Database Query Results : Resveratrol, , MMP9

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

MMP9, MMP9: Click to Expand ⟱

Source: HalifaxProj(suppress)

Type:

Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.

Scientific Papers found: Click to Expand⟱

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.

3078-

RES,

The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment

Review,

Pca,

*ROS↓, RSV appears to be both pro- and anti-oxidant, depending on the circumstances [76]. In non-cancer tissues, RSV serves as an antioxidant [77], and therefore RSV can exert a beneficial effect on a wide variety of issues, including neuronal [78], anti-in
ROS↑, However, to cancer cells with low pH environments due to the Warburg Effect, RSV shows more pro-oxidant characteristics.
DNAdam↑, RSV can induce cancer cell death by inducing ROS accumulation, which subsequently leads to oxidative DNA damage and apoptosis
Apoptosis↑,
Hif1a↑, Wang et al. demonstrated that RSV-enhanced cancer cell death is due to the upregulation of HIF1α, which enhances ROS concentration in the TME beyond the limit for survival
Casp3↑, superoxide can activate caspases 9 and 3, and subsequently promote the release of cytochrome C
Casp9↑,
Cyt‑c↑,
Dose↝, It is important to note that low concentration of RSV can serve as a pro-oxidant that favors cell survival, and pro-apoptotic effects occur only at relatively higher RSV concentrations to stimulate superoxide production.
MMPs↓, inhibitory effect of RSV on MMPs has been shown in many cancer types, and RSV is capable of inhibiting both MMP-2 and MMP-9
MMP2↓,
MMP9↓,
EMT↓, RSV can restore the epithelial phenotype of the mesenchymal cells and inhibit the expression of EMT-related markers
E-cadherin↑, RSV can inhibit EMT by up- and downregulating E-cadherin and N-cadherin, respectively, in prostate cancer cells.
N-cadherin↓,
AR↓, RSV can repress AR function by inhibiting AR transcriptional activity

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↓,

3083-

RES,

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MDA-MB-468

YAP/TEAD↓, we demonstrate that resveratrol decreases the expression of YAP target genes
Rho↓, Strikingly, we also demonstrate that resveratrol inactivates RhoA, leading to the activation of Lats1 and induction of YAP phosphorylation.
FAK↓, REV decreases breast cancer cell invasion by inhibiting FAK,44 Rac and Cdc4245 activities
MMP9↓, REV has been shown to downregulate MMP-9 expression
ChemoSen↑, REV enhances the anticancer effects of doxorubicin in breast cancer cells
RAS↓, we reported that REV suppresses LPA-induced EGF receptor activation and subsequent inhibition a Ras/RhoA/ROCK signaling in ovarian cancer cells
ROCK1↓,
TumCI↓, REV may be used to reduce invasion and metastasis of breast cancer cells to improve outcomes for this devastating disease.
TumMeta↓,

3086-

RES,

Resveratrol inhibits the tumor migration and invasion by upregulating TET1 and reducing TIMP2/3 methylation in prostate carcinoma cells

in-vitro,

Pca,

LNCaP

136.1uM± 1.043 Î¼M

in-vitro,

Pca,

PC3

in-vitro,

Pca,

DU145

162.5uM± 1.122 Î¼M at 48 hours,

TET1↑, Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level.
TumCMig↓, Res also inhibited the migration and invasion of PCa cells
TumCI↓,
TIMP2↑, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9.
TIMP3↑,
MMP2↓,
MMP9↓,

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

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↑,

4657-

RES,

Resveratrol, cancer and cancer stem cells: A review on past to future

Review,

Var,

CSCs↓, RSV is reported to regulate all the major CSC signaling pathways, but exact mechanisms of its interactions are not clearly understood
CD133↓, CD133(+) cells ↓
Shh↓, Sonic hedgehog (Shh) ↓
Twist↓, GBM Stem cell marker expression: Twist ↓, Snail↓, Slug ↓, MMP-2 ↓, MMP-9 ↓, Smad ↓
Snail↓,
MMP2↓,
MMP9↓,
Smad1↓,
CD44↓, CSC marker proteins: CD44, CD133, ALDH1A1, Oct-4, Nanog ↓
ALDH1A1↓,
OCT4↓,
Nanog↓,
STAT3↓, STAT3 ↓
survivin↓, Survivin, cyclin D1, Cox-2 and c-Myc ↓
cycD1/CCND1↓,
COX2↓,
cMyc↓,

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

3613-

RES,

Resveratrol for Alzheimer's disease

Review,

AD,

*SIRT1↑, Resveratrol is a potent activator of SIRT1, and thus may mimic caloric restriction to prevent diseases of aging.
*BioAv↝, Resveratrol (1) is detectable in cerebrospinal fluid (at low nanomolar levels),
*toxicity↓, (2) is safe and well tolerated
*ROS↓, Through SIRT1 activation, resveratrol may protect neurons from reactive oxygen species (ROS), hydrogen peroxide free radicals,
*antiOx↑, Similarly, its antioxidant capabilities may decrease the generation of Aβ through inhibition of ROS-activated enzymes
*Aβ↓,
*MMP9↓, 50% decrease in CSF matrix metalloproteinase 9 (MMP-9) level with resveratrol
*TNF-α↓, we found reduced plasma levels of the pro-inflammatory markers IL-1r4, IL-12P40, IL-12P70, and TNF-α in the treatment group

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

3095-

RES,

Resveratrol suppresses migration, invasion and stemness of human breast cancer cells by interfering with tumor-stromal cross-talk

in-vitro,

BC,

TumCP↓, Resveratrol inhibited proliferation, migration and invasion of human breast cancer cells treated with CAF conditioned media.
TumCMig↓,
TumCI↓,
cycD1/CCND1↓, Resveratrol suppressed the expression of cyclin D1, c-Myc, MMP-2, MMP-9 and Sox-2 in breast cancer cells stimulated with CAFs
cMyc↓,
MMP2↓,
MMP9↓,
SOX2↓,
Akt↓, Resveratrol inhibited activation of Akt and STAT3 induced in human breast cancer cells stimulated with CAF conditioned media.
STAT3↓,
α-SMA↓, resveratrol suppressed the proliferation of liver myofibroblasts through inhibition of α-smooth muscle actin (α-SMA)

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)

3092-

RES,

Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action

Review,

BC,

MDA-MB-231

Review,

BC,

MCF-7

TumCP↓, The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis.
tumCV↓,
TumCI↓,
TumMeta↓,
*antiOx↑, antioxidative, cardioprotective, estrogenic, antiestrogenic, anti-inflammatory, and antitumor properties it has been used against several diseases, including diabetes, neurodegenerative diseases, coronary diseases, pulmonary diseases, arthritis, and
*cardioP↑,
*Inflam↓,
*neuroP↑,
*Keap1↓, RES administration resulted in a downregulation of Keap1 expression, therefore, inducing Nrf2 signaling, and leading to a decrease in oxidative damage
*NRF2↑,
*ROS↓,
p62↓, decrease the severity of rheumatoid arthritis by inducing autophagy via p62 downregulation, decreasing the levels of interleukin-1β (IL-1β) and C-reactive protein as well as mitigating angiopoietin-1 and vascular endothelial growth factor (VEGF) path
IL1β↓,
CRP↓,
VEGF↓,
Bcl-2↓, RES downregulates the levels of Bcl-2, MMP-2, and MMP-9, and induces the phosphorylation of extracellular-signal-regulated kinase (ERK)/p-38 and FOXO4
MMP2↓,
MMP9↓,
FOXO4↓,
POLD1↓, The in vivo experiment involving a xenograft model confirmed the ability of RES to reduce tumor growth via POLD1 downregulation
CK2↓, RES reduces the expression of casein kinase 2 (CK2) and diminishes the viability of MCF-7 cells.
MMP↓, Furthermore, RES impairs mitochondrial membrane potential, enhances ROS generation, and induces apoptosis, impairing BC progression
ROS↑,
Apoptosis↑,
TumCCA↑, RES has the capability of triggering cell cycle arrest at S phase and reducing the number of 4T1 BC cells in G0/G1 phase
Beclin-1↓, RES administration promotes cytotoxicity of DOX against BC cells by downregulating Beclin-1 and subsequently inhibiting autophagy
Ki-67↓, Reducing the Ki-67
ATP↓, RES’s administration is responsible for decreasing ATP production and glucose metabolism in MCF-7 cells.
GlutMet↓,
PFK↓, RES decreased PFK activity, preventing glycolysis and glucose metabolism in BC cells and decreasing cellular growth rate
TGF-β↓, RES (12.5–100 µM) inhibited TGF-β signaling and reduced the expression levels of its downstream targets that include Smad2 and Smad3 and as a result impaired the progression of BC cells.
SMAD2↓,
SMAD3↓,
Vim?, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Snail↓,
Slug↓,
E-cadherin↑,
EMT↓,
Zeb1↓, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Fibronectin↓,
IGF-1↓, RES administration (10 and 20 µM) impaired the migration and invasion of BC cells via inhibiting PI3K/Akt and therefore decreasing IGF-1 expression and preventing the upregulation of MMP-2
PI3K↓,
Akt↓,
HO-1↑, The activation of heme oxygenase-1 (HO-1) signaling by RES reduced MMP-9 expression and prevented metastasis of BC cells
eff↑, RES-loaded gold nanoparticles were found to enhance RES’s ability to reduce MMP-9 expression as compared to RES alone
PD-1↓, RES inhibited PD-1 expression to promote CD8+ T cell activity and enhance Th1 immune responses.
CD8+↑,
Th1 response↑,
CSCs↓, RES has the ability to target CSCs in various tumors
RadioS↑, RES in reversing drug resistance and radio resistance.
SIRT1↑, RES administration (12.5–200 µmol/L) promotes sensitivity of BC cells to DOX by increasing Sirtuin 1 (SIRT1) expression
Hif1a↓, downregulating HIF-1α expression, an important factor in enhancing radiosensitivity
mTOR↓, mTOR suppression

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

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 18

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1,
Total Targets: 129

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 6, Catalase↑, 2, GPx↑, 2, GSH↑, 3, GSR↑, 1, GSTs↑, 1, H2O2↓, 1, HO-1↑, 4, Keap1↓, 1, lipid-P↓, 3, mt-lipid-P↓, 1, MDA↓, 1, Mets↝, 1, MPO↓, 1, NQO1↑, 1, NRF2↑, 2, ROS↓, 7, SOD↑, 2,

Mitochondria & Bioenergetics ⓘ

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

Core Metabolism/Glycolysis ⓘ

AMPK↑, 4, p‑CREB↑, 1, GlutMet↑, 1, NADH:NAD↑, 1, PPARγ↑, 1, SIRT1↑, 5,

Cell Death ⓘ

BAX↓, 1, Bcl-2↑, 1, Casp3↓, 1, Cyt‑c∅, 1, iNOS↓, 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↑, 2, MMP3↓, 1, MMP9↓, 5, PKA↑, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Barriers & Transport ⓘ

BBB↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, IL1β↓, 3, IL6↓, 2, Inflam↓, 5, NF-kB↓, 4, p65↓, 1, PGE2↓, 1, TLR4↓, 1, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

BDNF↑, 1, p‑tau↓, 1,

Protein Aggregation ⓘ

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

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BP↓, 1, IL6↓, 2,

Functional Outcomes ⓘ

cardioP↑, 2, chemoPv↑, 1, cognitive↑, 2, memory↑, 2, motorD↑, 1, neuroP↑, 5, toxicity↓, 1, toxicity∅, 1,
Total Targets: 75

Scientific Paper Hit Count for: MMP9, MMP9

18 Resveratrol

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#:203  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Resveratrol, , MMP9

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

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 ⓘ

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