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. 2021 Jun 17;12:665031. doi: 10.3389/fphar.2021.665031

TABLE 1.

Neuroprotective effects of quercetin and/or its derivatives against various neurodegenerative diseases and other brain disorders.

Quercetin/Derivatives/Source Test model in vitro/in vivo Exposure Effects/Molecular mechanisms References
Alzheimer’s disease
Quercetin HT-22 mouse hippocampal cells/in vitro Glutamate induced toxicity ↓lipid peroxidation, ↓GSH oxidation, ↓ROS Ishige et al. (2001)
HEK 293 human embryonic kidney cells/in vitro Aβ (1–42) ↓ Aβ peptides, ↓the performed mature fibrils Ono et al. (2003)
HT22 murine neuroblastoma cells/in vitro Aβ (25–35) ↓ amyloidogenic Aβ peptides Kim et al. (2005)
Primary hippocampal cultures/in vitro Aβ (1–42) ↓apoptosis, ↓ ROS, ↓mediated damage Ansari et al. (2009)
Quercetin/Ginkgo biloba SHSY5Y human neuroblastoma cells/in vitro Aβ (1–42) ↓Akt signaling pathways, ↓ERK1/2, ↓JNK, ↓Aβ toxicity, ↓platelet-activating factor Shi et al. (2009)
Quercetin-3′-glucoside PC12 cells/in vitro ↓H2O2 ↑CREB/BDNF signaling pathway, ↓Aβ, ↓ROS Yu et al. (2020)
Quercetin/ginkgoflavonols Double Transgenic (TgAPP/PS1) mice/in vivo - Reversed the spatial learning deficit Hou et al. (2010)
Quercetin APP stable cells/in vitro Aβ (25–35) ↓ROS, ↓BACE, ↓ Aβ, ↓GSH, ↓lipid peroxidation Jiménez-Aliaga et al. (2011)
Quercetin-3-O glucuronide APP695-transfected SH-SY5Y cells/in vitro
Tg2576 AD primary neuron cultures/in vitro
Aβ (1–42) ↓Aβ peptides, ↑CREB signaling, ↓Aβ aggregation, ↑mitogen-activated protein kinase, ↑neuronal survival, ↑c-Jun N-terminal kinases, ↓stress-induced impairments Ho et al. (2013)
Quercetin/Acanthopanax henr Cell free system/in vitro - ↓ acetylcholinesterase, ↑antioxidant activity Zhang et al. (2014)
Quercetin Triple-transgenic mouse model of AD/in vivo - ↓tauopathy, ↓β-amyloidosis, ↑memory, ↑learning ↓microgliosis, ↓astrogliosis Sabogal-Guáqueta et al. (2015)
APP23 AD model mice/in vivo - ↓eIF2α, ↓ATF4, ↓GADD34, ↑memory in aged mice, ↓deterioration in memory at the early stage of AD Hayakawa et al. (2015)
Parkinson’s disease
 Quercetin Microglial (N9)-neuronal (PC12) cells/in vitro MPP ↓iNOS in microglial cells, ↓DNA fragmentation, ↑apoptosis, ↓nuclear translocation of apoptosis-inducing factor, ↓caspase-3 activation Bournival et al. (2012)
 Quercetin glycoside PC12 cells/in vitro 6-OHDA ↑antioxidant activity, ↑GSH, ↑GPx Magalingam et al. (2016)
 Quercetin Wistar rats/in vivo 6-OHDA ↑spatial memory, ↓oxidative stress, ↓AChE activity, ↑antioxidant activity, ↓neuronal damage Sriraksa et al. (2012)
 Quercetin Mice/in vivo MPTP ↓striatal dopamine depletion, ↓motor deficits, ↑GPx, ↑SOD Lv et al. (2012)
 Quercetin Cell-free system α-Synuclein ↓Aβ fibrillation Zhu et al. (2013)
 Quercetin Wistar rats/in vivo Roteno ↓nigral GSH depletion, ↓ROS, ↓striatal DA loss, ↑mitochondrial complex, ↑activity and scavenging hydroxyl radical, ↓ neuronal death Karuppagounder et al. (2013)
 Isoquercetin PC12 cells/in vitro 6-OHDA ↓ROS, ↑SOD, ↑ antioxidant enzymes (GSH, catalase, glutathione peroxidase) Magalingam et al. (2014)
 Quercetin Wistar rats/in vivo Haloperidol MPTP ↑the cataleptic score, ↓actophotometer activity, ↑GSH, ↓lipid peroxidation, ↓ROS Pany et al. (2014)
 Quercetin + fish oil Wistar rats/in vivo Rotenone ↑mitochondrial functions, ↑GSH, ↑antioxidant defences Denny Joseph and Muralidhara (2013)
Hutington’s disease
 Quercetin Wistar rats/in vivo 3-NP ↑ATP, ↑activity of complex II and V enzyme of respiratory chain complex, ↓ROS, ↑SOD, ↑catalase, ↓lipid peroxidation Sandhir and Mehrotra (2013)
 Quercetin + fish oil Wistar rats/in vivo 3-NP ↓oxidative stress, ↑motor function Denny Joseph and Muralidhara (2013)
 Quercetin + sesamol Wistar rats/in vivo QA ↓neurochemical alterations in the rat brain, ↓behavioral, ↓biochemical, ↑antioxidant effects, ↑ anti-inflammatory activity Kuhad et al. (2013)
 Quercetin + lycopene Wistar rats/in vivo 3-NP ↓anxiety, ↓depression Jain and Gangshettiwar (2014)
 Quercetin Sprague dawley rats/in vivo 3-NP ↓gait despair, ↓microglial proliferation, ↓anxiety, ↑astrocyte numbers in the lesion core, ↓motor coordination deficits, ↓serotonin metabolism Chakraborty et al. (2014)
Multiple sclerosis
 Quercetin Human umbilical cord blood-derived cultured mast cells/in vitro IL-1 ↓demyelination, ↑PKC phosphorylation, ↑IL-6, ↓IL-1, ↑p38, ↓mast cell activation Kandere-Grzybowska et al. (2006)
 Quercetin Peripheral blood mononuclear cells isolated from MS patients/in vitro - ↑IL-6, ↓immune response, ↓TNF-α, ↓demyelination Sternberg et al. (2008)
Brain ischemic injury
 Quercetin Sprague- dawley rats/in vivo Traumatic brain injury ↓neutrophil infiltration, ↑GSH, ↓myeloperoxidase activity Graham et al. (2000)
 Quercetin Sprague- dawley rats/in vivo Acute traumatic spinal cord injury ↑iron clearance in the spinal cord through its ↑chelating effect, ↑motor function Schultke et al. (2010)
 Quercetin Swiss albino mice/in vivo High altitude hypoxia ↓HIF1α, ↓hypoxia, ↓VEGF, ↓brain dysfunction, ↓active caspase 3, ↓ubiquitin Sarkar et al. (2012)
 Quercetin-3-O methyl ether Sprague- dawley rats/in vivo MCAO rat model ↓ oedema, ↓oxidative stress-mediated damage, ↓behavioral deficit Jung et al. (2012), Lee et al. (2015)
 Quercetin Sprague– Dawley rats/in vivo MCAO rat model ↑PI3K/Akt, ↑antioxidative, ↑anti-apoptotic signaling Chang et al. (2014)
 Quercetin Wistar rats/in vivo Global cerebral ischemia ↑AKT, ↑anti-apoptotic signaling pathway, ↑antioxidant activity, ↓ROS Lei et al. (2015)
 Quercetin Sprague-dawley rats/in vivo Transient focal cerebral ischemia ↑Ca2+ into the mitochondrial matrix, ↑electron transport chain activity Nichols et al. (2015)
 Quercetin + vitamin E Primary cortical neurons/in vitro Induced ischemic stroke ↑CREB phosphorylation, ↑ NO, ↑autophosphorylation of CaMK II, IV, ↑Ca2+/calmodulin-dependent kinases II, IV, ↑mitochondrial biogenesis, ↑ BCl-2 Nichols et al. (2015)
Epilepsy
 Quercetin/Anisomeles malabarica Wistar rats/in vivo Diazepam + PTZ Stimulating GABAA receptors, NMDA receptors’ antagonist Choudhary et al. (2011)
 Quercetin Wistar rats/in vivo PTZ ↑anticonvulsant effects, ↓seizure severity, ↓lipid peroxidation via its ↑antioxidant effect, ↑memory retrieval in the passive avoidance task Nassiri-Asl et al. (2013)
 Quercetin Albino rats/in vivo PTZ ↑ antiseizure effect, ↑anticonvulsant effect Sefil et al. (2014)
 Quercetin Wistar rats/in vivo 6-OHDA ↓excitability in neurons involved in epilepsy,↓neuroplastic changes in neural circuits, ↓NMDA receptor functionality Mehdizadeh et al. (2009)
Miscellaneous neurotoxin
 Quercetin,/Opuntia ficus-indica Rat cortical cells/in vitro H2O2; xanthine/xanthine oxide ↑antioxidant activity Dok-Go et al. (2003)
 Quercetin Mice/in vivo Ethanol intoxication ↓cognitive impairment, ↑antioxidant mechanisms Singh et al. (2003)
 Quercetin SH-SY5Y neuroblastoma cells/in vitro 6-OHDA ↑antioxidant activity Kaariainen et al. (2008)
 Quercetin/Ginkgo biloba N2a cells/in vitro Juglone (5- hydroxy-1, 4-napthoquinone) ↓ROS Smith and Luo (2003)
 Quercetin-3-O-galactoside)/Hypericum perforatum PC12 cells/in vitro H2O2/tert-butyl hydroperoxide ↓apoptosis mediated cell death, ↓ROS, chelates the transition metal ions Liu et al. (2005)
 Quercetin-3-O-β-d-glucopyranoside/Echinophora cinerea PC12 cells/in vitro H2O2 ↓ ROS Shokoohinia et al. (2015)
 Quercetin PC12 cells/in vitro H2O2/Xanthine oxidase ↓neuronal injury (IC50 = 0.5–0.7 μg/ml), ↑antioxidative effect Shokoohinia et al. (2015)
 Quercetin SH-SY5Y cells/in vitro H2O2 ↓pro-apoptotic bax gene, ↓lactate dehydrogenase, ↑antiapoptotic Bcl-2, ↓caspase cascade, ↑DNA fragmentation, ↑apoptosis Suematsu et al. (2011)
 Quercetin ICR mice/in vivo Trimethyltin ↓acetylcholinesterase; ↓peroxidation of polyunsaturated fatty acid in membrane, ↑cognitive ability Choi et al. (2012)
 Quercetin Mice/in vivo High cholesterol-induced neurotoxicity ↑AMPK, ↓activation of microglia, ↓iNOS, ↓COX-2, ↓IL-1β, ↓TNF-α, ↓BACE1 Lu et al. (2010)
 Quercetin Wistar rats/in vivo Cadmium intoxication ↓AChE, ↓NTPDase, ↓ADA activities in cerebral cortex synaptosomes Abdalla et al. (2013)
 Quercetin Swiss Albino mice/in vivo Olfactory bulbectomy ↓NMDA receptors, ↑NO, ↓depression, ↑antioxidant activity Holzmann et al. (2015)
 Quercetin Chinese kunming mice/in vivo High-fat diet ↑HDL decrease, ↓ total cholesterol, ↑CREB, ↓oxidative damage, ↑PI3 K/AKT/Nrf2, ↓ROS, ↓MDA, ↑cognitive impairment Xia et al. (2015)
 3‘-O-(3-chloropivaloyl) quercetin (CPQ) BV-2 microglial cells/in vitro Lipopolysaccharides ↓NF-κB, ↓inflammatory mediators: ↓NO, ↓TNF-α, ↓iNOS; ↓ proliferation of BV-2 microglial cells Mrvova et al. (2015)
 Quercetin Albino rats/in vivo Aluminum ↓mitochondrial DNA oxidation, ↓ROS, ↓oxidative stress, ↑Bcl-2,, ↓p53, ↑MnSOD, ↓translocation of cytochrome-c, ↓Bax, ↓caspase-3, ↓DNA damage Sharma et al. (2016)
Aging and cognitive function
 Quercetin Kunming mice/in vivo Galactose ↑SOD, ↑cognitive impairment, maintain Ca2+ homeostasis, ↑GAP43 mRNA expression, ↑normal function of neurons Lu et al. (2006)
 Quercetin Caenorhabditis elegans/in vivo Thermal stress ↑radical scavenging activity, ↓MnSOD Saul et al. (2008)
 Quercetin/Quercetin caprylate HFL-1 primary human fibroblasts/in vitro - ↑cellular lifespan, ↑proteasome activation, ↑neuronal survival, ↑antiaging effect; ↑rejuvenating effect, ↑antioxidant properties Chondrogianni et al. (2010)