condition found tbRes List
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


chemoP, ChemoProtective: Click to Expand ⟱
Source:
Type:
Protects normal cells against the effect of Chemo.


Scientific Papers found: Click to Expand⟱
3071- RES,    Resveratrol and Its Anticancer Effects
- Review, Var, NA
chemoP↑, In this review, the effects of resveratrol are emphasized on chemopreventive, therapeutic, and anticancer.
SIRT1↑, RSV can directly activate Sirt1 expression and induce autophagy independently or dependently on the mammalian target of rapamycin (mTOR)
Hif1a↓, RSV suppresses tumor angiogenesis by inhibiting HIF-1a and VEGF protein
VEGF↓,
STAT3↓, RSV effectively prevents cancer by inhibiting STAT3 expression
NF-kB↓, also has an inhibitory effect on antiapoptotic mediators such as NF-kB, COX-2, phosphatidylinositol 3-kinase (PI3K), and mTOR (52).
COX2↓,
PI3K↓,
mTOR↓,
NRF2↑, Activation of the Nrf2/antioxidant response element (ARE) pathway by endogenous or exogenous stimuli under normal physiological conditions has the potential to inhibit cancer and/or cancer cell survival, growth, and proliferation
NLRP3↓, RSV downregulates the NLRP3 gene by activating the Sirt1 protein, thereby inducing autophagy
H2O2↑, RSV mediates cytotoxicity in cancer cells by increasing intracellular hydrogen peroxide (H2O2) and oxidative stress levels that will cause cell death
ROS↑,
P53↑, RSV activates p53, increases the expression of PUMA and BAX
PUMA↑,
BAX↑,

3056- RES,    Less is more for cancer chemoprevention: evidence of a non-linear dose response for the protective effects of resveratrol in humans and mice
- in-vivo, Nor, NA
*AMPK↑, Efficacy correlated with increased AMP-activated protein kinase (AMPK) activation and the senescence marker p21.
*P21↑,
*Dose↓, Our results show that low dietary exposures not only elicit biological changes in mouse and human tissues relevant to colorectal cancer chemoprevention, but they have superior efficacy compared to high doses
*chemoP↑, Superior cancer chemopreventive efficacy of low dose resveratrol

3063- RES,    Resveratrol: A Review of Pre-clinical Studies for Human Cancer Prevention
- Review, Var, NA
*Inflam↓, Resveratrol is known to have potent anti-inflammatory and anti-oxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells.
*antiOx↑,
*AntiAg↑,
*chemoP↑, Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis
ChemoSen↑,
BioAv↑, Compared to other known polyphenols, such as quercetin and catechin, trans-resveratrol is well absorbed much more efficiently following oral administration to humans
Half-Life↝, Compared to resveratrol, which has a plasma half-life of 8–14 min, the metabolites have a plasma half-life of about 9.2 hours
COX2↓, there was inhibited expression of anti-apoptotic proteins, such as survivin, and markers of tumor promotion, cyclooxygenase (COX)-2, and ornithine decarboxylase (ODC) were observed
cycD1↓, Resveratrol decreased the expression of cyclins D1 and D2, Cdk 2, 4 and 6, and proliferating cell nuclear antigen (PCNA) whereas p21WAF1/CIP1 was increased
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
MMP9↓, associated with decreased COX-2 and matrix metalloprotease-9 expression and suppression of NFκB activation
NF-kB↓,
Telomerase↓, Relatively high concentrations also substantially downregulate telomerase activity
PSA↓, Resveratrol downregulates PSA by a mechanism independent of changes in AR
MAPK↑, Resveratrol treatment of various prostate cells also accompanied the activation of MAPK signaling and an increase in cellular p53
P53↑,

1511- RES,  Chemo,    Combination therapy in combating cancer
- Review, NA, NA
eff↑, Our studies, as well as others, have shown the effectiveness of resveratrol in combination therapy in vitro and in vivo
*NRF2↓, chemopreventive effects through the activation of Nrf2 and consequently GSH expression
*GSH↑,
*ROS↓, In addition, curcuminoids upregulate glutathione levels which have been shown to reduce ROS levels and remove carcinogens, aiding in chemoprevention
chemoP↑,
ChemoSideEff↓, Our lab showed that this antioxidant compound has cytoprotective properties against the side effects of chemotherapy


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
BAX↑,1,   BioAv↑,1,   CDK2↓,1,   CDK4↓,1,   CDK6↓,1,   chemoP↑,2,   ChemoSen↑,1,   ChemoSideEff↓,1,   COX2↓,2,   cycD1↓,1,   eff↑,1,   H2O2↑,1,   Half-Life↝,1,   Hif1a↓,1,   MAPK↑,1,   MMP9↓,1,   mTOR↓,1,   NF-kB↓,2,   NLRP3↓,1,   NRF2↑,1,   P21↑,1,   P53↑,2,   PI3K↓,1,   PSA↓,1,   PUMA↑,1,   ROS↑,1,   SIRT1↑,1,   STAT3↓,1,   Telomerase↓,1,   VEGF↓,1,  
Total Targets: 30

Results for Effect on Normal Cells:
AMPK↑,1,   AntiAg↑,1,   antiOx↑,1,   chemoP↑,2,   Dose↓,1,   GSH↑,1,   Inflam↓,1,   NRF2↓,1,   P21↑,1,   ROS↓,1,  
Total Targets: 10

Scientific Paper Hit Count for: chemoP, ChemoProtective
4 Resveratrol
1 Chemotherapy
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:1171  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

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