Resveratrol / hepatoP 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


hepatoP, L,hepatoprotective: Click to Expand ⟱
Source:
Type:
Hepatoprotective is the ability of a chemical substance to prevent damage to the liver.

Grapefruit:
-hepatoprotective potential has emerged from the study of naringenin and naringin.
Blueberries/cranberries:
-proanthocyanidins
Grape:
Nopal (Cactus pear) and tuna (Cactus pear fruit) “Opuntia ficus-indica”:
Chamomile (Matricaria chamomilla or Chamomilla recutita):
Silymarin (Silybum marianum):
Blue green algae spirulina :
Propolis (bee glue):

POLYSACCHARIDES
β-glucans


Scientific Papers found: Click to Expand⟱
2206- AgNPs,  RES,    ENHANCED EFFICACY OF RESVERATROL-LOADED SILVER NANOPARTICLE IN ATTENUATING SEPSIS-INDUCED ACUTE LIVER INJURY: MODULATION OF INFLAMMATION, OXIDATIVE STRESS, AND SIRT1 ACTIVATION
- in-vivo, Nor, NA
*hepatoP↑, AgNPs + RV treatment significantly reduced pro-inflammatory cytokines, NF-κB activation, presepsin, PCT, 8-OHDG, and VEGF levels compared with the CLP group, indicating attenuation of sepsis-induced liver injury.
*Inflam↓,
*NF-kB↓,
*VEGF↓,
*SIRT1↑, Both RV and AgNPs + RV treatments increased SIRT1 levels, suggesting a potential role of SIRT1 activation in mediating the protective effects.
*ROS↓, alleviating sepsis-induced liver injury by modulating inflammation, oxidative stress, and endothelial dysfunction, potentially mediated through SIRT1 activation.
*Dose↝, 30 mg/kg of AgNPs + RV was given intraperitoneally to the rats
*Catalase↑, AgNPs + RV treatment exhibited a robust effect in bolstering CAT activity
*MDA↓, AgNPs + RV treatment effectively ameliorates sepsis-induced oxidative stress and inflammation in rat livers by reducing MDA, MPO, and NO levels
*MPO↓,
*NO↓,
*ALAT↓, AgNPs + RV effectively reduced the ALT and AST levels, returning them to values similar to those observed in the Sham group
*AST↓,
*antiOx↑, corroborates the antioxidant potential of RV and AgNPs observed in earlier studies

3057- RES,    The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*NRF2↑, Resveratrol stimulates the Nrf2 signaling through blockage of Keap1
*Keap1↓,
*ROS↓, Res ameliorates oxidative stress, apotosis and inflammatory indexes in several tissues.
*Apoptosis↓,
*Inflam↓,
*antiOx↑, Beneficial effects such as anti-inflammatory, antioxidant, hepatoprotective, neuroprotective, cardioprotective, renoprotective, anti-obesity, anti-diabetic, and anti-cancer
*hepatoP↑,
*neuroP↑, neuroprotective Res-associated effect resulting in the activation of Nrf2 signaling pathway.
*cardioP↑,
*RenoP↑,
*AntiCan↑,
*memory↑, Res could ameliorate the spatial memory in the experimental animals via increasing the SOD, glutathione peroxidase (GPx) and CAT expression and activity.
*SOD↑,
*GPx↑,
*Catalase↑,
*MDA↓, Res decreased malondialdehyde (MDA) brain levels in these mice activating the Nrf2/HO-1, indicating its potential to decrease the cell oxidative damage.
*NRF2↑,
*HO-1↑,
*ROS↓,
*Aβ↓, Res improved AD by reducing Aβ protein expression in the brain of treated mice
*iNOS↓, Res ameliorated Aβ-induced increase of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)(pro-inflammatory enzymes), reversed and decreased the mRNA expression levels of antioxidative genes (GPx1, SOD-1, Nrf2, CAT, glutathione, and
*COX2↓,
*GSH↑, Res, significantly reduced NSCs death and the MDA levels, raising proliferation, SOD activity, and GSH content after OGD/R damage
*HO-1⇅, through marked the Nrf2/HO-1 upregulation in hypoxia-ischemia pups
*SIRT1↑, restored activity and expression of SIRT1 mediated by Nrf2.

2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, Although resveratrol at high doses up to 5 g has been reported to be non-toxic [34], in some clinical trials, resveratrol at daily doses of 2.5–5 g induced mild-to-moderate gastrointestinal symptoms [
*BioAv↝, After an oral dose of 25 mg in healthy human subjects, the concentrations of native resveratrol (40 nM) and total resveratrol (about 2 µM) in plasma suggested significantly greater bioavailability of resveratrol metabolites than native resveratrol
*Dose↝, The total plasma concentration of resveratrol did not exceed 10 µM following high oral doses of 2–5 g
*hepatoP↑, hepatoprotective effects
*neuroP↑, neuroprotective properties
*AntiAg↑, Resveratrol possesses the ability to impede platelet aggregation
*COX2↓, suppresses promotion by inhibiting cyclooxygenase-2 activity
*antiOx↑, It is widely recognized that resveratrol has antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↓, antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↑, pro-oxidant properties when present in doses ranging from 10 to 40 μM
PI3K↓, It is known that resveratrol suppresses PI3-kinase, AKT, and NF-κB signaling pathways [75] and may affect tumor growth via other mechanisms as well
Akt↓,
NF-kB↓,
Wnt↓, esveratrol inhibited breast cancer stem-like cells in vitro and in vivo by suppressing Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
NRF2↑, Resveratrol activated the Nrf2 signaling pathway, causing separation of the Nrf2–Keap1 complex [84], leading to enhanced transcription of antioxidant enzymes, such as glutathione peroxidase-2 [85] and heme-oxygenase (HO-1)
GPx↑,
HO-1↑,
BioEnh?, Resveratrol was demonstrated to have an impact on drug bioavailability,
PTEN↑, Resveratrol could suppress leukemia cell proliferation and induce apoptosis due to increased expression of PTEN
ChemoSen↑, Resveratrol enhances the sensitivity of cancer cells to chemotherapeutic agents through various mechanisms, such as promoting drug absorption by tumor cells
eff↑, it can also be used in nanomedicines in combination with various compounds or drugs, such as curcumin [101], quercetin [102], paclitaxel [103], docetaxel [104], 5-fluorouracil [105], and small interfering ribonucleic acids (siRNAs)
mt-ROS↑, enhancing the oxidative stress within the mitochondria of these cells, leading to cell damage and death.
Warburg↓, Resveratrol Counteracts Warburg Effect
Glycolysis↓, demonstrated in several studies that resveratrol inhibits glycolysis through the PI3K/Akt/mTOR signaling pathway in human cancer cells
GlucoseCon↓, resveratrol reduced glucose uptake by cancer cells due to targeting carrier Glut1
GLUT1↓,
lactateProd↓, therefore, less lactate was produced
HK2↓, Resveratrol (100 µM for 48–72 h) had a negative impact on hexokinase II (HK2)-mediated glycolysis
EGFR↓, activation of EGFR and downstream kinases Akt and ERK1/2 was observed to diminish upon exposure to resveratrol
cMyc↓, resveratrol suppressed the expression of leptin and c-Myc while increasing the level of vascular endothelial growth factor.
ROS↝, it acts as an antioxidant in regular conditions but as a strong pro-oxidant in cancer cells,
MMPs↓, Main targets of resveratrol in tumor cells. COX-2—cyclooxygenase-2, SIRT-1—sirtuin 1, MMPs—matrix metalloproteinases,
MMP7↓, Resveratrol was shown to exert an inhibitory effect on the expression of β-catenins and also target genes c-Myc, MMP-7, and survivin in multiple myeloma cells, thus reducing the proliferation, migration, and invasion of cancer cells
survivin↓,
TumCP↓,
TumCMig↓,
TumCI↓,

2443- RES,    Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review
- Review, Var, NA
*antiOx↑, Resveratrol has shown strong antioxidant properties in many studies
*ROS↓,
*PTEN↑, resveratrol upregulated the phosphatase and tensin homolog (PTEN), which decreased Akt phosphorylation, leading to an upregulation of antioxidant enzyme mRNA levels such as catalase (CAT) and superoxide dismutase (SOD)
*Akt↓,
*Catalase↑,
*SOD↑,
*ERK↓, modulating antioxidant enzymes through downregulation of extracellular signal-regulated kinase (ERK)
*GSH↑, thus the levels of antioxidants like glutathione (GSH) increased, and free radicals were directly scavenged
*AMPK↑, resveratrol activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) to maintain the structural stability of forkhead box O1 (FoxO1)
*FOXO1↝,
*RNS↓, Generally, resveratrol protects against oxidative stress mainly by (i) reducing ROS/reactive nitrogen species (RNS) generation; (ii) directly scavenging free radicals; (iii) improving endogenous antioxidant enzymes (e.g., SOD, CAT, and GSH);
*Catalase↑,
*cardioP↑, In summary, the cardiovascular protective effects of resveratrol mainly depend on the capabilities of reducing oxidative stress and alleviating inflammation through Nrf2 and/or SIRT1 activation, PI3K/eNOS upregulation, and NF-κB downregulation.
*PI3K↑,
*eNOS↑,
hepatoP↑, Resveratrol has shown its protective impacts on several liver diseases in some studies

5857- RES,  CAP,  Rad,    Resveratrol and capsaicin as safer radiosensitizers for colorectal cancer compared to 5-fluorouracil
- in-vivo, Var, NA
RadioS↑, oral administration of resveratrol and capsaicin, but not resveratrol alone, allowed the radio-sensitization of subcutaneous colorectal tumors with similar efficiency to 5-FU.
hepatoP↝, Moreover, the global as well as the hematological toxicity of the BFC association was lower than those of 5-FU.
toxicity↓, This work establishes BFCs as effective enhancers of radiotherapy, offering a safer alternative to traditional radiosensitization with chemotherapy.

5788- RES,    Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans
- Trial, Nor, NA
*AMPK↑, In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels,
*SIRT1↑, Resveratrol, which was discovered in a small-molecule screen as a potent SIRT1 activator
*PGC-1α↑,
*BP↓, Systolic blood pressure dropped and HOMA index improved after resveratrol.
*CRM↑, 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.
*Dose↝, resveratrol (150 mg/day (99%); resVida™)
*mtDam↓, Resveratrol increases AMPK activity, increases mitochondrial efficiency and respiration on fatty acid substrates.
*ALAT↓, paralleled by lower plasma ALAT values, as mentioned before, both indicating improved liver function.
*hepatoP↑,

5781- RES,    Resveratrol improves health and survival of mice on a high-calorie diet
- in-vivo, Nor, NA
*AntiAge↑, Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK)
*IGF-1↓,
*AMPK↑,
*CRM↑, resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways.
*PGC-1α↑, activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function.
*mtDam↓,
*motorD↑, Surprisingly, the resveratrol-fed HC mice steadily improved their motor skills as they aged
*hepatoP↑, At 18 months of age it was apparent that the high-calorie diet greatly increased the size and weight of livers and that resveratrol prevented these changes
*Dose↝, this study shows that an orally available small molecule at doses achievable in humans can safely reduce many of the negative consequences of excess caloric intake, with an overall improvement in health and survival.


Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GPx↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↝, 1,   mt-ROS↑, 1,  

Core Metabolism/Glycolysis

cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   Warburg↓, 1,  

Cell Death

Akt↓, 1,   survivin↓, 1,  

Proliferation, Differentiation & Cell State

PI3K↓, 1,   PTEN↑, 1,   Wnt↓, 1,  

Migration

MMP7↓, 1,   MMPs↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

EGFR↓, 1,  

Barriers & Transport

GLUT1↓, 1,  

Immune & Inflammatory Signaling

NF-kB↓, 1,  

Drug Metabolism & Resistance

BioEnh?, 1,   ChemoSen↑, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers

EGFR↓, 1,  

Functional Outcomes

hepatoP↑, 1,   hepatoP↝, 1,   toxicity↓, 1,  
Total Targets: 33

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 4,   Catalase↑, 4,   GPx↑, 1,   GSH↑, 2,   HO-1↑, 1,   HO-1⇅, 1,   Keap1↓, 1,   MDA↓, 2,   MPO↓, 1,   NRF2↑, 2,   RNS↓, 1,   ROS↓, 5,   ROS↑, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics

mtDam↓, 2,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis

ALAT↓, 2,   AMPK↑, 3,   CRM↑, 2,   SIRT1↑, 3,  

Cell Death

Akt↓, 1,   Apoptosis↓, 1,   iNOS↓, 1,  

Proliferation, Differentiation & Cell State

ERK↓, 1,   FOXO1↝, 1,   IGF-1↓, 1,   PI3K↑, 1,   PTEN↑, 1,  

Migration

AntiAg↑, 1,  

Angiogenesis & Vasculature

eNOS↑, 1,   NO↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   Inflam↓, 2,   NF-kB↓, 1,  

Protein Aggregation

Aβ↓, 1,  

Drug Metabolism & Resistance

BioAv↝, 1,   Dose↝, 4,  

Clinical Biomarkers

ALAT↓, 2,   AST↓, 1,   BP↓, 1,  

Functional Outcomes

AntiAge↑, 1,   AntiCan↑, 1,   cardioP↑, 2,   hepatoP↑, 5,   memory↑, 1,   motorD↑, 1,   neuroP↑, 2,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 50

Scientific Paper Hit Count for: hepatoP, L,hepatoprotective
7 Resveratrol
1 Silver-NanoParticles
1 Capsaicin
1 Radiotherapy/Radiation
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#:1179  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

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