list in the complete paper: https://tomesphere.com/paper/PMC9027262/full.md

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Source: https://tomesphere.com/paper/PMC9027262