Database Query Results : Resveratrol, , NF-kB

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↓">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

NF-kB, Nuclear factor kappa B: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.

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,

Rats

*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

182-

CUR,

RES,

GI,

Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

LAPC-4

p38↓,
MKP5↑, MKP5 was up-regulated by curcumin and inhibited TNFa- and IL-1b-stimulated p38 phosphorylation, COX-2 up-regulation, NFjB activation and cytokine production in E-PZ cells
TNF-α↓,
COX2↓,
NF-kB↓,

4701-

PTS,

RES,

Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene

Review,

Var,

CSCs↓, Resveratrol and pterostilbene target CSCs
E-cadherin↑, " E-cadherin, # NF-jB, # EMT-associated molecules (Twist1,vimentin)
NF-kB↓,
EMT↓,
GRP78/BiP↓, GRP78
CD133↓, CD133
COX2↓, COX-2,
β-catenin/ZEB1↓,
NOTCH↓, Notch

3076-

RES,

Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells

Review,

Var,

IL6↓, A dose-dependent reduction of IL-6 by resveratrol led to attenuation of matrix metalloproteinases (MMPs), including MMP2 and MMP9
MMPs↓,
MMP2↓,
MMP9↓,
BioAv↓, The most important weakness of the usual form of resveratrol is its low absorption in the intestine and its low bioavailability
Half-Life↑, some covers such as liposomes and micelles also can facilitate absorption and increase half-life
BioAv↑, another study showed that carboxymethyl chitosan can increase bioavailability by more than 3.5 times
Dose↝, low concentrations of resveratrol (lower than 50 uM) cause no remarkable toxicity for normal cells, while higher concentrations are associated with increased oxidative injury
angioG↓, It is suggested that inhibition of STAT3, IL-10, and a reduction of vascular endothelial growth factor (VEGF) by resveratrol is involved in the suppression of macrophages and reduction of invasion and angiogenesis
IL10↓,
VEGF↓,
NF-kB↓, Inhibition of NF-kB by resveratrol can attenuate the expression of COX-2.
COX2↓,
SIRT1↑, Activation of Sirt-1 by resveratrol has a role in the suppression of NF-kB
Wnt↓, Resveratrol has also been shown that inhibit the Wnt/C-Myc pathway too
cMyc↓,
STAT3↓, Resveratrol has been shown that attenuate the expression of STAT3 through reduction of IL-6 level
PTEN↑, Downregulation of miR-17, miR-20a and miR-106b by resveratrol can activate PTEN, which leads to suppression of PI3K and induction of apoptosis in cancer cells
ROS↑, Resveratrol can trigger NOX5-induced ROS, leading to the induction of DNA damage and cancer cells senescence
RadioS↑, The combination of radiation and resveratrol has shown that has a synergic effect for stimulation of ROS production and induction of senescence in non-small cell lung carci- noma
Hif1a↓, Resveratrol can inhibit HIF-1Î± and its downstream proteins, including E-cadherin and vimentin
E-cadherin↓,
Vim↓,
angioG↓, Furthermore, resveratrol inhibits angiogenesis markers and tumor growth through the inhibition of HIF-1a

3077-

RES,

Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways

in-vitro,

Chon,

HTB94

MMP2↓, We found that resveratrol significantly inhibited MMP-2 and MMP-9, and induced the expression of type II collagen and sex-determining region Y-box (SOX)-9 and the production of sulfated proteoglycans in HTB94 chondrosarcoma cells.
MMP9↓,
SOX9↑,
MMPs↓,
p‑p38↑, Phosphorylation of p38 was increased and phosphorylation of c-Jun N-terminal kinase (JNK) was inhibited by resveratrol
p‑JNK↓,
NF-kB↓, Moreover, resveratrol reduced lung adenocarcinoma cell metastasis by suppressing heme oxygenase (HO)-1-mediated nuclear factor (NF)-κB pathway activation and subsequently downregulated the expression of MMPs.
HO-1↓, Resveratrol inhibited the transcription-activator function of HO-1 and subsequently MMP-2 and MMP-9 expression in human lung cancer cells as well.

3079-

RES,

Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action

Review,

Var,

angioG↓, Resveratrol suppresses angiogenesis and metastatic markers to reverse cancer spread.
TumMeta↓,
ChemoSen↑, Resveratrol chemosensitizes chemotherapy and synergizes anti-cancer phytochemicals.
NADPH↑, Both in vitro and in vivo studies indicates that resveratrol enhances various redox enzymes activity, especially nicotinamide adenine dinucleotide phosphate (NADPH)
SIRT1↑, resveratrol effectively modulates both the cytokine and chemokine profiles in immune and endothelial cells by the upregulation of sirtuin-1 (SIRT1)
NF-kB↓, suppression of NF-κB and prevention of the activation of NOD-like receptor family (Nrf) pyrin domain containing-3 inflammasome [
NLRP3↓,
Dose↝, The optimal dose of resveratrol being around 150 mg per day is considered safe by all means.
COX2↓, Cox2 ↓; MMP9 ↓
MMP9↓,
PGE2↓, Cox1 and 2; PGE2↓
TIMP1↑, Resveratrol suppresses the PMA-induced MMP activity in HepG2 cell line, while it also upregulates tissue inhibitor proteins of MMP, namely, TIMP1 and TIMP2, in dose-dependent manner
TIMP2↑,
Sp1/3/4↓, Resveratrol mitigates the expression of SP-1 by inhibiting both phosphorylation of JNK1/2 and expression of urokinase-type plasminogen activator in Huh-7 cell line
p‑JNK↓,
uPAR↓,
ROS↓, Resveratrol attenuates the excessive ROS production and inflammatory cytokine, IL-6, and CXCR4 receptor expression by downregulating Gli-1 expression.
CXCR4↓,
IL6↓,
Gli1↓,
*ROS↓, redox imbalance may be attenuated by resveratrol via downregulating ROS production and simultaneously inducing antioxidant enzymes, GST, SOD, CAT and GPx activities in the cells
*GSTs↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*lipid-P↓, [72] observed that resveratrol treatment not only reduces lipid peroxidation but also increases GSH and GST serum levels in CCl4-treated rats as compared to the CCl4-control animals
*GSH↑,
eff↑, Resveratrol, in combination with thymoquinone (TQ), has been demonstrated to provide a synergistic antiproliferative efficacy against HCC cell lines as reported by Ismail et al.
eff↑, Curcumin, a potential anticancer phytochemical, in combination with resveratrol has been reported to trigger synergistic apoptotic effects against Hepa1–6 cells
eff↑, berberine in combination with resveratrol lowers the cell viability and cell adhesion. At low concentration, berberine significantly induces cell death while resveratrol inhibits cell migration in HepG2 cells

3081-

RES,

Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?

Review,

CRC,

NF-kB↓, At 5 µM, resveratrol repressed inflammation (NF-κB), CRC progression (FAK, Ki-67, MMP-9, CXCR4) and CSC production (CD44, CD133, ALDH1).
FAK↓, Inhibition of FAK signaling pathway and thereby attenuation of invasion by resveratrol
Ki-67↓,
MMP9↓,
CSCs↓,
CD44↓,
CD133↓,
ALDH1A1↓,
EMT↓, resveratrol inhibits not only EMT but also enhances CRC cells‘ sensitivity to the standard chemotherapeutic drug 5-FU
ChemoSen↑,
Hif1a↓, Suppression of HIF-1α using β1-integrin receptors through resveratrol, thereby inhibition of inflammation
ITGB1↓,
Inflam↓,

3089-

RES,

The Role of Resveratrol in Cancer Therapy

Review,

Var,

angioG↓, resveratrol plays a role in inhibiting the expression of MMP (mainly MMP-9) [174,175,176,177] and angiogenesis markers such as VEGF, EGFR or FGF-2
VEGF↓,
EGFR↓,
FGF↑,
TumCMig↓, Resveratrol reduced the phorbo-12-myristate 13-acetate (PMA)-induced migration and invasion ability of liver cancer HepG2 and Hep3B cells.
TumCI↓,
TIMP1↑, resveratrol up-regulated TIMP-1 protein expression and down-regulated MMP-9 activity, while the activities of MMP-2 and MMP-9 were decreased,
MMP2↓,
MMP9↓,
NF-kB↓, via down-regulating the expression of NF-κB,
Hif1a↓, It has been reported that resveratrol suppresses the expression of VEGF and HIF-1α in human ovarian cancer cells via abrogating the activation of the PI3K/Akt and MAPK signaling pathways
PI3K↓,
Akt↓,
MAPK↓,
EMT↓, Many studies have shown that resveratrol suppresses the development of tumor invasion and metastasis through inhibiting signaling pathways associated with EMT
AR↓, Resveratrol suppressed prostate cancer growth via down-regulating the androgen receptor (AR) expression in the TRAMP model of prostate cancer

3071-

RES,

Resveratrol and Its Anticancer Effects

Review,

Var,

chemoPv↑, 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↑,

3069-

RES,

Resveratrol Inhibits NLRP3 Inflammasome-Induced Pyroptosis and miR-155 Expression in Microglia Through Sirt1/AMPK Pathway

in-vitro,

Nor,

*antiOx↑, antioxidant, anti-carcinogenic, anti-obesity, anti-aging, anti-inflammatory, immunomodulatory properties.
*Inflam↓,
*ROS↓, Our results demonstrated that resveratrol inhibits LPS- and ATP-activated NLRP3 inflammasome and protects microglial cells upon oxidative stress, proinflammatory cytokine production, and pyroptotic cell death resulting from inflammasome activation.
*NF-kB↓, resveratrol inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and activates AMPK/Sirt1 pathways.
*AMPK↑,
*SIRT1↑,
*miR-155↓, Furthermore, our results indicated that resveratrol downregulated inflammasome-induced miR-155 expression
*NLRP3↓, To sum up, our results suggest that resveratrol suppresses the NLRP3 inflammasome and miR-155 expression through AMPK and Sirt1 pathways in microglia.

3063-

RES,

Resveratrol: A Review of Pre-clinical Studies for Human Cancer Prevention

Review,

Var,

*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↑,
*chemoPv↑, 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/CCND1↓, 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↑,

3061-

RES,

The Anticancer Effects of Resveratrol: Modulation of Transcription Factors

Review,

Var,

AhR↓, Several reports demonstrate the inhibitory effects of resveratrol on AhR-mediated activation of phase I enzymes.
NRF2↑, Bishayee et al. (18) demonstrated that attenuation of DENA (diethyl nitrosamine)-induced liver carcinogenesis by resveratrol was mediated by increased Nrf2 expression.
*NQO1↑, Induction of Nrf2 signaling by resveratrol resulted in increased expression of NQO1, heme-oxygenase 1 (HO-1), and glutamate cysteine ligase catalytic subunit in cigarette smoke extract-treated bronchial epithelial cells
*HO-1↑,
*GSH↑, observed restored glutathione levels in cigarette smoke extract-treated A549 lung alveolar epithelial cancer cells by resveratrol;
P53↑, we highlight reported resveratrol-induced, p53-mediated anticancer mechanisms.
Cyt‑c↑, release of mitochondria proteins (e.g. cytochrome c, Smac/DIABLO, etc.) to the cytosol, thus triggering suppression of inhibitors of apoptosis proteins (e.g. Bcl2, Bcl-XL, survivin, XIAP, etc.) and caspase activation in several cancers
Diablo↑,
Bcl-2↓,
Bcl-xL↓,
survivin↓,
XIAP↓,
FOXO↑, activation of FoxO transcription factors is implicated in the observed anticancer activities of resveratrol.
p‑PI3K↓, resveratrol's ability to inhibit the phosphorylation of PI3K/Akt (
p‑Akt↓,
BIM↑, Bim/TRAIL/DR4/DR5/p27KIP1 induction and cyclin D1 inhibition) of resveratrol on prostate cancer cells
DR4↑,
DR5↑,
p27↑,
cycD1/CCND1↓,
SIRT1↑, resveratrol is considered a SIRT1 agonist
NF-kB↓, resveratrol not only curbs expression of NF-κB, but also impedes the phosphorylation of IκBα thereby keeping the constitutive NF-κB subunit in an inactive state, resulting in suppression of the inflammatory
ATF3↑, Furthermore, increased ATF3 expression by resveratrol facilitated induction of apoptosis

4286-

RES,

Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease

Review,

AD,

*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

102-

RES,

Effect of resveratrol on proliferation and apoptosis of human pancreatic cancer MIA PaCa-2 cells may involve inhibition of the Hedgehog signaling pathway

in-vitro,

PC,

MIA PaCa-2

HH↓, the levels of Ihh, Ptch and Smo were decreased by Res treatment
PTCH1↓,
Smo↓,
HH↓, Ihh
EMT↓,
PI3K/Akt↓, thru PI-3K/Akt/NF-κB↓
NF-kB↓,
TumCP↓, Res can inhibit the cell proliferative ability in a time- and dose-dependent manner.
Apoptosis↑, Res further induced apoptosis of MIA PaCa-2 cells in a dose-dependent manner.
ChemoSen↑, The apoptotic rate was significantly increased in cells treated with 5-Fu and Res, and the number of apoptotic cells increased with the increasing concentrations of Res

3612-

RES,

Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential

Review,

AD,

*other↑, Resveratrol demonstrates beneficial and protective effects in AD models and seems to provide a promising therapeutic alternative.
*Aβ↓, Disaggregation of Aβ-peptides
*Inflam↓, Activated microglia seem to be an important target of the neuroprotective activity of resveratrol, resulting in the reduc- tion of pro-inflammatory factors 3
*NF-kB↓, its ability to inhibit the NF-κB signaling pathway in activated microglia
*neuroP↑, Neuroprotective effects were also observed with the injection of resveratrol in rats (100 μM/5 μL),
*HO-1↑, which reduced amyloid accumulation, protected animals against neuronal death, increased antioxidant enzyme heme oxygenase-1 (HO-1) expression, and suppressed lipid peroxidation in the hippocampus.
*lipid-P↓,
*COX2↓, inhibiting the generation of TNF, APP, cyclooxygenase (COX)-2 and NF-κB phosphorylation in the hippocampus
*AMPK↑, Resveratrol is a potent activator of AMPK, thereby implicating another pathway through that its neuroprotective effects may be exerted
*Catalase↑, Resveratrol (10 μM) attenuated lipid peroxidation and upregulated antioxidant enzyme levels, such as catalase, superoxide dismutase (SOD), and glutathione reductase (GR).
*SOD↑,
*GSR↑,
*ROS↓, administration of resveratrol (10 and 20 μM) reduced ROS production in cells treated with AGEs
*MMP9↓, attenuated neuroinflammation, reduced proinflammatory markers, and decreased MMP-9 in the CSF
*cognitive↑, Resveratrol also attenuated the patients’ cognitive and functional decline
*SIRT1↑, neuroprotection is through the activation of the sirtuin 1 (SIRT1) pathway, which in turn inhibits the activation of the NF-κB signaling pathway.
*IL1β↓, reducing Aβ-induced memory and learning impairment and decreasing the expression of proinflammatory cytokines (IL-1β and IL-6)
*IL6↓,

3099-

RES,

Resveratrol and cognitive decline: a clinician perspective

Review,

Nor,

NA,

AD,

*antiOx↑, In preclinical models of cognitive decline, resveratrol displays potent antioxidant activity by scavenging free radicals, reducing quinone reductase 2 activity and upregulating endogenous enzymes.
*ROS↓,
*cognitive↑,
*neuroP↑,
*SIRT1↑, By inducing SIRT1, resveratrol may promote neurite outgrowth and enhance neural plasticity in the hippocampal region
*AMPK↑, Resveratrol also induces neurogenesis and mitochondrial biogenesis by enhancing AMP-activated protein kinase (AMPK), which is known to stimulate neuronal differentiation and mitochondrial biogenesis in neurons.
*GPx↑, figure 1
*HO-1↑,
*GSK‐3β↑,
*COX2↓,
*PGE2↓, Resveratrol also inhibits pro-inflammatory enzyme (i.e., COX-1 and -2) expression, reduces NF-κB activation as well as PGE2, NO, and TNF-α production, and cytokine release
*NF-kB↓,
*NO↓,
*Casp3↓,
*MMP3↓,
*MMP9↓,
*MMP↑, resveratrol attenuated ROS production and mitochondrial membrane-potential disruption; moreover, it restored the normal levels of glutathione (GSH) depleted by Aβ1-42
*GSH↑,
*other↑, resveratrol significantly increased cerebral blood flow (CBF) in the frontal cortex of young healthy humans.
*BioAv↑, receiving 200 mg/day of resveratrol in a formulation with quercetin 320 mg [53], in order to increase its bioavailability,
*memory↑, Resveratrol supplementation induced retention of memory and improved the functional connectivity between the hippocampus and frontal, parietal, and occipital areas, compared with placebo
*GlutMet↑, Also, glucose metabolism was improved and this may account for some of the beneficial effects of resveratrol on neuronal function.
*BioAv↓, The main problems related to the therapeutic or preventive use of resveratrol are linked to its low oral bioavailability and its short half-life in serum
*Half-Life↓,
*toxicity∅, On the other hand, the tolerability and safety profile of resveratrol is very high

3094-

RES,

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

CSCs↓, resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells
tumCV↓,
FASN↑, This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene
BNIP3↑, followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3.
*cardioP↑, cardio-protective effect of resveratrol has been extensively studied in various pre-clinical models, and it has been shown that the strong anti-oxidant activity of resveratrol
*antiOx↑,
NF-kB↓, down-regulation of NF-kappaB, COX and matrix metalloprotease-9 (MMP9) expression
COX2↓,
MMP9↓,
IGF-1↓, resveratrol as diet significantly reduced the onset of prostate cancer and exhibited a decrease in IGF1 (insulin-like growth factor 1) and phosphorylated-ERK1 (extracellular regulating kinase 1)
ERK↓,
lipid-P↓, resveratrol is indeed capable of suppressing lipid metabolism by blocking the FAS expression followed by induction of apoptosis in cancer stem-like cells
CD24↓, Resveratrol induces apoptosis in tumor stem-like cells by suppressing FAS (we first isolated cancer stem-like cells (CD24-/CD44+/ESA+) from MDA-MB231)

1489-

RES,

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer

Review,

Var,

RadioS↑,
ChemoSen↑,
*BioAv↓, However, in vivo experimental models have demonstrated that RSV is rapidly metabolized and eliminated, which leads to low bioavailability of the compound. 75% of RSV has been shown to be absorbed orally, only 1% is detected in the blood plasma
*BioAv↑, nanocarrier of RSV-loaded poly (ε-caprolactone)-poly (ethylene glycol) nanoparticles with an erythrocyte membrane. This system improved RSV’s poor water solubility
Ferroptosis↑, SV could induce ferroptotic cell death in colorectal cancer by initiating lipid peroxidation and suppressing the expression of SLC7A11 and GPX4
lipid-P↑,
xCT↓,
GPx4↓,
*BioAv↑, Bioactive or bioenhancer compounds have also been used (piperine, quercetin, biflavone ginkgetin) that, in combination with RSV, improve bioavailability, solubility, absorption, and cellular permeability
COX2↓, inhibiting Cyclooxygenase-COX
cycD1/CCND1↓,
FasL↓,
FOXP3↓,
HLA↑,
p‑NF-kB↓, decrease NF-ĸB phosphorylation
BAX↑,
Bcl-2↓,
MALAT1↓, decrease the expression of the lncRNA MALAT1 in colorectal and gastric cancer cells through the Wnt/β-catenin signaling pathway

2332-

RES,

Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism

Review,

Var,

Glycolysis↓, Resveratrol reduces glucose uptake and glycolysis by affecting Glut1, PFK1, HIF-1α, ROS, PDH, and the CamKKB/AMPK pathway.
GLUT1↓, resveratrol reduces glycolytic flux and Glut1 expression by targeting ROS-mediated HIF-1α activation in Lewis lung carcinoma tumor-bearing mice
PFK1↓,
Hif1a↓, Resveratrol specifically suppresses the nuclear β-catenin protein by inhibiting HIF-1α
ROS↑, Resveratrol increases ROS production
PDH↑, leading to increased PDH activity, inhibiting HK and PFK, and downregulating PKM2 activity
AMPK↑, esveratrol elevated NAD+/NADH, subsequently activated Sirt1, and in turn activated the AMP-activated kinase (AMPK),
TumCG↓, inhibits cell growth, invasion, and proliferation by targeting NF-kB, Sirt1, Sirt3, LDH, PI-3K, mTOR, PKM2, R5P, G6PD, TKT, talin, and PGAM.
TumCI↓,
TumCP↓,
p‑NF-kB↓, suppressing NF-κB phosphorylation
SIRT1↑, Resveratrol activates the target subcellular histone deacetylase Sirt1 in various human tissues, including tumors
SIRT3↑,
LDH↓, decreases glycolytic enzymes (pyruvate kinase and LDH) in Caco2 and HCT-116 cells
PI3K↓, Resveratrol also targets “classical” tumor-promoting pathways, such as PI3K/Akt, STAT3/5, and MAPK, which support glycolysis
mTOR↓, AMPK activation further inhibits the mTOR pathway
PKM2↓, inhibiting HK and PFK, and downregulating PKM2 activity
R5P↝,
G6PD↓, G6PDH knockdown significantly reduced cell proliferation
TKT↝,
talin↓, induces apoptosis by targeting the pentose phosphate and talin-FAK signaling pathways
HK2↓, Resveratrol downregulates glucose metabolism, mainly by inhibiting HK2;
GRP78/BiP↑, resveratrol stimulates GRP-78, and decreases glucose uptake,
GlucoseCon↓,
ER Stress↑, resveratrol-induced ER-stress leads to apoptosis of CRC cells
Warburg↓, Resveratrol reverses the Warburg effect
PFK↓, leading to increased PDH activity, inhibiting HK and PFK, and downregulating PKM2 activity

879-

RES,

Evidence that TNF-β induces proliferation in colorectal cancer cells and resveratrol can down-modulate it

in-vitro,

CRC,

HCT116

TumCP↓, resveratrol reversed the TNF-β-induced proliferation
NF-kB↓,

2987-

RES,

Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1

in-vivo,

Nor,

demonstrated in rat myocardial infarction (MI) model

*VEGF↑, effect of resveratrol on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI.
*iNOS↑, Pretreatment with resveratrol also increased nitric-oxide synthase (inducible NOS and endothelial NOS) along with increased antiapoptotic and proangiogenic factors nuclear factor (NF)-kappaB and specificity protein (SP)-1.
*NF-kB↑,
*Sp1/3/4↑,
*cardioP↑, demonstrate increased capillary density as well as improved left ventricular function by pharmacological preconditioning with resveratrol 3 wk after MI

2441-

RES,

Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions

Review,

Var,

*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↓,

2687-

RES,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

NA,

Review,

AD,

NF-kB↓, RES affects NF-kappaB activity and inhibits cytochrome P450 isoenzyme (CYP A1) drug metabolism and cyclooxygenase activity.
P450↓,
COX2↓,
Hif1a↓, RES may inhibit also the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) and thus may have anti-cancer properties
VEGF↓,
*SIRT1↑, RES induces sirtuins, a class of proteins involved in regulation of gene expression. RES is also considered to be a SIRT1-activating compound (STACs).
SIRT1↓, In contrast, decreased levels of SIRT1 and SIRT2 were observed after treatment of BJ cells with concentrations of RES
SIRT2↓,
ChemoSen⇅, However, the effects of RES remain controversial as it has been reported to increase as well as decrease the effects of chemotherapy.
cardioP↑, RES has been shown to protect against doxorubicin-induced cardiotoxicity via restoration of SIRT1
*memory↑, RES has been shown to inhibit memory loss and mood dysfunction which can occur during aging.
*angioG↑, RES supplementation resulted in improved learning in the rats. This has been associated with increased angiogenesis and decreased astrocytic hypertrophy and decreased microglial activation in the hippocampus.
*neuroP↑, RES may have neuroprotective roles in AD and may improve memory function in dementia.
STAT3↓, RES was determined to inhibit STAT3, induce apoptosis, suppress the stemness gene signature and induced differentiation.
CSCs↓,
RadioS↑, synergistically increased radiosensitivity. RES treatment suppressed repair of radiation-induced DNA damage
Nestin↓, RES decreased NESTIN
Nanog↓, RES was determined to suppress the expression of NANOG
TP53↑, RES treatment activated TP53 and p21Cip1.
P21↑,
CXCR4↓, RES downregulated nuclear localization and activity of NF-kappa-B which resulted in decreased expression of MMP9 and C-X-C chemokine receptor type 4 (CXCR4), two proteins associated with metastasis.
*BioAv↓, The pharmacological properties of RES can be enhanced by nanoencapsulation. Normally the solubility and stability of RES is poor.
EMT↓, RES was determined to suppress many gene products associated with EMT such as decreased vimentin and SLUG expression but increased E-cadherin expression.
Vim↓,
Slug↓,
E-cadherin↑,
AMPK↑, RES can induce AMPK which results in inhibition of the drug transporter MDR1 in oxaliplatin-resistant (L-OHP) HCT116/L-OHP CRCs.
MDR1↓,
DNAdam↑, RES induced double strand DNA breaks by interfering with type II topoisomerase.
TOP2↓, The DNA damage was determined to be due to type II topoisomerase poisoning.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt.
Akt↓,
Wnt↓, RES was shown to decrease WNT/beta-catenin pathway activity and the downstream targets c-Myc and MMP-7 in CRC cells.
β-catenin/ZEB1↓,
cMyc↓,
MMP7↓,
MALAT1↓, RES also decreased the expression of long non-coding metastasis associated lung adenocarcinoma transcript 1 (RNA-MALAT1) in the LoVo and HCT116 CRC cells.
TCF↓, Treatment of CRC cells with RES resulted in decreased expression of transcription factor 4 (TCF4), which is a critical effector molecule of the WNT/beta-catenin pathway.
ALDH↓, RES was determined to downregulate ALDH1 and CD44 in HNC-TICs in a dose-dependent fashion.
CD44↓,
Shh↓, RES has been determined to decrease IL-6-induced Sonic hedgehog homolog (SHH) signaling in AML.
IL6↓, RES has been shown to inhibit the secretion of IL-6 and VEGF from A549 lung cancer cells
VEGF↓,
eff↑, Combined RES and MET treatment resulted in a synergistic response in terms of decreased TP53, gammaH2AX and P-Chk2 expression. Thus, the combination of RES and MET might suppress some of the aging effects elicited by UVC-induced DNA damage
HK2↓, RES treatment resulted in a decrease in HK2 and increased mitochondrial-induced apoptosis.
ROS↑, RES was determined to shut off the metabolic shift and increase ROS levels and depolarized mitochondrial membranes.
MMP↓,

2566-

RES,

A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke

Review,

Stroke,

*neuroP↑, comprehensive overview of resveratrol's neuroprotective role in IS
*NRF2↑, Findings from previous studies suggest that Nrf2 activation can significantly reduce brain injury following IS and lead to better outcomes
*SIRT1↑, neuroprotective effects by activating nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) pathways.
*PGC-1α↑, IRT1 activation by resveratrol triggers the deacetylation and activation of downstream targets like peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and forkhead box protein O (FOXO)
*FOXO↑,
*HO-1↑, ctivation of NRF2 through resveratrol enhances the expression of antioxidant enzymes, like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), which neutralize reactive oxygen species and mitigate oxidative stress in the ischemic bra
*NQO1↑,
*ROS↓,
*BP↓, Multiple studies have demonstrated that resveratrol presented protective effects in IS, it can mediate blood pressure and lipid profiles which are the main key factors in managing and preventing stroke
*BioAv↓, The residual quantity of resveratrol undergoes metabolism, with the maximum reported concentration of free resveratrol being 1.7–1.9 %
*Half-Life↝, The levels of resveratrol peak 60 min following ingestion. Another study found that within 6 h, there was a further rise in resveratrol levels. This increase can be attributed to intestinal recirculation of metabolites
*AMPK↑, Resveratrol also increases AMPK and inhibits GSK-3β (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces ROS
*GSK‐3β↓,
*eff↑, Furthermore, oligodendrocyte survival is boosted by resveratrol, which may help to preserve brain homeostasis following a stroke
*AntiAg↑, resveratrol may suppress platelet activation and aggregation caused by collagen, adenosine diphosphate, and thrombin
*BBB↓, Although resveratrol is a highly hydrophobic molecule, it is exceedingly difficult to penetrate a membrane like the BBB. However, an alternate administration is through the nasal cavity in the olfactory area, which results in a more pleasant route
*Inflam↓, Resveratrol's anti-inflammatory effects have been demonstrated in many studies
*MPO↓, Resveratrol dramatically lowered the amounts of cerebral infarcts, neuronal damage, MPO activity, and evans blue (EB) content in addition to neurological impairment scores.
*TLR4↓, TLR4, NF-κB p65, COX-2, MMP-9, TNF-α, and IL-1β all had greater levels of expression after cerebral ischemia, whereas resveratrol decreased these amounts
*NF-kB↓,
*p65↓,
*MMP9↓,
*TNF-α↓,
*IL1β↓,
*PPARγ↑, Previous studies have shown that resveratrol activates the PPAR -γ coactivator 1α (PGC-1 α), which has free radical scavenging properties
*MMP↑, Resveratrol can prevent mitochondrial membrane depolarization, preserve adenosine triphosphate (ATP) production, and inhibit the release of cytochrome c
*ATP↑,
*Cyt‑c∅,
*mt-lipid-P↓, mitochondrial lipid peroxidation (LPO), protein carbonyl, and intracellular hydrogen peroxide (H2O2) content were significantly reduced in the resveratrol treatment group, while the expression of HSP70 and metallothionein were restored
*H2O2↓,
*HSP70/HSPA5↝,
*Mets↝,
*eff↑, Shin et al. showed that 5 mg/kg intravenous (IV) resveratrol reduced infarction volume by 36 % in an MCAO mouse model.
*eff↑, This study indicates that resveratrol holds the potential to improve stroke outcomes before ischemia as a pre-treatment strategy
*motorD↑, resveratrol treatment significantly reduced infarct volume and prevented motor impairment, increased glutathione, and decreased MDA levels compared to the control group,
*MDA↓,
*NADH:NAD↑, Resveratrol treatment significantly enhanced the intracellular NAD+/NADH ratio
eff↑, Pretreatment with resveratrol (20 or 40 mg/kg) significantly lowered the cerebral edema, infarct volume, lipid peroxidation products, and inflammatory markers
eff↑, Intraperitoneal administration of resveratrol at a dose of 50 mg/kg reduced cerebral ischemia reperfusion damage, brain edema, and BBB malfunction

4667-

RES,

CUR,

SFN,

Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models

Review,

Var,

CSCs↓, phytochemicals such as resveratrol, curcumin, sulforaphane, and others suppress CSC-associated pathways as well as sensitize CSCs to chemotherapy and radiotherapy
ChemoSen↑,
RadioS↑,
ALDH↓, deplete ALDH+ or CD44+ CSC pools, which ultimately decrease tumor initiation and recurrence.
CD44↓,
Wnt↓, graphical abstract
β-catenin/ZEB1↓,
NOTCH↓,
HH↓,
NF-kB↓,

3921-

VitD3,

RES,

Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice

in-vivo,

AD,

SAMP8 Mice

*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,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 26

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

cardioP↑, 1, chemoPv↑, 1,
Total Targets: 167

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 7, Catalase↑, 3, GPx↑, 2, GSH↑, 4, GSR↑, 1, GSTs↑, 1, H2O2↓, 1, HO-1↑, 5, lipid-P↓, 3, mt-lipid-P↓, 1, MDA↓, 2, Mets↝, 1, MPO↓, 2, NQO1↑, 2, NRF2↑, 1, ROS↓, 7, ROS↑, 1, SOD↑, 2,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1, MMP↑, 2, PGC-1α↓, 1, PGC-1α↑, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, AMPK↑, 5, p‑CREB↑, 2, GlutMet↑, 1, NADH:NAD↑, 1, PPARγ↑, 1, SIRT1↑, 7,

Cell Death ⓘ

BAX↓, 1, Bcl-2↑, 1, Casp3↓, 1, Cyt‑c∅, 1, iNOS↓, 1, iNOS↑, 1,

Kinase & Signal Transduction ⓘ

Sp1/3/4↑, 1,

Transcription & Epigenetics ⓘ

other↑, 2,

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↝, 1,

Proliferation, Differentiation & Cell State ⓘ

FOXO↑, 1, GSK‐3β↓, 1, GSK‐3β↑, 1,

Migration ⓘ

AntiAg↑, 3, miR-155↓, 1, MMP3↓, 1, MMP9↓, 4, PKA↑, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1, NO↓, 2, VEGF↓, 1, VEGF↑, 1,

Barriers & Transport ⓘ

BBB↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 3, IL1β↓, 3, IL6↓, 2, Inflam↓, 6, NF-kB↓, 6, NF-kB↑, 1, p‑NF-kB↓, 1, p65↓, 1, PGE2↓, 1, TLR4↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

BDNF↑, 1, p‑tau↓, 2,

Protein Aggregation ⓘ

Aβ↓, 3, BACE↓, 2, NLRP3↓, 2, PP2A↑, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 4, BioAv↑, 3, BioAv↝, 1, Dose↝, 2, eff↑, 3, Half-Life↓, 1, Half-Life↝, 1,

Clinical Biomarkers ⓘ

ALAT↓, 1, AST↓, 1, BP↓, 1, IL6↓, 2,

Functional Outcomes ⓘ

cardioP↑, 2, chemoPv↑, 1, cognitive↑, 3, hepatoP↑, 2, memory↑, 3, motorD↑, 1, neuroP↑, 7, toxicity↓, 1, toxicity∅, 1,
Total Targets: 88

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B

26 Resveratrol
2 Curcumin
1 Silver-NanoParticles
1 Ginger/6-Shogaol/Gingerol
1 Pterostilbene
1 Sulforaphane (mainly Broccoli)
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#:214  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Resveratrol, , NF-kB

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Home Page