Resveratrol / tau Cancer Research Results

RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- 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↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- 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 /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- 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- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


tau, tau: Click to Expand ⟱
Source:
Type:
In healthy neurons, tau binds to and stabilizes microtubules, which are essential for maintaining cell structure and facilitating axonal transport.

In AD, tau becomes abnormally hyperphosphorylated. This excessive phosphorylation reduces its affinity for microtubules, leading to destabilization of the cytoskeletal structure.
-Abnormal phosphorylated tau (p-tau) can be detected in cerebrospinal fluid (CSF) and blood plasma.
-Imaging techniques like tau PET scans can visualize tau deposits in the brain.
Natural Products targeting tau
-Curcumin                via GSK-3β inhibition
-Resveratrol             Activates SIRT1
-EGCG                    inhibits Tau, but BBB penetration is questionable
Scientific Papers found: Click to Expand⟱
4289- RES,    Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells
- in-vitro, AD, NA
*antiOx↑, *p‑tau↓, *GSK‐3β↓, *CaMKII ↓, *PP2A↑, *neuroP↑,
4288- RES,    Trans-resveratrol Inhibits Tau Phosphorylation in the Brains of Control and Cadmium Chloride-Treated Rats by Activating PP2A and PI3K/Akt Induced-Inhibition of GSK3β
- in-vivo, AD, NA
*memory↑, *GSH↑, *ROS↓, *MDA↓, *p‑tau↓, *PI3K↑, *Akt↑, *AMPK↑, *PP2A↑, *GSK‐3β↓,
4287- RES,    Resveratrol targeting tau proteins, amyloid-beta aggregations, and their adverse effects: An updated review
- Review, AD, NA
*p‑tau↓,
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↑, *Inflam↓, *antiOx↑, *GSH↑, *HO-1↑, *iNOS↓, *BDNF↑, *p‑CREB↑, *PKA↑, *Bcl-2↑, *BAX↓, *IL1β↓, *IL6↓, *MMP9↓, *memory↑, *AMPK↑, *PGC-1α↓, *NF-kB↓, *Aβ↓, *SIRT1↑, *p‑tau↓, *PP2A↑, *lipid-P↓, *NLRP3↓, *BACE↓,
4285- RES,    Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy
- in-vivo, AD, NA
*tau↓, *cognitive↑, *Inflam↓,
4284- RES,    Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex
- in-vitro, AD, HEK293 - NA, Stroke, NA - in-vivo, AD, NA
*p‑tau↓, *PP2A↑, *neuroP↑, *antiOx↑, COX2↓, *AntiAg↑, *SIRT1↑, *AMPK↑, *Acetyl-CoA↓, *FAO↑, *ADAM10↑, *BACE↓, *Aβ↓, *memory↑, *Inflam↓, *ROS↓,
6051- RES,  SeNPs,  Chit,    Resveratrol-loaded selenium/chitosan nano-flowers alleviate glucolipid metabolism disorder-associated cognitive impairment in Alzheimer's disease
- in-vivo, AD, NA
*Inflam↓, *ROS↓, *GutMicro↑, *lipid-P↓, *Aβ↓, *tau↓, *cognitive↑,
6058- SeNPs,  RES,  QC,  CAR,    Engineered nanoplatforms for brain-targeted co-delivery of phytochemicals in Alzheimer's disease: Rational design, blood-brain barrier penetration, and multi-target therapeutic synergy
- Review, AD, NA
*DDS↑, *cognitive↑, *Aβ↓, *tau↓, *Inflam↓, *antiOx↑, *BioAv↑, *BioAv↑, *neuroP↑, *BioAv↑, *AChE↓,
3921- VitD3,  RES,    Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice
- in-vivo, AD, NA
*cognitive↑, *Aβ↓, *BACE↓, *p‑tau↓, *p‑CREB↑, *p‑NF-kB↓, *neuroP↑,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Immune & Inflammatory Signaling ⓘ

COX2↓, 1,  
Total Targets: 1

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   GSH↑, 2,   HO-1↑, 1,   lipid-P↓, 2,   MDA↓, 1,   ROS↓, 3,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↓, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1,   AMPK↑, 3,   p‑CREB↑, 2,   FAO↑, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt↑, 1,   BAX↓, 1,   Bcl-2↑, 1,   iNOS↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 2,   PI3K↑, 1,  

Migration ⓘ

AntiAg↑, 1,   MMP9↓, 1,   PKA↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 5,   NF-kB↓, 1,   p‑NF-kB↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   ADAM10↑, 1,   BDNF↑, 1,   tau↓, 3,   p‑tau↓, 6,  

Protein Aggregation ⓘ

Aβ↓, 5,   BACE↓, 3,   NLRP3↓, 1,   PP2A↑, 4,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 3,   DDS↑, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 4,   memory↑, 3,   neuroP↑, 5,  
Total Targets: 43

Scientific Paper Hit Count for: tau, tau
9 Resveratrol
2 Selenium NanoParticles
1 chitosan
1 Quercetin
1 Carvacrol
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:1231  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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