CREB Cancer Research Results

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⟱
4279- Api,    The Beneficial Role of Apigenin against Cognitive and Neurobehavioural Dysfunction: A Systematic Review of Preclinical Investigations
- Review, NA, NA
*antiOx↑, potent antioxidant and has been shown to exhibit anti-inflammatory, antitumorigenic and antimicrobial activities
*Inflam↓,
*BBB↑, Its ability to cross the blood–brain barrier is important as it contributes to its pharmacological activity against neurological disorders
*5HT↑, Apigenin improved serotonin, dopamine and epinephrine levels, which were altered in depressive animals
*CREB↑, Apigenin further regulates the cAMP-CREB-BDNF signalling pathway and N-methyl-D-aspartate (NMDA) receptors, which play important roles in neuronal survival, synaptic plasticity, cognitive function and mood behaviour
*BDNF↑, Apigenin improved BDNF levels and enhanced ERK1/2 and CREB expression
*memory↑, All the studies showed that apigenin improved learning and memory, except for two studies.
*motorD↑, In the open field test, apigenin improved locomotor activity
*Mood↑, The splash test revealed that apigenin improved grooming activity and locomotion in streptozotocin-induced depressive-like behaviour in a mouse model via an improvement in grooming activity.
*cognitive↑, The studies included in this systematic review showed that apigenin improved cognitive function and neurobehaviour in impaired or stressed animals.
*ROS↓, inhibition of ROS production

3887- Api,    The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice
- in-vivo, AD, NA
*Inflam↓, anti-inflammatory, anticarcinogenic, and free radical-scavenging activities.
*ROS↓,
*Aβ↓, Recent studies revealed its protective effects against amyloid-β (Aβ)-induced neurotoxicity, but the mechanism was unclear. I
*memory↑, involving improvement of the learning and memory capabilities,
*AChE↓, improvement of cholinergic system involving the inhibition of AChE activity and elevation of ACh level, and modification of BNDF, TrkB, and phospho-CREB levels.
*Ach↑,
*Dose↑, Apigenin, at doses of 10 mg/kg and 20 mg/kg, promoted learning and memory
*BDNF↑, apigenin also increased BDNF level and up-regulated its receptor TrkB and pCREB in A25-35 -induced amnesic mice.
*TrkB↑,
*p‑CREB↑,
*BBB↑, Additionally, we found that treatment with apigenin was effective in preserving anatomical and functional integrity of the BBB per- meability.
*Ca+2?, A relevant effect of apigenin by suppressing the Ca 2+ influx through both voltage- and receptor-operated calcium channels might be attributed to the changes of rCBF

3884- Api,    Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model
- in-vivo, AD, NA
*memory↑, Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice.
*Aβ↓, Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels.
*BACE↓, we observed BACE1 level reduction treated with apigenin.
*antiOx↑, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase.
*BDNF↑, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex.
*p‑CREB↑, After long-term apigenin treatment, coupled with the elevation of BDNF level, enhanced phosphorylated ERK1/2 and CREB expression were detected in the cerebral cortex
*p‑ERK↑,
*ROS↓, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase (SOD) and GSH-Px.
*SOD↑,
*GPx↑,
*neuroP↑, observations are correlated with a prospective neuroprotective, anti-amyloidogenic and neurotrophic effects in AD deficits.

4274- BBR,    Berberine exerts antidepressant effects in vivo and in vitro through the PI3K/AKT/CREB/BDNF signaling pathway
- in-vivo, NA, NA
*IL1β↓, serum levels of IL-1β, IL-6, TNF-α and CRP in CRS mice were significantly increased, while berberine and fluoxetine could down-regulate the expression of the above cytokines.
*IL6↓,
*TNF-α↓,
*CRP↓,
*CREB↑, The results showed that the mRNA and protein expression (or phosphorylation) levels of CREB (Fig. 4B, D) and BDNF (Fig. 4C, E) were decreased in the hippocampus of CRS mice, which could be reversed by berberine treatment
*BDNF↑,

4277- BM,    Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri
- in-vivo, NA, NA
*BDNF↑, restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats
*p‑CREB↑,

3875- Carno,    Ionophore Ability of Carnosine and Its Trehalose Conjugate Assists Copper Signal in Triggering Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Activation In Vitro
- in-vitro, AD, NA
*IronCh↑, copper tuning effect on the ability of l-carnosine and, particularly its conjugate, to activate tyrosine kinase cascade pathways.
*CREB↑, As previously mentioned, Car (10 mM) is able: (i) to activate CREB and CREB related pathways, including BDNF expression and release, by activating Ca2+-related pathways in Caco-2 cell line
*BDNF↑,
*NGF↑, Car induces expression and secretion of NGF and BDNF in U-87 MG cells,
*antiOx↑, while antioxidant, oxygen free-radical scavenge
*ROS↓,

4260- CHr,    Chrysin modulates the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway: Acting in the improvement of cognitive flexibility and declarative, working and aversive memory deficits caused by hypothyroidism in C57BL/6 female mice
- in-vivo, NA, NA
*BDNF↑, Chrysin modulates the BDNF/TrkB/AKT/CREB signaling pathway in the brain.
*TrkB↑,
*Akt↑,
*CREB↑,
*memory↑, Chrysin treatment effectively reversed these memory deficits, restored cognitive flexibility, and improved protein levels
*cognitive↑,

4208- Cro,    Antidepressant Effect of Crocus sativus Aqueous Extract and its Effect on CREB, BDNF, and VGF Transcript and Protein Levels in Rat Hippocampus
- in-vivo, NA, NA
*BDNF↑, The protein levels of BDNF, CREB and p-CREB were significantly increased in saffron treated rats.
*CREB↑,
*p‑CREB↑,

4158- Cro,    Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus
- in-vivo, AD, NA
*CREB↑, 25 and 50 mg/kg of crocin increased the levels of CREB and BDNF significantly and dose dependently.
*BDNF↑,
*Mood↑, crocin has antidepressant-like action by increasing CREB, BDNF and VGF levels in hippocampus

4176- CUR,    Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling
- in-vivo, AD, NA
*BDNF↑, Upregulating Brain-Derived Neurotrophic Factor and CREB Signaling
*CREB↑,

4171- CUR,    Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons
- in-vivo, NA, NA
*BDNF↑, treatment of curcumin increased BDNF and phosphor-TrkB
*TrkB↑,
*CREB↑, curcumin-induced increase in phosphorylated cyclic AMP response element binding protein (CREB), which has been implicated as a possible mediator of antidepressant actions
*Mood↑,
*neuroP↑, Therefore, we hypothesize the neuroprotection of curcumin might be mediated via BDNF/TrkB-MAPK/PI-3K-CREB signaling pathway.

4178- DHA,    The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma
- in-vivo, NA, NA
*BDNF↑, We found that DHA supplementation, which elevates brain DHA content, normalized levels of brain-derived neurotrophic factor (BDNF), synapsin I (Syn-1), cAMP-responsive element-binding protein (CREB), and calcium/calmodulin-dependent kinase II (CaMKII
*CREB↑,
*cognitive↑, potential of dietary DHA to counteract broad and fundamental aspects of TBI pathology that may translate into preserved cognitive capacity.
*SOD↑, DHA diet also counteracted the FPI-reduced manganese superoxide dismutase (SOD) and Sir2 (a NAD+-dependent deacetylase).

4177- DHA,    Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats
- in-vivo, NA, NA
*BDNF↑, Supplementation of omega-3 fatty acids in the diet counteracted all of the studied effects of FPI, that is, normalized levels of BDNF and associated synapsin I and CREB, reduced oxidative damage, and counteracted learning disability.
*CREB↑,
*ROS↓,
*cognitive↑,

4250- Flav,    Dietary Flavonoids Interaction with CREB-BDNF Pathway: An 
Unconventional Approach for Comprehensive Management of Epilepsy
- Review, NA, NA
*ERK↑, Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF.
*BDNF↑,
*CREB↑, beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway.

4302- Gins,    Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease
- Review, AD, NA
*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,

4235- H2,    PPARα contributes to the therapeutic effect of hydrogen gas against sepsis-associated encephalopathy with the regulation to the CREB-BDNF signaling pathway and hippocampal neuron plasticity-related gene expression
- in-vivo, Sepsis, NA
*PPARα↑, H2 alleviates sepsis-induced brain injury in mice through the regulation of neurotrophins and hippocampal plasticity-related genes via PPARα by activating the CREB-BDNF signaling pathway.
*CREB↑,
*BDNF↑,
*OS↑, activation of PPARα in septic mice improved the survival rate and alleviated cognitive dysfunction.
*cognitive↑,

4241- HNK,    Effects of Honokiol on Neurological Injury and Cognitive Function in Mice with Intracerebral Hemorrhage by Regulating BDNF-TrkB-CREB Signaling Pathway
- in-vivo, Stroke, NA
*Apoptosis↓, Honokiol may alleviate hippocampal neuronal apoptosis and damage, and improve cognitive dysfunction in ICH mice by activating the BDNF-TrkB-CREB signaling pathway.
*cognitive↑,
*BDNF↑,
*TrkB↑,
*CREB↑,

4213- Hup,    Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia
- in-vivo, NA, NA
*cognitive↑, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice.
*SOD↑, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH.
*GPx↑,
*MDA↓,
*ROS↓,
*Iron↓, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression.
*TfR1/CD71↓,
*FTL↓,
*ERK↑, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity.
*PKA↑,
*CREB↑,
*BDNF↑,
*PSD95↑,
*neuroP↑, HuA-LIP showed a superior performance against neuronal damage induced by CIH.

4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity.
*antiOx↑,
*neuroP↑,
*BioAv↝, To increase the bioavailability of luteolin, several delivery methods have been developed; the most thoroughly studied include lipid carriers like liposomes and nanoformulations
*BBB↑, luteolin given intraperitoneally (ip) to mice can readily cross the blood-brain barrier (BBB) and enter the brain
*TNF-α↓, nhibiting pro-inflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), TNF-α, IL-β, IL-6, IL-8, IL-31, and IL-33 in several in vitro models of AD
*IL1β↓,
*IL6↓,
*IL8↓,
*IL33↓,
*NF-kB↓, inhibition of the NF-кB pathway
*BACE↓, leads to the inhibition of a downstream target– β-site amyloid precursor protein cleaving enzyme (BACE1), which is a key mediator in forming Aβ fibrils in AD pathology
*ROS↓, anti-oxidant activity mainly by reducing ROS levels and increasing SOD activity in in vitro models of AD
*SOD↑,
*HO-1↑, increase the expression of antioxidant enzymes such as heme oxygenase-1 (HO-1) via the nuclear factor erythroid 2–related factor 2/ antioxidant responsive element (Nrf-2/ARE) complex activation
*NRF2↑,
*Casp3↓, reducing the levels of caspase-3 and − 9 and improving the B-cell lymphoma protein 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, as it was reported in in vitro models of AD
*Casp9↑,
*Bax:Bcl2↓,
*UPR↑, enhancing the unfolded protein response (UPR) pathway, leading to an increase in endoplasmic reticulum (ER) chaperone GRP78 and a decrease in the expression of UPR-targeted pro-apoptotic genes via the MAPK pathway.
*GRP78/BiP↑,
*Aβ↓, evidence that suggests that luteolin can directly influence the formation of Aβ plaques by selectively inhibiting the activity of N-acetyl-α-galactosaminyltransferase (ppGalNAc-T) isoforms
*GSK‐3β↓, inactivating the glycogen synthase kinase-3 alpha (GSK-3α) isoform, suppressing Aβ and promoting tau disaggregation
*tau↓,
*CREB↑, luteolin promoted phosphorylation and activation of cAMP response element-binding protein (CREB) leading to the increased miR-132 expression, and eventually neurite outgrowth in PC12 cells
*ATP↑, ROS production was decreased by 40%, MMP levels were restored close to control N2a levels (202%), and ATP levels were improved by 444%).
*cognitive↑, protective effect of luteolin against cognitive dysfunction was also reported in the streptozotocin
*BloodF↑, Luteolin increased regional cerebral blood flow values, alleviated the leakage of the lumen of vessels, and protected the integrity of BBB
*BDNF↑, increasing the level of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor (TrkB) expression in the cerebral cortex
*TrkB↑,
*memory↑, luteolin supplementation significantly ameliorated memory and cognitive deficits in 3 × Tg-AD mice.
*PPARγ↑, attenuated mitochondrial dysfunction via peroxisome proliferator-activated receptor gamma (PPARγ) activation.
*eff↑, combination of luteolin with another compound– l-theanine (an amino acid found in tea) also improved AD-like symptoms in the Aβ25–35-treated rats

4147- MF,    PEMFs Restore Mitochondrial and CREB/BDNF Signaling in Oxidatively Stressed PC12 Cells Targeting Neurodegeneration
- in-vitro, AD, PC12
*ROS↓, PEMF treatment significantly counteracted H2O2- and Aβ-induced cytotoxicity by restoring cell viability, reducing reactive oxygen species production, and improving catalase activity.
*Catalase↑,
*MMP↑, PEMFs preserved the mitochondrial membrane potential and decreased caspase-3 activation and chromatin condensation
*Casp3↓,
*p‑ERK↓, Mechanistically, PEMFs inhibited ERK phosphorylation and enhanced cAMP levels, CREB phosphorylation, and BDNF expression
*cAMP↑,
*p‑CREB↑,
*BDNF↑,
*neuroP↑, PEMFs modulate multiple stress response systems, promoting neuroprotection under oxidative and amyloidogenic conditions.

5604- NaHCO3,    Mitochondrial metabolic reprogramming of macrophages and T cells enhances CD47 antibody-engineered oncolytic virus antitumor immunity
- vitro+vivo, Melanoma, B16-BL6 - in-vitro, BC, 4T1
eff↑, identified sodium bicarbonate (NaBi) as the potent metabolic reprogramming agent that enhanced antitumor responses in the acidic TME.
eff↑, NaBi and oAd-αCD47 therapy significantly inhibited tumor growth and produced complete immune control in various tumor-bearing mouse models.
TumMeta↓, suggesting its potential as an effective neoadjuvant treatment for preventing postoperative tumor recurrence and metastasis.
pH↑, NaBi improves the acidity of the TME and activates the CaMKII/CREB/PGC1α mitochondrial biosynthesis signaling pathway
CaMKII ↑,
CREB↑,
PGC-1α↑, NaBi increases the mitochondrial content of T cells and BMDMs by promoting the expression of PGC1α mediated by the Ca2+-CaMKII-CREB signaling pathway in an LA environment
AntiTum↑, oral NaBi enhances the antitumor effect of oAd-αCD47.
Imm↑, We proposed that sodium bicarbonate (NaBi) can act as an immunomodulator to reprogram metabolic disorders of CD8+ T cells and TAMs in an acidic environment.
CD8+↑, Combination therapy remodels the immunosuppressive microenvironment to promote activation of CD8+ T cells and TAMs
TAMS↑,

4224- NarG,    The Effect of Naringin on Cognitive-Behavioral Functions, CREB/BDNF Signaling, Cholinergic Activity, and Neuronal Density in the Hippocampus of an MSG-Induced Obesity Rat Model
- in-vivo, Obesity, NA - NA, AD, NA
*memory↑, Nar-treated rats demonstrated improvements in spatial working memory, reduced anxiety-related behaviors, elevated hippocampal CREB and BDNF genes and BDNF protein levels, and reduced AChE activity.
*Mood↑,
*CREB↑,
*BDNF↑,
*AChE↓,
*cognitive↑, These findings suggest that Nar enhances cognitive function and mitigates anxiety
*neuroP↑, exerting neuroprotective effects in the hippocampus.

4156- PB,    The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain
- in-vivo, AD, NA
*BDNF↑, SB treatment upregulated protein levels of BDNF, phospho-CREB and GFAP.
*CREB↑,

3930- PTS,    A Review of Pterostilbene Antioxidant Activity and Disease Modification
- Review, Var, NA - Review, adrenal, NA - Review, Stroke, NA
*BioAv↑, It has increased bioavailability in comparison to other stilbene compounds. pterostilbene was shown to have 80% bioavailability compared to 20% for resveratrol making it potentially advantageous as a therapeutic agent
*antiOx↑, Multiple studies have demonstrated the antioxidant activity of pterostilbene in both in vitro and in vivo models illustrating both preventative and therapeutic benefits.
*neuroP↑, anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes.
*Inflam↓,
*ROS↓, pterostilbene reduces oxidative stress (OS) and production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and superoxide anion (O2 −), which are implicated in the initiation and pathogenesis of several disease processes
*H2O2↓,
*GSH↑, pterostilbene have shown increased expression of the antioxidants catalase, total glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD).
*GPx↑,
*GSR↑,
*SOD↑,
TumCG↓, pterostilbene inhibit breast cancer in vitro and in vivo
PTEN↑, rats fed the blueberry diet exhibited higher mammary branching, increased nuclear immunoreactivity of tumor suppressor phosphatase and tensin homolog deleted in chromosome 10 (PTEN)
HGF/c-Met↓, blueberry extract significantly decreased human-growth-factor (HGF-) induced activation of the PI3 K/AkT/NK-κB pathway, which is implicated in breast carcinogenesis
PI3K↓,
Akt↓,
NF-kB↓,
TumMeta↓, inhibited the metastatic potential of breast cancer cells in vitro by inhibiting HGF-induced cell migration and matrix metalloproteinase-(MMP-) 2 and MMP-9 activity.
MMP2↓,
MMP9↓,
Ki-67↓, blueberry extract produced smaller tumors with decreased expression of Ki-67, a marker of cell proliferation, and increased expression of caspase-3, an apoptosis marker
Casp3↑,
MMP↓, increased mitochondrial depolarization,
H2O2↑, pterostilbene treatment increased GPx antioxidant activity and the production of H2O2 and singlet oxygen indicating a mechanism of ROS-induced apoptosis
ROS↑,
ChemoSen↑, pterostilbene treatment produced a synergistic inhibitory effect when combined with the chemotherapy drug Tamoxifen, demonstrating clinical potential in the treatment of breast cancer
*cardioP↑, blueberries, and pterostilbene alike, exhibit protective effects against cardiovascular disease possibly due to induction of antioxidant enzymes.
*CDK2↓, Pterostilbene also produced downregulation of the cell-cycle mediators, cyclin-dependent kinase (CDK)-2, CDK-4, cyclin E, cyclin D1, retinoblastoma (Rb), and proliferative cell nuclear antigen (PCNA), all of which promote unchecked VSMC proliferation
*CDK4↓,
*cycE/CCNE↓,
*cycD1/CCND1↓,
*RB1↓,
*PCNA↓,
*CREB↑, The authors found that treatment with blueberry extract decreased dopamine- (DA-) induced upregulation of the oxidative mediators, CREB and pPKCγ, indicating a significant antioxidant effect
*GABA↑, blueberry-fed aged rats had significant improvements in GABA potentiation and increased GSH compared to aged controls
*memory↑, 1- or 2-month blueberry diet showed significantly higher object memory recognition compared to control rats
*IGF-1↑, supplementation with blueberry extract was shown to enhance hippocampal plasticity and increase levels of insulin-like growth factor (IGF-) 1, IGF-2, and ERK resulting in improved spatial memory
*ERK↑,
TIMP1↑, increased endogenous tissue inhibitors of metalloproteinases (TIMPs)
BAX↑, ↑Bax, ↑cytochrome C, ↑Smac/Diablo, ↑MnSOD
Cyt‑c↑,
Diablo↑,
SOD2↑,

3922- PTS,    Pterostilbene attenuates amyloid-β induced neurotoxicity with regulating PDE4A-CREB-BDNF pathway
- in-vivo, AD, NA
*BioAv↑, Pterostilbene (PTS), a kind of resveratrol analog which showed higher scores on BBB and OB, could overcome Aβ-induced neurotoxicity in vitro and in vivo.
*BBB↑, PTS exhibited a much higher BBB index than Resveratrol, which meant a higher compound concentration in the brain
*memory↑, Behavioral tests further confirmed PTS’ potential of overcoming memory deficits in APP/PS1 mice (AD model).
*p‑CREB↑, PTS increased the pVASP, pCREB, BDNF, and PSD95 expression.
*BDNF↑,
*PSD95↑,
*neuroP↑, PTS would be a qualified natural product for alleviating Aβ-induced neurotoxicity in AD.

4296- QC,    A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders
- Review, AD, NA
*Inflam↓, Commonly recognized as an anti-inflammatory agent, quercetin not only limits capillary vessel permeability by inhibiting hyaluronidase but also blocks cyclooxygenases and lipoxygenases.
*COX2↓,
*5LO↓,
*antiOx↑, well-known antioxidant (recognized as one of the most potent antioxidant flavonoids, considered to be stronger than vitamin C or tocopherols
*BioAv↝, Quercetin-Loaded Nanocarriers—New Delivery to Better Availability
*GPx↑, Que at two higher doses improved the antioxidant enzymes (glutathione peroxidase, superoxide dismutase (SOD), Na+/K+-ATPase) supplies and elevated the levels of ACh
*SOD↑,
*Ach↑,
*4-HNE↓, whereas the levels of peroxidation product, 4-HNE, were reduced in the striatum
*CREB↑, A recent study showed a positive influence on the expression of the hippocampal FoxG1/CREB/BDNF signaling pathway [93]
*BDNF↑,
*ROS↓, quercetin exerted antioxidant (reducing ROS, increasing SOD, GST, GSH activity) as well as anti-inflammatory activity (suppressing IL-1β, IL-6, TNF-α, COX-2, microglial activation) [
*GSH↑,
*IL1β↓,
*IL6↓,
*TNF-α↓,

4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented
*Inflam↓, Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol contained in red wine, peanuts, and some berries, is known for its anti-atherosclerotic, anti-inflammatory, antioxidant, and longevity-promoting properties
*antiOx↑,
*GSH↑, ↑glutathione in brain
*HO-1↑, ↑HO-1 ↓iNOS in hippocampus
*iNOS↓,
*BDNF↑, ↑BDNF, ↑pCREB, ↑PKA, ↑BCl-2 expression, ↓BAX expression, ↓IL-1β, IL-6, in hippocampus
*p‑CREB↑,
*PKA↑,
*Bcl-2↑,
*BAX↓,
*IL1β↓,
*IL6↓,
*MMP9↓, ↓MMP-9 in cerebrospinal fluid
*memory↑, ↑memory performance
*AMPK↑, ↑AMPK, ↑PGC-1, ↓NF-κB / IL-1β / NLRP3 in hippocampus and prefrontal cortex
*PGC-1α↓,
*NF-kB↓,
*Aβ↓, may counteract the formation of neurotoxic Aβ
*SIRT1↑, Resveratrol via SIRT-1 can, therefore, be expected to reduce the level of hyperphosphorylated tau and provide protection against neurodegeneration.
*p‑tau↓,
*PP2A↑, resveratrol by lowering the expression of MID1 ubiquitin ligase increases protein phosphatase 2A (PP2A) activity and promotes tau dephosphorylation by preventing its accumulation
*lipid-P↓, resveratrol abolishes Aβ-induced lipid peroxidation and expression of heme oxygenase-1 (HO-1) reduction;
*NLRP3↓, Researchers achieved a significant reduction in the levels of NF-κB (nuclear factor κ-light-chain enhancer of activated B cell), interleukin 1β and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammation markers
*BACE↓, figure 1

4217- Sage,  RosA,  Aroma,    Neuroprotective Potential of Aromatic Herbs: Rosemary, Sage, and Lavender
- Review, AD, NA - Review, Park, NA
*Inflam↓, Aromatic plants, sage (Salvia officinalis), lavender (Lavandula angustifolia), and rosemary (Salvia Rosmarinus) have already shown anxiolytics, anti-inflammatory, antioxidant, and neuroprotective effects.
*antiOx↑,
*neuroP↑,
*ERK↑, exert neuroprotective effects mainly through increasing neurotransmitters and antioxidants, activating ERK/CREB/BDNF pathway, and inhibition of β-amyloid, pro-inflammatory cytokines, and Acetylcholine esterase (AChE) activity.
*CREB↑,
*BDNF↑,
*Aβ↑,
*AChE↓,
*memory↑, Rosmarinus officinalis led to improvement in long-term memory and cognitive responses in rats, through the inhibition of acetylcholinesterase (AChE) activity
*cognitive↑,

4198- SFN,    Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways
- vitro+vivo, AD, NA
*TrkB↑, Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice.
*CREB↑,
CaMKII ↑,
*ERK↑,
*ac‑H3↑, Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons
*ac‑H4↑,
*HDAC↓,
*HDAC2↓,
*BDNF↑, sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition.

4215- SY,    Safflower yellow alleviates cognitive impairment in mice by modulating cholinergic system function, oxidative stress, and CREB/BDNF/TrkB signaling pathway
- in-vivo, NA, NA
*memory↑, SY could shorten the escape latency and the time of the first crossing platform in the mice with memory acquisition and memory consolidation impairments, and increase the platform crossing times.
*AChE↓, SY decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress markers (SOD, MDA, and GSH-PX) in scopolamine-induced mice
*ChAT↑,
*SOD↓,
*MDA↓,
*GPx↑,
*BDNF↑, SY could activated BDNF/TrkB/CREB signaling pathway and reduced neuronal damage.
*TrkB↑,
*CREB↑,
*ROS↓, SY can restore the function of the cholinergic system, inhibit oxidative stress

4172- TQ,    Chronic Administration of Thymoquinone Enhances Adult Hippocampal Neurogenesis and Improves Memory in Rats Via Regulating the BDNF Signaling Pathway
- in-vivo, AD, NA
*cognitive↑, TQ-administered rats showed a profound beneficial effect on avoidance-related learning ability, associated with an increase in the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF),
*BDNF↑,
*p‑CREB↑, TQ stimulates the phosphorylation of cAMP-response element-binding protein (CREB), the upstream signaling molecule in the BDNF pathway.
*ROS↓, chronic administration of TQ decreased lipid peroxide and reactive oxygen species levels in the hippocampus.
*memory↑, TQ plays a role in memory improvement in adult rats and that the CREB/BDNF signaling pathways are involved in mediating the actions of TQ in hippocampal neurogenesis.

4173- TQ,    Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons
- in-vivo, NA, NA
*neuroP↑, TQ significantly increases the number of hippocampal neurons.
*Casp3↓, TQ significantly decreases the amount of Caspase-3 expression and the cleavage of poly ADP ribose polymerase, indicating a decrease in apoptosis.
*Apoptosis↓,
*ERK↑, ERK, GSK-3, JNK, CREB, and iNOS proteins are found to be positively regulated by TQ.
*JNK↑,
*CREB↑,
*iNOS↑,
*BDNF∅, gene expression of synapsin, synaptophysin, NGF, AKT, Bax, NFkB, and p53 and the protein expression of BDNF and nNOS are not affected by TQ.

4880- Uro,    Urolithins: A Prospective Alternative against Brain Aging
- Review, AD, NA
*cognitive↑, t has been reported that ET- or EA-rich food consumption improve cognition and memory in the elderly (summarized in Table 3), whereas the effect of Uros supplementation in the elderly is still unknown.
*memory↑,
*antiOx↑, aUros are potent antioxidants with good BBB permeability
*BBB↑,
*ROS↓, they effectively inhibited ROS formation and lipid peroxidation
*lipid-P↓,
*Catalase↑, UroA and UroB increased the activity of antioxidant enzymes, including catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase
*SOD↑,
*GSR↑,
*GPx↑,
*CREB↑, we found that UroA (5, 10 μM) treatment significantly increased protein kinase A (PKA)/cAMP-response element binding protein (CREB)/brain derived neurotrophic factor (BDNF) neurotrophic signaling pathway in H2O2-treated SH-SY5Y cells,
*BDNF↑,
*neuroP↑, CREB/BDNF neurotrophic signaling pathway might involve the neuroprotective effect of UroA against oxidative stress.
*Inflam↓, Mitigation of Neuroinflammatioin
*MitoP↑, Promotion of Mitophagy and Mitochondrial Function
*Aβ↓, inhibition of Aβ and tau pathology
*tau↓,
*NLRP3↓, UroA reduced the elevated expression and activity of NLRP3 and related neuroinflammation in AD mice
*SIRT1↑, UroA activates SIRT1 and SIRT3
*SIRT3↑,

3921- VitD3,  RES,    Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice
- in-vivo, AD, NA
*cognitive↑, The combination of VD and RSV significantly increased time spent in target quadrant and the number of crossing via MWM test
*Aβ↓, In hippocampus, the combined intervention significantly reduced soluble Aβ42 level and BACE1 protein expression
*BACE↓,
*p‑tau↓, combined treatment significantly reduced phosphorylation of tau at serine404 and p-p53, as well as enhanced p-CREB protein expression
*p‑CREB↑,
*p‑NF-kB↓, The combination also significantly reduced GFAP and p-NFκB p65 in both hippocampus and cortex
*neuroP↑, combined intervention might exert greater neuroprotective effects in SAMP8 mice,


Showing Research Papers: 1 to 34 of 34

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 34

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

H2O2↑, 1,   ROS↑, 1,   SOD2↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

CREB↑, 1,  

Cell Death ⓘ

Akt↓, 1,   BAX↑, 1,   Casp3↑, 1,   Cyt‑c↑, 1,   Diablo↑, 1,   HGF/c-Met↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,   PTEN↑, 1,   TumCG↓, 1,  

Migration ⓘ

Ki-67↓, 1,   MMP2↓, 1,   MMP9↓, 1,   TIMP1↑, 1,   TumMeta↓, 2,  

Angiogenesis & Vasculature ⓘ

TAMS↑, 1,  

Immune & Inflammatory Signaling ⓘ

Imm↑, 1,   NF-kB↓, 1,  

Cellular Microenvironment ⓘ

pH↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 30

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

4-HNE↓, 1,   antiOx↑, 9,   Catalase↑, 2,   GPx↑, 6,   GSH↑, 3,   GSR↑, 2,   H2O2↓, 1,   HO-1↑, 2,   Iron↓, 1,   lipid-P↓, 2,   MDA↓, 2,   NRF2↑, 2,   ROS↓, 13,   SIRT3↑, 1,   SOD↓, 1,   SOD↑, 7,  

Metal & Cofactor Biology ⓘ

FTL↓, 1,   IronCh↑, 1,   TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 1,   PGC-1α↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cAMP↑, 1,   CREB↑, 25,   p‑CREB↑, 9,   PPARα↑, 1,   PPARγ↓, 1,   PPARγ↑, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt↑, 2,   Apoptosis↓, 2,   BAX↓, 1,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Casp3↓, 3,   Casp9↑, 1,   iNOS↓, 1,   iNOS↑, 1,   JNK↑, 1,   MAPK↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 2,   ac‑H3↑, 1,   ac‑H4↑, 1,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

MitoP↑, 1,  

DNA Damage & Repair ⓘ

PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   RB1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 7,   p‑ERK↓, 1,   p‑ERK↑, 1,   GSK‐3β↓, 1,   HDAC↓, 1,   HDAC2↓, 1,   IGF-1↑, 1,   PI3K↑, 1,  

Migration ⓘ

5LO↓, 1,   APP↓, 1,   Ca+2?, 1,   MMP9↓, 1,   PKA↑, 3,  

Barriers & Transport ⓘ

BBB↑, 5,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL1β↓, 4,   IL33↓, 1,   IL6↓, 4,   IL8↓, 1,   Inflam↓, 8,   NF-kB↓, 2,   p‑NF-kB↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   AChE↓, 4,   ADAM10↑, 1,   BDNF↑, 29,   BDNF∅, 1,   ChAT↑, 1,   GABA↑, 1,   NGF↑, 1,   PSD95↑, 2,   tau↓, 2,   p‑tau↓, 3,   TrkB↑, 7,  

Protein Aggregation ⓘ

Aβ↓, 7,   Aβ↑, 1,   BACE↓, 5,   IDE↑, 1,   NLRP3↓, 2,   PP2A↑, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,   BioAv↝, 2,   Dose↑, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

BloodF↑, 1,   CRP↓, 1,   IL6↓, 4,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 14,   memory↑, 14,   Mood↑, 4,   motorD↑, 1,   neuroP↑, 14,   OS↑, 1,  
Total Targets: 109

Scientific Paper Hit Count for: CREB, cAMP Response Element Binding Protein
3 Apigenin (mainly Parsley)
2 Crocetin
2 Curcumin
2 Docosahexaenoic Acid
2 Pterostilbene
2 Resveratrol
2 Thymoquinone
1 Berberine
1 Bacopa monnieri
1 Carnosine
1 Chrysin
1 flavonoids
1 Ginseng
1 Hydrogen Gas
1 Honokiol
1 Huperzine A/Huperzia serrata
1 Luteolin
1 Magnetic Fields
1 Bicarbonate(Sodium)
1 Naringin
1 Phenylbutyrate
1 Quercetin
1 Salvia officinalis
1 Rosmarinic acid
1 Aromatherapy
1 Sulforaphane (mainly Broccoli)
1 Safflower yellow
1 Urolithin
1 Vitamin D3
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

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