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 | Aβ | ↓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) |