Database Query Results : Quercetin, , cognitive

QC, Quercetin: Click to Expand ⟱
Features:
Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose-, metal-, context-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction is a central apoptosis route in cancer cells
3 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Driver Growth and survival inhibition AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Reduced survival and inflammatory transcription NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5 MAPK signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation supports apoptosis downstream of redox stress
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects disruption of growth signaling
7 HIF-1α hypoxia signaling ↓ HIF-1α ↔ minimal Secondary Reduced hypoxia tolerance Quercetin interferes with hypoxia-driven transcriptional programs
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 induction reflects redox buffering rather than primary cytotoxicity


cognitive, cognitive: Click to Expand ⟱
Source:
Type:
Cognitive


Scientific Papers found: Click to Expand⟱
3336- QC,    Neuroprotective Effects of Quercetin in Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, Neuroprotection by quercetin has been reported in several in vitro studies
*lipid-P↓, It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation.
*antiOx↑, In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways.
*Aβ↓,
*Inflam↓,
*BBB↝, It also has low BBB penetrability, thus limiting its efficacy in combating neurodegenerative disorders.
*NF-kB↓, downregulating pro-inflammatory cytokines, such as NF-kB and iNOS, while stimulating neuronal regeneration
*iNOS↓,
*memory↑, Quercetin has shown therapeutic efficacy, improving learning, memory, and cognitive functions in AD
*cognitive↑,
*AChE↓, Quercetin administration resulted in the inhibition of AChE
*MMP↑, quercetin ameliorates mitochondrial dysfunction by restoring mitochondrial membrane potential, decreases ROS production, and restores ATP synthesis
*ROS↓,
*ATP↑,
*AMPK↑, It also increased the expression of AMP-activated protein kinase (AMPK), which is a key cell regulator of energy metabolism.
*NADPH↓, Activated AMPK can decrease ROS generation by inhibiting NADPH oxidase activity
*p‑tau↓, Inhibition of AβAggregation and Tau Phosphorylation

3602- QC,    The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice
- in-vivo, AD, NA
*BACE↓, significant reduction in the paired helical filament (PHF), β-amyloid (βA) 1–40 and βA 1–42 levels and a decrease in BACE1-mediated cleavage of APP (into CTFβ).
*cognitive↑, protects cognitive and emotional function in aged 3xTg-AD mice.
*ROS↓, These potential uses may be due to its high oxygen radical scavenging activity or its ability to inhibit xanthine oxidase and lipid peroxidation in vitro
*lipid-P↓,
*iNOS↓, inhibiting iNOS (Martinez-Florez et al., 2005) and regulating the expression of COX-2
*COX2↓,
*BBB↑, ability to penetrate the blood brain barrier
*neuroP↑, n addition to neuroprotection, quercetin has been suggested to exert other beneficial effects on the central nervous system (CNS), such as anti-anxiety and cognitive enhancement, by stimulating or inhibiting enzyme activities/signal transduction path
*other↓, remarkable reduction in the βA 1–40 and βA 1–42 levels in the hippocampus of the quercetin-treated 3xTg-AD mice compared to the vehicle-treated 3xTg-AD mice
*memory↑, Quercetin improves the spatial learning and memory task performance of 3xTg-AD mice

3607- QC,    Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More
- Review, AD, NA - Review, Park, NA
*neuroP↑, supportive evidence for neuroprotective effects of quercetin
*NRF2↑, nduction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2).
*PONs↑,
*antiOx↑,
*Inflam↓,
*SIRT1↑, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection.
*eff↑, Additionally, coadministration of quercetin and alpha-tocopherol has been shown to increase the transport of quercetin across the blood-brain barrier
*ROS↓, was shown to protect rodents from oxidative stress
*cognitive↑, quercetin ameliorates Alzheimer's disease pathology and related cognitive deficits in an aged triple transgenic Alzheimer's disease mouse model
*eff↑, combined oral supplementation of quercetin and fish oil enhanced neuroprotection in rats exposed to 3-nitropropionic acid
*lipid-P↓, Decreased lipid perox. in hippocampus;
*GSH↑, Decreased reduction of GSH, GPx (5, 50 mg/kg)
*GPx↑,
*SOD↑, Diminished reduction of DA levels, SOD, and GPx
*NRF2↑, Quercetin has been shown to counteract oxidative stress-induced cellular damage by activating the Nrf2-ARE pathway

3604- QC,    Quercetin enrich diet during the early-middle not middle-late stage of alzheimer’s disease ameliorates cognitive dysfunction
- in-vivo, AD, NA
*cognitive↑, early-middle stage of AD pathological development period ameliorates cognitive dysfunction and the protection effect was mainly related to increased Aβ clearance and reduced astrogliosis.
*Aβ↓, Quercetin enrich diet prevented cognitive dysfunction through increasing Aβ clearance and astrocyte function. has been demonstrated that it could inhibit the aggregation of Aβ
*neuroP↑, quercetin may have neuro-protective effects and slow down the progression of degenerative diseases
*BACE↓, The results showed that the protein level of CTFβ and BACE1 was decreased
*p‑SMAD2↓, protein level of p-Smad2 and p-STAT3 were decreased in quercetin enrich diet
*p‑STAT3↓,
*SPARC↓, quercetin enrich diet (1 month-9 months) significantly reduced the mRNA and protein level of Hevin and SPARC compared with normal diet.

3601- QC,    Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid
- Review, Var, NA - Review, AD, NA
*Inflam↓, known for its anti-inflammatory, antihypertensive, vasodilator effects, antiobesity, antihypercholesterolemic and antiatherosclerotic activities
*cardioP↑, beneficial effects include cardiovascular protection, anticancer, antitumor, anti-ulcer, anti-allergy, anti-viral, anti-inflammatory activity, anti-diabetic, gastroprotective effects, antihypertensive, immunomodulatory, and anti-infective.
AntiCan↑,
AntiTum↑,
*neuroP↑, The consumption of flavonoids rich food limits neurodegeneration and to reverse age-dependent loss in cognitive performance.
*cognitive↑,
*ROS↓, It is known to protect brain cells against the oxidative stress, which damages tissue leading to Alzheimer and other neurological conditions
*BP↓, Quercetin supplementation (150 mg/day) reduced systolic blood pressure and plasma oxidized LDL concentrations in overweight subjects
*LDL↓,

4297- QC,    Quercetin attenuates tau hyperphosphorylation and improves cognitive disorder via suppression of ER stress in a manner dependent on AMPK pathway
- in-vitro, AD, SH-SY5Y
*AMPK↑, administration of quercetin enhanced AMPK activity, inhibited IRE1α and PERK phosphorylation, NLRP3 expression and tau phosphorylation
*IRE1↓,
*p‑PERK↓,
*p‑tau↓,
*cognitive↑, and improved cognitive disorder in mice exposed to high fat diets
*antiOx↑, exert anti-oxidative, anti-ER stress, anti-inflammatory activities and regulating glucose homeostasis, which can prevent neurodegenerative disorders, diabetes, and obesity
*ER Stress↓,
*Inflam↓,
*neuroP↑,
*TXNIP↓, Quercetin and quercetin-3-O-glucuronide suppressed ER stress with decreased phosphorylation of IRE1α and PERK, thereby inhibited TXNIP and NLRP3 inflammasome activation,
*NLRP3↓, effectively protected neuronal cells from inflammatory insult by blocking ER stress/NLRP3 inflammasome activation.

3347- QC,    Recent Advances in Potential Health Benefits of Quercetin
- Review, Var, NA - Review, AD, NA
*antiOx↑, Its strong antioxidant properties enable it to scavenge free radicals, reduce oxidative stress, and protect against cellular damage.
*ROS↓,
*Inflam↓, Quercetin’s anti-inflammatory properties involve inhibiting the production of inflammatory cytokines and enzymes,
TumCP↓, exhibits anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis.
Apoptosis↑,
*cardioP↑, cardiovascular benefits such as lowering blood pressure, reducing cholesterol levels, and improving endothelial function
*BP↓, Quercetin‘s ability to reduce blood pressure was also supported by a different investigation
TumMeta↓, The most important impact of quercetin is its ability to inhibit the spread of certain cancers including those of the breast, cervical, lung, colon, prostate, and liver
MDR1↓, quercetin decreased the expression of genes multidrug resistance protein 1 and NAD(P)H quinone oxidoreductase 1 and sensitized MCF-7 cells to the chemotherapy medication doxorubicin
NADPH↓,
ChemoSen↑,
MMPs↓, Inhibiting CT26 cells’ migration and invasion abilities by inhibiting their expression of tissue inhibitors of metalloproteinases (TIMPs) inhibits their invasion and migration abilities
TIMP2↑,
*NLRP3↓, inhibited NLRP3 by acting on this inflammasome
*IFN-γ↑, quercetin significantly upregulates the gene expression and production of interferon-γ (IFN-γ), which is obtained from T helper cell 1 (Th1), and downregulates IL-4, which is obtained from Th2.
*COX2↓, quercetin is known to decrease the production of inflammatory molecules COX-2, nuclear factor-kappa B (NF-κB), activator protein 1 (AP-1), mitogen-activated protein kinase (MAPK), reactive nitric oxide synthase (NOS), and reactive C-protein (CRP)
*NF-kB↓,
*MAPK↓,
*CRP↓,
*IL6↓, Quercetin suppressed the production of inflammatory cytokines such as IL-6, TNF-α, and IL-1β via upregulating TLR4.
*TNF-α↓,
*IL1β↓,
*TLR4↑,
*PKCδ↓, Quercetin employed suppression on the phosphorylation of PKCδ to control the PKCδ–JNK1/2–c-Jun pathway.
*AP-1↓, This pathway arrested the accumulation of AP-1 transcription factor in the target genes, thereby resulting in reduced ICAM-1 and inflammatory inhabitation
*ICAM-1↓,
*NRF2↑, Quercetin overexpressed Nrf2 and targeted its downstream gene, contributing to increased HO-1 levels responsible for the down-regulation of TNF-α, iNOS, and IL-6
*HO-1↑,
*lipid-P↓, Quercetin acts as a potent antioxidant by scavenging ROS, inhibiting lipid peroxidation, and enhancing the activity of antioxidant enzymes
*neuroP↑, This helps to counteract oxidative stress and protect against neurodegenerative processes that contribute to AD
*eff↑, rats treated with chronic rotenone or 3-nitropropionic acid showed enhanced neuroprotection when quercetin and fish oil were taken orally
*memory↑, Both memory and learning abilities in the test animals increased
*cognitive↑,
*AChE↓, The increase in AChE activity brought on by diabetes was prevented in the cerebral cortex and hippocampus by quercetin at a level of 50 mg/kg body weight.
*BioAv↑, consumption of fried onions compared to black tea, suggesting that the form of quercetin present in onions is better absorbed than that in tea
*BioAv↑, This suggests that dietary fat can increase the absorption of quercetin [180]
*BioAv↑, potential of liposomes to enhance the bioactivity and bioavailability of quercetin has been the subject of several investigations
*BioAv↑, several emulsion types that may be employed to encapsulate quercetin, but oil-in-water (O/W) emulsions are the most widely utilized.
*BioAv↑, the kind of oil (triglyceride oils made up of either long-chain or medium-chain fatty acids) affected the bioaccessibility of quercetin and gastrointestinal stability, emphasizing the significance of picking a suitable oil phase

3367- QC,    Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments
- Review, Stroke, NA - Review, AD, NA
*NRF2↑, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus.
*neuroP↑,
*motorD↑, Que protected the blood-brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction.
*Inflam↓, (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex
*cognitive↑, (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1-4, antioxidant activity, and Nrf2 levels in the brain.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,  

Migration ⓘ

MMPs↓, 1,   TIMP2↑, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   MDR1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,  
Total Targets: 10

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   GPx↑, 1,   GSH↑, 1,   HO-1↑, 1,   lipid-P↓, 4,   NRF2↑, 4,   ROS↓, 5,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   LDL↓, 1,   NADPH↓, 1,   PONs↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

iNOS↓, 2,   MAPK↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   IRE1↓, 1,   p‑PERK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑STAT3↓, 1,  

Migration ⓘ

AP-1↓, 1,   PKCδ↓, 1,   p‑SMAD2↓, 1,   SPARC↓, 1,   TXNIP↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   BBB↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 1,   ICAM-1↓, 1,   IFN-γ↑, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 6,   NF-kB↓, 2,   TLR4↑, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 2,   p‑tau↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 2,   NLRP3↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 5,   eff↑, 3,  

Clinical Biomarkers ⓘ

BP↓, 2,   CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 8,   memory↑, 3,   motorD↑, 1,   neuroP↑, 8,  
Total Targets: 54

Scientific Paper Hit Count for: cognitive, cognitive
8 Quercetin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:557  State#:%  Dir#:%
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