flavonoids / CREB Cancer Research Results

Flav, flavonoids: Click to Expand ⟱
Features:

Flavonoids — a large class of plant polyphenols (natural products) including flavonols (quercetin, kaempferol), flavones (apigenin, luteolin), flavanones (naringenin), isoflavones (genistein), flavan-3-ols (EGCG/catechins), and anthocyanins. Sources: fruits/berries, tea/cocoa, legumes, herbs, and standardized extracts.

Primary mechanisms (conceptual rank):
1) Redox signaling modulation (often hormetic: low-dose NRF2 ↑; high-dose ROS ↑ in cancer)
2) Anti-inflammatory transcription suppression (NF-κB ↓; cytokines ↓)
3) Kinase signaling modulation (PI3K/AKT/mTOR ↓; MAPK context-dependent)
4) Mitochondrial stress → apoptosis (cancer; often high concentration only)
5) Iron/copper chelation + lipid-peroxidation effects (ferroptosis overlap in select contexts)

Bioavailability / PK relevance: Many flavonoids have low oral bioavailability (rapid phase II conjugation: glucuronidation/sulfation; microbiome-derived metabolites). Plasma free aglycone levels are typically low; tissue effects often reflect metabolites and chronic exposure.

In-vitro vs oral exposure: Many “anti-cancer” cytotoxic effects occur at micromolar aglycone concentrations exceeding typical systemic exposure from diet/supplements (high concentration only), unless specialized formulations or local GI exposure is the intent.

Clinical evidence status: Broad epidemiology + small human trials for cardiometabolic/inflammatory endpoints; oncology evidence mostly preclinical/adjunct-hypothesis; no class-wide RCT oncology approval.


Flavonoids are classified into seven structural classes:
1.flavanones
-Nargenin, Naringin, Hesperetin, Isosakuranetin, Eriodictyol, Taxifolin
2.flavonols
-Quercetin, Myrcetin, Fisetin, Rutin Morin, Kaempferol
3.chalcones
-Butein, Xanthohumol, Isoliquintigenin, Cardamonin, Bavachalone, Xanthohumol, Phloretin
4.flavanols
-Catechin, Gallocatechin, Epicatechin, Epigallocatechin-3-galate
5.anthocyanidins
-Cyanidin
6.flavones
-Chrysin, Apigenin, Luteolin, Vitexin, Orientin, Bacalein, Wogonin, Oroxylin A, Saponarin
7.isoflavonoids
-Daidzein, Genistein, Glycitein

Flavonoids — Cancer vs Normal Cell Pathway Map (Class-Level)

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS ↑ or ↓ (dose-dependent) ↓ (physiologic / adaptive) P/R Redox reprogramming Class hallmark: hormesis. Low–moderate exposure often antioxidant/mitochondrial-protective; high exposure can be pro-oxidant/cytotoxic in cancer models.
2 NRF2 (stress-defense; resistance role) ↑ (context-dependent) ↑ R/G Antioxidant gene induction Normal: cytoprotection. Cancer: NRF2 ↑ can reduce therapy sensitivity in some contexts (double-edged).
3 NF-κB / inflammatory cytokine programs ↓ ↓ R/G Anti-inflammatory transcription suppression One of the most consistent class-level effects across models.
4 PI3K/AKT/mTOR ↓ (model-dependent) ↔ / ↓ (metabolic/inflammatory improvement) R/G Reduced anabolic survival signaling Frequently reported but not uniform; often secondary to redox/inflammation changes.
5 MAPK (ERK/JNK/p38) ↑ stress MAPKs; ↓ ERK (context-dependent) ↔ P/R Stress-response tuning JNK/p38 often ↑ with pro-apoptotic stress; ERK effects vary by compound/model.
6 Intrinsic apoptosis (mitochondrial; caspases) ↑ (high concentration only) ↔ R/G Experimental tumor cytotoxicity Common in vitro endpoint; translation limited by PK and achievable free aglycone levels.
7 Cell-cycle checkpoints ↓ proliferation (model-dependent) ↔ G Checkpoint enforcement Often downstream of kinase/redox modulation.
8 Ferroptosis (iron/lipid peroxidation contexts) ↑ or ↓ (compound-dependent) ↔ R/G Lipid-ROS vulnerability shift Some flavonoids chelate iron (anti-ferroptotic) while others promote lipid peroxidation under stress (pro-ferroptotic); not class-uniform.
9 HIF-1α / Warburg coupling ↓ (model-dependent; high concentration only) ↔ G Reduced hypoxia-adaptation signaling Reported in some models (often via PI3K/mTOR or ROS), but not a universal class mechanism at dietary exposure.
10 Ca²⁺ / ER stress coupling ↑ or ↔ (stress-dependent) ↔ P/R UPR/excitability modulation Relevant mainly when apoptosis/UPR/excitotoxicity endpoints are measured; not a core class axis.
11 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — PK + heterogeneity Major constraints: low bioavailability, metabolite-dominant exposure, large heterogeneity across subclasses, and frequent in-vitro concentration gaps.

TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr



Flavonoids — AD relevance: Flavonoid-rich diets and select supplements are studied for neuroprotection via antioxidant/anti-inflammatory effects, cerebrovascular support, and synaptic plasticity signaling. Effects are generally supportive and exposure/metabolite dependent.

Primary mechanisms (conceptual rank):
1) ↓ Oxidative stress (ROS ↓; lipid peroxidation ↓)
2) ↓ Neuroinflammation (NF-κB/cytokines ↓; microglial tone ↓)
3) ↑ Synaptic plasticity signaling (BDNF/CREB ↑; network efficiency; chronic adaptation)
4) Vascular/endothelial support (NO signaling; perfusion coupling)
5) Secondary Aβ/tau pathway modulation (preclinical; not class-uniform)

Bioavailability / PK relevance: Brain effects likely mediated by metabolites and chronic intake; large variability by subclass and microbiome.

Clinical evidence status: Signals in small human trials (often with specific subclasses like cocoa flavanols/anthocyanins); AD disease-modification not established.

Flavonoids — AD / Neurodegeneration Pathway Map (Class-Level)

Rank Pathway / Axis Cells TSF Primary Effect Notes / Interpretation
1 ROS / lipid peroxidation ↓ P/R Reduced oxidative burden Core neuroprotection rationale; effect depends on subclass/metabolites and baseline oxidative stress.
2 Neuroinflammation (NF-κB, cytokines) ↓ R/G Lower inflammatory stress Common class-level effect; relevant to microglial activation tone.
3 NRF2 axis ↑ (adaptive; context-dependent) R/G Stress-defense upshift Often supports antioxidant enzymes; magnitude varies widely by compound and exposure.
4 BDNF / CREB / synaptic plasticity ↑ (supportive) G Plasticity and learning support Frequently invoked across flavonoid cognition studies; typically requires weeks–months intake.
5 Vascular/endothelial function (NO coupling) ↑ (supportive) R/G Perfusion and neurovascular support Often attributed to flavanols/anthocyanins; supports “vascular cognitive impairment” framing.
6 Aβ / tau-associated pathology ↔ / ↓ (preclinical; compound-dependent) G Pathology modulation (hypothesis) Not class-uniform; strongest evidence is preclinical, with limited biomarker-confirmed human replication.
7 Ca²⁺ homeostasis / excitotoxic vulnerability ↔ / stabilized (indirect) P/R Excitotoxic buffering Secondary to antioxidant/mitochondrial support; include as primary only with explicit Ca²⁺ endpoints.
8 Clinical Translation Constraint ↓ (constraint) — Heterogeneity + metabolite dependence Large differences across subclasses, dosing, and microbiome; effects generally supportive, not disease-modifying.

TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr
CREB, cAMP Response Element Binding Protein: Click to Expand ⟱
Source:
Type: transcription factor
CREB is a transcription factor that binds to specific DNA sequences, known as cAMP response elements (CRE), in the promoter regions of target genes.
CREB is activated by phosphorylation, which allows it to bind to CRE and recruit other transcriptional coactivators.
CREB regulates the expression of genes involved in various cellular processes, including:
    Cell growth and differentiation
    Apoptosis
    Metabolism
    Neurotransmission

CREB is also involved in the regulation of genes involved in cancer, including:
    Cell cycle progression
    Angiogenesis
    Invasion and metastasis

CREB is often overexpressed in cancer tissues.
High levels of CREB expression are associated with poor prognosis, increased tumor aggressiveness, and resistance to therapy. CREB can promote the expression of genes involved in cell survival and proliferation.
Scientific Papers found: Click to Expand⟱
4250- Flav,    Dietary Flavonoids Interaction with CREB-BDNF Pathway: An 
Unconventional Approach for Comprehensive Management of Epilepsy
- Review, NA, NA
*ERK↑, *BDNF↑, *CREB↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Core Metabolism/Glycolysis ⓘ

CREB↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: CREB, cAMP Response Element Binding Protein
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#:227  Target#:798  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page