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↓">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
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